Specific Patient Groups Research Articles

Ethics and end-of-life in pediatric and neonatal ICUs: a systematic review of recommendations.

Working in neonatal intensive care units (NICUs) or pediatric intensive care units (PICUs) entails making difficult decisions about children at the end of their lives that raise significant ethical issues. This review identified the ethical content of the papers containing expert guidelines and recommendations in relation to end-of-life decision-making in NICUs and PICUs, by analyzing ethical positions and ethical principles behind them. Systematic search was limited to the period from 1990 to 2023 and encompassed 6 bibliographic databases (Medline, PubMed, CINAHL, APA PsycINFO, Web of Science Core Collection, and Scopus), grey literature sources and relevant reference lists. The international, national, or institutional papers providing expert guidelines and recommendations comprehensively addressing either withholding/withdrawing of life sustaining treatment, palliative care, and/or intentional life terminating actions in NICUs and PICUs were included in analysis. Also, only papers published in English language were considered. Papers that were not developed by intensive care expert communities and those that were either too narrow (e.g., dealing with specific issues or specific patient groups) or broad (e.g., addressing issues of interest on general and abstract level) were excluded. The search data were gathered and deduplicated, partly by Mendeley software. Titles and abstracts were screened by three independent reviewers, and full-text papers further reviewed and assessed for eligibility. Subsequently, data of interest were extracted, and qualitative analysis was performed. Initial search retrieved 6784 papers from bibliographic databases and 363 from other utilized sources. Titles and abstracts from 2827 papers were screened. 17 full texts were further assessed resulting in a total number of 9 papers (6 from bibliographic databases and 3 from other sources) which met the inclusion criteria and were included for analysis. The papers were published from 2001 to 2021. Four papers primarily focus on NICU setting, while five on PICU. A total of 38 ethical positions were identified and were grouped under 5 themes according to the content of the positions, relating to: patients, parents, medical team, decision-making and treatment options. A total of 12 ethical principles were mentioned in the papers. The principle of beneficence emerged as the most prominent one. It was explicitly mentioned in all included papers except one. This review has shown that papers containing guidelines and recommendations on end-of-life decision-making in the NICU and PICU promote similar stances. The ethical principle of beneficence is at the core of the decision-making process, and all decisions are made focusing on the child's best interests.

Surgical complication index for pediatric patients (SCIPP): A novel pediatric frailty index predicting postoperative complications in a study of 133 pediatric neurosurgical patients.

A predictive index for surgical complications in pediatric patients is lacking in the current scientific literature. We have developed a simple index to accurately predict the likelihood of complications after surgery.The Surgical Complication Index for Pediatric Patients (SCIPP) is reliable and accurate for both heterogenous and specific groups of pediatric patients. A retrospective analysis of pediatric neurosurgical procedures from 2005 to 2023 was conducted. Logistic and linear regression analyses were performed to analyze the correlation with their respective SCIPP scores and post-operative complications and length of stay (LOS). Our cohort included 90 tethered cord patients and 43 surgeries consisting of craniotomies/craniectomies, laminectomies/laminotomies, and others. The mean SCIPP score across all 133 patients was 2.41 ± 1.76, with an average age of 5.37 ± 5.53years. From the logistic regression, each 1-point increase in SCIPP score was associated with increased odds of experiencing a complication after surgery in all patients (odds ratio: 1.57; p < 0.001) and tethered cord patients (odds ratio: 1.59; p = 0.007). The reduced 4-point SCIPP was associated with increased odds in all patients (odds ratio: 2.67; p < 0.001) and tethered cord patients (odds ratio: 2.89; p = 0.001) as well. Upon linear regression analysis, each 1-point increase in SCIPP was associated with a 0.49day increase in LOS (p = 0.002). Each 1-point increase in reduced SCIPP was associated with a 0.42day increase in LOS but was not statistically significant (p = 0.120). The SCIPP is a simple and accurate tool that predicts surgical complications and LOS in a variety of pediatric neurosurgical procedures and can be used to counsel patients and families on the risks of surgery.

HLA-matched related peripheral blood stem cell and bone marrow transplantation with RIC regimens yield comparable outcomes for adult AML.

