Search

BACKGROUND: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hs-cTn)-based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays. METHODS: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability (ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients. RESULTS: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline-recommended strategy. CONCLUSION: We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care. TRIAL REGISTRATION NUMBERS: Data of following cohorts were used for this project: BACC ( www. CLINICALTRIALS: gov ; NCT02355457), stenoCardia ( www. CLINICALTRIALS: gov ; NCT03227159), ADAPT-BSN ( www.australianclinicaltrials.gov.au ; ACTRN12611001069943), IMPACT ( www.australianclinicaltrials.gov.au , ACTRN12611000206921), ADAPT-RCT ( www.anzctr.org.au ; ANZCTR12610000766011), EDACS-RCT ( www.anzctr.org.au ; ANZCTR12613000745741); DROP-ACS ( https://www.umin.ac.jp , UMIN000030668); High-STEACS ( www. CLINICALTRIALS: gov ; NCT01852123), LUND ( www. CLINICALTRIALS: gov ; NCT05484544), RAPID-CPU ( www. CLINICALTRIALS: gov ; NCT03111862), ROMI ( www. CLINICALTRIALS: gov ; NCT01994577), SAMIE ( https://anzctr.org.au ; ACTRN12621000053820), SEIGE and SAFETY ( www. CLINICALTRIALS: gov ; NCT04772157), STOP-CP ( www. CLINICALTRIALS: gov ; NCT02984436), UTROPIA ( www. CLINICALTRIALS: gov ; NCT02060760).

BackgroundThere is limited "real-world" evidence examining treatment modalities and outcomes in patients with symptomatic peripheral arterial disease undergoing endovascular treatment of femoropopliteal (FP) in-stent restenosis (ISR).Materials and methodsWe compared outcomes in 2,895 patients from the XLPAD registry (NCT01904851) between 2006 and 2019 treated for FP ISR (n = 347) and non-ISR (n = 2,548) lesions. Primary endpoint included major adverse limb events (MALE) at 1 year, a composite of all-cause death, target limb repeat revascularization, or major amputation.ResultsISR patients were more frequently on antiplatelet (94.5% vs 89.4%, p=0.007) and statin (68.9% vs 60.3%, p=0.003) therapies. Lesion length was similar (ISR: 145 ± 99 mm vs. non-ISR: 142 ± 99 mm, p=0.55). Fewer treated ISR lesions were chronic total occlusions (47.3% vs. 53.7%, p=0.02) and severely calcified (22.4% vs. 44.7%, p < 0.001). Atherectomy (63.5% vs. 45.0%, p < 0.001) and drug-coated balloons (DCB; 4.7% vs. 1.7%, p < 0.001) were more frequently used in ISR lesions. The distal embolization rate was higher in ISR lesions (2.4% vs. 0.9%, p=0.02). Repeat revascularization (21.5% vs. 16.7%, p=0.04; Figure) was higher and freedom from MALE at 1 year was significantly lower (87% vs. 92.5%, p < 0.001) in the ISR group.ConclusionAtherectomy and DCB are more frequently used to treat FP ISR lesions. Patients with FP ISR have more intraprocedural distal embolization, higher repeat revascularization procedures, and lower freedom from MALE at 1 year.

Abstract Objectives This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care. Materials and Methods Fifty‐two adult volunteers aged 30–60 years were equally divided into CPC spray (n = 26) and control (n = 26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per‐protocol analysis was conducted for 44 subjects (CPC spray group, n = 23; control group, n = 21). Results At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group. Conclusions CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper. Clinical Trial Registration: University Hospital Medical Information Network UMIN000041140.

Objectives: This study explored the changes in bacterial flora composition and total bacterial count in the saliva and tongue coating, along with the change in the tongue coating index (TCI) following an intervention with 0.3% cetylpyridinium chloride (CPC) mouth spray after professional oral care. Materials and Methods: Fifty‐two adult volunteers aged 30–60 years were equally divided into CPC spray (n = 26) and control (n = 26) groups. All subjects underwent scaling and polishing. The CPC spray group was administered four puffs of CPC spray to the tongue dorsum four times a day for 3 weeks. The control group performed only routine daily oral care (brushing) and did not use any other spray. Bacteriological evaluation of saliva and tongue coating was performed using 16S ribosomal RNA gene sequencing and quantitative polymerase chain reaction. The tongue coating was evaluated to calculate the TCI. A per‐protocol analysis was conducted for 44 subjects (CPC spray group, n = 23; control group, n = 21). Results: At 1 and 3 weeks after CPC spray use, the flora of the saliva and tongue coating changed; the genus Haemophilus was dominant in the CPC spray group, whereas the genus Saccharibacteria was dominant in the control group. The sampling time differed among individual participants, which may have affected the bacterial counts. There was no significant intragroup change in TCI in either group. Conclusions: CPC spray affected the bacterial flora in the saliva and tongue coating, particularly with respect to an increase in the abundance of Haemophilus. However, CPC spray did not change the TCI. These results suggest that it may be optimal to combine CPC spray with a physical cleaning method such as using a tongue brush or scraper. Clinical Trial Registration: University Hospital Medical Information Network UMIN000041140. [ABSTRACT FROM AUTHOR]

