Specific Patient Research Articles

P807 HLA type impact on immunization and efficacy of ustekinumab in IBD patients: a multicenter study

Abstract Background About 30% of patients treated with ustekinumab will present primary or secondary failure. Outcomes and frequency of ustekinumab immunization are still controversial. Some HLA types (especially DQA1*05) appear to be predictive factors of anti TNFα immunization. This study aimed to assess the impact of HLA type on the risk of immunization and on the efficacy of ustekinumab. Methods IBD patients treatede with ustekinumab in Saint-Etienne and Lyon hospitals were included between 2017 and 2023. Ustekinulab through level was measured by ELISA and HLA type (DQA1, DQB1, DRB1) determined by PCR. Anti-drug antibodies (ADA) detection was done using both a "drug sensitive" assay (ELISA) and an innovative "drug tolerant" method based on anti human lambda chain. Data about clinical, biological (CRP, fecal calprotectin) and endoscopic responses were retrospectively collected. Results Among the 115 patients included (43% males, mean age of 40 years old), 98 had Crohn disease. Nighty-eight percent of the patients were previously treated with at least one anti-TNFα and 33% of them were immunized. In this study, 43 patients were immunized against ustekinumab with the "drug tolerant" assay and only 2 with the "drug sensitive" method. Immunization tended to reduce (not significatively) clinical, biological and endoscopic responses. Ustekinumab through level was significately higher for patients with good clinical (p = 0.009) and biological (p = 0.036). HLA DQA1*05 or DRB1*03 carriage was associated with higher risk of immunization (OR = 5.13, p = 0.048 / OR = 5.36, p = 0.006) and with a trend to decrease clinico-biological response. Other HLA types, notable DQA1*01 tended to be associated with a lower immunization (OR = 0.7, p=0.3) and a better response (OR = 2.55, p = 0.018). A small group involved (26 patients), combination therapy at induction had no significant benefit in terms of immunization prevention or therapeutic response. Sub-groups analysis seemed to confirm some HLA types involvement, by breaking free of imbalances due to haplotype transmission. Conclusion Our study suggests the usefulness of ustekinumab monitoring and a more common immunization than previously described. HLA type seem to influence immunization and ustekinumab response. Some specific HLA types and patients profiles tend to be associated with a higher risk of immunization not only to anti-TNFα but also to ustekinumab.

Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification in patients with suspected acute coronary syndrome

BackgroundThe clinical chemistry score (CCS) comprising high-sensitivity cardiac troponins (hs-cTn), glucose and estimated glomerular filtration rate has been previously validated with superior accuracy for detection and risk stratification of acute myocardial infarction (AMI) compared to hs-cTn alone. MethodsThe CCS was compared to other biomarker-based algorithms for rapid rule-out and prognostication of AMI including the hs-cTnT limit-of-blank (LOB, <3 ng/L) or limit-of-detection (LOD, <5 ng/L) and a dual marker strategy (DMS) (copeptin <10 pmol/L and hs-cTnT ≤14 ng/L) in 1506 emergency department (ED) patients with symptoms suggestive of acute coronary syndrome. Negative predictive values (NPV) and sensitivities for AMI rule-out, and 12-month combined endpoint rates encompassing mortality, myocardial re-infarction, as well as stroke were assessed. ResultsNPVs of 100% (95% CI: 98.3–100%) were observed for CCS = 0, hs-cTnT LoB and hs-cTnT LoD with rule-out efficacies of 11.1%, 7.6% and 18.3% as well as specificities of 13.0% (95% CI: 9.9–16.6%), 8.8% (95% CI: 7.3–10.5%) and 21.4% (95% CI: 19.2–23.8%), respectively. A CCS ≤ 1 achieved a rule-out in 32.2% of all patients with a NPV of 99.6% (95% CI: 98.4–99.9%) and specificity of 37.4% (95% CI: 34.2–40.5%) compared to a rule-out efficacy of 51.2%, NPV of 99.0 (95% CI: 98.0–99.5) and specificity of 59.7% (95% CI: 57.0–62.4%) for the DMS. Rates of the combined end-point of death/AMI within 30 days ranged between 0.0% and 0.7% for all fast-rule-out protocols. ConclusionsThe CCS ensures reliable AMI rule-out with low short and long-term outcome rates for a specific ED patient subset. However, compared to a single or dual biomarker strategy, the CCS displays reduced efficacy and specificity, limiting its clinical utility.

