Clinical Care Of Patients Research Articles

An in Vitro Pilot Study of the Role of Factor IX As an Alternative to Bypassing Agents in the Treatment of Breakthrough Bleeds in Patients with Hemophilia a and Inhibitors Treated with Emicizumab

Introduction: Hemophilia A(HA) is an X linked disorder characterized by a deficiency in Factor VIII. 30% of patients with severe HA develop alloantibodies that inhibit the coagulant activity of FVIII. Emicizumab, a substitution therapy that bridges factor IX and X, is approved in patients with severe HA with and without inhibitors. Indeed, it is now the standard of care prophylactic therapy for patients with inhibitors. Breakthrough bleeds and perioperative management require the use of bypassing agents in addition to emicizumab, with recombinant VIIa deemed the safest of these options. Nevertheless there are still concerns about thrombotic risks and inability to monitor bypassing agents given to patients on emicizumab. Since the rate limiting step for FXa generation in the plasma of patients receiving emicizumab is the concentration of generated FIXa, we conducted an in vitro pilot study to evaluate the hemostatic effect of adding FIX to the plasma of patients on emicizumab prophylaxis. Methods: After informed consent was obtained, blood was collected in citrated tubes prefilled with 1.45mM of corn trypsin inhibitor(CTI) from 25 patients with HA receiving emicizumab prophylaxis. Aligning with previously published data, the added hemostatic effect of rFVIIa was studied in platelet rich plasma (PRP), while all other products were studied in platelet poor plasma (PPP). PRP was spiked with 0, 45, 90 and 270mg/kg of rFVIIa, and PPP was spiked with 0, 10, 20, 30 and 50 IU/kg of activated prothrombin complex concentrate (aPCC); 0, 25, 50 and 100 IU/kg of recombinant FIX(rFIX) and 0, 25, 50 and 100 IU/kg of plasma derived FIX(pdFIX). Thrombin generation was run on these spiked samples using the CAT method. Coagulation was triggered in PRP samples with tissue factor 1pM. PPP samples were activated using 1pM of TF and 1.5pM FIXa. Mean endogenous thrombin potential (ETP, area under the thrombin generation curve) values were compared between the different experiments and with samples obtained from controls. Baseline FIX concentrations were determined in these patients using bovine chromogenic assay. The mean plasma emicizumab concentration (+Standard Deviation) was 44.45 µg/mL (+15.83). Results: As shown in fig 1, ETP was significantly improved with increasing concentrations of aPCC, rFIX and pdFIX in PPP(p<0.005). Fig 2 shows that ETP normalized with the addition of rFVIIa 45mg/kg (p<0.0001) in most of the patients tested. Moreover, we did not see ETP above the upper limit of the normal range when FIX was added, while 50 IU/kg of aPCC and 270 mg/kg of rFVIIa clearly surpassed the upper limit of the normal range, suggesting a risk of hypercoagulability and thrombosis. FIX levels varied between 63.9% and 248.9% with a mean of 134.27%. ETP obtained after adding rFIX 100 IU/kg was significantly greater than that attained with pdFIX (p=0.027), that might be explained by the presence of the activated form of FIX in rFIX concentrates. No statistical significant difference between the doses of 50 IU/Kg of FIX and 100 IU/KG was observed (p>0.05), with a noted tendency to increased ETP with 100IU/KG dose. Conclusion: Our in vitro study demonstrates excess thrombin generation (and potential thrombosis risk) with higher concentrations of rFVIIa and aPCC that are used in the clinical care of patients. While addition of FIX at a range of doses appears to improve thrombin generation without exceeding the upper normal limits. These data suggest that FIX therapy may safely improve hemostasis in patients with HA and inhibitors receiving emicizumab prophylaxis. A clinical study looking at a starting dose of rFIX at 50 IU/KG for mild to moderate bleeds and 100 IU/Kg for more severe bleeds is warranted. In addition to the advantage of monitoring levels with FIX therapy, the longer half-life of FIX offers the potential advantage of controlling hemostasis with single dose administration. Future prospective clinical trials are needed to investigate the efficacy and safety of this therapy in this patient population.

Impact of the 2014 NHLBI Hydroxyurea Guidelines on Cerebrovascular Events in Sickle Cell Disease

