UNASSIGNED: Despite ongoing interventions, SARS-CoV-2 continues to cause significant global morbidity and mortality. Early diagnosis and intervention are crucial for effective clinical management. However, prognostic features based on transcriptional data have shown limited effectiveness, highlighting the need for more precise biomarkers to improve COVID-19 treatment outcomes.
UNASSIGNED: We retrospectively analyzed 149 clinical features from 189 COVID-19 patients, identifying prognostic features via univariate Cox regression. The cohort was split into training and validation sets, and 77 prognostic models were developed using seven machine learning algorithms. Among these, the least absolute shrinkage and selection operator (Lasso) method was employed to refine the selection of prognostic variables by ten-fold cross-validation strategy, which were then integrated with random survival forests (RSF) to build a robust COVID-19-related prognostic model (CRM). Model accuracy was evaluated across training, validation, and entire cohorts. The diagnostic relevance of interleukin-10 (IL-10) was confirmed in bulk transcriptional data and validated at the single-cell level, where we also examined changes in cellular communication between mononuclear cells with differing IL-10 expression and other immune cells.
UNASSIGNED: Univariate Cox regression identified 43 prognostic features. Among the 77 machine learning models, the combination of Lasso and RSF produced the most robust CRM. This model consistently performed well across training, validation, and entire cohorts. IL-10 emerged as a key prognostic feature within the CRM, validated by single-cell transcriptional data. Transcriptome analysis confirmed the stable diagnostic value of IL-10, with mononuclear cells identified as the primary IL-10 source. Moreover, differential IL-10 expression in these cells was linked to altered cellular communication in the COVID-19 immune microenvironment.
UNASSIGNED: The CRM provides accurate prognostic predictions for COVID-19 patients. Additionally, the study underscores the importance of early IL-10 level testing upon hospital admission, which could inform therapeutic strategies.

Clinical practice guidelines for the management of chronic kidney disease (CKD) associated with type 2 diabetes (T2D) are designed to assist healthcare professionals with clinical decision making by providing recommendations on the screening, detection, management, and treatment of these conditions. However, primary care practitioners (PCPs) may have clinical inertia when it comes to routinely enacting CKD and T2D guideline recommendations in their clinical practices. Guideline developers have published a range of resources with the aim of facilitating easier access to guideline recommendations to support efficient and consistent implementation into clinical practice of PCPs. Challenges remain in providing strategies to reduce inertia in the application of guideline recommendations in primary care. In this review, we explore reasons behind the low level of awareness and poor uptake of published evidence-based care approaches to the optimal management of patients with T2D and CKD. Finally, we present suggestions on strategies to improve the implementation of guideline-directed recommendations in primary care.
Clinical practice guidelines for managing chronic kidney disease (CKD) for people who also have type 2 diabetes (T2D) provide healthcare providers with recommendations on how to identify, diagnose, and treat CKD. Although treatments cannot cure CKD, they can help to reduce the risk of CKD getting worse. The recommendations are based on results of clinical trials that tested how safe and how well a medication works among many people with CKD and T2D. If these clinical trials show that the medicine is beneficial for people with CKD and T2D, then it may be included in guideline recommendations. Most people living with T2D and early-stage CKD are treated by their primary care practitioner (PCP). If PCPs are not fully aware of guideline recommendations, then their patients may lose the opportunity to receive medications that can benefit them. PCPs have said that barriers to implementing guideline recommendations in their clinical practices include too many guidelines and that the guidelines are difficult to understand and use in their offices. Guideline developers have thought of ways to make the guidelines easier to access and use. This includes putting the guidelines onto mobile apps, providing online resources, making versions more relevant to PCPs, and combining multiple guidelines. These approaches are helpful, but more work is needed. This review article talks about the reasons why PCPs are not always aware of the most up-to-date guideline recommendations for CKD and T2D, how guideline developers have found different ways of sharing the guideline recommendations, and what more can be done.

BACKGROUND: Around 1 billion peripheral intravenous catheters (PIVC) fail annually worldwide before prescribed intravenous therapy is completed, resulting in avoidable complications, dissatisfaction, and avoidable costs surging to ∼€4bn. We aimed to provide an international consensus on relevance and feasibility of clinical practice guideline recommendations to reduce PIVC failure.
METHODS: e-Delphi study with three rounds through an online questionnaire from March-September 2020 recruiting a multispecialty panel formed by clinicians, managers, academic researchers, and experts in implementation from seven developed and three developing countries, reflecting on experience in PIVC care and implementation of evidence. Further, we included a panel of chronic patients with previous experience in the insert, maintenance, and management of PIVC and intravenous therapy from Ireland and Spain as public and patient involvement (PPI) panel. All experts and patients scored each item on a 4-point Likert scale to assess the relevance and feasibility. We considered consensus descriptor in which the median was 4 with less than or equal to 1,5 interquartile intervals.
RESULTS: Over 90% participants (16 experts) completed the questionnaire on all rounds and 100% PPI (5 patients) completed round 1 due to high consensus they achieved. Our Delphi approach included 49 descriptors, which resulted in an agreed 30 across six domains emerged from the related to (i) general asepsis and cutaneous antisepsis (n = 4), (ii) catheter adequacy and insertion (n = 3), (iii) catheter and catheter site care (n = 6), (iv) catheter removal and replacement strategies (n = 4), (v) general principles for catheter management (n = 10), and (vi) organisational environment (n = 3).
CONCLUSIONS: We provide an international consensus of relevant recommendations for PIVC, deemed feasible to implement in clinical settings. In addition, this methodological approach included substantial representation from clinical experts, academic experts, patient and public expertise, mitigating uncertainty during the implementation process with high-value recommendations to prevent PIVC failure based contextual and individual features, and economic resources worldwide.