Background: Nurses comprise the largest portion of the healthcare workforce worldwide. However, nurse representation in the leadership of clinical research and research funding is largely unknown. The Australasian Nursing and Midwifery Clinical Trials Network was established to provide a coordinated network, focussed on building research capacity in nursing and midwifery. To support this work, this scoping review of nurse‐led randomised controlled trials was conducted to summarise research activity, as well as highlight future research directions, gaps and resources. Midwife‐led trials will be reported elsewhere. Aim: To quantify number, type and quality of nurse‐led randomised controlled trials registered between 2000–2021. Design: A scoping review of RCTs. Data Sources: Medline, Emcare and Scopus were searched from 2000 to August 2021. ANZCTR, NHMRC, MRFF and HRC (NZ) registries were searched from inception to July 2021. Review Methods: This review was informed by the JBI scoping review framework using the PRISMA‐ScR. Results: Our search yielded 188 nurse‐led publications and 279 registered randomised controlled trials. Multiple trials had the same nurse leaders. There were more registrations than publications. Publications were predominantly of high methodological quality; however, there was a reliance on active controls and blinding was low. Trial registrations indicate that universities and hospital/healthcare organisations were the major sources of funding, while publications indicate that Governments and the National Health and Medical Research Council were the main funding bodies. Conclusion: A small number of high‐quality, large‐scale, nationally funded randomised controlled trials were identified, with a larger number of locally funded small trials. There was a disparity between the number of registered trials and those published. Additional infrastructure, funding and career frameworks are needed to enable nurses to design, conduct and publish clinical trials that inform the health system and improve health outcomes. Relevance to Clinical Practice: Research initiated and led by nurses has the potential to improve the health and well‐being of individuals and communities, and current nurse‐led research is of high methodological quality; however, there were very few nurse‐led RCTs, conducted by a small pool of nurse researchers. This gap highlights the need for support in the design, conduct and publishing of nurse‐led RCTs. Patient or Public Contribution: This is a scoping review; therefore, patient or public contribution is not applicable. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to evaluate the quality of intervention studies assessing CBT-I in adult populations with PTSD. Specifically examining overall quality, specific design elements and trends over time. Method: n > 1 studies assessing CBT-I in adult populations with PTSD were included. The Randomized Controlled Trial - Psychotherapy Quality Rating Scale (RCT-PQRS) was used to evaluate study quality. Correlations between overall study quality and publication year were calculated. Results: Nine studies were included. Overall, study quality was rated as moderate. Six design elements were not addressed adequately in most studies. No significant correlation was found. Conclusions: The evidence base is of moderate quality. However, several specific design elements limit their conclusions. Strategies to minimize limitations are discussed. [ABSTRACT FROM AUTHOR]

Clinical case reports (CCRs) provide an important means of sharing clinical experiences about atypical disease phenotypes and new therapies. However, published case reports contain largely unstructured and heterogeneous clinical data, posing a challenge to mining relevant information. Current indexing approaches generally concern document-level features and have not been specifically designed for CCRs. To address this disparity, we developed a standardized metadata template and identified text corresponding to medical concepts within 3,100 curated CCRs spanning 15 disease groups and more than 750 reports of rare diseases. We also prepared a subset of metadata on reports on selected mitochondrial diseases and assigned ICD-10 diagnostic codes to each. The resulting resource, Metadata Acquired from Clinical Case Reports (MACCRs), contains text associated with high-level clinical concepts, including demographics, disease presentation, treatments, and outcomes for each report. Our template and MACCR set render CCRs more findable, accessible, interoperable, and reusable (FAIR) while serving as valuable resources for key user groups, including researchers, physician investigators, clinicians, data scientists, and those shaping government policies for clinical trials.

Aims: Traditionally, evidence in public health has been founded in health sciences using the hierarchy of evidence. In this Commentary, we argue that we need a combination of evidence based on a broad range of scientific disciplines and methodologies to best translate research into improved public health. Methods: Using existing concepts of evidence such as the hierarchy of evidence and the evidence typology, we discuss their pitfalls in public health science and suggest a way forward. We use the case of the MAMAACT intervention to exemplify our claims. Results: Public health does not apply an either/or perspective, but an integrated, theoretically informed approach based on mixed and multiple methods to understand complex health problems and how to tackle them. Ideally, public health decisions should always incorporate scientific evidence, although we need to fully acknowledge that the quality of evidence is defined by more than just being placed highest in the hierarchy of evidence. No method or study design is superior in obtaining evidence, but we need the combined and supplemented contributions from a range of scientific approaches to form a whole. Thus, we propose an integrated, multidisciplinary concept of evidence in the form of cogwheels, where the public health problem followed by the research question(s) will guide the components to be studied and the use of method(s) in an interplay with the decisions of the scientific perspective(s) that include choice of theories. Conclusions: We cannot understand or solve public health challenges without multidisciplinary approaches in a complimentary formation. [ABSTRACT FROM AUTHOR]

BackgroundHuman immunodeficiency virus (HIV) infection is associated with worse outcomes after stroke, but this association is less well-described in sub-Saharan Africa (SSA). We reviewed literature on stroke among people living with HIV (PLWH) in SSA.MethodsWe systematically reviewed published literature for original clinical stroke studies conducted in SSA that included PLWH. We included studies that reported data on presenting characteristics, risk factors, and/or outcomes after stroke.ResultsSeventeen studies (N = 478) met inclusion criteria. At the time of stroke presentation, PLWH had a median age ranging from 32 to 43 years. Subjects had low CD4 counts (median CD4, 108-225 cells/µl), and most were antiretroviral therapy-naïve. Fever, seizures, and concurrent opportunistic infections were common at presentation. Ischemic stroke accounted for up to 96% of strokes, which were mostly located in the anterior circulation territory. In studies comparing PLWH with HIV-uninfected individuals, PLWH had more frequent coagulopathy, greater stroke severity, (72% versus 36% National Institutes of Health Stroke Scale >13, P = .02), longer hospital length of stay (30.5 versus

We describe the National Institutes of Health rare disease consortium for Prader-Willi syndrome (PWS) developed to address concerns regarding medical care, diagnosis, growth and development, awareness, and natural history. PWS results from errors in genomic imprinting leading to loss of paternally expressed genes due to 15q11-q13 deletion, maternal disomy 15 or imprinting defects. The 8 year study was conducted at four national sites on individuals with genetically confirmed PWS and early-onset morbid obesity (EMO) with data accumulated to gain a better understanding of the natural history, cause and treatment of PWS. Enrollment of 355 subjects with PWS and 36 subjects with EMO began in September 2006 with study completion in July 2014. Clinical, genetic, cognitive, behavior, and natural history data were systematically collected along with PWS genetic subtypes, pregnancy and birth history, mortality, obesity, and cognitive status with study details as important endpoints in both subject groups. Of the 355 individuals with PWS, 217 (61%) had the 15q11-q13 deletion, 127 (36%) had maternal disomy 15, and 11 (3%) had imprinting defects. Six deaths were reported in our PWS cohort with 598 cumulative years of study exposure and one death in the EMO group with 42 years of exposure. To our knowledge, this description of a longitudinal study in PWS represents the largest and most comprehensive cohort useful for investigators in planning comparable studies in other rare disorders. Ongoing studies utilizing this database should have a direct impact on care and services, diagnosis, treatment, genotype-phenotype correlations, and clinical outcomes in PWS.

