Standard Of Care Research Articles

Development and Initial Implementation of a Clinical Monitoring Strategy in a Non-regulated Trial: a research note from the ReStOre II Trial

Background Data and Safety Monitoring is integral to quality assurance of clinical trials. Although monitoring is a core legal component of regulated clinical trials, non-regulated trials are not mandated to incorporate monitoring. Consequently, the monitoring process has been underutilised and underreported in this setting. This research report outlines the development and plans for implementing a bespoke Clinical Monitoring Strategy within the ‘Rehabilitation Strategies Following Oesophagogastric and Hepatopancreaticobiliary Cancer (ReStOre II) Trial’, a non-regulated trial comparing a 12-week multidisciplinary programme of rehabilitation to standard care in a cohort of 120 cancer survivors. Methods This research note provides a detailed overview of the ReStOre II Clinical Monitoring Strategy and describes the development of the strategy pre and post awarding of the grant. The strategy consists of the establishment and implementation of a comprehensive trial governance structure, inclusive of a Trial Management Group, Trial Steering Committee Meeting, and Independent Data Monitoring Committee. In addition, external trial monitoring by the Clinical Research Facility at St James’s Hospital. Three monitoring visits will be conducted during the trial; i) site initiation visit, ii) interim monitoring visit, and iii) close our visit. Results The Clinical Monitoring Strategy has been finalised and is currently being implemented within the ReStOre II Trial. Two site initiation visits and one interim monitoring visit have been completed to date. Conclusion This research note provides a template for implementation of a Clinical Monitoring Strategy in a non-regulated clinical trial. Registration ReStOre II Trial: https://clinicaltrials.gov/ct2/show/NCT03958019

Lactobacillus rhamnosus Helps to Reduce the Duration of Bleeding in Breastfed Infants with Allergic Proctocolitis.

Background: Cow's milk protein allergy (CMPA) is the most common food allergy in infants. The current standard of care (SOC) involves eliminating the allergen from both the infant's and mother's diet for 2-4 weeks. The purpose of this study is to assess the effectiveness of Lactobacillus rhamnosus (Ramnoflor) in reducing the duration of bleeding in these infants. Methods: This randomized clinical trial was conducted at Bahrami Children's Hospital on breastfed infants who were diagnosed with CMPA and had a positive occult blood (OB) test. Patients were randomly assigned to either the control or case groups. All patients received SOC therapy, with the case group receiving Ramnoflor and the control group receiving a placebo. Data were recorded on the checklist, and the children were followed and visited three times during the study, with an OB assessment at each visit. Results: The study enrolled 48 infants. Among the infants in the case group, the OB test was positive in four cases (8.3%) on the fifth day. However, there were no positive cases on the 14th and 30th days. The prevalence of this test was significantly lower in patients who received probiotics compared to the control group on the fifth day (p < 0.001). There were no positive OB tests on the 14th and 30th days in any of the groups, and no significant difference was observed between the groups. Conclusion: The addition of L. rhamnosus to SOC therapy led to a decrease in the duration of rectal bleeding in infants with CMPA compared to the control group.

Ten-Year Trends in Venous Thromboembolism Prophylaxis at a High-Volume Arthroplasty Center

Introduction: Venous thromboembolism (VTE) prophylaxis is the standard of care after total joint arthroplasty. However, there have been changes in the prevalence of certain medication classes used by institutions over time driven by the literature and national clinical practice guidelines. The purpose of this study was to analyze the patterns of VTE medications over the past 10 years at our institution. Methods: We identified 25,095 patients who underwent a primary total joint arthroplasty between 2012 and 2022. Medications for VTE prophylaxis included aspirin, warfarin, unfractioned heparin (UFH), low-molecular-weight heparin (LMWH), factor-Xa inhibitors (FXa), and antiplatelet agents different from aspirin and thrombin inhibitors. Tranexamic acid use was recorded. The rates of symptomatic VTE were calculated and categorized as deep vein thrombosis or pulmonary embolism. Results: Venous thromboembolism rates decreased from 1.1% in 2012 to 0.2% in 2022 and ranged between 0.4% and 1.2% during the ten-year period. Although VTE incidence decreased in the past 4 years, an isolated increase was noted in 2021(1%). In 2012, the use of aspirin, warfarin, FXa, and UFH were 52.1%, 30.7%, 0%, and 16.2%, respectively, whereas in 2022, the rates for the same medications were 83.3%, 0.3%, 10.4%, and 1.8%, respectively. The use of LMWH, thrombin inhibitors, and other antiplatelet agents had minimal variation, and none of these medications surpassed 5% during this period. The aspirin dose changed from 325 mg in 2012 (96.5%) to 81 mg in 2022 (98.8%). Similarly, TXA use increased from 30.8% in 2012 to 84.9% in 2022. Conclusion: In the past 10 years, our institution has transitioned from warfarin, UFH, and high-dose aspirin to low-dose aspirin and FXa, exhibiting acceptably low deep vein thrombosis and diminishing pulmonary embolism rates during that time.