BACKGROUND: In 2021, the Spanish Ministry of Health launched the CIBERPOSTCOVID project to establish what post COVID was. The present study reports the level of agreement among stakeholders on post COVID and its clinical and diagnostic characteristics in the Spanish health system.
METHODS: The agreement on post COVID among clinicians, public health managers, researchers and patients\' representatives was explored in a real-time, asynchronous online Delphi. In a two-wave consensus, respondents rated from 1 (total disagreement) to 6 (total agreement) 67 statements related to terminology, duration, etiology, symptoms, impact on quality of life, severity, elements to facilitate diagnosis, applicability in the pediatric population, and risk factors. Consensus was reached when 70 % of ratings for a statement were 5 or 6, with an interquartile range equal or less than 1.
RESULTS: A total of 333 professionals and patients participated in this eDelphi study. There was agreement that post COVID was \"a set of multi-organic symptoms that persist or fluctuate after acute COVID-19 infection and are not attributable to other causes\" with a minimum duration of 3 months. The highest levels of agreement were found in the most frequent symptoms and its impacts on everyday activities. Aspects related to the diagnostic process and the measurement of its severity reached a lower level of consensus. There was agreement on the need to rule out previous health problems and assess severity using validated functional scales. However, no agreement was reached on the risk factors or specific features in the pediatric population.
CONCLUSIONS: This policy-based consensus study has allowed the characterization of post COVID generating collective intelligence and has contributed to an operational definition applicable in clinical practice, health services management and useful for research purposes in Spain and abroad. Agreements are consistent with existing evidence and reference institutions at European and international level.

BACKGROUND: We describe the development and feasibility of using an online consensus approach for diagnosing cognitive impairment and dementia in rural South Africa.
METHODS: Cognitive assessments, clinical evaluations, and informant interviews from Cognition and Dementia in the Health and Aging in Africa Longitudinal Study (HAALSI Dementia) were reviewed by an expert panel using a web-based platform to assign a diagnosis of cognitively normal, mild cognitive impairment (MCI), or dementia.
RESULTS: Six hundred thirty-five participants were assigned a final diagnostic category, with 298 requiring adjudication conference calls. Overall agreement between each rater\'s independent diagnosis and final diagnosis (via the portal or consensus conference) was 78.3%. A moderate level of agreement between raters\' individual ratings and the final diagnostic outcomes was observed (average κ coefficient = 0.50).
CONCLUSIONS: Findings show initial feasibility in using an online consensus approach for the diagnosis of cognitive impairment and dementia in remote, rural, and low-resource settings.

Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.

Because pregnancy outcomes tend to be worse in women with inflammatory bowel disease (IBD) than in those without, we aimed to update consensus statements that guide the clinical management of pregnancy in patients with IBD.
A multidisciplinary working group was established to formulate these consensus statements. A modified RAND/UCLA appropriateness method was used, consisting of a literature review, online voting, discussion meeting and a second round of voting. The overall agreement among the delegates and appropriateness of the statement are reported.
Agreement was reached for 38/39 statements which provide guidance on management of pregnancy in patients with IBD. Most medications can and should be continued throughout pregnancy, except for methotrexate, allopurinol and new small molecules, such as tofacitinib. Due to limited data, no conclusion was reached on the use of tioguanine during pregnancy. Achieving and maintaining IBD remission before conception and throughout pregnancy is crucial to optimise maternofetal outcomes. This requires a multidisciplinary approach to engage patients, allay anxieties and maximise adherence tomedication. Intestinal ultrasound can be used for disease monitoring during pregnancy, and flexible sigmoidoscopy or MRI where clinically necessary.
These consensus statements provide up-to-date, comprehensive recommendations for the management of pregnancy in patients with IBD. This will enable a high standard of care for patients with IBD across all clinical settings.