We reviewed clinical data for niraparib monotherapy in BRCA-mutated (BRCAm) epithelial ovarian cancer (OC), contextualizing results with data from other poly(ADP-ribose) polymerase inhibitors (PARPis). Niraparib reduced the likelihood of progression or death by 60% as first-line maintenance therapy and by 73-78% in recurrent disease. In heavily pretreated OC, efficacy was greater in the BRCAm versus non-BRCAm cohort. Quality-of-life (QoL) was maintained throughout treatment. Adverse events were consistent with the known niraparib safety profile. Cumulative efficacy, safety and QoL evidence demonstrate niraparib maintenance monotherapy has a positive benefit:risk ratio in BRCAm OC. Niraparib significantly improved progression-free survival as first-line maintenance therapy in all patients with OC (i.e., of any biomarker status). [ABSTRACT FROM AUTHOR]

Objective: The use of propolis-based materials within endodontics to promote pulp wound healing or disinfect the root canal system has been a recent focus of scientists and clinicians. This is mainly because of the well-documented antimicrobial, anti-inflammatory, immunomodulatory and wound healing properties of propolis. This scoping review critically appraises the literature on the clinical applications of propolis-based compounds during endodontic therapy of primary and permanent teeth., Methods: An electronic literature search was performed in Scopus, PubMed, and Web of Science up to and including October 2023 to identify studies assessing the use of propolis during endodontic therapy of primary and permanent teeth. A combination of relevant MeSh terms and keywords was used. Only human clinical studies written in English were included. The identified manuscripts were screened and assessed for inclusion by two independent authors. Eligible manuscripts were then subjected to critical appraisal and data extraction with the information being summarised according to their clinical application., Results: A total of 26 human clinical studies were identified and included in the analysis. Propolis was investigated for use in the primary and permanent dentitions as a direct pulp capping or pulpotomy material as well as in root canal disinfection and root filling of teeth with non-vital pulps. Overall, the studies reported that the use of propolis was associated with promising outcomes in terms of efficacy to control inflammation, enhance tissue repair, and disinfection of the root canal system. However, a critical appraisal of the studies revealed a range of methodological and reporting deficiencies, resulting in unreliable results and conclusions in terms of the clinical outcomes reported., Conclusion: Although the studies on the use of propolis-based materials in endodontics reported promising clinical outcomes, they had a range of methodological and reporting flaws. Further well-designed and properly reported controlled clinical studies are essential to derive sound evidence-based conclusions on propolis-based materials. Furthermore, guidelines for quality assurance and safe use of propolis-based materials are necessary to enhance their production for commercial use in endodontics.

Aim: This study illustrates parameters, procedures, and calculations for the statistical determination of sample size for different clinical study designs., Materials and Methods: In any research process, the sample size is an important consideration for the implementation of the planned study. From time to time, literature on sample size has been documented in the medical literature. However, the situations covered under them lack comprehensiveness in terms of different study designs, demonstration of calculations, and overreliance on statistical software., Results: The present study provides various facets of sample size determination, such as prerequisite parameters, mathematical formulation, and calculations for clinical study designs [descriptive studies, randomized controlled trials (RCT), correlational studies, comparison of multiple outcomes, survival analysis, sensitivity, and specificity], which will be quite useful., Conclusion: This communication will be a good education and learning source for medical professionals to pick and choose a specific scenario and estimate the sample size., (© Journal of the Association of Physicians of India 2024.)

Introduction: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa., Methods: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients., Discussion: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community., Trial Registration: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213., (© 2024. The Author(s).)

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for the treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies, and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a collaboration of 41 North American centers studying therapy for rare primary immune deficiency diseases (PIDs), including severe combined immune deficiency (SCID), Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD). An additional 3 European centers have partnered with the PIDTC to study CGD. Natural history protocols of the PIDTC analyze outcomes of treatment for rare PIDs in multicenter longitudinal retrospective, prospective, and cross-sectional studies. Since 2009, participating centers have enrolled more than 800 subjects on PIDTC protocols for SCID, and enrollment in the studies on WAS and CGD is underway. Four pilot projects have been funded, and 12 junior investigators have received fellowship awards. Important publications of the consortium describe the outcomes of hematopoietic cell transplantation for SCID during 2000-2009, diagnostic criteria for SCID, and the pilot project of newborn screening for SCID in the Navajo Nation. The PIDTC Annual Scientific Workshops provide an opportunity to strengthen collaborations with junior investigators, patient advocacy groups, and international colleagues. Funded by the National Institute of Allergy and Infectious Diseases and the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, the PIDTC has recently received renewal for another 5 years. Here we review accomplishments of the group, projects underway, highlights of recent workshops, and challenges for the future.

BackgroundElectronic medical records (EMRs) contain vast amounts of data that is of great interest to physicians, clinical researchers, and medial policy makers. As the size, complexity, and accessibility of EMRs grow, the ability to extract meaningful information from them has become an increasingly important problem to solve.MethodsWe develop a standardized data analysis process to support cohort study with a focus on a particular disease. We use an interactive divide-and-conquer approach to classify patients into relatively uniform within each group. It is a repetitive process enabling the user to divide the data into homogeneous subsets that can be visually examined, compared, and refined. The final visualization was driven by the transformed data, and user feedback direct to the corresponding operators which completed the repetitive process. The output results are shown in a Sankey diagram-style timeline, which is a particular kind of flow diagram for showing factors' states and transitions over time.ResultsThis paper presented a visually rich, interactive web-based application, which could enable researchers to study any cohorts over time by using EMR data. The resulting visualizations help uncover hidden information in the data, compare differences between patient groups, determine critical factors that influence a particular disease, and help direct further analyses. We introduced and demonstrated this tool by using EMRs of 14,567 Chronic Kidney Disease (CKD) patients.ConclusionsWe developed a visual mining system to support exploratory data analysis of multi-dimensional categorical EMR data. By using CKD as a model of disease, it was assembled by automated correlational analysis and human-curated visual evaluation. The visualization methods such as Sankey diagram can reveal useful knowledge about the particular disease cohort and the trajectories of the disease over time.