Understanding differences in clinical outcomes between PBSCT and BMT is important, and this study compared outcomes of HLA-matched related PBSCT and BMT using reduced-intensity conditioning (RIC) in adult acute myeloid leukemia (AML) patients. Data from 402 patients who underwent either PBSCT (n=294) or BMT (n=108) between 2000 and 2022 were analyzed using the Japanese nationwide registry database. The primary endpoint was overall survival (OS), and secondary endpoints included disease-free survival (DFS), non-relapse mortality (NRM), and GVHD. Results indicated no significant difference in 3-year OS (44.6% for PBSCT vs. 46.9% for BMT, HR 1.173, P=0.299) and DFS (42.1%vs. 41.8%, HR 1.073, P=0.639). PBSCT was more beneficial for avoiding relapse (20.3%vs. 12.4%, HR, 0.715, P=0.059). However, PBSCT was associated with higher NRM (20.3%vs. 12.4%, HR 1.801, P=0.025) due to more frequent, chronic GVHD (HR 1.889, P=0.035). Subgroup analysis did not reveal specific patient groups that benefited more from PBSCT or BMT. Incidence of extensive chronic GVHD and NRM has improved in PBSCT recipients in recent years (2014-2022). We conclude that related PBSCT with RIC regimens offers comparable prognosis to BMT for adult AML patients. Further optimization of prophylactic strategies for chronic GVHD is required to improve outcomes after PBSCT.

P-303. Mupirocin Resistance is Common in Tampa, Florida Staphylococcus aureus Clinical Isolates

Abstract Background Mupirocin (Mup) is a topical drug used to decolonize carriers of Staphylococcus aureus (SA) to prevent later SA infection. A spot survey of SA isolates at Tampa General Hospital (TGH) revealed a prevalence in Mup resistance of ∼40%, leading to a change of decolonization protocol from mupirocin to povidone iodine in January 2020, just prior to the COVID pandemic. We determined the prevalence of Mup resistance in a random sampling of clinical isolates before and after change in decolonization protocol. Methods A total of 211 PreCOVID (before 2020) and 173 PostCOVID (after 2021) samples from various sources (blood, bone, eye, fluid, respiratory, urine, and wound) were tested with minimum inhibitory concentration for Mup resistance using literature values for susceptible, low resistance, and high resistance. Oxacillin sensitivity, to verify MRSA isolates, was tested in parallel. Results were analyzed via χ² for significance (p=0.05). Results Comparison of Mup resistance levels between the Pre- and PostCOVID time points showed no significant difference (p=0.460). PreCOVID: 71.1% susceptible, 8.1% low resistance, 20.9% high resistance. PostCOVID: 74.0% susceptible, 9.8% low resistance, and 16.2% high resistance. MRSA status correlated with Mup resistance in both Pre- (p&amp;lt; 0.001) and PostCOVID samples (p=0.001). Blood vs Non-Blood samples differed in Mup resistance in the PreCOVID period (20.7% blood vs 34.1% non-blood, p=0.037), whereas samples in the PostCOVID period showed no significant difference in Mup resistance (22.8% blood vs 28.7% non-blood, p=0.375). Notably, 46.2% PreCOVID Respiratory were resistant to Mup (p=0.016). 26.3% PostCOVID Respiratory were resistant to Mup (p=0.651). Conclusion Change in decolonization protocol did not influence the overall prevalence of Mup resistance. Respiratory samples made up a significant proportion of the resistant samples in the PreCOVID time point, suggesting differences in prevalence of Mup resistance in different clinical sites. Further molecular epidemiological studies are needed to determine if specific sites of infection or specific patient groups are more likely to be colonized with Mup resistant SA isolates. Disclosures All Authors: No reported disclosures

P-19. The Adjuvanted Recombinant Zoster Vaccine Is Effective in Preventing Herpes Zoster (HZ) Among Patients ≥ 50 Years of Age (YOA) With Selected Autoimmune Diseases in the United States: A Real-World Database Analysis (2018–2021)