Neoadjuvant Chemotherapy for Adults with Osteogenic Sarcoma.

Osteosarcoma is the most common primary malignant bone tumor in adolescents and adults. The 5-year survival rate is 65% when localized; however, survival drops dramatically to 10-20% in cases of metastatic disease. Therapy for osteosarcoma saw its first significant advancement in the 1970-80's, with the introduction of our current standard of care, consisting of the neo/adjuvant treatment regimen methotrexate, doxorubicin (Adriamycin), and cisplatin (collectively referred to as MAP) and surgical resection. Since MAP, development of a better therapeutic approach has stalled, creating a plateau in patient outcomes that has persisted for 40 years. Despite substantial research into a variety of pathways for novel treatment options, clinical trials have not produced sizeable improvements in outcomes. In this article, we discuss our current neoadjuvant standard of care therapy, followed by a review of contemporary therapeutic options, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), monoclonal antibodies (mAbs), and chimeric antigen receptor (CAR) T cells. Lastly, we consider the challenges hindering the success of novel treatment options and future research directions.

Fluid balance neutralization secured by hemodynamic monitoring versus protocolized standard of care in patients with acute circulatory failure requiring continuous renal replacement therapy: results of the GO NEUTRAL randomized controlled trial.

Net ultrafiltration (UFNET) during continuous renal replacement therapy (CRRT) can control fluid balance (FB), but is usually 0ml·h-1 in patients with vasopressors due to the risk of hemodynamic instability associated with CRRT (HIRRT). We evaluated a UFNET strategy adjusted by functional hemodynamics to control the FB of patients with vasopressors, compared to the standard of care. In this randomized, controlled, open-label, parallel-group, multicenter, proof-of-concept trial, adults receiving vasopressors, CRRT since ≤ 24h and cardiac output monitoring were randomized (ratio 1:1) to receive during 72h a UFNET ≥ 100ml·h-1, adjusted using a functional hemodynamic protocol (intervention), or a UFNET ≤ 25ml·h-1 (control). The primary outcome was the cumulative FB at 72 h and was analyzed in patients alive at 72 h and in whom monitoring and CRRT were continuously provided (modified intention-to-treat population [mITT]). Secondary outcomes were analyzed in the intention-to-treat (ITT) population. Between June 2021 and April 2023, 55 patients (age 69 [interquartile range, IQR: 62; 74], 35% female, Sequential Organ Failure Assessment (SOFA) 13 [11; 15]) were randomized (25 interventions, 30 controls). In the mITT population, (21 interventions, 24 controls), the 72 h FB was -2650 [-4574; -309] ml in the intervention arm, and 1841 [821; 5327] ml in controls (difference: 4942 [95% confidence interval: 2736-6902] ml, P < 0.01). Hemodynamics, oxygenation and the number of HIRRT at 72 h, and day-90 mortality did not statistically differ between arms. In patients with vasopressors, a UFNET fluid removal strategy secured by a hemodynamic protocol allowed active fluid balance control, compared to the standard of care.

SNMMI Procedure Standard/EANM Practice Guideline for Brain [18F]FDG PET Imaging, Version 2.0.

PREAMBLEThe Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional nonprofit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The EANM was founded in 1985. SNMMI and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine.The SNMMI and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated.Each practice guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, both the SNMMI and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Surgical Ethics in the Safavid Era, 16th Century AD.