Objective: The COVID-19 pandemic has imposed a great challenge on health research because of the pressing need to respond promptly and effectively to this crisis situation. It is important to offer a high level perspective of the main barriers and facilitators found when conducting health science studies during the COVID-19 crisis and to discuss the research initiatives suggested by global, regional or local health research authorities. Materials and methods: A systematic scoping review was carried out. A literature search was conducted in the Medline, Cochrane Library, Lilacs and Google Scholar databases. Original research studies, review and opinion articles and editorials available in full text published in Spanish, English or Portuguese between January 2020 and May 2021 were included. Two authors working independently selected the papers and collected the data. The barriers and facilitators identified were described and organized in four categories according to the literature: sociocultural, administrative, organizational and methodological. Official documents and communications from global, regional and local health and research authorities were also included. Results are presented in narrative and table form. Results: Overall, 26 documents were selected for data analysis and synthesis. The barriers most frequently mentioned in the literature include issues with access to participants, ethics committees paperwork, biological risk for the researchers, and lack of inter and intra-institutional coordination. On the other hand, the facilitators identified include the adoption of on-line solutions, cooperative work among research actors, and a more flexible informed consent process. Regarding the initiatives disseminated by health and research authorities, four strategies were identified: prioritization of research questions, cooperation and inclusion promotion, fight against infodemia, and strengthening of the methodological quality of the studies. Conclusions: Continued cooperation and interoperability among institutions, countries and disciplines to facilitate future research processes is a challenge in the context of the pandemic; similarly, it is now important to maintain open science and funding of cooperative studies when other priorities emerge. Likewise, there is an evident need to develop and sustain efficient information management systems to help with decision-making. Ongoing review of the effects of the pandemic on health research practice is needed in order to gain comprehensive insights of what we need to learn as a society from this crisis. [ABSTRACT FROM AUTHOR]

Sarah Lehmann,1,2 René Allard,2 Yvonne-Beatrice Boehler1 1Faculty of Applied Natural Sciences, TH Koeln - University of Applied Sciences, Leverkusen, Germany; 2Grünenthal Innovation, Drug Development, Data Sciences’ Grünenthal GmbH, Aachen, GermanyCorrespondence: René Allard Herrengrabenweg 34, Basel 4054, SwitzerlandTel +41 6176 824 0864Email u-allard@t-online.dePurpose: The clinical study report (CSR) documents of a full clinical development pathway (CDP) have been publicly available on the European Medicines Agency (EMA; Amsterdam, Netherlands) clinical data website (ECDW) since October 2016. Our analysis aimed to determine the extent to which the available clinical development program could be assessed.Methods: The documents available on the ECDW up to April 1, 2018 and the corresponding European Public Assessment Report (EPAR) were reviewed. Information extracted from the available CSRs focused on dates, phase of development, module leaf structure, and number of protocol amendments. Data analyses included generalized activity normalization time table (GANTT) charts and network analyses.Results: Of the 86 available CDPs, 55 were initial marketing authorizations covering a diverse range of clinical developments from generics to advanced therapy in the electronic common technical documents (eCTDs). Non-redacted dates were available in 444 CSRs from 15 CDPs to perform retrospective project clinical development management analyses. In these 15 marketing authorizations, the median timespan to submission was 9.3 years (range: 6.2–22.2). The timespan within these 15 clinical developments ranged from 5.9 to 21.4 years (median 8.3). The median time to first-subject-in in the first controlled clinical study pertinent to the claimed indication (CCSPCI) was 4.4 years (range: 0–12.1); the duration of the CCSPCI ranged from 2.4 to 16.9 years (median: 4.4; interquartile range: 4.2–7.0). Four CDPs had concurrent subject enrolment, while seven CDPs had seamless study designs. Subject participation ranged from 52% to 97% of a clinical development timeline.Conclusion: The publication of CSR documents by the EMA has enabled insights into timelines and project management aspects of the clinical development of medications.Keywords: drug approval, clinical studies as topic, health information management, EMA Policy 0070, information dissemination

Aim: Although bulk fill composites have been widely used as restorative material, there is no consensus regarding the best clinical protocol in terms of composite technique and adhesive system. Therefore, this clinical trial evaluated the clinical performance of bulk fill composites for class I restorations under different protocols. Methods: A randomized clinical trial including 155 class I restorations was conducted using different adhesive systems: conventional technique (phosphoric acid + conventional three-step adhesive system) (Group 1, 2 and 3); or self-etching adhesive system (Groups 4, 5 and 6). Control groups 1 and 4 were restored with conventional composite; groups 2 and 5 with low viscosity bulk fill and conventional composite as occlusal coverage; groups 3 and 6 with high viscosity bulk fill. The FDI criteria was used for clinical evaluation at baseline and after 6 months. Results: All groups showed good clinical performance. At baseline, the adhesive system did not affect postoperative hypersensitivity. After 6 months, group 5 showed a significant reduction in color and translucency; group 6 a reduction in terms of anatomical form and for postoperative sensitivity and an improvement in patient satisfaction (p

Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss.

