Tuberculosis screening for patients on biologic Medications: A Single-Center experience and Society guideline Review, Monroe County, New York, 2018-2021.

Rationale: Biologic medications for immune-mediated inflammatory diseases may increase the risk of tuberculosis (TB) reactivation, but data on screening for TB in low TB prevalence areas are limited. Objective: To assess the real-world practice patterns of TB screening among prescribers of biologic medications. Methods: We conducted a retrospective observational study at a single, university-based healthcare facility in a low TB prevalence area. We enrolled adult patients prescribed a biologic medication between October 2018 and December 2021, and collected data on demographics, biologic medications and TB test results. For patients with positive TB tests, further data including prescriber specialty and response to positive tests were obtained. We reviewed pertinent major society guidelines/ consensus statements regarding TB screening among patients treated with biologic medications. Results: 4,085 patients were included. 3024 (74.0%) had at least one screening TB test and 42 were positive. Among patients treated with tumor necrosis factor-alpha (TNFα) inhibitors, 1779 of 2129 patients (83.6%) underwent TB testing and 25 (1.4%) were positive. Most with positive TB test results were prescribed biologic medication by gastroenterology (11 patients, 26%), dermatology (12, 29%), or rheumatology (15, 36%) providers. 32 (76%) patients had imaging and roughly half were treated for latent TB infection. Biologic medications were temporarily held for 27 patients (67%). Nine out of 13 society guidelines recommend TB screening for TNFα inhibitors but have differing recommendations for other biologic medications. Conclusions: Significant practice pattern differences in TB screening for patients receiving biologic medications exist. Multiple society guidelines continue to recommend TB screening even for drugs with no known increased risk of TB reactivation.

Campylobacter Infection Introduced Following Fecal Microbiota Transplantation.

Fecal microbiota transplantation is an evidence-based therapeutic option for recurrent Clostridium difficile infection, involving the transfer of healthy donor fecal material to restore gut microbial balance. Despite meticulous donor screening, Campylobacter jejuni, a prevalent cause of bacterial gastroenteritis, is not routinely tested, potentially impacting fecal microbiota transplant safety. We present a case of a female with recurrent C. difficile infection treated with fecal microbiota transplantation, complicated by a subsequent C. jejuni infection. The emergence of Campylobacter post fecal microbiota transplantation underscores the importance of comprehensive donor screening protocols. Our case prompts a reevaluation of fecal microbiota transplantation safety measures and advocates for inclusive screening to enhance patient outcomes.

Overview of global monitoring systems for the side effects and adverse events associated with medicinal cannabis use: a scoping review using a systematic approach.

OBJECTIVES: The use of cannabis-based medicine (CBM) as a therapeutic has surged in Australia over the past 5 years. Historically, the United Nations Single Convention on Narcotic Drugs (1961) prohibited cannabis use in Europe, the USA, the UK and Australia, leading to legislative resistance and limited preclinical data on CBM. Existing safety monitoring systems for CBM are poorly structured and do not integrate well into the workflows of busy health professionals. As a result, postmarketing surveillance is inconsistent. This review aims to evaluate international systems for monitoring CBM side effects and adverse events. DESIGN: To undertake a scoping review with a systematic approach, we used the Population, Intervention, Comparison, Outcome (PICO) framework to develop keyword elements, and two search queries to maximise search sensitivity and specificity. DATA SOURCES: Search queries were entered into Embase and Scopus for peer-reviewed literature, and additional searches for grey literature were conducted on 23 June 2023. ELIGIBILITY CRITERIA: We included 54 full-text articles in the review: 39 from peer-reviewed searches, 8 from grey literature and 7 from citations of relevant texts. DATA EXTRACTION AND SYNTHESIS: Our search yielded two main forms of monitoring systems: databases and registries. Out of the 24 monitoring systems identified, there were 10 databases and 14 registries, with databases often created by regulatory authorities. Systems differed in methods of causality assessment, level of detail collected, terminology and affiliations. RESULTS: Within the monitoring systems with enough published data for analysis, all except one remain active at the time of this review. VigiBase is the largest centralised monitoring system, receiving international case reports, however data heterogeneity persists. CONCLUSIONS: Our study emphasises the need for a centralised, consistent and accessible system for the postmarketing surveillance of side effects and adverse events associated with medicinal cannabis use.

