Disease-related Group Research Articles

Bevacizumab in combination with chemotherapy for treating patients with advanced RET+ non-small cell lung cancer.

8647 Background: RET inhibitors (RETi) are currently the preferred first-line treatment in advanced RET fusion-positive (RET+) non-small cell lung cancer (NSCLC). Despite impressive efficacy of RETi, resistance is inevitable, and the optimal therapy beyond RETi remains unclear. Immunotherapy has shown limited efficacy in these patients. This study aims to investigate the impact of adding bevacizumab to chemotherapy regimens on treatment outcomes. Methods: This multicenter, retrospective study included patients with RET+ advanced NSCLC who received either a platinum-doublet chemotherapy (D) (+/-anti-PD-L(1) agents (ICB)) or a non-platinum monotherapy (M), with or without bevacizumab (Bev). Non-platinum agents were limited to pemetrexed, paclitaxel, or docetaxel. Only the first administration of the regimen was considered. Objective responses (OR), progression-free survival (PFS), and overall survival (OS) from the start of treatment were compared between patients receiving and not receiving Bev. Results: Of 185 patients, 20 received Bev in doublet chemotherapy (D+Bev, none with ICB) and 165 did not (D, 68 with ICB). Additionally, 40 underwent single-agent chemotherapy, with 8 on Bev (M+Bev) and 32 without (M). D+Bev patients were younger (median age: 54 vs. 61 years, p=0.026), less often treated with RETi (55% vs. 79%, p=0.023), with no other demographic or disease-related group differences. Both D+Bev and D had a median of 1 treatment line [IQR 1-1]. M+Bev and M had a median of 3 and 2 treatment lines, respectively (p=0.3), and numerically more M+Bev patients had brain metastases (25% vs. 13%, p=0.6). In the D+Bev vs D (+/-ICB) comparison, the OR was 55% vs 47% (p=0.7), and the median PFS was significantly longer in the D+Bev group (17 months vs. 8.8 months, p=0.018). When comparing D+Bev with D+ICB, D+Bev still showed a significant advantage in median PFS (17 months vs 9.7 months, p=0.05). The median OS was 51.4 months for D+Bev compared to 38.7 months for D (p=0.89). Multivariate analysis revealed that Bev use was independently associated with longer PFS (hazard ratio [HR] 0.4, p=0.01), while ECOG>1 (HR 4.3, p<0.0001) and male sex (HR 1.7, p=0.01) were associated with shorter PFS. In the M+Bev versus M group, the OR was 13% versus 25% (p=0.6), median PFS was 2.4 months versus 4.1 months (p=0.06), and median OS was 12.1 months versus 39 months (p=0.06). Conclusions: Bevacizumab with platinum-doublet chemotherapy seems to outperform platinum-doublet with or without ICB in progression-free survival. Prospective research is needed to evaluate the extent of bevacizumab's benefit for RET+ NSCLC.

System-wide approach on biosimilars adoption in oncology: Strategic plan on switching and cost savings.