DOP28 Yield of surveillance colonoscopy in patients with Primary Sclerosing Cholangitis

Abstract Background Patients with primary sclerosing cholangitis (PSC) have a higher risk of developing colorectal cancer (CRC), in particular in patients with concurrent diagnosis of inflammatory bowel disease (IBD). Therefore, strict surveillance colonoscopy in patients with PSC and PSC-IBD is recommended with consideration of random biopsies. The aim of this study was to assess the method and yield of surveillance colonoscopy in patients with PSC and PSC-IBD in routine practice in the Netherlands. Methods An observational cohort study was performed within the EpiPSC2 cohort in The Netherlands. Patients with a confirmed PSC diagnosis were included from January 2008 onwards. Data were collected retrospectively from the date of diagnosis until inclusion, and prospectively from that date forward. Patient demographics, PSC and IBD disease characteristics were collected at study inclusion and during annual follow-up. For this study, data collection was expanded retrospectively with colonoscopy and pathology reports. Outcomes were endoscopic surveillance technique, whether random or targeted biopsies were taken, if polypectomy was performed, dysplasia detection rate and type of dysplasia. Results The study population included 1,203 PSC patients, of whom 82.1% had large duct PSC, and 70.6% concomitant IBD (table 1). A total of 4,099 colonoscopies were performed in 759 individual patients, with a median of 4 colonoscopies per patient (IQR 2 – 8). The median follow-up duration was 11 years (IQR 12 – 17). In total, 11.5% (n=473) of colonoscopies were performed with chromo-endoscopy. Among the conducted colonoscopies, 2,543 included biopsies, 355 involved polypectomies, and 86 comprised both biopsies and polypectomies. Dysplasia was identified in 11.4% (341 out of 2,984) of the colonoscopies, including 14.1% indefinite for dysplasia (n=48), 75.1% low grade dysplasia (n=256), 7.6% high grade dysplasia (n=26), and 5.9% adenocarcinoma (n=20). The detection of dysplasia occurred through random biopsies in 89 colonoscopies (26.1%), targeted biopsies in 114 colonoscopies (33.4%) and polypectomy in 153 colonoscopies (44.9%) (figure 1). Dysplasia was observed in 195 (26%) individual patients, of whom 80.5% had PSC-IBD. Conclusion Our data highlights the importance of colonoscopic surveillance in PSC and PSC-IBD patients. Dysplasia was detected in over a quarter of patients undergoing surveillance colonoscopy. Notably, 26.1% of dysplasia cases were identified through random biopsies, emphasizing the importance of incorporating random biopsies into surveillance protocols for this specific patient population.

Applications of artificial intelligence in the field of oral and maxillofacial pathology: a systematic review and meta-analysis

BackgroundSince AI algorithms can analyze patient data, medical records, and imaging results to suggest treatment plans and predict outcomes, they have the potential to support pathologists and clinicians in the diagnosis and treatment of oral and maxillofacial pathologies, just like every other area of life in which it is being used. The goal of the current study was to examine all of the trends being investigated in the area of oral and maxillofacial pathology where AI has been possibly involved in helping practitioners.MethodsWe started by defining the important terms in our investigation's subject matter. Following that, relevant databases like PubMed, Scopus, and Web of Science were searched using keywords and synonyms for each concept, such as "machine learning," "diagnosis," "treatment planning," "image analysis," "predictive modelling," and "patient monitoring." For more papers and sources, Google Scholar was also used.ResultsThe majority of the 9 studies that were chosen were on how AI can be utilized to diagnose malignant tumors of the oral cavity. AI was especially helpful in creating prediction models that aided pathologists and clinicians in foreseeing the development of oral and maxillofacial pathology in specific patients. Additionally, predictive models accurately identified patients who have a high risk of developing oral cancer as well as the likelihood of the disease returning after treatment.ConclusionsIn the field of oral and maxillofacial pathology, AI has the potential to enhance diagnostic precision, personalize care, and ultimately improve patient outcomes. The development and application of AI in healthcare, however, necessitates careful consideration of ethical, legal, and regulatory challenges. Additionally, because AI is still a relatively new technology, caution must be taken when applying it to this industry.