Objective: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study)., Methods: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study., Results: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change., Conclusions: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Pediatric patients with homozygous familial hypercholesterolemia (HoFH) have an increased risk of atherosclerotic cardiovascular disease and difficulty meeting low-density lipoprotein cholesterol (LDL-C) goals. In this post hoc analysis, we evaluated pooled safety and efficacy data from 3 studies in pediatric patients with HoFH treated with the PCSK9 (proprotein convertase subtilisin/kexin type 9) monoclonal antibody inhibitor evolocumab., Methods: Patients with HoFH aged 10 to 17 years received treatment with open-label evolocumab 420 mg subcutaneously monthly or biweekly in the TAUSSIG, RAMAN, or HAUSER-OLE clinical studies. All patients received background statins with or without ezetimibe. Study duration ranged from 12 to 260 weeks. The primary end point was treatment-emergent adverse events per 100 patient-years. Efficacy end points were changes from baseline to week 12 in lipids and PCSK9., Results: Of the 39 patients in the pooled analysis, 69.2% were males, median age was 13.0 years, and 79.5% (31/39) had genotyped HoFH with LDLR pathogenic variants. Overall, median exposure to evolocumab was 18.2 (Q1, Q3: 3.0, 18.5) months. Treatment-emergent adverse events with an exposure-adjusted patient incidence rate of ≥5% were upper respiratory tract infection (6.6%), influenza (5.2%), and acne (5.0%) per 100 patient-years. Exposure-adjusted patient incidence of serious treatment-emergent adverse events was 13.3% per 100 patient-years. Excluding 4 patients receiving lipoprotein apheresis, week 12 median percentage change from baseline in LDL-C was -2.9% (Q1, Q3: -21.7, 1.5); however, 42.9% (15/35) of patients achieved ≥15% reduction in LDL-C from baseline. Residual LDLR (LDL receptor) activity was not associated with a reduction in LDL-C., Conclusions: In this pooled data analysis from 3 studies in pediatric patients with HoFH, evolocumab was well tolerated, with no new safety signals reported. These safety findings are consistent with findings from previous studies of evolocumab. Patients showed marked variability in LDL-C reduction. Results from this pooled analysis support guidelines suggesting a trial of PCSK9 inhibitor therapy regardless of estimated residual LDLR function., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01624142, NCT03403374, and NCT02624869., Competing Interests: Disclosures F.J. Raal has received research grants, honoraria, or consulting fees for professional input and lectures from Sanofi, Regeneron, Amgen, and Novartis; and travel support to attend the 2023 European Atherosclerosis Society (EAS) Congress from EAS. R.A. Hegele reports receiving consulting fees from Acasti, Aegerion, Akcea/Ionis, Amgen, Boston Heart, HLS Therapeutics, Novartis, Pfizer, Regeneron, Sanofi, and Ultragenyx; and lecture fees from Amgen, HLS Therapeutics, and Novartis. A. Ruzza is a former employee and a stockholder of Amgen. He is a current employee and a stockholder of GlaxoSmithKline. He holds a pending patent application PCT/US2021/034489 on PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors and methods of use thereof to treat cholesterol-related disorders. J.A.G. López, A.K. Bhatia, H. Wang, and J. Wu are employees and stockholders of Amgen. D. Gaudet reports receiving research grants, honoraria, or consulting fees for professional input and lectures from Alnylam, Amgen, Applied Therapeutics, Arrowhead, Boehringer Ingelhein, Chiesi (Amryt), CRISPR Therapeutics, Eli Lilly, Esperion, Ionis, Kowa, New Amsterdam Pharma, Novartis, Novo Nordisk, Pfizer, Regeneron, Sanofi, Ultragenyx, Uniqure, and Verve Therapeutics. A. Wiegman reports research support for pharmaceutical trials of lipid-lowering agents from Amgen, Sanofi-Regeneron Pharmaceuticals, Novartis, Silence Therapeutics, Esperion, and Ultragenyx; and is member of a safety board for Amryt. R.D. Santos reports receiving consulting fees and lecture fees from Abbott, Amgen, Amryt, AstraZeneca, Aché, Biolab, Getz Pharma, Eli Lilly, Libbs, Merck, PTC Therapeutics, Novo Nordisk, Novartis, and Sanofi-Regeneron Pharmaceuticals; and grant support from Amgen, Kowa, Esperion, Novartis, and Sanofi-Regeneron Pharmaceuticals. The other author reports no conflicts.

Background: Long covid (post covid-19 condition) is a complex condition with diverse manifestations, uncertain prognosis and wide variation in current approaches to management. There have been calls for formal quality standards to reduce a so-called "postcode lottery" of care. The original aim of this study-to examine the nature of quality in long covid care and reduce unwarranted variation in services-evolved to focus on examining the reasons why standardizing care was so challenging in this condition., Methods: In 2021-2023, we ran a quality improvement collaborative across 10 UK sites. The dataset reported here was mostly but not entirely qualitative. It included data on the origins and current context of each clinic, interviews with staff and patients, and ethnographic observations at 13 clinics (50 consultations) and 45 multidisciplinary team (MDT) meetings (244 patient cases). Data collection and analysis were informed by relevant lenses from clinical care (e.g. evidence-based guidelines), improvement science (e.g. quality improvement cycles) and philosophy of knowledge., Results: Participating clinics made progress towards standardizing assessment and management in some topics; some variation remained but this could usually be explained. Clinics had different histories and path dependencies, occupied a different place in their healthcare ecosystem and served a varied caseload including a high proportion of patients with comorbidities. A key mechanism for achieving high-quality long covid care was when local MDTs deliberated on unusual, complex or challenging cases for which evidence-based guidelines provided no easy answers. In such cases, collective learning occurred through idiographic (case-based) reasoning, in which practitioners build lessons from the particular to the general. This contrasts with the nomothetic reasoning implicit in evidence-based guidelines, in which reasoning is assumed to go from the general (e.g. findings of clinical trials) to the particular (management of individual patients)., Conclusion: Not all variation in long covid services is unwarranted. Largely because long covid's manifestations are so varied and comorbidities common, generic "evidence-based" standards require much individual adaptation. In this complex condition, quality improvement resources may be productively spent supporting MDTs to optimise their case-based learning through interdisciplinary discussion. Quality assessment of a long covid service should include review of a sample of individual cases to assess how guidelines have been interpreted and personalized to meet patients' unique needs., Study Registration: NCT05057260, ISRCTN15022307., (© 2024. The Author(s).)

Background: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited., Aims: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function., Methods: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI)., Results: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition)., Conclusions: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

Background: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations., Methods: We previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome., Results: Between April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77-0.82]) and 12-month (AUC 0.74 [95% CI 0.71-0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69-0.78) both alone and when combined with some EEG features (accuracies 0.73-0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02-1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04-3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40-5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12-5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41-15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46-4.19])., Conclusions: Our results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge., (© 2023. The Author(s).)

Background: Opioid agonist treatment (OAT) for patients with opioid use disorder (OUD) has a convincing evidence base, although variable retention rates suggest that it may not be beneficial for all. One of the options to include more patients is the introduction of heroin-assisted treatment (HAT), which involves the prescribing of pharmaceutical heroin in a clinical supervised setting. Clinical trials suggest that HAT positively affects illicit drug use, criminal behavior, quality of life, and health. The results are less clear for longer-term outcomes such as mortality, level of function and social integration. This protocol describes a longitudinal evaluation of the introduction of HAT into the OAT services in Norway over a 5-year period. The main aim of the project is to study the individual, organizational and societal effects of implementing HAT in the specialized healthcare services for OUD., Methods: The project adopts a multidisciplinary approach, where the primary cohort for analysis will consist of approximately 250 patients in Norway, observed during the period of 2022-2026. Cohorts for comparative analysis will include all HAT-patients in Denmark from 2010 to 2022 (N = 500) and all Norwegian patients in conventional OAT (N = 8300). Data comes from individual in-depth and semi-structured interviews, self-report questionnaires, clinical records, and national registries, collected at several time points throughout patients' courses of treatment. Qualitative analyses will use a flexible inductive thematic approach. Quantitative analyses will employ a wide array of methods including bi-variate parametric and non-parametric tests, and various forms of multivariate modeling., Discussion: The project's primary strength lies in its comprehensive and longitudinal approach. It has the potential to reveal new insights on whether pharmaceutical heroin should be an integral part of integrated conventional OAT services to individually tailor treatments for patients with OUD. This could affect considerations about drug treatment even beyond HAT-specific topics, where an expanded understanding of why some do not succeed with conventional OAT will strengthen the knowledge base for drug treatment in general. Results will be disseminated to the scientific community, clinicians, and policy makers., Trial Registration: The study was approved by the Norwegian Regional Committee for Medical and Health Research Ethics (REK), ref.nr.:195733., (© 2024. The Author(s).)