1600 Background: Biosimilars provide competitive, lower-cost alternatives to biologic drugs in cancer treatment. As more agents become available in the US, institutions have to implement a strategy for successful adoption that is feasible, safe and provide price competition among biosimilar manufacturers. Methods: We aimed to standardize biosimilar utilization across the Cedars-Sinai Health System (CSHS) by integrating institutionally developed clinical pathways and insurance prior-authorization into the existing electronic health record (EHR). The initial study was limited to bevacizumab, rituximab and trastuzumab. To align with CSHS guideline recommendations, biosimilar indications for use were reviewed by each disease related group (DRG). Biosimilar brands for each drug were selected through a formulary process vetted by the Pharmacy & Therapeutics Committee. Physicians were permitted to opt-out of switching via an option provided within the electronic order set. To test feasibility of this approach, patients were divided into two groups as 1) main medical center (Cedars Sinai Medical Center) and 2) Cedars-Sinai Cancer affiliated sites. Feasibility was defined as a compliance rate of 80% or greater at the main medical center and 75% or greater at the affiliated sites. This study was powered to detect a minimum difference at 5.7% and 8.9%, respectively. Results: Between January 2021 to September 2022, a total of 1,139 cancer patients who initiated treatment with bevacizumab, rituximab or trastuzumab were identified through the EHR, of whom 650 were eligible (age 18-96; 61% female, 39% male). Using our approach, the compliance rate was 86% at the main site (p<0.001, 95%CI: 82.5-89.1) and 88% (p<0.001, 95%CI: 82.1-91.7) at the affiliated sites, resulting in a 56% improvement from baseline (86% vs. 55%, p<0.001). Among 14% of patients who did not switch to institutional-preferred biosimilar brands, the most common reasons for this were payer mandated use of an alternate brand (5%), off-label indication (4%), enrolled in patient assistance program (3%) and physician preference (2%). Five patients (<1%) did not switch to biosimilars due to history of infusion reactions. Insurance type (HMO, PPO, Medicare, others) was not associated with non-compliance (p=0.876). Cost savings were projected to be over $4 million over a duration of two years. Conclusions: Enterprise-wide switching to one specific biosimilar brand is feasible and facilitated through leveraging of the EHR. This approach optimized exiting organizational infrastructure to standardize biosimilar utilization and promote substantial cost savings.[Table: see text]

EE326 Malnutrition Prevalence and Economic Burden Among US Hospitalized Older Adult Patients with and without COVID-19

Malnutrition is a prevalent condition affecting 30-50% of hospitalized patients. Malnutrition is linked to impairments in health outcomes and increased economic burden on healthcare systems. We assessed the prevalence and burden of malnutrition by examining demographic characteristics, Disease Related Group (DRG) payments and associated claims among Medicare inpatients (65+ years) with and without COVID-19. Hospital inpatient COVID-19 claims from the Centers for Medicare & Medicaid Services (CMS) Inpatient Prospective Payment System (IPPS) between October 2020 - September 2021 were analyzed. The International Classification of Diseases, Tenth Revision, and Clinical Modification (ICD-10-CM) were used for malnutrition diagnoses. Demographic variables were compared based on the COVID-19 status; economic burden was analyzed by DRG payment of malnutrition cases with and without COVID-19. Among 7,394,657 Medicare inpatient claims, only 12% had a documented malnutrition diagnosis. Of these patients, 1.2% had COVID-19. Regardless of COVID-19 status, malnourished patients averaged 75 years of age, and were predominantly female (54%) and White (78%) followed by Black (14%), and Hispanic (2%). Sepsis, kidney failure, and urinary tract infection (UTI) were the most common primary diagnoses in malnourished patients, regardless of COVID-19 status. Malnourished patients with COVID-19 had significantly higher DRG payments ($27,407 vs. $18,327) and increased cost of outlier payment ($3,208 vs. $2,049) compared to those without COVID-19, regardless of other diagnoses. Malnutrition diagnosis was confirmed in only 12% of the Medicare inpatients, thus suggesting that malnutrition continues to be underdiagnosed and undertreated --- evidenced by high rates of hospitalizations/claims and payments in both COVID-19 and non-COVID-19 cases. It is imperative for hospitals to implement nutrition-focused protocols to identify, diagnose and address malnutrition among all Medicare inpatients regardless of COVID-19 status (and especially among patients with sepsis, kidney failure, and UTI). Nutrition-focused protocols can effectively improve patient health outcomes and reduce healthcare costs.