RATIONALE, AIMS AND OBJECTIVES: The development of clinical practice guidelines (CPG) suffers from the lack of an explicit and transparent framework for synthesising the key elements necessary to formulate practice recommendations. We matched deliberations of the American Society of Haematology (ASH) CPG panel for the management of pulmonary embolism (PE) with the corresponding decision-theoretical constructs to assess agreement of the panel recommendations with explicit decision modelling.
Five constructs were identified of which three were used to reformulate the panel\'s recommendations: (1) standard, expected utility threshold (EUT) decision model; (2) acceptable regret threshold model (ARg) to determine the frequency of tolerable false negative (FN) or false positive (FP) recommendations, and (3) fast-and-frugal tree (FFT) decision trees to formulate the entire strategy for management of PE. We compared four management strategies: withhold testing versus d-dimer → computerized pulmonary angiography (CTPA) (\'ASH-Low\') versus CTPA→ d-dimer (\'ASH-High\') versus treat without testing.
Different models generated different recommendations. For example, according to EUT, testing should be withheld for prior probability PE < 0.13%, a clinically untenable threshold which is up to 15 times (2/0.13) below the ASH guidelines threshold of ruling out PE (at post probability of PE ≤ 2%). Three models only agreed that the \'ASH low\' strategy should be used for the range of pretest probabilities of PE between 0.13% and 13.27% and that the \'ASH high\' management should be employed in a narrow range of the prior PE probabilities between 90.85% and 93.07%. For all other prior probabilities of PE, choosing one model did not ensure coherence with other models.
CPG panels rely on various decision-theoretical strategies to develop its recommendations. Decomposing CPG panels\' deliberation can provide insights if the panels\' deliberation retains a necessary coherence in developing guidelines. CPG recommendations often do not agree with the EUT decision analysis, widely used in medical decision-making modelling.

OBJECTIVE: The purpose of this study was to assess chiropractic interns\' knowledge and adherence to radiographic clinical practice guidelines (CPGs) and compare their clinical decisions to previous surveys of established practitioners in Canada and Australia.
METHODS: A clinical decision-making survey was administered to 88 interns. The survey contained clinical scenarios and vignettes with inquiries regarding indications for radiographic referral, the likelihood of referral, and the application of CPGs.
RESULTS: Forty-four percent (43.75%) of the interns were aware of CPGs, 38.75% were unsure, and 17.5% were not aware. When asked specific questions about the appropriateness of diagnostic imaging, the interns\' responses were similar to those of practitioners in Canada and Australia. When interns evaluated a clinical vignette, there was lower compliance with CPGs.
CONCLUSIONS: The interns\' clinical decisions regarding the use of diagnostic radiography did not significantly differ from those of practitioners who were surveyed in other related studies. Interns were inconsistent in applying their decision making in clinical cases. Notwithstanding the similarities with practitioners, some deviation from the guidelines indicates the need for further intern education to improve the implementation of CPGs for optimal cost-effective and clinically appropriate care.

UNASSIGNED: The UK National Institute for Health and Care Excellence (NICE), recommended in 2017 the use of the faecal immunochemical test (FIT) to guide investigations in patients presenting with NICE-defined low-risk symptoms suspicious for colorectal cancer (CRC). At that time, NICE did not recommend FIT use for high-risk symptoms. This is the first systematic review to evaluate the diagnostic accuracy of FIT in NICE-defined high and low-risk symptoms and was designed to inform the joint ACPGBI/BSG guidelines.
UNASSIGNED: We performed a systematic literature review and meta-analysis. PROSPERO registration number CRD42021224674. Medline and EMBASE databases were searched from inception to 31st March 2022. We included studies recruiting adult patients presenting with suspected CRC symptoms in whom FIT was performed and diagnostic accuracy data for CRC detection could be derived at a limit of detection (LoD) and/or 10 µg haemoglobin/gram faeces threshold in four commonly used analysers. FIT performance was assessed for high-risk, low-risk and individual symptoms where possible. Bivariate meta-analysis was performed where study numbers allowed.
UNASSIGNED: Thirty-one studies (79566 patients) met inclusion criteria. At 10 µg/g, for \"all symptoms\" (n = 35,945) sensitivity and specificity were 91.0% (95% CI: 88.9, 92.7) and 75.2% (95% CI: 69.6, 80.1); for \"high-risk\" symptoms (n = 18,264), 88.7% (95% CI: 84.4, 92.0) and 78.5% (95% CI: 73.0, 83.2); and for \"low-risk\" symptoms (n = 2161), 88.7% (95% CI: 78.1, 95.3) and 88.5% (95% CI: 87.1, 89.9), respectively. At LoD, for \"all symptoms\" (n = 26,056) sensitivity and specificity were 94.7% (95% CI: 90.5, 97.1) and 66.5% (95% CI: 58.7, 73.6); for \"high-risk\" symptoms (n = 16,768), 92.8% (95% CI: 86.4, 96.3) and 70.3% (95% CI: 66.5, 73.8); and for \"low-risk\" symptoms (n = 2082), 94.7% (95% CI: 85.4, 98.9) and 71.9% (95% CI: 69.9, 73.9), respectively. Summary estimates were similar across different analysers.
UNASSIGNED: FIT sensitivity for CRC detection is maximised at the LoD; its performance is similar in high and low-risk symptoms, and across different analysers where a common threshold is used. FIT performance for CRC detection is adequate and transferrable to clinical diagnostic pathways.
UNASSIGNED: This review was part-funded by NHS England awarded to RM Partners. RB and RC were funded by research fellowships awarded by Croydon University Hospital.