With or without biopsy in coeliac children?-Impact on dietary compliance and quality of life.

Critics of the ESPGHAN guidelines on CD question the acceptance of the no-biopsy policy by patients and parents against the backdrop of a lifelong diagnosis. The aim of this study was to investigate the impact of the no-biopsy approach on dietary adherence and health-related quality of life (HRQOL). In this retrospective cohort study, patients ≤ 18 years diagnosed with CD between 2007 and 2017 were sent two questionnaires: a dietary interview and a CD-specific HRQOL questionnaire (CDDUX). Included patients were divided into group A (with biopsies <2012), B (with biopsies >2012) and C (without biopsies >2012). Fisher exact test and ANOVA were used to analyze the impact of the new diagnostic strategy. Forty-seven percent (82/173 patients) consented to participate in the study. Of them, 63% had a biopsy-confirmed diagnosis (40% before 2012 (group A), 23% after 2012 (group B)), and 37% were diagnosed without biopsies (group C). Dietary compliance was similar in all groups (p = 0.67). Group A scored significantly better on the subscale 'Having CD' compared to both groups diagnosed after 2012 (p = 0.003). Group A and group C seemed to score better on the total CDDUCX score when compared to group B (86 and 80% versus 61% respectively, p = 0.13). This was also observed within the subscale Diet; Group A and C scored significantly better than group B (62 and 72% versus 39% respectively, p = 0.09). CONCLUSIONS: Omitting duodenal biopsies in the diagnostic approach of our CD cohort had no adverse effect on dietary adherence and HRQOL. WHAT IS KNOWN: • Since the publication of the ESPGHAN guideline of 2012, duodenal biopsies are no longer obligatory in the diagnostic approach of CD if IgA-antibodies for transglutaminase 2 are ≥10× ULN, endomysial antibodies are positive in a second blood sample and the patient/family agrees with the no-biopsy approach. • Literature on the effect of the no-biopsy approach on dietary adherence and HRQOL is scarce. WHAT IS NEW: • Omitting duodenal biopsies does not influence dietary adherence and quality of life. • In our cohort, lower quality of life measured with the CDDUX subscale 'Having CD' is more likely to be related to shorter disease duration than to the diagnostic approach.

Suboptimal monitoring and management in patients with unrecorded stage 3 chronic kidney disease in real-world settings: Insights from REVEAL-CKD.

BACKGROUND: Clinical practice guidelines for patients with chronic kidney disease (CKD) recommend regular monitoring and management of kidney function and CKD risk factors. However, the majority of patients with stage 3 CKD lack a diagnosis code, and data on the implementation of these recommendations in the real world are limited. AIM: To assess the implementation of guideline-directed monitoring and management practices in the real world in patients with stage 3 CKD without a recorded diagnosis code. METHODS: REVEAL-CKD (NCT04847531) is a multinational, observational study of patients with stage 3 CKD. Eligible patients had ≥2 consecutive estimated glomerular filtration rate (eGFR) measurements indicative of stage 3 CKD recorded >90 and ≤730 days apart, lacked an International Classification of Diseases 9/10 diagnosis code corresponding to CKD any time before and up to 6 months after the second eGFR measurement. Testing of key measures of care quality were assessed. RESULTS: The study included 435,971 patients from 9 countries. In all countries, the prevalence of urinary albumin-creatinine ratio and albuminuria testing was low. Angiotensin-converting enzyme inhibitor, angiotensin receptor blocker and statin prescriptions were highly variable, and sodium-glucose cotransporter-2 inhibitor prescriptions remained below 21%. Blood pressure measurements were recorded in 20.2%-89.9% of patients. CONCLUSIONS: Overall, a large proportion of patients with evidence of stage 3 CKD did not receive recommended, guideline-directed monitoring and management. The variability in standard of care among countries demonstrates a clear opportunity to improve monitoring and management of these patients, most likely improving long-term outcomes.