Abstract 4394: Feasibility analysis of querying EHR databases for cancer clinical trial criteria

Abstract Background: In order to enroll patients for clinical trials (CT), it is common to run queries in clinical databases using CT eligibility criteria as filters and specifications. However, CT eligibility criteria are often unavailable as discrete data fields, which can interfere with CT recruitment. The purpose of this study was to identify the most commonly needed eligibility criteria that are specified in cancer CT to investigate whether and how they could be found in clinical databases. Design: We examined the data elements needed for the trial eligibility criteria that would be used in queries for all the Breast, Gastrointestinal, Genitourinary, Head and Neck, and Cutaneous Cancer treatment trials open for enrollment across our health system. We then performed a sort-rank exercise for these eligibility criteria terms. Results: The analysis included 33 trials and 12 data elements. Table 1 shows the number of times each eligibility criterion appeared in the 33 CTs and its feasibility for an EHR query. The data elements that appeared most frequently were Organ/Cancer Site (100%), Tumor Morphology (66.7%), Presence of Metastases (51.5%), TN Staging (39.4%), and Days Since Diagnosis (24.2%). Of these, only Organ/Cancer Site and Days Since Diagnosis were accessible as structured datapoints in our clinical databases. Conclusions: The lack of feasibility for EHR query is likely due to the fact that healthcare information is generally stored in a discrete, structured form as a means of completing care transactions (drug orders or laboratory values) and ensuring billing compliance (ICD and outpatient CPT codes). This presents a critical challenge when data are required for CT enrollment, quality assurance metrics, and prospective and retrospective clinical research. Health systems—and by extension, their patients—would benefit from investing in structured data schemas involving AJCC staging, tumor morphology, and presence of metastases. Eligibility criteria with corresponding number of appearances in CTs and feasibility for EHR query Eligibility criterion Number of trials with each criterion Feasibility for EHR query Organ/Cancer Site 33 (100%) Accessible (ICD codes very detailed for site and used consistently for purpose of billing) Tumor Morphology 22 (66.7%) Not accessible (Code have not been created in ICD system, SNOMED is not widely adopted, not needed for billing) Presence of Metastases 17 (51.5%) Not accessible (Not coded consistently, coded in ICD as a “secondary” malignancy but generally does not affect billing) TN Staging 13 (39.4%) Not accessible (Not coded in ICD system) Days Since Diagnosis 8 (24.2%) Accessible (Structured data captured for purpose of initial transaction) Tumor Markers and Other Lab Results 4 (12.1%) Accessible (Structured data captured by laboratory instrument for purpose of initial transaction) Immunohistochemical Biomarkers 4 (12.1%) Not accessible (Pathologist assessment documented as narrative text) History of Systemic Therapy 3 (9.1%) Accessible (NDC drug code captured with initial order in order to complete the initial transaction) Feasibility of Resection 3 (9.1%) Not accessible (Surgeon assessment documented as narrative text) Disease progression 3 (9.1%) Not accessible (Radiologist assessment documented as narrative text) Surgical Procedure 2 (6.1%) Accessible as CPT codes for outpatient surgeries as needed for billing. Not accessible for inpatient surgeries where billing is capitated as a single fee for entire hospitalization based on disease related groups Margins 2 (6.1%) Not accessible (Pathologist assessment documented as narrative text) Citation Format: Dylan J. Cooper, Joseph Herman, Nalan Yurtsever, Sergio Garza, Daniel A. King, Yonah Ziemba. Feasibility analysis of querying EHR databases for cancer clinical trial criteria. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4394.

Socioeconomic and geographic inequalities in headache disability in Brazil: The 2019 National Health Survey.