Background: Estimated plasma volume status (ePVS) estimated by the Duarte formula is associated with clinical outcomes in patients with heart failure. It remains unclear the predictive value of the ePVS to the postoperative hypotension (POH) in percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) treating hypertrophic obstructive cardiomyopathy (HOCM)., Methods: Data of HOCM patients who underwent PIMSRA were retrospectively collected. Preoperative ePVS was calculated using the Duarte formulas which derived from hemoglobin and hematocrit ratios. Clinical variables including physical assessment, biological and echocardiographic parameters were recorded. Patients were labeled with or without POH according to the medical record in the hospital. Univariable and multivariable logistic regression were performed to evaluate the association between ePVS and POH. Using different thresholds derived from quartiles and the best cutoff value of the receiver operating characteristic curve, the diagnostic performance of ePVS was quantified., Results: Among the 405 patients included in this study, 53 (13.1%) patients were observed with symptomatic POH. Median (IQR) of ePVS in overall patients was 3.77 (3.27~4.40) mL/g and in patients with POH were higher than those without POH. The ePVS was associated with POH, with the odds ratio of 1.669 (95% CI 1.299 ~ 2.144) per mL/g. After adjusted by potential confounders, ePVS remained independently associated with POH, with the approximate odds ratio in different models., Conclusion: The preoperative ePVS derived from the Duarte formulas was independently associated with postoperative hypotension in HOCM patients who underwent PIMSRA and showed prognostic value to the risk stratification of postoperative management., Trial Registration: NCT06003478 (22/08/2023)., (© 2024. The Author(s).)

Background: Autoimmune hemolytic anemia (AIHA) may be associated with transfusion reactions and risk of alloimmunization., Objectives: To evaluate the transfusion policy and rate of alloimmunization and its clinical significance in AIHA., Methods: Data from 305 AIHA patients followed at a reference hematologic Center in Milan, Italy from 1997 to 2022 were retrospectively/prospectively collected (NCT05931718)., Results: Overall, 33% patients required transfusions with a response rate of 83% and eight transfusion reactions (7%), none hemolytic. Alloantibodies were detected in 19% of patients, being associated with higher transfusion burden (p = 0.01), lower Hb increase post-transfusion (p = 0.05), and transfusion reactions (p = 0.04). Along decades, the rate of RBC transfusions decreased from 53% to 20% and that of alloimmunization dropped from 30% to 6% likely due to the adoption of prestorage leukoreduction, the use of more restrictive Hb thresholds, and the implementation of molecular typing., Conclusions: Severe symptomatic AIHA may be safely transfused provided appropriate matching of patients and donors., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: High somatic comorbidity is common among patients in treatment for opioid use disorder (OUD). The present study aims to investigate changes in self-reported somatic health conditions and somatic symptoms among patients entering opioid maintenance treatment (OMT) programs., Methods: We used data from the Norwegian Cohort of Patients in OMT and Other Drug Treatment (NorComt) study. Of 283 patients who entered OMT, 176 were included for analysis at a 1-year follow-up. Participants provided self-reported data during structured interviews on somatic conditions, somatic symptoms, substance use severity measures, and mental distress. A multivariable linear regression analysis identified factors associated with changes in the burden of somatic symptoms., Results: Patients entering OMT reported a high prevalence of somatic conditions at the beginning of treatment, with 3 of 5 patients reporting at least one. The most prevalent condition was hepatitis C, followed by asthma and high blood pressure. Patients reported experiencing a high number of somatic symptoms. The intensity of these symptoms varied across a wide spectrum, with oral health complaints and reduced memory perceived as the most problematic. Overall, for the entire sample, there was no significant change in somatic symptoms from baseline to 1 year. Further analysis indicated that those who reported a higher burden of somatic symptoms at baseline had the greatest improvement at the 1-year follow-up. A higher number of somatic conditions and higher mental distress at baseline was associated with improvements in somatic symptoms burden at follow-up., Conclusions: Patients in OMT report a range of somatic conditions and somatic symptoms. Given the wide range of symptoms reported by patients in OMT, including some at high intensity levels, healthcare providers should take into consideration the somatic healthcare needs of individuals in OMT populations., Clinical Trial Registration: Clinicaltrials.gov no. NCT05182918. Registered 10/01/2022 (the study was retrospectively registered)., (© 2024. The Author(s).)