Abstract Background The adjuvanted recombinant zoster vaccine (RZV) was approved by the US Food and Drug Administration (FDA) for HZ prevention in adults ≥50 YOA in 2017 and for adults ≥18 YOA who are at increased risk of HZ due to immunodeficiency or immunosuppression in 2021 (FDA, 2023. Shingrix. STN: 125614). Autoimmune disease (AID) patients are at increased risk of developing HZ compared to the general population. This real-world evidence (RWE) study assessed RZV vaccine effectiveness (VE) in patients ≥50 YOA with selected AIDs (rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, psoriasis and psoriatic arthritis). Study Design Methods This retrospective matched cohort study was conducted in patients ≥50 YOA with selected AIDs using Optum’s de-identified Clinformatics Data Mart database from Jan 2018 to Dec 2021. Patients who received 2 doses of RZV (RZV 2-dose cohort) were matched (1:3) by age, medication category and propensity scores to unvaccinated counterparts (non-RZV cohort), as shown in Figure 1. Incidence rates (IRs) of HZ and VE were calculated overall, stratified by condition, age, gender, time interval between the 2 doses, and time since vaccination. Cox regression models were used to estimate hazard ratios (HRs). VE as % was calculated as (1−HR) × 100. A similar approach was used to evaluate VE for patients who received 1 RZV dose. Baseline characteristics of the AID patient population post-matching (2-dose cohort) Results We identified 36,645 RZV vaccinated and 109,229 matched non-RZV vaccinated AID patients in the 2-dose analysis (Table). Median follow-up was 1.29 (interquartile range [IQR]: 0.73–2.12) and 1.07 (IQR: 0.59–1.95) years for RZV and non-RZV cohorts. IR of HZ was 4.33/1,000 person-years (PY) in the RZV 2-dose cohort and 12.86/1,000 PY in the non-RZV cohort, resulting in an overall VE of 66.3% (95% confidence intervals [CIs]: 61.4–70.7) for AID patients. IRs and VE overall and stratified by each selected AID and variables are presented in Figure 2. Overall VE for AID patients who received 1 RZV dose was 58.3% (95% CIs: 45.8–68.0). IRs of HZ and VE overall and stratified by selected AID (2-dose cohort) (A); IRs of HZ and VE overall and stratified by age, gender, time interval between doses and time since vaccination (2-dose cohort) (B) Conclusion This analysis provides RWE that RZV vaccination is effective in preventing HZ in patients ≥50 YOA with selected AIDs. Our findings are consistent with the available literature on RZV effectiveness, which shows that RZV vaccination is beneficial to specific patient groups. Funding: GSK Disclosures Dagna Constenla, PhD, MPA, MPhil, BA, GSK: Employment|GSK: Stocks/Bonds (Private Company) Germain Lonnet, MSc., GSK: Employment Emmanuel Aris, PhD, GSK: Employment|GSK: Stocks/Bonds (Public Company) Nathalie Servotte, PhD, GSK: Employment Ramsanjay RK, B.Tech Mechanical Engineering, GSK: Employment Agnes Mwakingwe-Omar, MD, PhD, GSK: Employed|GSK: Stocks/Bonds (Private Company) Huifeng Yun, MD, PhD, GSK: fulltime employee of GSK|GSK: Stocks/Bonds (Public Company)

Epidemiology, treatment, and mortality of femoral neck fractures in patients over the age of 65 years: a nationwide retrospective cohort study of 83,789 cases in Turkey.

A population-based study delineating the epidemiologic, clinical, and treatment characteristics of femoral neck fractures (FNFs) in elderly patients has not yet been conducted in Turkey. In this nationwide study, the epidemiologic, clinical, and treatment characteristics of patients aged ⩾65 years with FNFs who underwent osteosynthesis, hemiarthroplasty (HA), or total hip arthroplasty (THA) were examined. Patients aged ⩾65 years with FNFs were identified in this retrospective, nationwide study. Then, the patients who underwent osteosynthesis or total/hemiarthroplasty from 2016 to 2021 were included. All the outcome variables were collected from patient medical records stored in the e-health database of the Republic of Turkey Ministry of Health. A total of 83,789 FNFs treated surgically were analysed. Osteosynthesis was performed on 21,130 FNFs (25.2%), HA on 56,378 FNFs (67.3%), and THA on 6281 FNFs (7.5%). From 2016 to 2021, the overall revision rates for THA and HA were 14.6% (914/5367 patients) and 5.9% (3301/53,077 patients), respectively. The rate of revision prosthetic surgery was significantly higher after THA than after HA (p < 0.001). Mortality rates at 1 year were 25% (n = 5293) for osteosynthesis, 14.7% (n = 924) for THA, and 71.1% (n = 40,109) for HA (p = 0.001). The multivariate model of 1-year postoperative mortality revealed 7 independent predictors: male sex (odds ratio [OR] 1.694; 95% confidence interval [CI], 1.640-1.751), use of a cemented femoral stem (OR 1.182; 95% CI, 1.117-1.250), acute myocardial infarction (AMI) (OR 1.317; 95% CI, 1.240-1.400), cerebrovascular accident (CVA) (OR 1.379; 95% CI, 1.333-1.425), chronic liver disease (CLD) (OR 2.188; 95% CI, 1.802-2.489), diabetes mellitus (DM) (OR, 1.160; 95% CI, 1.122-1.200), and age >81.50 years (OR 2.654; 95% CI, 2.569-2.742). Our study suggested that a hemiarthroplasty is the most common treatment modality for FNF followed by osteosynthesis (25.2%) and THA (7.5%) in Turkey. Revision rates after THA for FNF are concerning. The 1-year mortality rates are highest after HA, followed by osteosynthesis and THA. Male sex, cemented fixation, CVA, CLD, liver failure, DM, and age >81.50 are the independent predictive factors for postoperative 1-year mortality in this specific group of patients.