To map the socioeconomic and geographic inequalities in headache disability in Brazil. Headache disability and its social determinants are poorly investigated in Brazil. This is a secondary, cross-sectional analysis of the 2019 National Health Survey database, a representative sample of the Brazilian population. Working-aged Brazilians (aged ≥14 years) were included in the analyses (n=225,563). Headache disability was inquired through questions on the number of days the respondent was unable to perform customary daily activities in the past 2 weeks. Proportion estimates and the mean days lost were compared between socioeconomic categories. Sample weights were used. Among 14 disease-related disability groups, headache disability (n=1228) was the second most prevalent disability in adolescents and fifth among adults aged <50 years. In the headache disability sample, there was a higher proportion of females at 72.4% (95% confidence interval [CI] 68.5%-75.9%), with a mean (95% CI) age of 41.1(40.1-42.0)years and days lost due to disability of 3.4(3.2-3.6)days. The sociodemographic distribution across income strata (quartiles) of the headache disability sample showed the highest proportions at the lowest income quartile in the Northeast region (15.4%, 95% CI 12.8%-18.4%), for people of Brown color (17.5%, 95% CI 14.7%-20.7%), and with the lowest education level (l3.6%, 95% CI 11.3%-16.2%). Black people, those from the North region, and those with the lowest education level had more days lost than White people (mean [95% CI] 4.1 [3.5-4.6] vs. 3.1 [2.8-3.4]days, p=0.008), those from the Southeast region (mean [95% CI] 3.8 [3.4-4.2] vs. 2.8 [2.4-3.3]days, p=0.022), and people with the highest education level (mean [95% CI] 3.9 [3.6-4.2] vs. 2.8 [2.3-3.3]days, p=0.005), respectively. In Brazil, headache disability is one of the leading causes of disability and it is characterized by socioeconomic inequalities.

Disease Staging: Prevalence of Cardiorespiratory Complications in Type 2 Diabetes Mellitus

Introduction: The incidence of cardiorespiratory complications in diabetic patients is a major concern for healthcare organizations and providers in Portugal. The objectives of this study were (1) to study the prevalence of cardiorespiratory complications during hospitalization in the diabetic population and (2) to identify their associated factors.Methods: This is a cross-sectional study and included 7,347 diabetic patients admitted to all specialty services enrolled between January 1, 2018 and December 31, 2018 in 32 public hospitals in Portugal. Hospital discharge summary data and both Disease-Related Diagnosis Groups and Disease Staging were used. Descriptive statistical analysis was used where the distribution and rates of cardiorespiratory complications were calculated. Logistic regression using the risk adjustment model was used to calculate the associated risk factors for cardiorespiratory complications.Results: The total rate of cardiorespiratory complications was 18.2% cardiorespiratory complications; in women it was 21.5% and in men 15.6%. The comorbidity of congestive heart failure (98.0%) was significantly higher (P<0.001) among patients undergoing medical treatment, and the comorbidities bacterial pneumonia and coronary artery disease without prior coronary revascularization were significantly higher (63.9%, 45.1%, and 33.4%, P<0.001).Discussion: The use of different therapies to control glucose levels and the absence of antibiotic prophylaxis during medical treatment may account for these data.Conclusions: Cardiorespiratory complications were higher in women than in men and in those who received medical treatment. Comorbidities such as congestive heart failure, such as bacterial pneumonia and coronary artery disease without prior coronary revascularization were identified as risk factors.

Cortical profiles of numerous psychiatric disorders and normal development share a common pattern.

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.

Abstract 14712: PCI is Safe and Increasing Among Cancer Patients: Nationally Representative Propensity Score Adjusted and Machine Learning Augmented Study of 100 Million Hospitalizations

Introduction: The greater use of antithrombotic and antiplatelet agents in the growing population of patients with cardiovascular disease and cancer contrasts with the limited evidence-base on appropriate revascularization management for these patients. Methods: This is the first nationally representative multi-year cardio-oncology mortality study of thrombocytopenia (platelets &lt;150,000) and coronary intervention including percutaneous coronary intervention (PCI), and the first such study using machine learning augmentation and propensity score (PS). Utilizing the 2016-2018 National Inpatient Sample (NIS), the PS for receiving PCI was generated, balance confirmed, and regression adjustment completed (also including age, sex, race, income, urban, region, metastasis, NIS-calculated mortality risk by disease-related group), and multivariable regression model performance was optimized using backward propagation neural networks. Results: Of the 101,521,656 hospitalized adult patients, 6,456,777 (6.36%) had active cancer of whom 6.14% had thrombocytopenia. Among thrombocytopenia patients, patients with versus without active cancer were significantly (p&lt;0.001) less likely to receive left heart catheterization (1.88 vs. 5.41%) and PCI (0.48 vs. 1.35%). Among cancer patients, patients with versus without thrombocytopenia were more likely to have acute myocardial infarction (4.06 vs. 2.35%) and to receive intravascular ultrasound (62.65 vs. 56.75%) but had comparable rates of fractional flow reserve and optical coherence tomography. PCI nearly doubled from 2016 to 2018 among patients with thrombocytopenia (10.33 vs. 6.16%). In multivariable regression in PCI, neither active cancer (OR 0.89, 95%CI 0.45-1.75; p=0.738) nor any of the 32 tested primary malignancies significantly increased mortality. Conclusions: This nationally representative longitudinal study suggests inpatient PCI is safe and is increasing among patients with active cancer regardless of their primary malignancy.