Background: Cerebrovascular disease (CVD) is a common cause of morbidity in patients with sickle cell disease (SCD). An estimated 37% of children with SCD have silent cerebral infarcts (SCI) by age 14, leading to increased stroke risk and neurocognitive impairment. In the DISPLACE trial (Kanter et al, 2021), 2.9% of patients had abnormal cerebral blood flow as measured on transcranial Doppler ultrasound (TCD). The 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend hydroxyurea (HU) for all patients with SCD-SS and SCD-Sβ 0 starting at age 9 months, a significant shift from prior practice. In patients who have already developed TCD abnormalities, HU is protective against stroke and CVD progression. The real-world impact of universal early HU on the development of CVD, particularly on SCI, is not well defined . We hypothesize that the 2014 guidelines led to an increase in HU use and a reduction in the initial development of CVD. Methods: We performed a single center, retrospective cohort study investigating trends in HU prescriptions and CVD before and after the publication of the 2014 NHLBI guidelines. Patients with SCD-SS and SCD-Sβ 0 who initiated hematology care at the Children's Hospital of Philadelphia between 2009 and 2023 were identified using an institutional registry. Incident HU was defined as the first outpatient HU prescription in patients with a minimum of two orders. Incident CVD was defined as a composite outcome consisting of the first documentation of: abnormal TCD, brain magnetic resonance imaging (MRI) with silent infarct, or overt ischemic stroke. Patients with known CVD before care initiation, prematurity < 28 weeks gestational age, or non-SCD neurologic disease were excluded. For time-to-HU analysis, patients with HU prescriptions before enrollment at our center also were excluded. Patients were followed from their first hematology visit until the outcome of interest or censoring. Censoring criteria included loss to follow up, transition of care, or bone marrow transplant. All brain MRI and TCD reports were manually reviewed. Ages at HU initiation pre- and post- guideline were compared using the Wilcoxon rank-sum test . Times to 1) HU and 2) CVD were summarized using Kaplan-Meier estimators, with the guideline publication date of September 1, 2014 incorporated as a time-varying exposure. Unadjusted associations were calculated using a Cox proportional hazard regression. Results: A total of 446 patients met inclusion criteria and contributed to analyses. Median age at baseline was 2.4 months, and median duration of follow-up was 5.0 years (IQR: 2.3-8.7). Most patients (430/446, 96%) had SCD SS, and 51% were male. The proportion of patients ever prescribed HU increased with time (Fig 1), with a peak prevalence of 82% in 2022. Of 385 patients not exposed to HU at baseline, 277 (72%) were prescribed HU during study follow-up. Incident HU prescriptions significantly increased after NHLBI guideline publication (HR 3.40, CI: 2.50 to 4.63, p < 0.001) with an older age at HU initiation before (median 4.0 y, IQR 2.5-7.7) than after (median 2.9 y, IQR 1.1-5.8) publication of the guideline (p = 0.002). Over a total of 2,395 person-years of follow-up, 66 incident CVD outcomes occurred in this longitudinal cohort, corresponding to a cumulative incidence of 14.8%. These events included 53 SCI, 10 abnormal TCD, and 3 overt ischemic strokes. CVD outcome occurrence was lower after guideline publication than before (HR 0.58, CI: 0.32-1.05), though the association did not reach statistical significance (p = 0.071, Fig. 2). Discussion: After the NHLBI guideline publication, HU prescriptions increased significantly at our center.Our data suggest that the 2014 guideline-directed care may have led to a greater than 40% reduction in CVD, though this reduction was not statistically significant in our small sample size. Despite guideline recommendations and strong evidence for the role of HU in reducing pain and acute chest syndrome, few patients across the United States are prescribed HU therapy. Adherence and care continuity challenges further lessen the number of patients benefitting from HU. Evidence of efficacy of early and universal HU in CVD prevention would strengthen guideline recommendations and improve clinical care in patients with SCD. Ongoing analysis includes an expanded cohort and adjustment for clinical covariates to better examine the direct impact of early HU on CVD.

Clonal Hematopoiesis and Inflammation in the Vasculature (CHIVE), a Prospective, Longitudinal Clonal Hematopoiesis Cohort and Biorepository

Introduction Clonal hematopoiesis (CH), the expansion of a clonal population of hematopoietic cells, is an age-associated phenomenon leading to increased risk of both hematologic malignancy and non-malignant organ dysfunction. There have been significant advances in our understanding of the underlying pathophysiology of CH in recent years. However, additional studies are needed to better understand clinical trajectories and optimal care of patients with CH. To address this gap, the prospective, longitudinal CHIVE (Clonal Hematopoiesis and Inflammation in the VasculaturE) registry and biorepository was created to support multidisciplinary CH clinics. Methods Adults without active hematological malignancy who were clinically identified to have CH or who were at risk for CH were sequentially enrolled utilizing a multidisciplinary referral approach between October 2020 to April 2023 at Vanderbilt University Medical Center (VUMC). Research samples were procured at the time of routine clinical blood draws or bone marrow biopsies and stored in a newly established biorepository, equipped to store DNA, plasma, and viably cryopreserved cells to enable a spectrum of downstream applications. Specimens were sequenced on a highly cost efficient (~$6/sample) targeted next generation sequencing capture panel that identified mutations residing in the 24 most frequently mutated CHIP genes.The VUMC CH clinic, which serves as a referral pool, were included in Arm A of CHIVE (n=57). We also sought out a population at risk for CH which included patients over 18 years of age with a history of solid tumor, cardiovascular disease, renal disease, rheumatologic disease, or diabetes, who were included in Arm B (n=122). Patients from Arm A or B were included in the CH-positive (CH+) group if they met criteria for CH on the research assay at any time during their enrollment in the study. All other genotyped patients who were not found to have CH by the research assay, regardless of their clinical CH status at study enrollment, were included in the CH-negative (CH-) group.Anthropometric data and clinical assessments, including laboratories and cardiovascular studies obtained in the course of routine clinical care were extracted from the electronic health record, and recorded and maintained in the CHIVE database. Results 261 patients were approached for consent to enroll in CHIVE and 179 were ultimately enrolled. More than one half (54%) of all participants had a CH mutation (CH+) and of those, 49.5% were female. Median age of CH+ patients was 71.9 (IQR 64.0-77.5). DNMT3A (n=44) and TET2 (n=39) were the most commonly mutated genes, while variant allele fractions (VAF) ranged from 2.1 - 79.8% (Figure 1). 246 samples were serial samples collected from 89 patients at regular intervals. Significantly more CH+ patients had a diagnosis of coronary artery disease compared to CH- patients (55.7% vs 32.9%, p=0.004). CH+ patients also had increased rates of hypertension and heart failure compared to the CH- group (p<0.001, 0.035, respectively). Laboratory evaluation showed CH+ patients to have a lower median white blood cell count, hemoglobin, and platelets, and elevated blood urea nitrogen values compared to CH- patients, differences that did not meet statistical significance. 8.2% of the CH+ patients progressed to frank hematologic malignancy over the course of the 2.5-year study (Table 1). Eight of the 97 CH+ and 2 of the 82 CH- patients died over the course of the study period resulting in a trend toward decreased survival in CH+ patients (p=0.112). Conclusions We demonstrate the feasibility of a prospective, observational study of CH patients utilizing a robust referral network to support both clinical care and translational research. A well-genotyped and phenotyped cohort of CH patients will be critical to future translational research efforts and clinical trials - a key function of our study design. Early clinical findings from our cohort recapitulate large scale retrospective datasets where CH patients are at an increased risk of development of hematologic malignancy, end organ damage, and all-cause mortality. Scaling this resource in collaboration with other centers is underway and will ultimately enable the development of clinical guidelines and treatment strategies for this increasingly recognized patient population.