Medicine-and specifically surgery and surgical ethics-have long been part of the history of science. Surgical ethics play a pivotal role in ensuring successful outcomes and maintaining the highest standards of patient care. It includes the ethics of surgeons, the responsibility of surgeons, surgical errors, and the competence of a surgeon. Many works have been written about surgery, including during Iran's Safavid period (1501 to 1736)-a period in which a surgeon needed to have a set of moral principles in addition to practical surgical skills. One of the most valuable is Dhakhīrıh Kāmılıh, written by military surgeon Hakim Mohammad in the sixteenth and seventeenth centuries. In this work, Ḥakim Muhāmmad dedicates a chapter specifically to the topic of surgical ethics, aiming to provide moral and legal recommendations for surgeons in addition to explaining surgical techniques and methods. Some of these recommendations include improving surgical skills through observation and practical training, paying attention to hygiene to prevent the spread of infection, and giving patients hope for recovery. Dhakhīrıh Kāmılıh is a landmark text in the history of surgical ethics.

Outcomes of Radiofrequency Ablation for Autonomously Functioning Thyroid Adenomas-Mayo Clinic Experience.

Autonomously functioning thyroid nodules (AFTNs) constitute 5% to 7% of thyroid nodules and represent the second most common cause of hyperthyroidism following Graves' disease. Currently, radioactive iodine (RAI) and surgery are the standard treatment options, and both incur a risk of postprocedural hypothyroidism and other surgery and radiation-related complications. This work aimed at assessing the efficacy of radiofrequency ablation (RFA) as an alternative treatment option for resolving hyperthyroidism and the nodule volume rate reduction (VRR) and its associated adverse events. A total of 22 patients underwent RFA for a solitary AFTN. Seventy-two percent (n = 16) had subclinical hyperthyroidism, 9% (n = 2) had overt hyperthyroidism, and 18% (n = 4) were biochemically euthyroid on antithyroid medication. Average pretreatment TSH was 0.41 mIU/L (SD = 0.98) and free T4 1.29 ng/dL (SD = 0.33). Following a single RFA session, hyperthyroidism resolved in 90.9% (n = 20) and average VRR (61.13%) was achieved within 3 to 6 months following the ablation. Except for 1 nodule, none of the nodules grew during the follow-up period (16.5 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and 2 developed mild hypothyroidism requiring levothyroxine therapy. Two patients developed recurrent hyperthyroidism and elected to undergo lobectomy and repeat RFA respectively. No serious adverse effects were noted in this cohort. RAI and/or surgery represent the standard of care for toxic adenomas, but RFA shows excellent efficacy and safety profile. Therefore, at centers with RFA expertise, it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.

Evolving Practice and Outcomes in Grade 2 Glioma: Real-World Data from a Multi-Institutional Registry.

Background: Grade-2 gliomas (G2-glioma) are uncommon. In 2016, RTOG9802 established the addition of chemotherapy after radiation (CRT) as a new standard of care for patients with high-risk G2-glioma, defined as subtotal resection or age ≥40 yrs. Here, we report current practices using real-world data. Methods: Patients diagnosed with G2-glioma from 1 January 2016 to 31 December 2022 were identified in BRAIN, a prospective clinical registry collecting data on patients with brain tumours. High- and low-risk were defined as per RTOG9802. Two time periods, January 2016-December 2019 (TP1) and January 2020-December 2022 (TP2), were defined. Survival was estimated using the Kaplan-Meier method. Results: 224 patients were identified. Overall, 38 (17%) were low-risk, with 35 (91%) observed without further treatment. A total of 186 (83%) were high-risk, with 96 (52%) observed, 63 (34%) receiving CRT, and 19 (10%) receiving radiation. Over time, CRT use increased (TP1 vs. TP2: 22% vs. 36%, p = 0.004), and the rate of biopsy (TP1 vs. TP2: 35% vs. 20%, p = 0.02) and radiotherapy alone (TP1 vs. TP2: 14% vs. 4%, p = 0.01) decreased. Median progression-free survival (PFS) was significantly longer in high-risk patients who received CRT (NR) over observation (39 months) (HR 0.49, p = 0.007). In high-risk patients who were observed, 59 (61%) were progression-free at 12 months and 10 (10%) at 5 years. OS data remains immature. Conclusions: Congruent with RTOG9802, real-world BRAIN data shows CRT is associated with improved PFS compared to observation in high-risk G2-glioma. Whilst CRT use has increased over time, observation after surgery remains the most common strategy, with some high-risk patients achieving clinically meaningful PFS. Validated biomarkers are urgently required to better inform patient management.