Personalized Multimodal Lifestyle Intervention as the Best-Evidenced Treatment for Chronic Pain: State-of-the-Art Clinical Perspective

Chronic pain is the most prevalent disease worldwide, leading to substantial disability and socioeconomic burden. Therefore, it can be regarded as a public health disease and major challenge to scientists, clinicians and affected individuals. Behavioral lifestyle factors, such as, physical (in)activity, stress, poor sleep and an unhealthy diet are increasingly recognized as perpetuating factors for chronic pain. Yet, current management options for patients with chronic pain often do not address lifestyle factors in a personalized multimodal fashion. This state-of-the-art clinical perspective aims to address this gap by discussing how clinicians can simultaneously incorporate various lifestyle factors into a personalized multimodal lifestyle intervention for individuals with chronic pain. To do so the available evidence on (multimodal) lifestyle interventions targeting physical (in)activity, stress, sleep and nutritional factors, specifically, was reviewed and synthetized from a clinical point of view. First, advise is provided on how to design a personalized multimodal lifestyle approach for a specific patient. Subsequently, best-evidence recommendations on how to integrate physical (in)activity, stress, sleep and nutritional factors as treatment targets into a personalized multimodal lifestyle approach are outlined. Evidence supporting such a personalized multimodal lifestyle approach is growing, but further studies are needed.

Treatment decision for recurrences in non-small cell lung cancer during or after adjuvant osimertinib: an international Delphi consensus report.

Osimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence. To reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy. Panellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made. This study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment.

2035 The Feasibility to Staff of Patient Specific Music Choice on Elderly Care Wards - A Post Intervention Survey

Abstract Introduction Receptive music listening has been shown to reduce depression, anxiety, and agitation in older adults. However, unfiltered and disruptive noise can increase confusion and agitation. Yet, during hospitalization older patients often have little control over when and for how long they are exposed to music, the genre which is heard, or they may have no access to music. Furthermore, older persons have reduced ability to use modern technology to counter this and their sensory and functional impairments may further isolate them. This study aimed to assess the feasibility of offering two one-hour daily sessions of patient specific music (PSM) choices on an elderly-care ward. Methods On a district general hospital elderly-care ward a 5-day trial of offering two one-hour daily sessions of PSM, using enhanced wireless speakers optimally positioned with daily amended music playlists based on specific patient choice. Ambient noise was minimised with regular decibel monitoring. A post-intervention staff survey was completed to assess the feasibility of continuing, the perceived impact on staff and patients and potential barriers to continuation. Thematic analyses were completed on the survey. Results In the post-intervention feasibility survey (n=14) the majority of staff (86%) agreed that it was possible, implementable and the procedure easy to use. In the impact assessment (n=19) 80% of staff stated it had a positive effect on patients and 89% stated it had a positive effect on staff. Thematic analyses on impact identified benefits to: work, engagement, enjoyment, physical activity and well-being. Barriers that were identified included patient choice, repetition of music, patients unable to engage with the process and staff availability for consistent delivery. Conclusion Playing patient specific music choice was feasible and acceptable to staff with a perceived positive influence on both staff and patients. Further studies are now required to assess the impact on patient outcomes.

The Ross Procedure: Imaging, Outcomes and Future Directions in Aortic Valve Replacement.

The Ross procedure is gaining recognition as a significant option for aortic valve replacement (AVR), and is particularly beneficial in specific patient groups. Although categorized as a class IIb recommendation in the 2020 American College of Cardiology (ACC)/American Heart Association (AHA), and the European Society of Cardiology (ESC) management guidelines on valvular heart disease, recent studies bolster its credibility. Research, including a propensity-matched study, underlines the Ross procedure's association with enhanced long-term survival and reduced adverse valve-related events compared to other AVR types. This positions the Ross procedure as a primary option for AVR in young and middle-aged adults within specialized centers, and potentially the only choice for children and infants requiring AVR. This review meticulously examines the Ross procedure, covering historical perspectives, surgical techniques, imaging, and outcomes, including hemodynamic performance and quality of life, especially focusing on pediatric and young adult patients. It explores contemporary techniques and innovations like minimally invasive approaches and tissue engineering, underscoring ongoing research and future directions. A summarization of comparative studies and meta-analyses reiterates the Ross procedure's superior long-term outcomes, valve durability, and preservation of the left ventricular function, accentuating the crucial role of patient selection and risk stratification, and pinpointing areas for future research.