Inpatient Mortality in People With Type 2 Diabetes: A Cross-sectional Study

Objective: This study aimed to estimate inpatient mortality rate for diabetes and identify its associated factors. Materials and methods: This is a cross-sectional study. The population was comprised between January 1 and December 31, 2019 in 32 public hospitals in Portugal, using summary hospital discharge data. We used both the Disease-Related Diagnosis Groups and the Disease Staging. Patients were grouped into survivors and non-survivors, and inpatient mortality was compared using competing event regression. Results: A total of 7980 patients were admitted with type 2 diabetes mellitus, there were 747 (10.3%) non-survivors. The advanced age (OR = 1.772; 95% CI 1.625–1.932), the stage (3) severity of type 2 diabetes mellitus (OR = 4.301; 95% CI 2.564–7.215), comorbid lung, bronchial or mediastinal malignant neoplasm (OR = 5.118; 95% CI 2.222–11.788), comorbid bacterial pneumonia (OR = 3.214; 95% CI 2.539–4.070), other respiratory system disorders (OR = 2.187; 95% CI 1.645–2.909), comorbid rhino-, adeno- and coronavirus infections (OR = 1.680; 95% CI 1.135–2.488) were determinants for inpatient mortality. Conclusions: Elderly patients with diabetes with micro- and macrovascular complications of the disease, who have bacterial pneumonia and who enter the emergency department are those who have a lower survival rate.

The Relationship Between Gluten Enteropathy and Nail Capileroscopy Findings and Disease Activation

Objective: Nailfold Videocapilloroscopy (NVC) is an examination method that is used as an aid in the diagnosis, follow-up, and treatment strategy of rheumatic diseases such as systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and gives an idea about microcirculation by examining the vascular bed. It is a cheap, easily applicable, and quickly accessible method. Because of these features, we aimed to use the NVC method in patients with Gluten Enteropathy (GE) to determine whether this method will be a helpful technique in the diagnosis, activation decision, remission follow-up, and treatment strategy in patients with GE. Methods: In this study, 67 patients diagnosed with GE (n=35 disease-active group (AGE), n=32 disease-related remission group (RGE), and control group (CG)-27 healthy people whose diagnosis of GE was ruled out were included in this study. Group and CG were divided into ten parameters in capillary pathologies (capillary density loss, dilated capillary, giant capillary, microhemorrhage, avascular area, tortuosity, branched capillary, disorganization, extravasation, angiogenesis). They were divided into two groups as RGE and compared with the results obtained from NVC measurements Results: When patients diagnosed with GE and CG were evaluated in terms of capillary disorder with NVC, While all of the patients with capillary disorders were in the GE group, no capillary disorders were found in the control group (p&amp;lt;0.01). When patients diagnosed with GE were divided into two groups (AGE and RGE), NVC measurements were compared; All patients with capillary disorders were found in the AGE group (p&amp;lt;0.01). Capillary density loss and/or avascular area were detected in 80.9% of patients with capillary disorders. Conclucion: Our study found a statistically significant difference in NVC measurements between GE patients and CG (p&amp;lt;0.01). The fact that all patients with capillary disorders were in the active group in terms of the disease and no capillary disorders were detected in any patients in remission showed that this method could be used as an auxiliary technique in the diagnosis of GE, making the decision of activation or remission, monitoring the disease and determining treatment strategies.