Assessing post-operative dietary intake in older adult hip fracture patients: An observational study protocol.

Background: Fragility fractures of the hip are a common injury in England. Meeting post-operative resting energy expenditure (REE) needs are fundamental to recovery from trauma that with greater nutritional intake, post-operative complications and length of stay can be reduced. However, dietary intake can be overlooked when the goal is prompt surgery to reduce pain and lower the risks of mortality at 30 days and 1 year. Aims: The primary aim of this study is to observe if post-operative dietary energy intake (kJ/kcal) of older adult hip fracture patients meets their post-operative REE needs to mobilise post-surgery. Secondly, we aim to explore if there is a relationship between length of stay, comorbidity and post-operative complications in relation to dietary intake. Methods and analysis: Using a weighed food method, all food and fluid intake from the day of surgery until post-operative day three inclusive will be recorded for a cohort of 30 older adult hip fracture patients. Dietary intake per day will be compared against REE and macronutrient requirements. Baseline sociodemographic and medical history data will be obtained, along with admission data such as malnutrition screening and type of fracture. Regression analysis will be used to explore associations between dietary intake, post-operative complications and length of stay where indicated and to identify if there are areas for further dietary development in this specific patient group. Ethics and dissemination: The Health Research Authority approved this study (REC 24/NE/0034). Findings will be published in peer-reviewed, scientific journals and presented at academic conferences.

Development and validation of a sport-specific shoulder score questionnaire for functional fitness and weightlifting athletes.

So-called scores are a frequently used evaluation system in clinical examinations to assess the function or limitations of a joint such as the shoulder. However, research indicates that these general scores often have limited validity for specific patient groups, such as athletes. Known as a demanding patient population, athletes have unique needs. We address this by introducing a sport-specific shoulder score questionnaire developed specifically for functional fitness and weightlifting populations. Utilizing MRIs (magnet resonance imaging) and clinical examinations from a group of 51 athletes in the functional fitness and weightlifting field who are experiencing shoulder pain, we initially validated a sport-specific score system. With these data and an approach via PCA (principal component analyze), the weights for the questionnaire were calculated, Later, we conducted clinical examinations and interviews with 92 athletes from the same field, comprising both athletes with no clinical issues and athletes with shoulder pain. With the help of the N.=92 individuals, we validated the questionnaire and adjusted the weighting of the questions where necessary. The principle of the PCA was to show which questions were most frequently answered with a high score by those athletes with structural damage in the MRI or positive clinical tests. A total of 143 athletes were analyzed, all having undergone clinical examinations with a primary focus on rotator cuff and long head of the biceps (LHB) pathologies, as well as glenohumeral instability. In N.=51 an additional MRI was available. The sensitivity was found to be 89%, precision was 67%, and specificity was 42%. The calculated F1 score was 0.76. The scoring threshold for the questionnaire was set at 22 out of 100. This score offers a cost-effective, risk-free tool for identifying shoulder pathologies in weightlifting athletes, boasting a high sensitivity of 89%. It is intended to be an extension of existing score questionnaires that are more focused on a specific, very demanding patient population such as weightlifting and functional fitness athletes.

Comparison of the EQ-5D-3L and EQ-5D-5L instruments in patients undergoing unicompartmental knee arthroplasty.

The purpose of this investigation is to assess and contrast the effectiveness of the two EuroQol five dimensions questionnaire (EQ-5D) versions-EQ-5D-3L and EQ-5D-5L-in assessing one-year quality of life outcomes for patients with knee osteoarthritis (KOA) undergoing unicompartmental knee arthroplasty (UKA). From the medical records at the Honghui Hospital, Xi'an Jiaotong University, 402 individuals aged 50 and above, who were one-year post-operation, were selected to fill out survey questionnaires during their return hospital visits. Of these, 231 respondents (57.5%) completed the questionnaire; 228 completed both versions, and 56 completed the EQ-5D retest questionnaire. The assessment included missing data, ceiling effects, informativity and discriminatory power, as well as response consistency, redistribution properties, and inconsistency. Reliability and validity were also evaluated. The results indicate that the EQ-5D-5L surpasses the EQ-5D-3L in construct validity, informativity, detection precision, and discriminatory power. Consistency reliability is also better in the EQ-5D-5L than in the EQ-5D-3L. Both instrument versions maintained reliable levels of test-retest reliability. In patients with KOA undergoing UKA, the EQ-5D-5L has proven superior in measurement capabilities when compared with the EQ-5D-3L one-year post-operation. Thus, it is advised to utilize the EQ-5D-5L for ongoing assessments of quality of life in this specific group of patients.