Clearance of residual genome editing components used for ex vivo genome-editing of allogeneic cell therapy products.

BACKGROUND AIMS: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-associated genome editing (GE) components (e.g., nucleases, guide RNAs (gRNAs), and plasmids) are used to genetically modify cells during development of ex vivo genome-edited cell therapies. Prolonged presence of GE components may increase the risk of unintended genome modifications (e.g., off-target editing and chromosomal rearrangements). This risk is a function of the stability of the GE components, culture conditions (i.e., culture length, media changes, etc.), and the nature of the GE component (i.e., only plasmids can be integrated into a cell's genome). Testing for residual GE components on ex vivo genetically edited drug products is generally recommended in current regulatory guidance (CBER 2024). For allogenic cell therapies derived from induced pluripotent stem cells (iPSC), cells typically undergo clonal selection and extensive culturing following completion of genome editing. This post-engineering clonal selection substantially reduces the amount of residual GE components while the long-duration cell culture significantly reduces the presence of active residual GE components. Here we present a case in which the need for testing of the drug product for residual GE components has been eliminated. METHODS: In silico modeling was used to estimate clearance mechanisms across a variety of relevant assumptions, including disposition of extracellular GE components via media changes and dilution of intracellular GE components via cell expansion. Determining the ability of each GE component-alone or in complex with other GE components-to modify genomic material was assessed by a series of both in vitro and ex vivo (i.e., engineering cells) studies. For the in vitro studies, a DNA cutting assay was developed to assess the ability of the component to cut a representative DNA strand. For the ex vivo modification of cells, an assessment of the knock-out of the relevant gene was completed by flow cytometry specifically assessing the presence or absence of protein expression on the modified cells. The persistence and stability of GE components were examined under cell-mimicking conditions and in ex vivo modified cells. The components were stressed under multiple conditions mimicking a range of culture conditions and tested in the aforementioned DNA cutting assay. The presence of residual gRNA was directly assessed in the ex vivo modified cells via a gRNA-specific digital droplet polymerase chain reaction (ddPCR) assay. RESULTS: Simulations estimating genome editing residual clearance via dilution for extracellular residuals (via media changes) or intracellular residuals (via cell doubling) demonstrate clearance of measurable residuals within 28 days of cell culture. Studies simulating the stability of genome editing residuals estimate less than 7 days for the nuclease, gRNA and ribonucleoprotein (RNP) complex. gRNA was undetectable by 8 days post-engineering under actual engineering conditions. Additionally, without gRNA present, CRISPR Cas12a nucleases did not demonstrate evidence of cutting. In contrast, plasmid DNA can be randomly integrated into the genome and free plasmid is highly stable under cell culture-like conditions (50+ days). Additionally, plasmid DNA integrated in cells will propagate during mitosis, leading to the additional risk of expansion of an unintentional integration event. CONCLUSIONS: Both the gRNA and nuclease in the RNP complex are required for DNA cutting. Neither individual component nor the complex are stable beyond 7 days in culture-mimicking conditions. These findings suggest that the risk of unplanned genomic modification resulting from residual gRNA or nuclease is minimal for processes in which extensive culture is performed after the completion of genome editing and clonal selection. However, the risk of residual plasmid DNA integration is significantly higher regardless of the manufacturing process. The residual plasmid itself is quite stable (at least 50 days) and the risk of random, off-target integration is present. By establishing the stability of these components, we have demonstrated that testing for residual gRNA or nuclease is not warranted for clonally derived allogeneic cell therapies.

Current type 2 diabetes guidelines: Individualized treatment and how to make the most of metformin.