Objective: Heart failure with preserved ejection fraction (HFpEF) is a common heterogeneous syndrome that remains imprecisely defined and consequently has limited treatment options and poor outcomes., Methods: The UK Heart Failure with Preserved Ejection Fraction Registry (UK HFpEF) is a prospective data-enabled cohort and platform study. The study will develop a large, highly characterised cohort of patients with HFpEF. A biobank will be established. Deep clinical phenotyping, imaging, multiomics and centrally held national electronic health record data will be integrated at scale, in order to reclassify HFpEF into distinct subgroups, improve understanding of disease mechanisms and identify new biological pathways and molecular targets. Together, these will form the basis for developing diagnostics and targeted therapeutics specific to subgroups. It will be a platform for more effective and efficient trials, focusing on subgroups in whom targeted interventions are expected to be effective, with consent in place to facilitate rapid recruitment, and linkage for follow-up. Patients with a diagnosis of HFpEF made by a heart failure specialist, who have had natriuretic peptide levels measured and a left ventricular ejection fraction >40% are eligible. Patients with an ejection fraction between 40% and 49% will be limited to no more than 25% of the cohort., Conclusions: UK HFpEF will develop a rich, multimodal data resource to enable the identification of disease endotypes and develop more effective diagnostic strategies, precise risk stratification and targeted therapeutics., Trial Registration Number: NCT05441839., Competing Interests: Competing interests: CAM has served on advisory boards for AstraZeneca, Boehringer Ingelheim and Lilly Alliance, Novartis, and PureTech Health; serves as an advisor for HAYA Therapeutics; and has received speaker fees from Boehringer Ingelheim and Novo Nordisk, conference attendance support from AstraZeneca and research support from Amicus Therapeutics, AstraZeneca, Guerbet Laboratories, Roche and Univar Solutions. RTL has received research grants from Pfizer and has provided consultancy for FITFILE and HealthLumen. SEP provides consultancy to Circle Cardiovascular Imaging, Calgary, Alberta, Canada., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: The treatment of complex infra-inguinal disease with drug-coated balloons (DCBs) is associated with a significant number of patients undergoing provisional stenting to treat a suboptimal result. To determine the potential long-term impact of DCB treatment with provisional bare metal stenting in complex lesions in real-world patients, a post hoc analysis was performed on data from the IN.PACT Global Study (The IN.PACT Global Clinical Study for the Treatment of Comprehensive Superficial Femoral and/or Popliteal Artery Lesions Using the IN.PACT Admiral Drug-Eluting Balloon). Five-year outcomes were compared between participants who were stented after DCB treatment versus those treated with DCB alone., Methods: The IN.PACT Global Study enrolled 1535 participants with intermittent claudication and/or ischemic rest pain caused by femoropopliteal lesions; 1397 patients were included in this subgroup analysis (353 stented and 1044 nonstented). Effectiveness was assessed as freedom from clinically driven target lesion revascularization through 60 months. The primary safety composite end point was defined as freedom from device- and procedure-related death through 30 days, and freedom from major target limb amputation and clinically driven target vessel revascularization through 60 months., Results: Lesions in the stented group were longer (15.37 versus 10.98 cm; P <0.001) and had more total occlusions (54.7% versus 28.6%; P <0.001) compared with the nonstented group. The 5-year Kaplan-Meier estimated freedom from clinically driven target lesion revascularization was similar between groups (66.8% stented versus 70.0% nonstented group, log-rank P =0.22). The safety composite end point was achieved in 64.5% stented versus 68.2% nonstented participants (log-rank P =0.19) as estimated by the Kaplan-Meier method. No significant difference was observed in the cumulative incidence of major adverse events (49.1% stented versus 45.0% nonstented; log-rank P =0.17), including all-cause death (19.6% stented versus 19.3% nonstented, log-rank P =0.99)., Conclusions: In this real-world study, revascularization of complex femoropopliteal artery lesions with DCB angioplasty alone or DCB followed by provisional bare metal stenting in certain lesions achieved comparable long-term safety and clinical effectiveness., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01609296., Competing Interests: Disclosures Dr Ansel is a consultant for Boston Scientific, Medtronic, Veryan Medical, Cook Medical, Becton Dickinson, Alucent, and Surmodics. Dr Brodmann has received honoraria from Bard Peripheral Vascular, Biotronik, Medtronic, Philips-Spectranetics, and VIVA Physicians. Dr Brodmann is a consultant for Bard Peripheral Vascular, Biotronik, Medtronic, and Philips-Spectranetics. Dr Rocha-Singh is a consultant for Alucent Biomedical and Philips-Spectranetics and received research grant monies from Boston Scientific, Medtronic, and Philips. Mr Menk is a full time employee of Medtronic. Dr Zeller has received honoraria from Abbott Vascular, BIBA Medical, Biotronik, Boston Scientific, Cook Medical, Efemoral, Gore & Associates, Medtronic, Philips-Spectranetics, Shockwave, and Veryan, consulted for Bayer, Boston Scientific, CSI, Gore & Associates, Medtronic, Philips–Spectranetics, Intact Vascular, Shockwave, Veryan, and Vesper Medical Research, and received clinical trial or drug study funds from B. Braun, Bard Peripheral Vascular, Biotronik, Boston Scientific, Cardiovascular Systems, Inc, Cook Medical, Gore & Associates, Intact Vascular, Med Alliance, Medtronic, Philips-Spectranetics, Pluristem, PQ Bypass, Shockwave, Terumo, TriReme, University of Jena, and Veryan, and holds common stock in QT Medical.