The role of preoperative immunonutrition on morbidity and immune response after cystectomy: protocol of a multicenter randomized controlled trial (INCyst Trial)

IntroductionCancer, malnutrition, and surgery negatively impact patient’s immune system. Despite standardized surgical technique and the development of new perioperative care protocols, morbidity after cystectomy remains a serious challenge for urologists. Most common postoperative complications, such as infections and ileus, often lead to longer length of stay and worse survival. The immune system and its interaction with the gut microbiota play a pivotal role in cancer immunosurveillance and in patient’s response to surgical stress. Malnutrition has been identified as an independent and modifiable risk factor for both mortality and morbidity. Immunonutrition (IN) may improve the nutritional status, immunological function, and clinical outcome of surgical patients. Aims of the study are (1) to evaluate the impact of IN on morbidity and mortality at 30 and 90 days after cystectomy and (2) to determine immune and microbiota signature that would predict IN effect.MethodsThis is a randomized, multicentric, controlled, pragmatic, parallel-group comparative study, supported by the Swiss National Science Foundation. A total of 232 patients is planned to be enrolled between April 2023 and June 2026. Three participating centers (Lausanne, Bern, and Riviera-Chablais) have been selected. All patients undergoing elective radical and simple cystectomy will be randomly assigned to receive 7 days of preoperative IN (Oral Impact®, Nestlé, Switzerland) versus standard of care (control group) and followed for 90 days after surgery. For the exploratory outcomes, blood, serum, urine, and stool samples will be collected in patients treated at Lausanne. In order to determine the impact of IN on immune fitness, patients enrolled at Lausanne will be vaccinated against influenza and the establishment of the vaccine-specific immune response will be followed. Analysis of the microbiota and expression of argininosuccinate synthetase 1 as potential biomarker will also be performed.Discussion and conclusionStrengths of the INCyst study include the randomized, multicenter, prospective design, the large number of patients studied, and the translational investigation. This study will challenge the added value of preoperative IN in patients undergoing cystectomy, assessing the clinical effect of IN on the onset of postoperative morbidity and mortality after cystectomy. Furthermore, it will provide invaluable data on the host immune response and microbiota composition.Trial registrationClinicalTrials.gov NCT05726786. Registered on March 9, 2023.

Insights into the Rising Threat of Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa Epidemic Infections in Eastern Europe: A Systematic Literature Review.

Antimicrobial resistance is a major global public health challenge, particularly with the rise of carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CRPA). This study aimed to describe the characteristics of CRE and CRPA infections in Eastern Europe, focusing on Bulgaria, Croatia, Czechia, Greece, Hungary, Poland, Romania, Serbia, Slovakia, and Slovenia. Following MOOSE and PRISMA guidelines, a systematic literature review of articles published between 1 November 2017 and 1 November 2023 was conducted using the MEDLINE, Embase, Web of Science, CDSR, DARE, and CENTRAL databases. The search strategy used a combination of free text and subject headings to gather pertinent literature regarding the incidence and treatment patterns of CRE and CRPA infections. A total of 104 studies focusing on infections in both children and adults were included in this review. This review revealed a significant prevalence of carbapenem-resistant Gram-negative isolates and underscored the effectiveness of imipenem/relebactam and ceftazidime/avibactam (CAZ/AVI) against Klebsiella pneumoniae carbapenemase-producing Enterobacterales and of ceftolozane/tazobactam, imipenem/relebactam and ceftazidime/avibactam against non-metallo-β-lactamase-producing CRPA strains. This study highlights the urgent need for comprehensive measures to combat the escalating threat of CRE and CRPA infections in Eastern European countries. At the same time, it shows the activity of the standard of care and new antimicrobials against carbapenem-resistant Gram-negative pathogens in Eastern Europe. Clinical real-world data on the treatment of carbapenem-resistant infections in Eastern Europe are needed.