Evidence-based guidelines provide the premise for the delivery of quality care to preserve health and prevent disabilities and premature death. The systematic gathering of observational, mechanistic and experimental data contributes to the hierarchy of evidence used to guide clinical practice. In the field of diabetes, metformin was discovered more than 100 years ago, and with 60 years of clinical use, it has stood the test of time regarding its value in the prevention and management of type 2 diabetes. Although some guidelines have challenged the role of metformin as the first-line glucose-lowering drug, it is important to point out that the cardiovascular-renal protective effects of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists were gathered from patients with type 2 diabetes, the majority of whom were treated with metformin. Most national, regional and international guidelines recommend metformin as a foundation therapy with emphasis on avoidance of therapeutic inertia and early attainment of multiple treatment goals. Moreover, real-world evidence has confirmed the glucose-lowering and cardiovascular-renal benefits of metformin accompanied by an extremely low risk of lactic acidosis. In patients with type 2 diabetes and advanced chronic kidney disease (estimated glomerular filtration rate 15-30 mL/min/1.73m2), metformin discontinuation was associated with an increased risk of cardiovascular-renal events compared with metformin persistence. Meanwhile, it is understood that microbiota, nutrients and metformin can interact through the gut-brain-kidney axis to modulate homeostasis of bioactive molecules, systemic inflammation and energy metabolism. While these biological changes contribute to the multisystem effects of metformin, they may also explain the gastrointestinal side effects and vitamin B12 deficiency associated with metformin intolerance. By understanding the interactions between metformin, foods and microbiota, healthcare professionals are in a better position to optimize the use of metformin and mitigate potential side effects. The United Kingdom Prospective Diabetes Study and the Da Qing Diabetes Prevention Program commenced 40 years ago provided the first evidence that type 2 diabetes is preventable and treatable. To drive real-world impact from this evidence, payors, practitioners and planners need to co-design and implement an integrated, data-driven, metformin-based programme to detect people with undiagnosed diabetes and prediabetes (intermediate hyperglycaemia), notably impaired glucose tolerance, for early intervention. The systematic data collection will create real-world evidence to bring out the best of metformin and make healthcare sustainable, affordable and accessible.

News Media Framing of Suicide Circumstances and Gender: Mixed Methods Analysis.

BACKGROUND: Suicide is a leading cause of death worldwide. Journalistic reporting guidelines were created to curb the impact of unsafe reporting; however, how suicide is framed in news reports may differ by important characteristics such as the circumstances and the decedent's gender. OBJECTIVE: This study aimed to examine the degree to which news media reports of suicides are framed using stigmatized or glorified language and differences in such framing by gender and circumstance of suicide. METHODS: We analyzed 200 news articles regarding suicides and applied the validated Stigma of Suicide Scale to identify stigmatized and glorified language. We assessed linguistic similarity with 2 widely used metrics, cosine similarity and mutual information scores, using a machine learning-based large language model. RESULTS: News reports of male suicides were framed more similarly to stigmatizing (P<.001) and glorifying (P=.005) language than reports of female suicides. Considering the circumstances of suicide, mutual information scores indicated that differences in the use of stigmatizing or glorifying language by gender were most pronounced for articles attributing legal (0.155), relationship (0.268), or mental health problems (0.251) as the cause. CONCLUSIONS: Linguistic differences, by gender, in stigmatizing or glorifying language when reporting suicide may exacerbate suicide disparities.

One out of two idiopathic infertile men has pathologic sperm DNA fragmentation values: Potential implications for clinical practice.