Efficacy of bronchial thermoplasty in a patient panel with uncontrolled severe persistent asthma

Background Bronchial thermoplasty (BT) is an approved procedure to manage uncontrolled severe persistent asthma. Many insurance providers are reluctant to pay for BT without proven benefit among their specific patient panel. Objective Determine if BT is effective in a panel patient panel with uncontrolled severe persistent asthma. Study design and methods This was an unblinded prospective study of adult subjects with uncontrolled severe persistent asthma who underwent BT. Outcomes were assessed at baseline and then 3-, 6-, 12-, 18- and 24-months post-BT. The primary metric was an improved Asthma Quality of Life Questionnaire (AQLQ) score. Other metrics included improved Asthma Control Test (ACT), peak expiratory flow rates (PEFR), spirometry, fractional excretion of nitric oxide (FeNO), number of unscheduled medical visits, and lost days of work/activity. Respiratory adverse events were assessed during the BT treatment period and at each post-BT visit. Results Twenty-nine subjects completed the study; the median interquartile range (IQR) age was 47 (42-61), and the majority were female (69%), white (93%), and non-Hispanic (90%). After BT, mean (±std) AQLQ scores improved by 1.6(±1.1) at 3 months (p < 0.0001), 1.6(±1.2) at 6 months (p < 0.0001), 1.4(±1.0) at 12 months (p < 0.0001), 1.8(±1.1) at 18 months (p < 0.0001), and 1.6 (±1.5) at 24 months (p < 0.0001). There were significant improvements in ACT, PEFR, unscheduled medical visits and lost days of work and activity. Spirometry and FeNO metrics were unchanged. The average cost for subjects completing all 3 BT procedures was approximately $15,000. Conclusion BT is an effective adjunctive therapeutic modality in subjects with uncontrolled severe persistent asthma.

TG468: a text graph convolutional network for predicting clinical response to immune checkpoint inhibitor therapy.

Enhancing cancer treatment efficacy remains a significant challenge in human health. Immunotherapy has witnessed considerable success in recent years as a treatment for tumors. However, due to the heterogeneity of diseases, only a fraction of patients exhibit a positive response to immune checkpoint inhibitor (ICI) therapy. Various single-gene-based biomarkers and tumor mutational burden (TMB) have been proposed for predicting clinical responses to ICI; however, their predictive ability is limited. We propose the utilization of the Text Graph Convolutional Network (GCN) method to comprehensively assess the impact of multiple genes, aiming to improve the predictive capability for ICI response. We developed TG468, a Text GCN model framing drug response prediction as a text classification task. By combining natural language processing (NLP) and graph neural network techniques, TG468 effectively handles sparse and high-dimensional exome sequencing data. As a result, TG468 can distinguish survival time for patients who received ICI therapy and outperforms single gene biomarkers, TMB and some classical machine learning models. Additionally, TG468's prediction results facilitate the identification of immune status differences among specific patient types in the Cancer Genome Atlas dataset, providing a rationale for the model's predictions. Our approach represents a pioneering use of a GCN model to analyze exome data in patients undergoing ICI therapy and offers inspiration for future research using NLP technology to analyze exome sequencing data.

Community pharmacists' knowledge, attitudes, and practices regarding counselling on vitamins and dietary supplements in Malaysia: A study on complementary medicines

BackgroundThe utilization of vitamins and dietary supplements (DSs) among consumers in Malaysia has seen a notable increase. However, there is limited research available on how pharmacists in Eastern countries manage the provision of these products. ObjectiveThis study aims to assess the knowledge, attitudes, and practices of community pharmacists in Malaysia regarding the provision of counselling services on vitamins and DSs. The findings will inform education strategies in this area. MethodsA cross-sectional quantitative study was conducted from February to April 2022 using a validated online-based questionnaire. The survey was distributed to community pharmacists across Malaysia through social media channels. t-test and ANOVA test were used for data analysis. ResultsAmong the 260 participants, 73.5% were categorized as having average product knowledge. Key concerns included a lack of knowledge about the indications of new products and when to discontinue their use. Regarding dosing in specific patient groups, 33.5% of pharmacists only occasionally consulted references and primarily relied on product labels. Furthermore, 29% of pharmacists believed it was unnecessary to refer patients to doctors when they experienced ongoing symptoms while taking vitamins or DSs. Interestingly, 44.6% of pharmacists believed there was a correlation between the efficacy of vitamins and their price, often recommending more expensive brands despite similar content. ConclusionThere is an opportunity to enhance the knowledge of pharmacists in Malaysia regarding vitamins and DSs. Education interventions should focus on areas such as dosing for specific patient groups, when to discontinue products, understanding new products, evidence-based efficacy of products for specific conditions, and providing a framework for appropriate referral to support pharmacists in their practice.