P01.15.A SURGICAL RESECTION-INDUCED ISCHEMIA DRIVES GLIOBLASTOMA CELL PLASTICITY AND TUMOR MICROENVIRONMENT ADAPTATION

Abstract BACKGROUND Glioblastoma IDH-wildtype (GBM) treatment involves a combination of surgical resection, radiation therapy, and chemotherapy with temozolomide. Despite the aggressive standard of care, 90% of patients experience recurrence a few months after treatment, typically marked by the regrowth of highly invasive cells spreading from the peritumoral brain resection zone. The impact of chemoradiotherapy has been studied, but the impact of microsurgical resection on the tumor microenvironment (TME) and the plasticity of GBM cells remains unknown. Hence, the objective of this work was to study histopathological and transcriptomic changes induced by microsurgical resection on residual tumor cells and TME. MATERIAL AND METHODS Syngeneic GBM cell lines CT2A and GL261 were orthotopically implanted in C57Bl6j mice brains meanwhile P3 xenografts were injected in immunosuppressed nude mice. We developed an optimized microsurgical resection protocol for GBM in mice, mirroring the steps performed in patients. In a size-matched study, mice were randomly assigned to four groups: control (pre-surgery) and 1, 3, and 7 days post-surgery. Tumor tissues were studied with a multilevel strategy composed of time-resolved bulk and single-cell RNA sequencing, immunohistochemistry and intravital multiphoton microscopy (IVM). RESULTS Our analyses showed that microsurgical resection induced pronounced proneural-to-mesenchymal transition (PMT) and stimulation of hypoxia-driven pathways in residual GB cells. Further, we detected significant changes in the TME relative to the immune response and vascular function in line with ischemia exposure, which could humper the response to treatment by altering the adequate effect and distribution of the subsequent chemoradiotherapy. CONCLUSION Microsurgical resection consequences play a crucial role in shaping the phenotypic landscape of GBM tumor cells and the TME, marked by a transient ischemic TME triggering PMT in GBM cells and potentially preventing the effective response to chemoradiotherapy.

Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis.

Cutaneous leishmaniasis (CL), caused by protozoan parasites of the Leishmania genus, is prevalent in tropical and subtropical regions, with important morbidity, particularly in low- to middle-income countries. Current systemic treatments, including pentavalent antimonials and miltefosine, are associated with significant toxicity, reduced efficacy, and are frequently ineffective in cases of severe or chronic CL. Immunotherapies leverage the immune system to combat microbial infection and offer a promising adjunct or alternative approach to the current standard of care for CL. However, the heterogeneous clinical presentation of CL, which is dependent on parasite species and host immunity, may require informed clinical intervention with immunotherapies. This review explores the clinical and immunological characteristics of CL, emphasising the current landscape of immunotherapies in in vivo models and clinical studies. Such immune-based interventions aim to modulate immune responses against Leishmania, with additive therapeutic effects enabling the efficacy of lower drug doses and decreasing the associated toxicity. Understanding the mechanisms that underlie immunotherapy for CL provides critical insights into developing safer and more effective treatments for this neglected tropical disease. Identifying suitable therapeutic candidates and establishing their safety and efficacy are essential steps in this process. However, the feasibility and utility of these treatments in resource-limited settings must also be considered, taking into account factors such as cost of production, temperature stability, and overall patient access.

Robotic-Assisted Versus Laparoscopic Approach for Treatment of Acute Cholecystitis in Children.

Introduction: Laparoscopic cholecystectomy (Lap-C) is the standard of care for patients requiring cholecystectomy in the acute setting. Although robotic-assisted cholecystectomy (RA-C) performance has increased, utilization in the acute setting has not been widely reported. We describe the feasibility of RA-C for pediatric patients undergoing acute inpatient cholecystectomy. Methods: A single institutional retrospective review of patients receiving RA-C while admitted for acute cholecystitis and/or choledocholithiasis (June 2017-June 2022) was compared with a matched cohort who underwent traditional multiport Lap-C (June 2021-June 2022). Demographic, perioperative, and postoperative data were analyzed. Results: Fifty patients were included: 25 each in the RA-C and Lap-C groups. Fifty-four percent were female; 66% were non-Hispanic white. Median age (15.7 years [interquartile range, IQR 14.7, 17.3] versus 15.3 years [IQR 14.5, 16.9], P = .91) and preoperative weight (92.6 kg [IQR 60, 105.9] versus 72.3 kg [IQR 61.6, 85.6], P = .15) were similar between the RA-C and Lap-C groups, respectively. No differences were observed in median operating time (89 minutes [IQR 76, 103] versus 88 minutes [IQR 77, 137], P = .70), postoperative length of stay (22.5 hours [21.4, 24.9] versus 20.6 hours [18.0, 25.1], P = .06), or 30-day complications (12% versus 16%, P = .69). Although opioid utilization (.23 milliequivalents/kilogram [MME/kg] [IQR .03, .30] versus .03 MME/kg [0, .09], P = .02) was higher in the RA-C cohort overall, no differences were detected during an analysis of the most recent 2 years (P = .96). Conclusion: RA-C in the acute setting can be performed safely in the pediatric population with comparable procedural times as well as perioperative and 30-day outcomes.