OBJECTIVES: To investigate the distribution of sperm DNA fragmentation (SDF) values and their association with clinical and seminal parameters in idiopathic infertile men. DESIGN, PATIENTS, MEASUREMENTS: Data from 3224 primary infertile men (belonging to couples having failed to conceive a pregnancy within 12 months) who underwent a thorough diagnostic work-up were analysed. A SDF value ≥ 30% (according to Sperm Chromatin Structure Assay) was considered pathologic. We excluded: (1) men with genetic abnormalities; (2) men with history of cryptorchidism; (3) men with biochemical hypogonadism; (4) men with clinical varicocele; and (5) men with other possible known aetiological factors. Descriptive statistics and logistic regression analyses were used to describe the whole cohort. RESULTS: Of all, 792 (23%) men with at least one abnormal WHO semen parameter but without any identified aetiologic factor for infertility, were considered as idiopathic infertile men. Of 792, 418 (52.7%) men had SDF ≥30%. Men with pathologic SDF were older (p = .02), had higher Follicle-stimulating hormone (FSH) (p = .04) but lower total testosterone (p = .03) values than those with SDF <30%. The homoeostatic model assessment index for insulin resistance (HOMA-IR) was higher in men with SDF ≥30% (p = .01). Idiopathic infertile men with SDF ≥30% presented with lower sperm concentration (p < .001) and lower progressive sperm motility (p < .01) than those with SDF < 30%. Logistic regression analysis revealed that older age (OR: 1.1, p = .02) and higher HOMA-IR score (OR: 1.8, p = .03) were associated with SDF ≥ 30%, after accounting for FSH and sperm concentration values. CONCLUSIONS: Approximately half of infertile men categorized as idiopathic had pathologic SDF values. Idiopathic infertile men with pathologic SDF showed worse clinical, hormonal and semen parameters than those with normal SDF values. These results suggest that including SDF testing could be clinically relevant over the real-life management work-up of infertile men.

Hospital falls clinical practice guidelines: a global analysis and systematic review.

BACKGROUND: Hospital falls continue to be a persistent global issue with serious harmful consequences for patients and health services. Many clinical practice guidelines now exist for hospital falls, and there is a need to appraise recommendations. METHOD: A systematic review and critical appraisal of the global literature was conducted, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, Embase, CINAHL, MEDLINE, Epistemonikos, Infobase of Clinical Practice Guidelines, Cochrane CENTRAL and PEDro databases were searched from 1 January 1993 to 1 February 2024. The quality of guidelines was assessed by two independent reviewers using Appraisal of Guidelines for Research and Evaluation Global Rating Scale and Appraisal of Guidelines of Research and Evaluation Recommendation Excellence (AGREE-REX). Certainty of findings was rated using Grading of Recommendations Assessment, Development and Evaluation Confidence in Evidence from Reviews of Qualitative Research. Data were analysed using thematic synthesis. RESULTS: 2404 records were screened, 77 assessed for eligibility, and 20 hospital falls guidelines were included. Ten had high AGREE-REX quality scores. Key analytic themes were as follows: (i) there was mixed support for falls risk screening at hospital admission, but scored screening tools were no longer recommended; (ii) comprehensive falls assessment was recommended for older or frail patients; (iii) single and multifactorial falls interventions were consistently recommended; (iv) a large gap existed in patient engagement in guideline development and implementation; (v) barriers to implementation included ambiguities in how staff and patient falls education should be conducted, how delirium and dementia are managed to prevent falls, and documentation of hospital falls. CONCLUSION: Evidence-based hospital falls guidelines are now available, yet systematic implementation across the hospital sector is more limited. There is a need to ensure an integrated and consistent approach to evidence-based falls prevention for a diverse range of hospital patients.

Pneumocystis jirovecii pneumonia in non-HIV patients: need for a more extended prophylaxis.

Background: Pneumocystis jirovecii pneumonia (PCP) has a significant mortality rate for non-HIV immunocompromised patients. Prevention is primarily based on combined trimethoprim and sulfamethoxazole (TMP-SMX) but guidelines on pneumocystosis prophylaxis are scattered and not consensual. Objectives: This study aims to describe PCP in non-HIV patients and to review case by case the prior indication of prophylaxis according to specific guidelines.We included patients with confirmed diagnosis of PCP admitted to one university hospital from 2007 to 2020. Prior indication for pneumocystis prophylaxis was assessed according to the specific guidelines for the underlying pathology or treatment. Results: Of 150 patients with a medical diagnosis of PCP, 78 were included. Four groups of underlying pathologies were identified: hematological pathologies (42%), autoimmune diseases (27%), organ transplantation (17%), and other pathologies at risk of PCP (14%). A small subgroup of 14 patients (18%) had received a prior prescription of pneumocystis prophylaxis but none at the time of the episode. Transfer to intensive care was necessary for 33 (42%) patients, and the mortality rate at 3 months was 20%. According to international disease society guidelines, 52 patients (59%) should have been on prophylaxis at the time of the pneumocystis episode. Lowest compliance with guidelines was observed in the hematological disease group for 24 patients (72%) without prescription of indicated prophylaxis. Conclusion: Infectious disease specialists should draw up specific prophylactic guidelines against pneumocystis to promote a better prevention of the disease and include additional criteria in their recommendations according to individual characteristics to prevent fatal cases.