Unveiling survival strategies: The impact of treatment modalities on patients with esophageal cancer and the role of racial disparities.

257 Background: Managing esophageal cancer (EC) involves neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy as the standard of care. However, some patients may remain unsuitable for esophagectomy. This study explores real-world outcomes in EC patients across different treatments, considers prognostic factors, and examines potential racial disparities. Methods: Data from 44,181 patients diagnosed with locally advanced EC between 2004-2017 were extracted from the National Cancer Database. The cohort was stratified into three groups: nCRT followed by esophagectomy, definitive RT (dCRT), single-modality RT. The dataset included 24,676 patients who received nCRT with esophagectomy or dCRT (N=17,534) and 1,971 patients who received single-modality RT. Endpoints included overall survival (OS). Cox Proportional Hazards Model was employed for multivariate survival analysis. Chi-square test was applied to the covariate demographic data. Results: nCRT followed by esophagectomy significantly improved OS compared to dCRT (mOS 43.5 vs. 20.1 months, p &lt; 0.001). Single-modality RT had an mOS of 14.4 months. In the RT group, 73% were over 65 years old compared to 59% in the dCRT group (p &lt; 0.001). Over 60% of patients had node-positive disease in both RT and dCRT groups (69% vs. 61.4%). More privately insured patients received multimodal treatment compared to publicly insured patients (27.3% vs. 16.8%, p &lt; 0.001). Over 70% of patients were willing to travel within 20 miles for treatment, 60% underwent treatment in community programs. Racial disparities were observed, with Black patients experiencing worse outcomes compared to all other groups, while Asian and Hispanic patients had better outcomes (table1). In the squamous cell histology subset treated with dCRT, mOS was 22 (20.6 – 23.6 months) for Black patients, 27 (26 – 28) months for White patients, 36 (30-46) months for Hispanic patients, and 37 (30-44) months for Asian/Pacific Islander patients (p &lt; 0.001). Conclusions: This real-world data analysis underscores the effectiveness of nCRT followed by esophagectomy in providing the best survival benefit for EC patients compared to dCRT or RT alone. Racial disparities emerged as significant factors influencing cancer survival outcomes. These identified factors including race and age can assist clinicians in making better-informed decisions regarding treatment pathways for specific patient populations. [Table: see text]

Genome-wide association study (GWAS) and novel prognostic markers in metastatic colorectal cancer (mCRC).