Evaluation of ISTH Severe Bleeding Criteria and Development of a Mortality Prognosis Model for Hospitalized Immune Thrombocytopenia Patients: A Multicenter, Retrospective and Prospective Cohort Study

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by the immune system's erroneous destruction of platelets, which play a crucial role in blood clot formation. This condition precipitates a decreased platelet count and consequently heightens the risk of bleeding events, ranging from mild petechiae to severe, potentially fatal occurrences such as intracranial hemorrhage. Therefore, accurate anticipation and management of these severe bleeding risks form an integral facet of clinical care for ITP patients. The International Society on Thrombosis and Hemostasis (ISTH) has instituted criteria designed to classify and forecast severe bleeding in patients with thrombotic disorders. Despite their widespread use in diverse clinical scenarios, the validity and efficacy of these criteria for ITP patients remain underexplored. Furthermore, disparities in the application and interpretation of these criteria among practitioners underscore the necessity for a comprehensive evaluation within the ITP context. Consequently, our study is poised to fill these crucial gaps. We intend to evaluate the performance and applicability of the ISTH severe bleeding criteria specifically within the ITP patient population. Concurrently, we aspire to develop and validate a robust, reliable mortality prediction model for this unique group of hospitalized patients. Methods: This study was a multicenter, retrospective cohort investigation conducted across 20 medical centers nationwide. A total of 1487 adult patients diagnosed with immune thrombocytopenia were enrolled. The study period spanned from Jan 2020 to Jan 2023, ensuring a comprehensive assessment of patient outcomes. To further evaluate the joint impact of multiple prognostic factors, a multivariate Cox regression model was constructed. Prospective observational cohorts were subsequently established with the objective of assessing the real-world performance of the mortality prognosis model. Results: In our study, out of the 1487 enrolled adult patients with immune thrombocytopenia (ITP), 420 patients (28.24%) experienced bleeding events. The incidence of major bleeding types among these patients was assessed based on the critical bleeding diagnostic criteria. Intracranial bleeding was found to be the most common type, occurring in 229 patients (54.46%). This was followed by respiratory compromise in 87 patients (20.66%) and hemodynamic instability bleeding in 76 patients (18.08%). Intramuscular bleeding was the least common, observed in only 3 patients (0.70%). Furthermore, we evaluated the efficacy of the ISTH severe bleeding criteria in predicting mortality among ITP patients. Our analysis unveiled a significant association between meeting the ISTH severe bleeding criteria and increased mortality rates. Patients who met the criteria demonstrated a higher incidence of death compared to those who did not meet the criteria. Additionally, we developed a mortality prognosis model for hospitalized ITP patients, incorporating various clinical and laboratory parameters. The model considered the presence of intracranial bleeding, admission platelet count, cardiovascular disease, diabetes mellitus, and admission creatinine levels as predictive factors. The mortality prognosis model demonstrated strong predictive power, with an area under the receiver operating characteristic curve of 0.82. This indicates its ability to distinguish between patients at high and low risk of mortality. Kaplan‒Meier survival analyses further confirmed significant survival differences between patients who met the ISTH severe bleeding criteria and those who did not. Conclusions: Our study reaffirms the substantial relevance of ISTH severe bleeding criteria in assessing bleeding profiles and prognosis among hospitalized ITP patients. The developed mortality prognosis model demonstrates excellent predictive capabilities for mortality in this patient population and is currently undergoing validation in a prospective cohort. These findings emphasize the importance of individualized management strategies to optimize outcomes in ITP patients. Further research and validation are warranted to refine and validate the mortality prognosis model for broader clinical application.

The Clinical Complexity of Langherans Cell Histiocytosis in Adult Patients: Experience of the Institute of Hematology of Bologna