Navigating phenylketonuria management to improve it in Latin America: a systematic literature review and applicability analysis.

Introduction: Phenylketonuria (PKU) is an autosomal recessive metabolic disorder resulting from phenylalanine hydroxylase deficiency, which impacts neurodevelopment. Lifelong low-phenylalanine diets and multidisciplinary care are pivotal for managing PKU. Latin American challenges in PKU care include diverse newborn screening programs, limited specialized healthcare, and resource scarcity. Methods: A systematic literature review was conducted (2010-2023) on PKU management following PRISMA guidelines. Inclusion criteria encompassed English/Spanish articles focusing on PKU management guidelines approved by an organization as well as articles focusing on PKU management in Latin America. After screening 127,276 results, 6 articles were included. Results: Six articles were analyzed, highlighting shared principles like multidisciplinary care, lifelong dietary adherence, personalized plans, and regular monitoring. Guides emphasized regional variations, breastfeeding complexities, and challenges for pregnant women with PKU. Discussion: Multidisciplinary care emerges as critical, incorporating physicians, psychologists, dietitians, nurses, and genetic counselors. Lifelong adherence to low-phenylalanine diets and personalized strategies for different life stages are emphasized. Challenges in Latin America include healthcare gaps, scarce resources, and reliance on international guidance. The importance of breastfeeding, preconception care, and comprehensive support for pregnant women with PKU is underscored. Conclusion: Collaborative efforts are essential to address PKU challenges in Latin America. Advocacy for awareness, specialized training, regional databases, and international collaborations can enhance diagnosis and management, ensuring a better quality of life for PKU individuals in the region. Embracing lessons from existing guides will contribute to improved PKU care and overall well-being.

Author Response: Unanswered Questions and Contradictory Statements in the Antibiotics Prescription Guidelines.

How to cite this article: Khilnani GC, Tiwari P, Mittal S. Author Response: Unanswered Questions and Contradictory Statements in the Antibiotics Prescription Guidelines. Indian J Crit Care Med 2024;28(7):717-718.

Pediatric femoral shaft fractures: the American Academy of Orthopaedic Surgeons clinical practice guidelines versus actual management in a teaching hospital.

Background: In 2009, the clinical practice guidelines (CPG) were released by the American Academy of Orthopaedic Surgeons (AAOS), which outline an age-based approach for treating pediatric femoral shaft fractures (PFSF), both nonoperatively and operatively. The aim of the current study was to investigate potential disparities between the recommended treatments for PFSF based on the AAOS-CPG and the actual treatments administered in The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Methods: A retrospective review was conducted on the medical charts and radiographs of all PFSF treated at The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University from January 2014 to January 2022. We identified 445 children who met our inclusion criteria and evaluated their treatments according to the AAOS-CPG. Actual treatments were then compared with the treatments recommended by the AAOS-CPG. Binomial and multivariate logistic regression was used to examine whether different factors could predict the choice between operative and nonoperative management. Results: Operative treatments were undertaken in 102 of 215 (47.4%) fractures in children younger than 6 years, in 102 of 122 (83.6%) fractures in those between 6 and 12 years of age, and in 107 of 108 (99.1%) fractures in those older than 12 years. Nonoperative management was conducted in 113 of 215 (52.6%) fractures in children younger than 6 years, in 20 of 122 (16.4%) fractures in those between 6 and 12 years of age, and in 1 of 108 (0.9%) fractures in those older than 12 years of age. Surgeon decisions for non-surgery were in agreement with the CPG 52.6% of the time, whereas agreement reached 90.9% for surgical choices. Predictors of actual operative management were age (P=0.01), patient weight (P<0.001), fracture pattern (P<0.001), presence of other orthopedic injuries requiring surgery (P=0.002), and polytrauma (P=0.02). Conclusions: There was limited concordance between actual treatments and CPG recommendations, particularly for the nonoperative management of fractures in children under 6 years old. Age, patient weight, fracture pattern, presence of other orthopedic injuries requiring surgery, and polytrauma were the main predictors of our operative decision-making process.