174 Background: Few genome-wide investigations have examined germline variants associated with mCRC outcomes following primary treatment. Here, we performed a GWAS meta-analysis to explore the impact of germline genetic variation on progression-free survival (PFS) and overall survival (OS) in four clinical trials of mCRC. Methods: The GWAS comprised 1,324 mCRC patients (pts) enrolled in four randomized Phase II/III trials for first line treatment: FIRE-3 (FOLFIRI-bevacizumab [bev]; FOLFIRI-cetuximab[cet]), MAVERICC (FOLFIRI-bev; FOLFOX6-bev), TRIBE (FOLFIRI-bev; FOLFOXIRI-bev), and TRIBE2 (mFOLFOX6-bev; FOLFOXIRI-bev). DNA isolated from blood was genotyped using the OncoArray and imputed against the Haplotype Reference Consortium panel. In each trial arm, associations between SNPs and PFS and OS were assessed using an additive coding in a Cox proportional hazard framework, adjusting for trial specific patient characteristics and principal components. Meta-analysis was carried out using an inverse-variance weighted fixed effect model. All reported GWAS p-values were adjusted for genomic inflation. To further investigate significant hits, we evaluated associations between gene expression measured from FFPE tumor samples and PFS and OS in 433 pts enrolled in an independent randomized first-line Phase III trial, CALGB/SWOG 80405. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in multivariable Cox models for expression levels in the top (Q4, high) vs the bottom quartile (Q1, low). Results: Two SNPs in the MLPH intronic region and one SNP in the TYR intronic region surpassed the GWAS significance threshold for PFS and OS, respectively. The top ranked SNPs associated with PFS and OS, rs13409241 (A&gt;G, PFS HR: 1.35, 95% CI [1.21, 1.51], P=4.34E-8) and rs10765199 (T&gt;A, OS HR: 1.45, 95%CI [1.27, 1.65], P=4.69E-8), showed similar effects across all eight treatment arms ( I2 = 0% and 38.5%, respectively). No significant heterogeneity variant was found. In the CALGB/SWOG 80405 cohort, pts with MLPH-low tumors (N=109) showed significantly longer PFS (median 14.8 vs 7.6 months, low vs. high (as reference) adjusted HR 0.53, 95% CI [0.38, 0.74], P=2.1E-4) and OS (median 35.8 vs. 18.2 months, adjusted HR 0.65, 95% CI [0.46, 0.92], P=0.015) compared to MLPH-high (N=107). No significant associations for TYR expression and outcomes were found. MLPH and TYR are involved in melanosome transport and melanogenesis. Melanin has been shown to reduce vitamin D levels, which can affect CRC prognosis. MLPH has also been reported to accelerate epithelial-mesenchymal transition and metastasis in lung and prostate cancers. Conclusions: These results suggest that germline genetic variation in MLPH and TYR may affect mCRC prognosis via a mechanism that involves melanin and possibly the epithelial-mesenchymal transition. Note: Authors Millstein and Lenz contributed equally to this work.

Cost-utility analysis of sutureless and rapid deployment versus conventional aortic valve replacement in patients with moderate to severe aortic stenosis in Thailand.

Sutureless and rapid deployment aortic valve replacement (SUAVR) has become an alternative to conventional aortic valve replacement (CAVR) for aortic stenosis (AS) treatment due to its advantages in reducing surgery time and improving outcomes. This study aimed to assess the cost-utility of SUAVR vs. CAVR treatment for patients with moderate to severe AS in Thailand. A two-part constructed model was used to estimate the lifetime costs and quality-adjusted life years (QALYs) from both societal and healthcare perspectives. Data on short-term mortality, complications, cost, and utility data were obtained from the Thai population. Long-term clinical data were derived from clinical studies. Costs and QALYs were discounted annually at 3% and presented as 2022 values. The incremental cost-effectiveness ratio (ICER) was calculated to determine additional cost per QALY gained. Deterministic and probabilistic sensitivity analyses were performed. SUAVR treatment incurred higher costs compared with CAVR treatment from both societal (THB 1,733,355 [USD 147,897] vs THB 1,220,643 [USD 104,150]) and healthcare provider perspectives (THB 1,594,174 [USD 136,022] vs THB 1,065,460 [USD 90,910]). In addition, SUAVR treatment resulted in lower health outcomes, with 6.20 life-years (LYs) and 4.95 QALYs, while CAVR treatment achieved 6.29 LYs and 5.08 QALYs. SUAVR treatment was considered as a dominated treatment strategy using both perspectives. Sensitivity analyses indicated the significant impact of changes in utilities and long-term mortality on the model. SUAVR treatment is not a cost-effective treatment strategy compared with CAVR treatment for patients with moderate-severe AS in Thailand, as it leads to higher costs and inferior health outcomes. Other important issues related to specific patients such as those with minimally invasive surgery, those undergoing AVR with concomitant procedures, and those with calcified and small aortic root should be taken into account.

Factors associated with patient-to-healthcare personnel (HCP) and HCP-to-subsequent patient transmission of methicillin-resistant Staphylococcus aureus.