Automatic International Classification of Diseases Coding System: Deep Contextualized Language Model With Rule-Based Approaches.

BackgroundThe tenth revision of the International Classification of Diseases (ICD-10) is widely used for epidemiological research and health management. The clinical modification (CM) and procedure coding system (PCS) of ICD-10 were developed to describe more clinical details with increasing diagnosis and procedure codes and applied in disease-related groups for reimbursement. The expansion of codes made the coding time-consuming and less accurate. The state-of-the-art model using deep contextual word embeddings was used for automatic multilabel text classification of ICD-10. In addition to input discharge diagnoses (DD), the performance can be improved by appropriate preprocessing methods for the text from other document types, such as medical history, comorbidity and complication, surgical method, and special examination.ObjectiveThis study aims to establish a contextual language model with rule-based preprocessing methods to develop the model for ICD-10 multilabel classification.MethodsWe retrieved electronic health records from a medical center. We first compared different word embedding methods. Second, we compared the preprocessing methods using the best-performing embeddings. We compared biomedical bidirectional encoder representations from transformers (BioBERT), clinical generalized autoregressive pretraining for language understanding (Clinical XLNet), label tree-based attention-aware deep model for high-performance extreme multilabel text classification (AttentionXLM), and word-to-vector (Word2Vec) to predict ICD-10-CM. To compare different preprocessing methods for ICD-10-CM, we included DD, medical history, and comorbidity and complication as inputs. We compared the performance of ICD-10-CM prediction using different preprocesses, including definition training, external cause code removal, number conversion, and combination code filtering. For the ICD-10 PCS, the model was trained using different combinations of DD, surgical method, and key words of special examination. The micro F1 score and the micro area under the receiver operating characteristic curve were used to compare the model’s performance with that of different preprocessing methods.ResultsBioBERT had an F1 score of 0.701 and outperformed other models such as Clinical XLNet, AttentionXLM, and Word2Vec. For the ICD-10-CM, the model had an F1 score that significantly increased from 0.749 (95% CI 0.744-0.753) to 0.769 (95% CI 0.764-0.773) with the ICD-10 definition training, external cause code removal, number conversion, and combination code filter. For the ICD-10-PCS, the model had an F1 score that significantly increased from 0.670 (95% CI 0.663-0.678) to 0.726 (95% CI 0.719-0.732) with a combination of discharge diagnoses, surgical methods, and key words of special examination. With our preprocessing methods, the model had the highest area under the receiver operating characteristic curve of 0.853 (95% CI 0.849-0.855) and 0.831 (95% CI 0.827-0.834) for ICD-10-CM and ICD-10-PCS, respectively.ConclusionsThe performance of our model with the pretrained contextualized language model and rule-based preprocessing method is better than that of the state-of-the-art model for ICD-10-CM or ICD-10-PCS. This study highlights the importance of rule-based preprocessing methods based on coder coding rules.

Hospital-Based Health Technology Assessment of Machine Perfusion Systems for Human Liver Transplantation

Based on published data, we have carried out a hospital-based health technology assessment of machine perfusion in adult liver transplantation using cold storage as a comparator, and within the perspective of a national health system-based hospital practice and disease-related group reimbursement policy. A systematic literature review on machine perfusion for adult liver transplantation was conducted exploring the Pubmed, CINAHL, Scopus, Embase, and Cochrane databases. The literature was analyzed with the intent to provide information on 6 dimensions and 19 items of the hospital-based health technology assessment framework derived from previous studies. Out of 705 references, 47 (6.7%) were retained for current analysis. Use of machine perfusion was associated with advantages over cold storage, i.e., a 10%–50% reduced risk for early allograft dysfunction, 7%–15% less ischemia reperfusion injury; 7%–50% fewer ischemic biliary complications, comparable or improved 1-year graft and patient survival, and up to a 50% lower graft discard rate. Hospital stay was not longer, and technical failures were anecdotal. Information on costs of machine perfusion is limited, but this technology is projected to increase hospital costs while cost-effectiveness analysis requires data over the transplant patient lifetime. No hospital-based health technology assessment study on machine perfusion in liver transplantation was previously conducted. From the hospital perspective, there is evidence of the clinical advantages of this novel technology, but strategies to counterbalance the increased costs of liver transplantation are urgently needed. Further studies should focus on the ethical, social, and organizational issues related to machine perfusion.