Mechanical dyssynchrony as a selection criterion for cardiac resynchronization therapy: Design of the AMEND-CRT trial.

AIMS: One third of patients do not improve after cardiac resynchronization therapy (CRT). Septal flash (SF) and apical rocking (ApRock) are deformation patterns observed on echocardiography in most patients eligible for CRT. These markers of mechanical dyssynchrony have been associated to improved outcome after CRT in observational studies and may be useful to better select patients. The aim of this trial is to investigate whether the current guideline criteria for selecting patients for CRT should be modified and include SF and ApRock to improve therapy success rate, reduce excessive costs and prevent exposure to device-related complications in patients who would not benefit from CRT. METHODS: The AMEND-CRT trial is a multicentre, randomized, parallel-group, double-blind, sham-controlled trial with a non-inferiority design. The trial will include 578 patients scheduled for CRT according to the 2021 ESC guidelines who satisfy all inclusion criteria. The randomization is performed 1:1 to an active control arm ('guideline arm') or an experimental arm ('echo arm'). All participants receive a device, but in the echo arm, CRT is activated only when SF or ApRock or both are present. The outcome of both arms will be compared after 1 year. The primary outcome measures are the average change in left ventricular end-systolic volume and patient outcome assessed using a modified Packer Clinical Composite Score. CONCLUSIONS: The findings of this trial will redefine the role of echocardiography in CRT and potentially determine which patients with heart failure and a prolonged QRS duration should receive CRT, especially in patients who currently have a class IIa or class IIb recommendation.

Treatment and management of medullary thyroid microcarcinoma: a 10-year retrospective study from a single center.

OBJECTIVE: To explore individualized treatment and management methods for medullary thyroid microcarcinoma (MTMC). METHODS: Clinical data of patients with medullary thyroid carcinoma with a diameter ≤1 cm admitted to the First Affiliated Hospital of Kunming Medical University from June 2013 to June 20× were collected. Combined with different treatment guidelines for medullary thyroid carcinoma, factors affecting lymph node metastasis and postoperative disease status were analyzed. RESULTS: Twenty-nine patients with MTMC were included in the analysis, including 24 patients who underwent total thyroidectomy, 5 who underwent thyroid gland lobectomy, and 13 who experienced postoperative lymph node metastasis. Multifocal tumor and calcitonin (Ctn) were the influencing factors, while multifocal tumor, Ctn, lymph node metastasis, and AJCC stage affected the dynamic risk stratification of postoperative disease. CONCLUSION: Calcitonin detection is an important method for detecting MTMC. A tumor diameter ≤1 cm does not indicate that the tumor is in the early stage. The presence of multifocal tumors and Ctn should be used as important indicators for preoperative evaluation. Dynamic stratified risk assessment is critical in postoperative follow-up.

Impact of the Children's Oncology Group's supportive care clinical practice guideline endorsement program: An institutional survey.

BACKGROUND: Supportive care clinical practice guidelines (CPGs) facilitate the incorporation of the best available evidence into pediatric cancer care. We aimed to assess the impact of the work of the Children's Oncology Group (COG) Supportive Care Guideline Task Force on institutional supportive care practices. PROCEDURE: An online survey was distributed to representatives at 209 COG sites to assess the awareness, use, and helpfulness of COG-endorsed supportive care CPGs. Availability of institutional policies regarding 13 topics addressed by current COG-endorsed CPGs was also assessed. Respondents described their institutional processes for developing supportive care policies. RESULTS: Representatives from 92 COG sites responded to the survey, and 78% (72/92) were "very aware" of the COG-endorsed supportive care CPGs. On average, sites had policies that addressed seven COG-endorsed supportive care CPG topics (median = 7, range: 0-12). Only 45% (41/92) of sites reported having institutional processes for developing supportive care policies. Of these, most (76%, 31/41) reported that the COG-endorsed CPGs have a medium or large impact on policy development. Compared with sites without processes for supportive care policy development, sites with established processes had policies on a greater number of topics aligned with current COG-endorsed CPG topics (mean = 6.6, range: 0-12 vs mean = 7.9, range: 2-12; p = 0.027). CONCLUSIONS: Most site respondents were aware of the COG-endorsed supportive care CPGs. Less than half of the COG sites represented in the survey have processes in place to implement supportive care policies. Improvement in local implementation is required to ensure that patients at COG sites receive evidence-based supportive care.