Transient acquisition of methicillin-resistant Staphylococcus aureus (MRSA) on healthcare personnel (HCP) gloves and gowns following patient care has been examined. However, the potential for transmission to the subsequent patient has not been studied. We explored the frequency of MRSA transmission from patient to HCP, and then in separate encounters from contaminated HCP gloves and gowns to a subsequent simulated patient as well as the factors associated with these 2 transmission pathways. We conducted a prospective cohort study with 2 parts. In objective 1, we studied MRSA transmission from random MRSA-positive patients to HCP gloves and gowns after specific routine patient care activities. In objective 2, we simulated subsequent transmission from random HCP gloves and gowns without hand hygiene to the next patient using a manikin proxy. For the first objective, among 98 MRSA-positive patients with 333 randomly selected individual patient-HCP interactions, HCP gloves or gowns were contaminated in 54 interactions (16.2%). In a multivariable analysis, performing endotracheal tube care had the greatest odds of glove or gown contamination (OR, 4.06; 95% CI, 1.3-12.6 relative to physical examination). For the second objective, after 147 simulated HCP-patient interactions, the subsequent transmission of MRSA to the manikin proxy occurred 15 times (10.2%). After caring for a patient with MRSA, contamination of HCP gloves and gown and transmission to subsequent patients following HCP-patient interactions occurs frequently if contact precautions are not used. Proper infection control practices, including the use of gloves and gown, can prevent this potential subsequent transmission.

Accelerated enhanced recovery after colon cancer surgery with discharge within one day after surgery: a systematic review

BackgroundRecent studies have demonstrated that accelerated enhanced recovery after colorectal surgery is feasible for specific patient populations. The accelerated enhanced recovery protocols (ERP) tend to vary, and the majority of studies included a small study population. This hampers defining the optimal protocol and establishing the potential benefits. This systematic review aimed to determine the effect of accelerated ERPs with intended discharge within one day after surgery.MethodsPubMed (MEDLINE), Embase, Cochrane and Web of Science databases were searched using the following search terms: colon cancer, colon surgery, accelerated recovery, fast track recovery, enhanced recovery after surgery. Clinical trials published between January 2005 – February 2023, written in English or Dutch comparing accelerated ERPs to Enhanced Recovery After Surgery (ERAS) care for adult patients undergoing elective laparoscopic or robotic surgery for colon cancer were eligible for inclusion.ResultsThirteen studies, including one RCT were included. Accelerated ERPs after colorectal surgery was possible as LOS was shorter; 14 h to 3.4 days, and complication rate varied from 0–35.7% and readmission rate was 0–17% in the accelerated ERP groups. Risk of bias was serious or critical in most of the included studies.ConclusionsAccelerated ERPs may not yet be considered the new standard of care as the current data is heterogenous, and data on important outcome measures is scarce. Nonetheless, the decreased LOS suggests that accelerated recovery is possible for selected patients. In addition, the complication and readmission rates were comparable to ERAS care, suggesting that accelerated recovery could be safe.

Perspective to precision medicine in scleroderma.

Systemic sclerosis (SSc) is a rare and heterogeneous disease with no relevant environmental trigger or significant responsible gene. It has been and will continue to be difficult to identify large enough patients to conduct classic population-based epidemiologic exposure/non-exposure studies with adequate power to ascertain environmental and genetic risk factors for these entities. The complexity of pathogenesis and heterogeneity are likely to require personalized/precision medicine for SSc. Since several potential drugs are currently available for specific patients if not whole SSc, classification of SSc seems to form the foundation for a better therapeutic strategy. To date, SSc has been classified based on the extent/severity of the affected area as well as some disease markers, including the autoantibody profile. However, such an analysis should also lead to improvements in the design of appropriately stratified clinical trials to determine the effects and prediction of targeted therapies. An approach based on drug response preclinically conducted using patients' own fibroblasts in vitro, can provide a precise disease marker/therapeutic selection for clinical practice. Because scleroderma dermal fibroblasts have a persistent hyper-productive phenotype occurring not only in person, but also in cell culture conditions. Thus, an accumulating approach based on disease markers ensures progression and de-escalation to re-establish a better life with a personally optimized drug environment after the onset of SSc.

Standardizing default electronic health record tools to improve safety for hospitalized patients with Parkinson's disease.