Gastrointestinal, Behaviour and Anxiety Outcomes in Autistic Children Following an Open Label, Randomised Pilot Study of Synbiotics vs Synbiotics and Gut-Directed Hypnotherapy.

Alterations of the microbiome-gut-brain (MGB) axis have been associated with autism spectrum disorder (ASD) and disorders of gut-brain interaction (DGBI). DGBI are highly prevalent in autistic children and are associated with worsening behaviour and anxiety. Treatments such as probiotics, prebiotics and gut-directed hypnotherapy (GDH) have shown efficacy in improving gut symptoms in children. The primary objective of the study was to compare changes in gastrointestinal (GI) scores following a 12-week intervention of synbiotics (prebiotic + probiotic) +/- GDH with a follow-up at 24 weeks. Secondary objectives included changes in behavioural and anxiety symptoms, while changes in gut microbiome composition were assessed as an exploratory objective. Children diagnosed with ASD aged 5.00-10.99 years (n = 40) were recruited and randomised (1:1) to a 12-week intervention of either synbiotics (SYN group) or synbiotics + GDH (COM group). Both the SYN and COM group experienced significant reductions in total GI scores post-intervention and at follow-up (p < 0.001), with no superiority of the COM treatment over the SYN treatment. The COM group showed beneficial reductions in anxiety scores (p = 0.002) and irritability behaviours (p < 0.001) which were not present in the SYN group. At follow-up, only those in the COM group maintained significant reductions in GI pain scores (p < 0.001). There were significant changes in gut microbiota such as increases in Bifidobacterium animalis and Dialister in both groups over time. In conclusion,synbiotics with or without GDH may help support standard care for autistic children who suffer comorbid DGBI. The trial was prospectively registered at clinicialtrials.gov on 16 November 2020 (NCTO4639141).

Rethinking atherosclerotic cardiovascular disease prevention in the era of expanding therapies: could plaque stabilization reduce the need for lifelong treatments and polypharmacy?

This review examines current evidence on pharmacologically induced plaque stabilization in the context of a growing range of new therapies. It explores the potential for a paradigm shift in atherosclerotic cardiovascular disease (ASCVD) prevention, where treatments may not need to be lifelong to achieve lasting benefits. Since 2015, over 14 novel therapies have been introduced, each shown to reduce ASCVD risk when added to standard care with statins and aspirin. More than 80% of ischemic heart disease patients are now eligible for one or more of these treatments, increasing the risk of polypharmacy, treatment burden, and adverse side effects. As more therapies become available, this challenge is expected to grow. Many of these treatments have demonstrated plaque regression and stabilization, as evidenced by both intravascular ultrasound and computed tomography angiography, which likely explains much of their efficacy. The increasing number of novel therapies presents challenges in preventing ASCVD without leading to lifelong polypharmacy and increased patient burden. Since many of these drugs act through plaque stabilization, a new approach may be feasible - using these treatments for shorter durations to induce plaque regression, followed by less intensive maintenance therapies to preserve stability. This approach warrants further investigation in future studies.

Cost-Effectiveness of Teduglutide for Pediatric Patients with Short Bowel Syndrome in Japan, Including Caregiver Burden.

Short bowel syndrome (SBS) is associated with a significant mental and physical burden for patients and caregivers. Standard of care (SOC) for SBS includes parenteral support (PS) to optimize intestinal function. Teduglutide, a recombinant human glucagon-like peptide2 analogue, reduces the need for PS in patients with SBS. In this study, we assessed the cost-effectiveness of teduglutide in pediatric patients with SBS from multiple perspectives, considering the caregiver's burden. A Markov model was used to evaluate cost (Japanese yen, JPY) and effectiveness (quality-adjusted life years, QALYs) of teduglutide compared with SOC for pediatric patients with SBS in Japan. We conducted a base-case analysis and selected sensitivity and scenario analyses from three perspectives: (1) the public healthcare payer, (2) the public healthcare and long-term care payer, and (3) society. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) was 9,533,412 JPY per QALY from the public healthcare payer perspective, 6,335,980 JPY per QALY from the public healthcare and long-term care payer perspective, and 3,510,371 JPY per QALY from the societal perspective. The probability that cost-effectiveness of teduglutide is favorable from a societal perspective was 59.3%. In all scenario analyses, consistent with the base-case analysis, ICERs for teduglutide compared with SOC were different depending on whether caregiver utility and productivity loss were considered. Incorporating the caregiver's burden in the cost-effectiveness analysis of teduglutide for pediatric patients with SBS provided a more comprehensive assessment of the value of teduglutide for patients, their families, and society. This approach enhances our understanding of the overall value of a treatment, especially for diseases with significant caregiver burden.