Therapeutic Drug Monitoring of Vancomycin in Hemodialysis Patients in a Hospital in North-East Romania.

Background/Objectives: Vancomycin is a reserve antibiotic that is frequently prescribed for central venous catheter (CVC)-associated infections in hemodialysis patients. Hemodialysis patients are very fragile patients and the presence of CVCs increases the risk of sepsis. We conducted a prospective study, evaluating the needs of changes in vancomycin dosing for treatment based on the use of the new 2020 vancomycin dosing guidelines, to increase drug safety (preventing subtherapeutic or supratherapeutic doses and offering therapeutic concentrations of the drug) in a particular group of patients with sepsis caused by catheter infections and being on intermittent hemodialysis. Methods: This prospective study included patients with sepsis caused by catheter infections and being on intermittent hemodialysis, treated with vancomycin, admitted in the nephrology department and intensive care unit (ICU). Vancomycin levels were adjusted according to the 2020 vancomycin guidelines. Results: In our study, nine (45%) patients had a vancomycin AUC between 400 and 600 mcg × h/mL, five (25%) patients had a subtherapeutic AUC, and six (30%) patients had a supratherapeutic AUC. It is important to mention that in 10 (50%) of the patients included in the study, the loading and maintenance doses mentioned in the protocol were respected, but 50% of them had a supratherapeutic AUC. We observed that a supratherapeutic AUC occurred when the loading dose was 1500 mg or 2000 mg, and in one case at 1000 mg with a low BMI. Conclusions: a therapeutic level of vancomycin can often be difficult to achieve because of different reasons, mainly in hemodialysis patients.

Development and testing the psychometric properties of 20 bolt-on items for the EQ-5D-5L across 31 rare diseases.

Our objective was to develop and assess the psychometric properties of relevant bolt-on items for the EQ-5D-5L in patients with rare diseases (RDs). Nineteen new EQ-5D-5L bolt-ons were developed based on literature review, expert input and qualitative interviews and focus groups with patients, caregivers and representatives of patient associations. A nationwide, cross-sectional, web-based survey in China included patients or caregivers of patients with 31 RDs in China (n=9,190). In each RDs, participants completed the EQ-5D-5L and three out of 20 [one existing and 19 newly-developed] bolt-ons. Ceiling, explanatory power, convergent, divergent and known-group validity were examined. Among the bolt-ons, itching had the lowest ceiling (6.5%), while social relationships had the highest (42.2%). The absolute reduction in the ceiling of the EQ-5D-5L with the addition of any bolt-ons was limited, ranging from 0 (respiratory problems) to 8.3%-points (isolation). Dignity and vitality resulted in the largest increase in explained variance in EQ VAS. The isolation, fertility and visual acuity bolt-ons showed good divergent validity from the EQ-5D-5L items. There was strong convergent validity between SF-12 and conceptually-related bolt-ons (e.g., physical health composite and muscle problems bolt-on). Various bolt-ons improved the known-groups validity in specific patient groups, e.g., Huntington's disease (oral expressions), scleroderma (dexterity), myasthenia gravis (muscle problems), neuromyelitis optica and multiple sclerosis (fatigue), Marfan syndrome (self-image) and Pompe disease (safety). The EQ-5D-5L shows sufficient validity in most RDs, but incorporating relevant specific bolt-ons could enhance its ability to more comprehensively assess health-related quality of life in these patients.

Modelling sensory attenuation as Bayesian causal inference across two datasets.