Langerhans cell histiocytosis (LCH) in adult patients is a rare disease with protean manifestations, including single system unifocal (SSU) or multifocal (SSM) presentation or multisystemic (MS) involvement. Clinical care of adult patients is based on case series and reports. Regimens applied in pediatric patients show unacceptable toxicity in the adult setting. Our single-center experience with LCH is presented. Data on 30 patients diagnosed between 1997 and 2022 have been reviewed. Patients with isolated pulmonary histiocytosis were excluded. Responses to any treatment were classified according to the acknowledged criteria. Progression-free survival (PFS) after frontline treatment was calculated on all treated patients. Overall survival (OS) was determined on the whole cohort irrespective of any treatment received. Eighteen male and 12 female patients received a diagnosis of LCH at a median age of 46 years (range 20-75). Sixteen patients had single system (SS) disease, with SSU involvement in 12 cases and SSM involvement in 4 cases. The skeleton was the mostly involved system (Figure), while SSU extra-skeletal disease was detected in 25% of cases. Fourteen patients had MS disease: axial skeleton, lungs, hypophysis, skull, skin and appendicular skeleton were the predominantly involved sites, in this order. Ten patients with SS disease received chemotherapy because of symptoms (mostly bone pain) or due to multifocal dissemination. Two patients underwent radiotherapy (RT), 2 had their disease completely excised and 1 received systemic steroids. One patient was observed. A complete response (CR) was obtained in 60% of treated cases, while a partial response (PR) in 27%. Four patients relapsed after frontline therapy and were rescued with RT or autologous transplant. Among patients with MS disease, chemotherapy (MACOP/VNCOP-B, cladribine, vinblastine) was applied in 6 cases; 2 patients received RT and 1 systemic steroids. One patient underwent surgery and 4 were observed because of asymptomatic disease. A CR was obtained in 70% of treated patients and a PR in 10%. Five patients relapsed, with symptomatic disease requiring treatment (chemotherapy and RT) in 3 cases. Median PFS among all treated patients was 177 months. OS was 91% at 20 years. Appropriate treatment based on disease extension, site involvement and clinical manifestations yields high remission rates and long term PFS and OS. The optimal approach to relapsed patients remains undefined.

Enhancing flexibility and strength-to-weight ratio of polymeric stents: A new variable-thickness design approach

This paper presents a new design strategy to improve the flexibility and strength-to-weight ratio of polymeric stents. The proposed design introduces a variable-thickness (VT) stent that outperforms conventional polymeric stents with constant thickness (CT). While polymeric stents offer benefits like flexibility and bioabsorption, their mechanical strength is lower compared to metal stents. To address this limitation, thicker polymer stents are used, compromising flexibility and clinical performance. Leveraging advancements in 3D printing, a new design approach is introduced in this study and is manufactured by the Liquid Crystal Display (LCD) 3D printing method and PLA resin. The mechanical performance of CT and VT stents is compared using the Finite Element Method (FEM), validated by experimental tests. Results demonstrate that the VT stent offers significant improvements compared to a CT stent in bending stiffness (over 20%), reduced plastic strain distribution of expansion (over 26%), and increased radial strength (over 10%). This research showcases the potential of the VT stent design to enhance clinical outcomes and patient care.

Clinical factors associated with illness perception, worry and mental health in sclerosing cholangitis: A single centre prospective study

BackgroundA reduced quality of life and symptoms of depression and anxiety are reported in patients with primary sclerosing cholangitis (PSC), however specific risk factors and the effect of sclerosing cholangitis (SC) with autoimmune features are not known. ObjectiveTo integrate mental wellbeing assessment into routine clinical care for patients with SC, and evaluate factors associated with measures relating to quality of life, illness perception and mental health. MethodsA prospective study of adult non-transplant patients with SC attending the outpatient clinic over a 1 year period. Self-reported questionnaires were sent to patients electronically prior to clinic to assess worry, illness perception, depression and anxiety. Demographic and clinical information was collected. ResultsQuestionnaires were completed in 52/130 (40 %) patients with SC who attended clinic. Worry related to quality of life, mental and physical health, and future health were common. There was no difference in overall worry or illness perception in patients treated with ursodeoxycholic acid; whilst patients with PSC had a higher illness perception (P = 0.04) than those with SC and autoimmune features. Both worry (P = 0.047) and illness perception (P = 0.01) were higher in patients with elevated alkaline phosphatase, whilst there was no difference in patients with and without cirrhosis. There were high screening test scores for both depression (21.1 %) and anxiety (9.6 %), with no association with patient factors. ConclusionsWe integrated an electronic questionnaire for completion prior to clinic for patients with SC with good uptake. We identified a high prevalence of patient worries and symptoms of depression and anxiety, which may be more common in PSC with elevated alkaline phosphatase and without autoimmune features. We recommend the adoption of similar tools into routine clinical practice for patients with SC.

Advances in Anesthesia for Shoulder Surgery: A Comprehensive Review of Dexmedetomidine-Enhanced Interscalene Brachial Plexus Block.

Surgical procedures on the shoulder pose distinctive challenges in managing pain during the perioperative period, underscoring the importance of exploring innovative anesthesia techniques. This comprehensive review article delves into integrating dexmedetomidine, an alpha-2 adrenergic agonist, within interscalene brachial plexus blocks for shoulder surgery. The review initiates by underscoring the pivotal role of effective anesthesia in shoulder surgery and elucidates the rationale behind investigating dexmedetomidine as an adjunct. It meticulously examines the anatomy and physiology of the brachial plexus, emphasizing its critical significance in shoulder surgery. Furthermore, the article expounds on dexmedetomidine's mechanisms of action and pharmacokinetics, encompassing its safety profile and potential side effects. The conventional interscalene brachial plexus block techniques, along with their limitations and challenges, are discussed, laying the foundation for the integration of dexmedetomidine. The review subsequently delves into exploring the role of dexmedetomidine in regional anesthesia, covering previous studies, mechanisms of action, and the potential advantages of incorporating it into nerve blocks. The review's core concentrates on the practical application of dexmedetomidine-enhanced interscalene brachial plexus blocks. This includes discussions on administration techniques, dosage guidelines, and compelling evidence supporting its utilization. Clinical scenarios where this approach proves most advantageous are thoroughly explored, comparing its effectiveness with traditional techniques in terms of pain control and patient outcomes. A comprehensive examination of relevant clinical trials and case studies highlights the evidence supporting its efficacy. The review also underscores safety considerations associated with dexmedetomidine. It proposes strategies for mitigating risks to ensure patient safety. Insights into future directions and research are provided, encompassing ongoing studies, areas necessitating further investigation, and potential refinements in technique. Finally, the article summarizes key findings, emphasizing the practicality of dexmedetomidine-enhanced interscalene brachial plexus blocks in shoulder surgery and its far-reaching implications for clinical practice and patient care.