Electronic Health Record (EHR) systems are often configured to address challenges and improve patient safety for persons with Parkinson's disease (PWP). For example, EHR systems can help identify Parkinson's disease (PD) patients across the hospital by flagging a patient's diagnosis in their chart, preventing errors in medication and dosing through the use of clinical decision support, and supplementing staff education through care plans that provide step-by-step road maps for disease-based care of a specific patient population. However, most EHR-based solutions are locally developed and, thus, difficult to scale widely or apply uniformly across hospital systems. In 2020, the Parkinson's Foundation, a national and international leader in PD research, education, and advocacy, and Epic, a leading EHR vendor with more than 35% market share in the United States, launched a partnership to reduce risks to hospitalized PWP using standardized EHR-based solutions. This article discusses that project which included leadership from physician informaticists, movement disorders specialists, hospital quality officers, the Parkinson's Foundation and members of the Parkinson's community. We describe the best practice solutions developed through this project. We highlight those that are currently available as standard defaults or options within the Epic EHR, discuss the successes and limitations of these solutions, and consider opportunities for scalability in environments beyond a single EHR vendor. The Parkinson's Foundation and Epic launched a partnership to develop best practice solutions in the Epic EHR system to improve safety for PWP in the hospital. The goal of the partnership was to create the EHR tools that will have the greatest impact on outcomes for hospitalized PWP.

The use of ribociclib in real clinical practice: results of a single-center observational retrospective study

Introduction. The standard initial treatment for patients with hormone receptor positive, HER2 negative, metastatic breast cancer (HR+/HER2– mBC) involves the use of CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy. The combination therapy has proven effectiveness in numerous Phase II and III randomized controlled trials (RCTs). Nonetheless, RCTs may not fully represent real-world clinical situations due to their stringent inclusion criteria, resulting in a specific patient population.Aim. Analyze of ribociclib using for treating patients with HR+/HER2– advanced breast cancer (mBC) at the Republican Clinical Oncology Dispensary.Materials and methods. Patients diagnosed with HR+/HER2– mBC who were treated in clinical routine with ribociclib in combination with different endocrine agents between 2016 and 2020 were identified and enrolled in this retrospective study. Clinicopathological characteristics and clinical outcomes were recorded with particular emphasis on ribociclib therapy course (progression-free survival (PFS), toxicity, dose reduction).Results. Data from n = 101 patients were evaluated. The mean patient age was 61 years. The study included 67 (66.3%) patients with progression after radical treatment and 34 (33.7%) patients with primary disseminated breast cancer. Dose reduction due to adverse events was performed in n = 14 cases (13.9%). Presence of prior therapy lines and lower ECOG status were associated with shorter PFS, whereas estrogen positivity and the choice of fulvestrant over aromatase inhibitor were positively associated with PFS. Metastatic pattern, progesterone positivity and dose reduction due to toxicity did not significantly impact on PFS.Conclusion. Our real-world data analysis on ribociclib treatment in Russian regional hospital supports data from RCTs regarding both treatment efficacy and safety of CDK4/6i for treatment of patients with HR+/HER2– mBC. Currently, by expanding our experience with CDK4/6 inhibitors in different groups of patients with mBC, we will be able to provide patients with optimal treatment options.

The prevalence of pulmonary hypertension in post-tuberculosis and active tuberculosis populations: a systematic review and meta-analysis.

The prevalence of tuberculosis (TB)-associated pulmonary hypertension (PH) has not previously been quantified, resulting in an underappreciated burden of disease. We aimed to estimate the prevalence of PH in post-TB and active TB populations. In this systematic review and meta-analysis, we searched PubMed/Medline, Cochrane Library, EBSCOhost, Scopus, African Journals Online and Google Scholar, with no language restriction, for available literature published after 1950. Eligible studies described adult participants (≥16 years), with documented evidence of active or prior TB, diagnosed with PH. Study quality was assessed using a risk of bias tool specifically developed for prevalence studies. Aggregate prevalence estimates with 95% confidence intervals were synthesised using a random-effects meta-analysis model, incorporating the Freeman-Tukey transformation. Subgroup analysis was conducted to ascertain prevalence estimates in specific patient populations. We identified 1452 unique records, of which 34 met our inclusion criteria. 23 studies, with an acceptable risk of bias and where PH was diagnosed at right heart catheterisation or echocardiography, were included in the meta-analysis. In post-TB studies (14/23), the prevalence of PH was 67.0% (95% CI 50.8-81.4) in patients with chronic respiratory failure, 42.4% (95% CI 31.3-54.0) in hospitalised or symptomatic patients and 6.3% (95% CI 2.3-11.8) in nonhealthcare-seeking outpatients (I2=96%). There was a lower estimated prevalence of PH in studies of populations with active TB (9.4%, 95% CI 6.3-13.0), I2=84%). Our results highlight the significant burden of PH in post-TB and active TB populations. We emphasise the need for increased recognition of TB-associated PH and additional high-quality prevalence data.