Survey based assessment of the quality of reporting guidelines of carotid artery stenosis.

BACKGROUND: No evaluation of the quality of different carotid guidelines using validated scales has been performed to date. The present study aims to analyze three carotid stenosis guidelines, apprizing their quality and reporting using validated tools. METHODS: A survey-based assessment of the quality of the European Society for Vascular Surgery (ESVS) 2023, European Stroke Organisation (ESO) 2021, and the Society for Vascular Surgery (SVS) 2021 carotid stenosis guidelines, was performed by 43 vascular surgeons, cardiologists, neurologist or interventional radiologists using two validated appraisal tools for quality and reporting guidelines, the AGREE II instrument and the RIGHT statement. RESULTS: Using the AGREE II tool, the ESVS, SVS, and ESO guidelines had overall quality scores of 87.3%, 79.4%, and 82.9%, respectively (p=0.001) The ESVS and ESO had better scores in the scope and purpose domain, and the SVS in the clarity of presentation domain. In the RIGHT statement, the ESVS, SVS, and ESO guidelines had overall quality scores of 84.0.7%, 74.3%, and 79.0%, respectively (p=0.001). All three guidelines stood out for their methodology for search of evidence and formulating evidence-based recommendations. On the contrary, were negatively evaluated mostly in the cost and resource implications in formulating the recommendations. CONCLUSION: The 2023 ESVS carotid stenosis guideline was the best evaluated among the three guidelines, with scores over 5% higher than the other two guidelines. Efforts should be made by guideline writing committees to take the AGREE II and RIGHT statements into account in the development of future guidelines to produce high-quality recommendations.

Evaluation of adherence to STARD for Abstracts in a diverse sample of diagnostic accuracy abstracts published in 2012 and 2019 reveals suboptimal reporting practices.

OBJECTIVE: To evaluate the completeness of reporting in a sample of abstracts on diagnostic accuracy studies before and after the release of STARD for Abstracts in 2017. METHODS: We included 278 diagnostic accuracy abstracts published in 2012 (N=138) and 2019 (N=140) and indexed in EMBASE. We analyzed their adherence to 10 items of the 11-item STARD for Abstracts checklist and explored variability in reporting across abstract characteristics using multivariable Poisson modeling. RESULTS: Most of the 278 abstracts (75%) were published in discipline-specific journals, with a median impact factor of 2.9 (IQR: 1.9-3.7). The majority (41%) of abstracts reported on imaging tests. Overall, a mean of 5.4/10 (SD: 1.4) STARD for Abstracts items was reported (range: 1.2-9.7). Items reported in less than one-third of abstracts included 'eligible patient demographics' (24%), 'setting of recruitment' (30%), 'method of enrolment' (18%), 'estimates of precision for accuracy measures' (26%), and 'protocol registration details' (4%). We observed substantial variability in reporting across several abstract characteristics, with higher adherence associated with the use of a structured abstract, no journal limit for abstract word count, abstract word count above the median, one-gate enrolment design, and prospective data collection. There was no evidence of an increase in the number of reported items between 2012 and 2019 (5.2 vs. 5.5 items; adjusted reporting ratio 1.04 [95%CI: 0.98-1.10]). CONCLUSION: This sample of diagnostic accuracy abstracts revealed suboptimal reporting practices, without improvement between 2012 and 2019. The test evaluation field could benefit from targeted knowledge translation strategies to improve completeness of reporting in abstracts.