Assessing Readiness for Transition From Pediatric to Adult Gender Affirming Care

PurposeTransitioning from pediatric to adult care is a critical juncture in the health of adolescents. Little is known about how best to optimize transition to adult care among transgender and nonbinary (TGNB) youth. While the Transition Readiness and Assessment Questionnaire (TRAQ) has been validated in other pediatric populations, it has not been studied in TGNB youth. Our aims were to pilot the use of the TRAQ for TGNB patients, describe transition readiness patterns, and identify factors associated with transition readiness. MethodsThe TRAQ was introduced into routine clinical care for patients and their caregivers in a large, urban pediatric gender program in the spring of 2021. We performed a retrospective chart review comparing TRAQ responses based on demographic and clinical data. ResultsWe collected TRAQs from 153 adolescents (mean age: 19 years [standard deviation 2.36], range: 11–24). The TRAQ demonstrated good internal reliability with a Cronbach alpha of 0.926. Patients scored highest in the TRAQ subdomains of talking with providers and tracking health issues and lowest in the subdomains of managing medications and appointment keeping. Age and presenting to the appointment alone were associated with higher TRAQ scores. DiscussionWe found that the TRAQ is internally reliable in a sample of TGNB youth. Factors associated with higher TRAQ scores and patterns identified in TRAQ score subdomains provide an insight into the needs of TGNB youth preparing to transition to adult gender-affirming care. Future research should focus on tracking transition readiness longitudinally, developing and evaluating interventions to improve transition readiness, and assessing post-transition outcomes.

Genetic counselling considerations with genetic/genomic testing in Neonatal and Pediatric Intensive Care Units: A scoping review.

Genetic and genomic technologies can effectively diagnose numerous genetic disorders. Patients benefit when genetic counselling accompanies genetic testing and international guidelines recommend pre- and post-test genetic counselling with genome-wide sequencing. However, there is a gap in knowledge regarding the unique genetic counselling considerations with different types of genetic testing in the Neonatal Intensive Care Unit (NICU) and the Pediatric Intensive Care Unit (PICU). This scoping review was conducted to identify the gaps in care with respect to genetic counselling for infants/pediatric patients undergoing genetic and genomic testing in NICUs and PICUs and understand areas in need of improvement in order to optimize clinical care for patients, caregivers, and healthcare providers. Five databases (MEDLINE [Ovid], Embase [Ovid], PsycINFO [Ebsco], CENTRAL [Ovid], and CINHAL [Ebsco]) and grey literature were searched. A total of 170 studies were included and used for data extraction and analysis. This scoping review includes descriptive analysis, followed by a narrative account of the extracted data. Results were divided into three groups: pre-test, post-test, and comprehensive (both pre- and post-test) genetic counselling considerations based on indication for testing. More studies were conducted in the NICU than the PICU. Comprehensive genetic counselling was discussed in only 31% of all the included studies demonstrating the need for both pre-test and post-test genetic counselling for different clinical indications in addition to the need to account for different cultural aspects based on ethnicity and geographic factors.

Post-mortem dignity between piety and professionalism. Plea for a moment of silence in everyday clinical practice

IntroductionDeath is an inevitable part of clinical practice and affects, in its very own way, not only next of kin and friends but also the members of the clinical team, in particular physicians and nurses, as those who take care of a patient in the very last moments of his or her life. Nevertheless, in clinical everyday life, it is no matter of course to meet the end of human life not only on a physical but also metaphysical level.Definition of the problemIn Western sociocultural contexts, silence is commonly regarded as an adequate expression of respect in the context of death. Considering that time is a more than limited resource in Western healthcare systems, it can, however, be challenging for the clinical team to pause and pay respect to the life that has passed and to generally deal with the unfathomability of human finiteness. Instead, death tends to become drowned out by a strident clinging to the common routines of patient care, in the course of which everyday clinical noises can turn into a roaring, almost inhuman cacophony—a cacophony that may not do justice to the dignity of the deceased, the relatives, or the clinic team.ObjectiveWith that said, this article focuses on forms of bidding farewell in clinical patient care, with an emphasis on post-mortem silence. Drawing on examples from literature, medical ethics, and the law, I will plead for a moment of silence in everyday clinical practice as a possible means to interrupt the noise of medicine in the immediate aftermath of death to honor the dignity of both the dead and the living.

Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore.

Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD).The treatment for SHPT includessynthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore. Methods This study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT.The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals. Results A total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications. Conclusion Etelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

Assessment of Incidence of Distress and Utilization of Supportive Care Services in Multiple Myeloma Patients, a Retrospective Single Center Experience