To interact with the environment, it is crucial to distinguish between sensory information that is externally generated and inputs that are self-generated. The sensory consequences of one's own movements tend to induce attenuated behavioral- and neural responses compared to externally generated inputs. We propose a computational model of sensory attenuation (SA) based on Bayesian Causal Inference, where SA occurs when an internal cause for sensory information is inferred. Experiment 1investigates sensory attenuation during a stroking movement. Tactile stimuli on the stroking finger were suppressed, especially when they were predictable. Experiment 2 showed impaired delay detection between an arm movement and a video of the movement when participants were moving vs. when their arm was moved passively. We reconsider these results from the perspective of Bayesian Causal Inference (BCI). Using a hierarchical Markov Model (HMM) and variational message passing, we first qualitatively capture patterns of task behavior and sensory attenuation in simulations. Next, we identify participant-specific model parameters for both experiments using optimization. A sequential BCI model is well equipped to capture empirical patterns of SA across both datasets. Using participant-specific optimized model parameters, we find a good agreement between data and model predictions, with the model capturing both tactile detections in Experiment 1 and delay detections in Experiment 2. BCI is an appropriate framework to model sensory attenuation in humans. Computational models of sensory attenuation may help to bridge the gap across different sensory modalities and experimental paradigms and may contribute towards an improved description and understanding of deficits in specific patient groups (e.g. schizophrenia).

Diagnostika a trénink neurovizuálních funkcí v rehabilitaci a ve sportu

Sensory integration plays a crucial role in the smooth execution of movements. However, the repeated intake of suboptimal information from our surroundings can disrupt the motor learning process. Sight stands out as the dominant human sense, providing visual information that is integrated at the central nervous system (CNS) level. This integration occurs alongside inputs from other sensory organs, constantly influencing motor activity. The term “neuro-visual system” (NVS) is now widely recognized in the fields of rehabilitation and sports, highlighting the crucial eye–brain–body axis connection. This article provides an overview of recent findings on the NVS exploring diagnostic procedures relevant to NVS in clinical settings. These procedures include tests for visual acuity, eye motility, and the near point of convergence. Drawing on existing literature, it identifies specific patient groups for whom neuro-visual training (NVT) could significantly enhance rehabilitation outcomes. Additionally, it discusses the potential benefits of NVT for athletes as an integral part of their sports training regimen. Included in the publication are two case studies illustrating NVS assessment and the application of NVT in clinical practice. The first case involves an adolescent with attention disorder and congenital diplopia, and the second, a young tennis player suffering from headaches. These examples underscore the practical value of NVS diagnostics and neuro-visual training in addressing specific health and performance issues.

Cumulative incidence of chronic pain after visiting a Dutch emergency department with acute pain

BackgroundChronic pain is a substantial problem in modern healthcare resulting in health care overutilization. The cumulative incidence of developing chronic pain after visiting the emergency department with acute pain has been determined for specific patient groups only. If the cumulative incidence of chronic pain in emergency department patients with acute pain is high, more proactive measures are justified to limit development of chronic pain. The primary objective was to study the cumulative incidence of chronic pain in patients visiting Dutch emergency departments with acute pain. In addition, we compared the Health-Related Quality of Life (HRQOL) and pain related interference with work.MethodsIn this prospective multicenter cohort study data was collected from adult patients visiting the emergency department with acute pain. Chronic pain was defined by means of a numeric rating scale (NRS) of ≥ 1 measured 90 days after the initial visit. HRQOL was measured with European Quality of Life (EQ-5D-5 L) and Short Form (SF-36) questionnaires.Results1906 patients were included of which 825 had complete data. Of these, 559 patients (67.8%; 95%CI: 64.5 − 70.9%) scored an NRS ≥ 1 after 90 days. Incidence with completed analyses (with imputed data) was similar. Patients with chronic pain reported a significantly lower HRQOL; EQ-5D-5 L index (median 0.82 vs. 1.00) and significantly more pain related hindrance (median 1.00 vs. 0.00).Conclusions67.8% of the responders scored NRS ≥ 1 90 days after ED-visit with acute pain. Regardless of the used definition, chronic pain is associated with a lower HRQOL and more pain related hindrance.

Important tool in our rare disease toolbox: hybrid retrospective-prospective natural history studies serve well as external comparators for rare disease studies