Knowledge abstraction and filtering based federated learning over heterogeneous data views in healthcare

Robust data privacy regulations hinder the exchange of healthcare data among institutions, crucial for global insights and developing generalised clinical models. Federated learning (FL) is ideal for training global models using datasets from different institutions without compromising privacy. However, disparities in electronic healthcare records (EHRs) lead to inconsistencies in ML-ready data views, making FL challenging without extensive preprocessing and information loss. These differences arise from variations in services, care standards, and record-keeping practices. This paper addresses data view heterogeneity by introducing a knowledge abstraction and filtering-based FL framework that allows FL over heterogeneous data views without manual alignment or information loss. The knowledge abstraction and filtering mechanism maps raw input representations to a unified, semantically rich shared space for effective global model training. Experiments on three healthcare datasets demonstrate the framework’s effectiveness in overcoming data view heterogeneity and facilitating information sharing in a federated setup.

Neuropsychological outcomes following endovascular clot retrieval and intravenous thrombolysis in ischemic stroke.

Cognitive impairment, anxiety, depression, fatigue, and dependence in instrumental activities of daily living (ADL) are common after stroke; however, little is known about how these outcomes may differ following treatment with endovascular clot retrieval (ECR), intravenous tissue plasminogen activator (t-PA), or conservative management. Patients were recruited after acute treatment and invited to participate in an outcome assessment 90-120 days post-stroke. The assessment included a cognitive test battery and several questionnaires. The COVID-19 pandemic led to significant disruptions in recruitment and data collection, and the t-PA and conservative management groups were combined into a standard medical care (SMC) group. Sixty-two participants were included in the study (ECR = 31, SMC = 31). Mean age was 66.5 (20-86) years, and 35 (56.5%) participants were male. Participants treated with ECR had significantly higher National Institutes of Health Stroke Scale scores at presentation and significantly lower education. After adjusting for stroke severity, premorbid intellectual ability, and age, treatment with ECR was associated with significantly better performances on measures of cognitive screening, visual working memory, and verbal learning and memory. Participants treated with ECR also experienced less fatigue and were more likely to achieve independence in basic and instrumental ADLs. Despite this, cognitive impairment and fatigue were still common among participants treated with ECR and anxiety and depression symptoms were experienced similarly by both groups. Cognitive impairment and fatigue were less common but still prevalent following treatment with ECR. This has important practical implications for stroke rehabilitation, and routine assessment of cognition, emotion, and fatigue is recommended for all stroke survivors regardless of stroke treatment and functional outcome.

Evidence Review for the American College of Surgeons Quality Verification Part III: Standardization, Protocols, and Achieving Better Outcomes for Patient Care.

After decades of experience supporting surgical quality and safety by the American College of Surgeons, the ACS Quality Verification Program (ACS QVP) was developed to help hospitals improve surgical quality and safety. This review is the final installment of a three-part review aimed to synthesize evidence supporting the main principles of the ACS QVP. Evidence was systematically reviewed for three principles: standardized team-based care across five phases of surgical care, disease-based management, and external regulatory review. MEDLINE was searched for articles published from inception to January 2019 and two reviewers independently screened studies for inclusion in a hierarchical fashion, extracted data, and summarized results in a narrative fashion. A total of 5,237 studies across these three topics were identified. Studies were included if they evaluated the relationship between the standard of interest and patient-level or organization measures within the last twenty years. After applying inclusion criteria, a total of 150 studies in systematic reviews and primary studies were included for assessment. Despite institutional variation in standardized clinical pathways, evidence demonstrated improved outcomes such as reduced length of stay (LOS), costs, and complications. Evidence for multidisciplinary disease-based care protocols was mixed, though trended towards improving patient outcomes such as reduced LOS and readmissions. Similarly, the evidence for accreditation and adherence to external process measures was also mixed, though several studies demonstrated the benefit of accreditation programs on patient outcomes. The identified literature supports the importance of standardized multidisciplinary and disease-based processes and external regulatory systems to improve quality of care.