Introduction: Multiple myeloma (MM) is the second most common hematological malignancy. Current literature represents substantial underutilization of guideline-recommended supportive services (SS) in MM patients. Earlier studies have shown that most patients with MM have focal osseous lesions leading to skeletal-related events, fractures, pain, and debility. These events may negatively affect the treatment course and result in poor quality of life. Recent NCCN and ASCO guidelines recommend utilization of SS in all patients by early integration of cancer care for symptom control while being treated for primary malignancy. We evaluated the level of distress in patients (pts), SS utilization, ED visits, and hospitalization in pts with MM. Methods: We included adult patients (≥18 years) with newly diagnosed or relapsed/refractory MM at Levine Cancer Institute who had completed an electronic distress survey (EDS) within three months of diagnosis or relapse. Amyloidosis and plasma cell leukemia diagnoses were excluded. The EDS includes questions related to sociodemographic, patient-reported outcomes (PROs): distress level, physical symptoms (scale 0 - 10), screening for depression (PHQ-2, scale 0 - 6), anxiety (GAD-2, scale 0 - 6),Utilization of at least one SS (social work, palliative medicine, psych-oncology, cancer rehab, integrative medicine, and nutrition) within 6 months of EDS and emergency department visits/hospitalizations within 1 year of EDS were collected, retrospectively, from the electronic medical record. The PROs were summarized overall and compared among three distress groups [Distress score (DS) &amp;lt;4, 4-6, ≥7] with Wilcoxon rank sum tests for the EDS symptom scores and Fisher's exact tests for other categorical endpoints. Results: 541 MM pts were identified with an EDS within 3 months of diagnosis or relapse (assessment date range: January 2017 - May 2022), with 71.5% of those occurring near diagnosis, and 28.5% occurring around relapse. The mean age was 64.9 years, 58.6% were male, and additional patient characteristics are presented in Table 1. There were 33.8% (n=183) pts with DS&amp;lt;4, 30.9% (167) with DS 4-6, and 35.3% (191) with DS of ≥7. The highest scoring EDS symptoms were pain (mean score 4.7), fatigue (5.1) and sleep disturbance (3.6). Broadly, patients with higher distress scores had higher symptom scores (p&amp;lt;0.05 for all symptoms). There were 77.6% (420) pts with anxiety GAD-2 score of 0-2, 12.9% (70) pts with a score of 3-4 and 9.4% (51) pts with a score of 5-6. Similarly, for depression, 76.9% (416) pts reported a PHQ-2 score of 0-2, 15% (81) with a score of 3-4, and 8.1% (44) with a score of 5-6. For anxiety and depression, patients with higher DS had higher depression and anxiety screening scores (p &amp;lt;0.001), as shown in Table 2. 64.3% (348) pts utilized at least one SS within six months of their initial EDS assessment. The rate of utilization of at least one SS increased with DS (49.2% in DS &amp;lt;4, 67.1% in DS 4-6, and 76.7% in DS ≥7; p value&amp;lt;0.001). Numerically, more patients with high distress had at least one ED visit within a year of EDS (25.7% DS &amp;lt;4, 33.5% DS 4-6, 36.1% DS ≥7, p = 0.08). There was no significant difference in hospitalization within 1 year between the DS groups. There were 147 (36.8%) pts with high-risk cytogenetics, of which 43.5% had a distress score of ≥7. The rate of utilization of SS, ED visits, and hospitalizations was numerically higher in pts with newly diagnosed MM (68.5%, 34.4%, 63.1%, respectively), as compared to pts with RRMM (64.3%, 25.3%, 48.7%). Conclusion: The disease-specific symptoms predict clinically significant DS &amp;gt;4 on EDS. There were about 20% of pts with screening score &amp;gt;2 for anxiety (GAD-2) &amp; depression (PHQ-2) that may warrant further exploration regarding the detail and nature of symptoms related to the diagnosis. There was a higher rate of utilization of SS and ED visits in pts with higher DS. Given these findings, there is a need to identify the optimal healthcare pathways for better utilization &amp; incorporation of these EDS and PROs in the clinical care of distressed patients. Our study indicates that more work is needed to align needs with resources in order to optimize quality of life and disease outcomes for our pts.

Vaccine-Preventable Infections in Multiple Myeloma: A Population-Based Study on 8672 Myeloma Patients Diagnosed 2008-2021 from the Swedish Myeloma Registry

Background: Infections are a major clinical problem in the management of multiple myeloma (MM) due to both disease and treatment related factors. Measures to prevent infection, such as vaccination, are therefore of paramount importance in the clinical care of MM patients. Data on vaccine-preventable infections in MM treated with modern therapy is sparse. Aim: To estimate the risk of vaccine-preventable infections in myeloma patients compared to a healthy population using real-world data. Methods: The study population included all patients with symptomatic MM diagnosed between 2008 and 2021 and included in the Swedish Myeloma Registry (n=8,672). Four controls per MM patient were identified randomly from the Swedish population database matched for age, sex and county of residence (n=34,567). Diagnoses of infectious diseases were retrieved from the Swedish patient registry, with good coverage on diagnostic codes for different infections among inpatient and outpatient registries. Both MM patients and controls were followed until death or till 31 st December 2022. A multi-state Cox proportional hazard model with infection as a time dependent co-variate was used to estimate the overall, 1-and 5-year risk of infections compared to controls. All models were adjusted for sex, age and year of diagnosis. Hazard-ratios (HR) with 95% Confidence Intervals were calculated. Effects of age, sex and autologous stem cell transplantation (auto-SCT) were evaluated separately. When total number of cases with a specific infectious diseases were below 10, no statistical analyses were performed. The Cause of Death Registry was used to find deaths where specific infections were listed as cause of death or contributing to cause of death. We used a logistic regression model to estimate the difference between patients and controls. Odds-ratios (OR) with 95% Confidence Intervals were calculated. Results: A majority of patients (73 %) were 65 years or older at diagnosis, 57 % were male and 30 % were treated with up-front autologous stem cell transplantation (auto-SCT). The median time of follow-up was 5 years. The risk of acquiring a vaccine-preventable infection was 8-fold in MM patients compared to matched controls (HR=7.5; [7.0-8.0]). The risk- and number of infections for vaccine preventable infections are shown in Table 1. The risk of acquiring vaccine-preventable infections was higher in males (p=0.03). In the group treated with auto-SCT, the risk of vaccine preventable infections was slightly higher (HR=1.4; [1.2-1.6]) compared to patients not treated with auto-SCT, where the risk of herpes zoster was more than two-fold (HR=2.2; [1.7-2.8]). The incidence of vaccine preventable infections was 6-fold higher in MM patients compared to controls in the first year following diagnosis and remained high or increased for certain infections (pneumococcal infection, influenza and herpes zoster) during follow-up. See Figure 1. The risk of dying from influenza was 3-fold higher (0.5% vs 0.2%), OR=2.7; [1.4-5.3], p=0.002, in myeloma patients compared to controls. The risk of dying from a pneumococcal infection was low: 0.1% vs 0.04%, but 4-fold higher in MM-patients (OR=3.7; [1.0-14.8], p=0.049). Conclusion: The risk of vaccine-preventable infections was high in MM patients, especially pneumococcal infection where the risk compared to a healthy population was 17-fold. The risk of influenza, herpes zoster and haemophilus influenzae was manyfold in patients with MM and remained high or increased during follow-up. Recent studies have shown that vaccinations are underutilized in multiple myeloma and the current results suggest that they should be encouraged.