Natural history studies (NHS) can support regulatory decision-making at different stages of the drug product life cycle and are especially important in the context of rare diseases, which are associated with not only delayed or erroneous diagnoses but also a lack of approved treatments. Real-world evidence can fill knowledge gaps and support treatment decision-making, thereby benefiting affected patients. In this context, there are three important options for NHS design: retrospective, prospective, and cross-sectional. Each of these has been successfully used to support regulatory approval as external comparator arms (ECAs) for clinical studies, especially single-arm trials (SATs). While longitudinal data obtained from retrospective or prospective designs have been more commonly used and have been the focus of regulatory guidance documents, hybrid designs that combine retrospective and prospective data collection are particularly powerful for rare disease studies. This is due, in part, to the smaller number of patients impacted by each rare disease. In these settings, retrospective or prospective data collection alone may not be sufficient or fit-for-purpose for an external comparator. Rather, a strategic combination of all available data, regardless of timing, can deliver the right information of the desired quality and completeness to answer these important questions and support regulatory evidentiary needs. For instance, patients included in retrospective studies may differ from recently treated patients in terms of disease severity, disease variants, clinical management, or other important aspects of the disease that may impact patient outcomes. Further, retrospectively collected data may lack specific data elements required to achieve adequate comparison with the treated group in single-arm studies. In the context of prospective designs, the recruitment of sufficient new patients for prospective follow-up may not be feasible or may be prolonged due to the rarity of the disease. Further, the potential for premature truncation of patient follow-up may result in insufficient longitudinal data, or prospectively collected data alone may not provide insights into the disease course for specific groups of patients. In these situations, primary data collection in a prospective study may be supplemented with retrospectively collected data from chart reviews, registries, or electronic medical record databases, either for the same patients, in an ambispective design, or for a different set of patients. These hybrid designs allow for broader and more robust contextual information on the patient journey and the natural course of the disease to be obtained, which can improve the suitability of the data as an external comparator for SATs or studies that lack internal control in situations where a prospective design alone might not be sufficient. Because retrospective and prospective data, or any two data sources that are being combined, may differ in availability and quality, there are unique challenges alongside the strengths of these designs. In this paper, we discuss considerations for the design, analysis, and conduct of hybrid NHS intended as ECAs for single-arm studies in clinical development programs for rare diseases.

Effect of Adjuvant Chemotherapy Cycles on Patients with Node-Negative Gastric Cancer Following Neoadjuvant Chemotherapy: Multicenter Cohort Study.

Research investigating the potential impact of postoperative adjuvant chemotherapy cycles on patients with lymph node-negative gastric cancer following neoadjuvant chemotherapy is currently sparse. This study aims to explore the effect of adjuvant chemotherapy cycles on the prognosis of this specific patient group. We analyzed clinicopathological data from patients at four institutions between 2010 and 2020. Independent risk factors associated with 3-year overall survival (OS) were identified using a Cox proportional hazards regression model. We enrolled a total of 219 patients in this study. Patients with lymph node-negative gastric cancer who received neoadjuvant chemotherapy and underwent at least five cycles of adjuvant chemotherapy (AC ≥ 5) after surgery had a significantly higher 3-year overall survival rate of 86.8% compared with those who received fewer than five cycles (AC < 5) with a survival rate of 68.1% (P = 0.016). Multivariate analysis identified several factors, including AC ≥ 5 (HR 0.367, 95% CI 0.166-0.815, P = 0.014), ypT stage ≥ 2 (HR 2.779, 95% CI 1.199-6.438, P = 0.017), and poorly differentiated tumors (HR 2.501, 95% CI 1.385-4.517, P = 0.002), as independently associated with 3-year OS in this patient group. Stratified analysis further revealed that AC ≥ 5 significantly enhanced long-term outcomes in patients with ypT stage ≥2 (3-year OS, 82.5% vs. 62.6%, P = 0.025) and in those with poorly differentiated tumors (3-year OS, 82.6% vs. 53.3%, P = 0.021). Patients who have lymph node-negative gastric cancer following neoadjuvant chemotherapy, with either ypT stage ≥ 2 or poorly differentiated gastric cancers, may experience benefits from undergoing at least five cycles of adjuvant chemotherapy.

Biological Markers of Myeloproliferative Neoplasms in Children, Adolescents and Young Adults.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic cancers characterized by hyperproliferation of the myeloid lineages. These clonal marrow disorders are extremely rare in pediatric patients. MPN is reported to occur 100 times more frequently in adults, and thus research is primarily focused on this patient group. At present, modern diagnostic techniques, primarily genetic, facilitate the identification of the biology of these diseases. The key genes are JAK2, MPL, and CALR, namely, driver mutations, which are present in approximately 90% of patients with suspected MPN. Moreover, there are more than 20 other mutations that affect the development of these hematological malignancies, as evidenced by a review of the literature. The pathogenic mechanism of MPNs is characterized by the dysregulation of the JAK/STAT signaling pathway (JAK2, MPL, CALR), DNA methylation (TET2, DNMT3A, IDH1/2), chromatin structure (ASXL1, EZH2), and splicing (SF3B1, U2AF2, SRSF2). Although rare, myeloproliferative neoplasms can involve young patients and pose unique challenges for clinicians in diagnosis and therapy. The paper aims to review the biological markers of MPNs in pediatric populations-a particular group of patients that has been poorly studied due to the low frequency of MPN diagnosis.