Goals: To identify factors associated with transplantation and death in alcohol-associated liver disease (ALD) patients presenting with first evidence of ascites., Background: Ascites development is a poor prognostic sign for patients with cirrhosis. Among ALD patients, the baseline factors at time of ascites development that are associated with eventual transplantation or death are currently unknown., Study: Adult patients with ascites in the "Evaluating Alcohol Use in Alcohol-related Liver Disease Prospective Cohort Study" (NCT03267069 clinicaltrials.gov) were identified from 2016 to 2020. Demographic, clinical, and laboratory factors at initial ascites presentation were identified as potential predictors of transplant and death as competing risks., Results: A total of 96 patients were identified. Median (interquartile range) follow-up time was 2.00 years (0.87 to 3.85). By last follow-up, 34/96 patients had been transplanted (35.4%) and 11/96 had died (11.4%). Prognostic factors for transplant included age per decade [hazard ratio (HR): 0.52 (95% CI, 0.33 to 0.83)], employed status [HR: 0.35 (95% CI, 0.14 to 0.90)], and sodium [HR: 0.94 (95% CI, 0.90 to 0.99)], whereas prognostic factors for death were body mass index [HR: 1.11 (95% CI, 1.00 to 1.22)], Charlson index [HR: 2.14 [95% CI, 1.13 to 4.08]), Maddrey Discriminant Function >32 (HR: 5.88 (95% CI, 1.18, 29.39)], aspartate aminotransferase [HR: 0.99 (95% CI, 0.98 to 0.997)], and a prior 12-month abstinence period [HR: 5.53 (95% CI, 1.10 to 27.83)], adjusted for age, sex, and ALD subcategory., Conclusions: Several factors at initial ascites presentation are associated with increased risk of transplantation or death and validation in larger cohorts will allow for improved risk stratification for ALD patients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Pembrolizumab plus lenvatinib was recently approved for the treatment of advanced or recurrent endometrial carcinoma in women with disease progression on or following prior treatment with a platinum‑containing therapy in any setting, and who are not candidates for curative surgery or radiation (KEYNOTE-775/Study-309; NCT03517449). The objective was to assess the cost effectiveness of pembrolizumab plus lenvatinib compared with chemotherapy from a Swedish healthcare perspective., Materials and Methods: A lifetime partitioned-survival model with three health states (progression free, progressed disease, death) was constructed. Chemotherapy was represented by paclitaxel or doxorubicin. Overall survival, progression-free survival, time on treatment, and utility data were obtained from KEYNOTE-775 (database lock: March 1, 2022). Costs (in 2020 Swedish Krona [SEK]) included drug acquisition and administration, health state, end of life, adverse event management, subsequent treatment, and societal (scenario analysis). Outcomes were calculated as quality-adjusted life-years (QALY) and life-years. Model results were presented as incremental cost-effectiveness ratios for all-comers, patients with proficient mismatch repair tumors, and deficient mismatch repair tumors. Deterministic and probabilistic sensitivity analyses were conducted., Results: Pembrolizumab plus lenvatinib is a cost-effective treatment when compared with chemotherapy, with estimated deterministic and probabilistic incremental cost-effectiveness ratios of SEK 795,712 and 819,757 per QALY gained. Pembrolizumab plus lenvatinib was associated with a large incremental QALY and life-year gain per person versus chemotherapy over the model time horizon (1.49 and 1.76)., Limitations: Time-to-event data were incomplete and semiparametric and parametric curves were utilized for lifetime extrapolation. Willingness-to-pay thresholds, costs, and utility weights vary by country, which would vary the treatment's cost effectiveness in different countries., Conclusions: This partitioned survival analysis suggests that pembrolizumab plus lenvatinib is cost effective compared with chemotherapy in Sweden for women with advanced or recurrent endometrial carcinoma following previous systemic therapy. Results were robust to mismatch repair status and to changes in parameters/assumptions.

Purpose: We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study., Materials and Methods: Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes., Results: The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis., Conclusion: In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

With the emergence of health data warehouses and major initiatives to collect and analyze multi-modal and multisource data, data organization becomes central. In the PACIFIC-PRESERVED (PhenomApping, ClassIFication, and Innovation for Cardiac Dysfunction - Heart Failure with PRESERVED LVEF Study, NCT04189029) study, a data driven research project aiming at redefining and profiling the Heart Failure with preserved Ejection Fraction (HFpEF), an ontology was developed by different data experts in cardiology to enable better data management in a complex study context (multisource, multiformat, multimodality, multipartners). The PACIFIC ontology provides a cardiac data management framework for the phenomapping of patients. It was built upon the BMS-LM (Biomedical Study -Lifecycle Management) core ontology and framework, proposed in a previous work to ensure data organization and provenance throughout the study lifecycle (specification, acquisition, analysis, publication). The BMS-LM design pattern was applied to the PACIFIC multisource variables. In addition, data was structured using a subset of MeSH headings for diseases, technical procedures, or biological processes, and using the Uberon ontology anatomical entities. A total of 1372 variables were organized and enriched with annotations and description from existing ontologies and taxonomies such as LOINC to enable later semantic interoperability. Both, data structuring using the BMS-LM framework, and its mapping with published standards, foster interoperability of multimodal cardiac phenomapping datasets., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease (CVDs) is the leading cause of death worldwide. The main risk factors are hypertension, diabetes, obesity, and increased serum lipids. The peanut (Arachis hypogaea L.), also known as the groundnut, goober, pindar, or monkey nut, belongs to the Fabaceae family and is the fourth most cultivated oilseed in the world. The seeds and skin of peanuts possess a rich phytochemical profile composed of antioxidants, such as phenolic acids, stilbenes, flavonoids, and phytosterols. Peanut consumption can provide numerous health benefits, such as anti-obesity, antidiabetic, antihypertensive, and hypolipidemic effects. Accordingly, peanuts have the potential to treat CVD and counteract its risk factors., Purpose: This study aims to critically evaluate the effects of peanuts on metabolic syndrome (MetS) and CVD risk factors based on clinical studies., Method: This review includes studies indexed in MEDLINE-PubMed, COCHRANE, and EMBASE, and the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were adhered to., Results: Nineteen studies were included and indicated that the consumption of raw peanuts or differing forms of processed foods containing peanut products and phytochemicals could improve metabolic parameters, such as glycemia, insulinemia, glycated hemoglobin, lipids, body mass index, waist circumference, atherogenic indices, and endothelial function., Conclusion: We propose that this legume and its products be used as a sustainable and low-cost alternative for the prevention and treatment of MetS and CVD. However, further research with larger sample sizes, longer intervention durations, and more diverse populations is needed to understand the full benefit of peanut consumption in MetS and CVD., Competing Interests: Declaration of Competing Interest The authors declare no competing interest exists., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Copyright of Der Diabetologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: To present the characteristics and level of evidence (LOE) of clinical studies published in leading oral implantology journals during 2008–2018 and to explore whether the LOE of a study is associated with its scientific and social impact. Materials and methods: Clinical studies with direct relevance to the evaluation of healthcare interventions published in 2008, 2013, and 2018 in six oral implantology journals were identified via hand searches. A modified 4‐level Oxford 2011 LOE tool was used to assess the LOE of all eligible studies. The citation count and Altmetric Attention Score (AAS) of each study were extracted from Web of Science and Altmetric Explorer, respectively. Thereafter, multivariable generalized estimation equation analyses were used to investigate the association between LOE, citation counts, and AAS, adjusting for potential confounding factors and clustering effects. Results: A total of 763 clinical studies were included, among which the proportion of level‐1, level‐2, level‐3, and level‐4 studies was 2.4%, 30.4%, 40.2%, and 27.0%, respectively. During 2008–2018, the proportion of high LOE studies (level‐1 and level‐2) increased substantially from 24.6% to 43.1%, although the number of systematic reviews that only include randomized controlled trials has remained limited. According to multivariable analyses, the citation count (p =.002) and AAS (p =.005) of high LOE studies were both significantly greater than those of low LOE studies. Conclusions: During the past decade, the proportion of high LOE studies has increased substantially in the field of oral implantology. Clinical studies with higher LOE tend to have greater scientific and social impact. [ABSTRACT FROM AUTHOR]