Symptom trajectory for patients utilizing remote symptom monitoring during gastrointestinal cancer treatment.

345 Background: Use of electronic patient-reported outcome data allows patients to report symptoms in real time. This analysis aims to better understand the trajectory for symptoms reported via Remote Symptom Monitoring (RSM) by patients receiving gastrointestinal (GI) cancer treatment. Methods: This retrospective cohort study included patients initiating GI cancer treatment (chemotherapy, targeted therapy, and immunotherapy) between August 2022 and April 2023 at USA Health Mitchell Cancer Institute (MCI). Patients were eligible if they were starting a new treatment or had started treatment in the past 30 days. Patients received a weekly symptom survey over the course of 24 weeks through text message or e-mail. Patients were monitored for a total of 24 weeks regardless of their enrollment date. Patients reported symptoms as mild, moderate, severe, or very severe. All moderate and severe alerts were sent to the clinical nurse via the electronic medical record (EMR) to be acknowledged. After enrollment, health information including age, race, sex, zip code, ethnicity, cancer type, and cancer stage were extracted from the EMR. Descriptive statistics were calculated to examine frequencies of reported symptoms and their severity over time. Results: Of 75 GI patients approached, 63 patients (84%) were enrolled in RSM; 44% were female; 30% of patients were Black or African American, and median age was 65 (range 30-82). GI cancer types varied; Pancreatic (21%), Rectal (13%), Colorectal (14%), Colon (13%), Gastric (11%), Liver (11%), and other (17%). Over 24 weeks, 424 alerts were reported. Pain (31%), nausea and vomiting (21%), and decreased appetite (17%) were the most reported symptoms. 311 alerts were moderate (73%) and 113 were severe (27%). At week 0 (baseline; n = 63) 37 moderate alerts and 21 severe alerts were reported. At week 24 (final week; n = 63) 7 moderate alerts and 6 severe alerts were reported. Overall, there was a decreasing trajectory from week to week for moderate and severe alerts, with outliers noted at weeks 8 and 20. Conclusions: Findings suggest that RSM allows for an improvement in symptom trajectory for GI cancer patients based on the decrease in moderate and severe alerts reported from baseline to week 24. This decrease suggests that reported symptoms are being appropriately monitored and addressed by the patient's clinical care team due to improvement of symptoms or improvement of symptom management. Future research is needed to determine the benefits of prolonged RSM utilization by patient-reported quality of life as well as survival rate.

Invited Symposium 3: Pediatric Neuropsychology Medical Advances and Life Span Outcomes

Abstract &amp; Learning Objectives:Medical advances continue to improve the outlook for pediatric patients with a variety of acquired and congenital medical conditions. Such critical advances have an impact on lifespan outcomes for affected individuals. Neuropsychology plays a critical role in evaluating outcomes and informing clinical care for pediatric patients, with an increasing role in prevention. Neuropsychologists are essential members of interdisciplinary teams and ongoing medical management. Our symposium will present examples of the latest progress made over the last decade in the areas of sickle cell disease, demyelinating disorders, congenital heart disease, and cancer. Highlights include recent research on neurocognitive surveillance for pediatric patients with sickle cell disease including identification of risk and resilience factors and ways to reduce cognitive decline; discovery of the anti-MOG antibody in patients with demyelinating disorders and associated neuropsychological outcomes; advances in the understanding of congenital heart disease, the latest initiatives in the field, and discussion of neuropsychology’s role in the care of these patients; and advances in targeted therapies for childhood cancer, risks associated with cancer and its treatment into adulthood, and an application of a developmental, lifespan approach in the care of childhood cancer survivors. Following each presentation, there will be an opportunity for discussion and questions. Upon conclusion of this course, learners will be able to: 1.Describe recent advances in medical care for pediatric sickle cell disease, demyelinating disorders, congenital heart disease, and cancer2.Explain long-term neuropsychological outcomes in pediatric medical disorders3.Assess the role of neuropsychology in advancing the field across pediatric medical disorders

Deferasirox in Patients with Chronic Kidney Disease: Assessing the Potential Benefits and Challenges.