P08 Study on the impact of COVID-19 infection in patients with moderate-to-severe plaque psoriasis on biologics: a tertiary centre experience in India

Abstract Introduction As the world faced COVID-19 pandemic, significant concerns were raised regarding its impact on specific patient groups due to paucity of real-world evidence. Individuals with psoriasis undergoing biologic therapy face heightened vulnerability to severe disease. This study aimed to examine the effects of COVID-19 infection on patients with moderate-to-severe plaque psoriasis treated with biologic agents. Materials and Methods Medical records of patients with moderate-to-severe plaque psoriasis undergoing biologic treatment at a tertiary care centre were retrospectively reviewed from March 2021 to June 2021. Patients with confirmed COVID-19 infection, identified through positive polymerase chain reaction tests, were included. Data on patient demographics, disease characteristics, symptoms, and vaccination status were collected and analysed. Results Among 34 infected patients (26 males, 8 females), median age was 50 years (range: 18–70) with a median psoriatic disease duration of 12 years (range: 12–32). Median psoriasis area and severity index (PASI) was 14, with 22.2% of patients having psoriatic arthritis. Comorbidities included overweight (34.4%), obesity (39.2%), dyslipidaemia (24.4%), diabetes mellitus (11.7%), arterial hypertension (7.0%), and coronary artery disease (2.3%). Most patients experienced mild COVID-19 symptoms; 3 required hospitalization due to dyspnoea and hypoxia. At the time of infection, 80% had received at least one dose of mRNA vaccine. Conclusion Our findings suggest that patients receiving biologic therapy for psoriasis did not exhibit a higher risk of severe COVID-19 outcomes. Also, biologic treatment did not appear to impact disease severity adversely indicating potential benefits such as reduced infection risk and milder symptoms. Continuation of biologic therapy in psoriasis patients, even during the pandemic, is essential for effective disease management. Patient education and counselling regarding hesitancy are equally important in such difficult times.

Inpatient Care Experiences Differ for VA and Non-VA Hospitals, With Different Patterns by Health, Race, and Ethnicity.

This article estimates differences and difference-in-differences in patient experiences for Veterans Health Administration (VA) compared to non-VA patients in 2017, when there was concern about the health quality of VA hospitals, and in 2021, the second year of the COVID-19 pandemic, both overall, and for specific patient groups. We used data from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. In 2017, HCAHPS performance was somewhat better for non-VA than for VA hospitals, with Care Transition being the only measure for which VA hospitals performed better on average. By 2021, HCAHPS performance was better for VA than for non-VA hospitals for all but two measures (Quietness and Discharge Information), for which there were no differences from non-VA hospitals. In 2017, the VA provided worse experiences than non-VA hospitals for Black and poor-health patients; in 2021, VA hospitals outperformed non-VA hospitals for these, and all patient subgroups examined.

Laparoscopic resections for stage IV colorectal cancer - safety and effectiveness of the method as a guarantee for an uncomplicated postoperative period and optimal pharmacotherapeutic results

Introduction: Primary tumor resection can prevent future tumor-related complications in patients with stage IV colorectal cancer. This may influence the quality of life and prevent colostomies associated with the emergency surgery. Laparoscopic approach plays an important role in attempts to reduce perioperative complications in this specific group of patients. Purpose: The aim is to assess early perioperative results in a group of 17 patients with stage IV colorectal cancer—multiple incurable liver metastases and/or pulmonary/peritoneal metastases of the disease. On the other hand, postoperative complications may delay administration of chemotherapy and influence survival. Materials and methods: We analyze retrospectively the perioperative results in a group of 17 patients with laparoscopic palliative colorectal resections for stage IV colorectal cancer. Assessment includes perioperative complications, median hospital stay, perioperative blood loss, need for blood transfusion, operative time, and type of surgical procedure. Results: We performed totally laparoscopic 10 sigmoid resections, five left colectomies, and two right colectomies. Fourteen simultaneous liver biopsies were performed during laparoscopy. No perioperative deaths were registered. Perioperative mortality rate is 0%. Perioperative morbidity rate is 0%. No perioperative complications. The median perioperative stay is 5.3 days. Median blood loss is 47.9 mL. Overall, three units of blood were transfused. The median transfusion rate is 0.17 units per patient. The median operative time is 130.2 minutes. Conclusion: The laparoscopic approach is associated with very good perioperative results in patients with stage IV colorectal cancer and palliative resection of the primary tumor. Early hospital discharge and minimal operative trauma may not influence early administration of chemotherapy.