Chronic kidney disease (CKD) is a major global health concern, affecting millions of people worldwide. The progressive decline in kidney function often necessitates renal replacement therapy, such as hemodialysis (HD) or peritoneal dialysis (PD), to maintain a patient's health. Iron overload, which is common in CKD patients on dialysis, can lead to severe complications, including cardiovascular disease and infections where most of the existing iron chelators are deemed unsuitable due to their suboptimal clearance in patients with compromised renal function, it becomes a significant challenge to effectively manage iron overload. Deferasirox (DFX), an oral iron chelator, has emerged as a promising treatment option for managing iron overload in these patients. However, the use of DFX comes with its unique set of challenges, such as its cost, potential side effects, and the need for close monitoring of patients, as well as the noticeable scarcity of comprehensive and rigorous clinical studies confirming its efficacy and safety of DFX. In this review, we delve into both the promising prospects and the emerging challenges associated with DFX use in managing CKD patients on HD or PD, striving for a comprehensive understanding that informs better clinical practice and patient care.

Frequency of standardized patient-reported outcome measures in routine clinical care of patients with cancer.

342 Background: Patient-reported outcomes (PROs) assess a patient’s self-reported health status, including disease symptoms, treatment experience, functional outcomes, and quality of life. Incorporation of PROs has been linked to improved patient symptom control and increased shared decision making. Standardized PRO measures (PROMs) are becoming more frequent as an endpoint for clinical trials, however their use is less frequent in routine care for patients with cancer. The goal of this study was to assess the utilization of PROMs and identify barriers to their use. Methods: US-licensed oncologists/hematologists convened at one of three live meetings in 2023 to review recent clinical updates. Respondent demographics were collected ahead via an online survey. During the meetings, participants responded to queries on their use and perceptions of PROs and PROMs. Responses were captured via audience response system technology; not all participants answered every question. Pooled data were summarized using descriptive statistics. Results: Of the 146 respondents, 77.4% self-identified as community-setting providers, spent 84.3% of their time seeing patients, saw an average of 19.8 patients/day, and averaged 17.7 years of experience. Respondents found PROs to be most useful in early detection/management of treatment toxicities and symptoms (63.8%) and tailoring of clinical/supportive care (56%). The majority of PROs are typically recorded through informal verbal inquiries, while 18.1% and 10.9% of respondents use validated and non-validated PROMs, respectively. Few respondents (11.3%) administer PROMs to every patient at every visit, while over one-third (38.3%) never administer PROMs. Within the practice, medical assistants and nurses are most likely to be the provider administering PROMs. PROMs are most commonly administered when the patient is in the office and are infrequently administered through other means. Lack of time to administer or review PRO surveys (45.1%), and lack of reimbursement (38.9%) and EMR integration (38.9%) were the most common reported barriers to using PROMs in the respondents’ practices. Conclusions: Despite the majority of respondents finding PROs useful in practice, a minority use formal measures to record PROs. Further, usage is infrequent across patient visits. Lack of time, lack of reimbursement, and logistic barriers are the most common reasons for not using PROMs in routine care. These barriers may be overcome by efforts or guideline changes from regulatory agencies, payors, or clinical guideline organizations. Future work will assess how physicians are using PROMs in treatment selection for their patients with cancer.

Implementing a Prenatal Oral Health Program for Dental Students: Lessons Learned.

The Prenatal Oral Health Program (pOHP) was developed to educate dental students on prenatal oral health and promote access to dental care for pregnant women. Program advancement has occurred in support of quality improvement. This mixed-methods design combined quantitative data from fourth-year dental students who participated the pOHP (N = 81) and qualitative data from a student-faculty-staff focus group discussion (N = 7). Different clinical structures, appropriate leveling in the curriculum, management with a patient care coordinator, and inclusion of interprofessional learning experiences (IPE) were compared. The survey response rate was 96.4% (N = 81). Trends were noted between students who provided clinical care for a pregnant patient (31%) versus those who did not. Results indicated that an integrated clinic was preferred, though students who had treated a pOHP patient showed greater support for a standalone clinic model. Survey and focus group data agreed that pOHP should occur during the third-year dental school training; however, students with patient experience favored second-year placement. Survey and focus group data emphasize the importance of a patient care coordinator for clinical management and IPE as an essential learning element. Innovating new clinical models requires a period of evolution to determine preferred and sustainable infrastructure. Results reveal the advantages and disadvantages of various program implementation models and demonstrate that student perceptions were influenced by their clinical experiences. Study findings will inform implementation and guide other programs as they create and modify existing curricula to enhance prenatal oral health.

Implementing patient-centred outcome measures in palliative care clinical practice for adults (IMPCOM): Protocol for an update systematic review of facilitators and barriers.

Background: Despite the development of patient-centred or patient-reported outcome measures (PCOMs or PROMs) in palliative and end-of-life care over recent years, their routine use in practice faces continuing challenges. Objective: To update a highly cited literature review, identify and synthesise new evidence on facilitators, barriers, lessons learned, PCOMs used, models of implementation, implementation outcomes, costs, and consequences of implementing PCOMs in palliative care clinical practice. Methods: We will search MEDLINE, PsycINFO, CINAHL, Embase, Emcare, SCI-Expanded, SSCI, ESCI, and BNI. The database search will be supplemented by a list of studies from the expert advisory committee, hand-searching of reference lists for included articles, and citations of the original review. We will include primary studies using a PCOM during clinical care of adult patients with advanced disease in palliative care settings and extract data on reported models of implementation, PCOMs, facilitators, barriers, lessons learned, costs, and implementation outcomes. Gough's Weight of Evidence Framework will be used to assess the robustness and relevance of the studies. We will narratively synthesise and tabulate the findings. This review will follow PRISMA, PRISMA-Abstract, PRISMA-P, and PRISMA-Search as the reporting guidelines. Source of funding: Marie Curie. The funder is not involved in designing or conducting this study. Protocol registration: CRD42023398653 (13/02/2023).