Biomarkers of Age-Related Frailty and Frailty Related to Diseases: An Exploratory, Cross-Sectional Analysis from the MAPT Study

BackgroundFrailty may in most cases result from two main causes: the aging process (age-related frailty) and diseases (evolving chronic conditions or acute medical illnesses — disease-related frailty). The biological determinants characterizing these two main causes of frailty may be different.ObjectivesThe aim of this study is to compare the biological and neuroimaging profile of people without frailty, those with age-related frailty, and subjects with disease-related frailty in community-dwelling older adults.Material and MethodsWe performed a secondary, cross-sectional analysis from the Multidomain Alzheimer Preventive Trial (MAPT). We included 1199 subjects without frailty throughout the 5-year follow-up, 82 subjects with incident age-related frailty, and 53 with incident disease-related frailty. Available blood biomarkers involved nutritional (eg, vitamin D, omega-3 fatty acids), inflammatory-related (IL-6, TNFR1, GDF15), neurodegenerative (eg, beta-amyloid, neurofilament light chain) and neuroimaging markers (MRI, Amyloid-PET).ResultsAlthough not statistically significant, the results of the unadjusted model showed increasing gradients for inflammatory markers (GDF15, TNFR1) and decreasing gradients for nutritional and neuroimaging markers (omega 3 index, hippocampal volume) from age-related frailty participants to individuals with disease-related frailty. Considering the linear models we observed higher GDF15 values in disease-related frailty group compared to age-related frailty individuals [β = 242.8 (49.5, 436.2)]. We did not find any significant difference between subjects without frailty and those with age-related frailty. Subjects with disease-related frailty compared to subjects without frailty had lower values of DHA [β = −2.42 (−4.76, −0.08)], Omega 3 Index [β = −0.50 (−0.95, −0.06)] and hippocampal volume [β = −0.22 (−0.42,−0.02)]. They also had higher values of GDF15 [β = 246.1 (88.9, 403.4)] and TNFR1 [β = 157.5 (7.8, 307.2)].ConclusionAge-related frailty and disease-related frailty may represent different degrees of frailty severity on a biological level. Further research is needed to identify biomarkers potentially able to distinguish these classifications of frailty.

The Saudi Ministries Twitter communication strategies during the COVID-19 pandemic: A qualitative content analysis study

ObjectivesTo understand government communication strategies during the COVID-19 pandemic by examining topics related to COVID-19 posted by Saudi governmental ministries on Twitter and situating our findings within existing health behavior theoretical frameworks. Study designRetrospective content analysis of COVID-19 related tweets. MethodsOn November 7th, 2020, we extracted relevant tweets posted by five Saudi governmental ministries. After we extracted the data, we developed and applied a coding schema. ResultsA total of 3,950 tweets were included in our dataset. Topics fell into two groups: disease-related (49.2%) and non-disease related (50.8%). The disease-related group included seven categories: awareness (18.5%), symptom (0.6%), prevention (7.7%), disease transmission (1.9%), treatment (0.3%), testing (3.4%), and reports (16.7%). The non-disease related group included eight categories: lockdown (5.9%), online learning (12.8%), digital platforms (4.3%), empowerment (12.0%), accountability (1.1%), non-disease reports (2.1%), local and international news (10.8%), and general statements (1.9%). Based on the correlation analysis, we found that the top positively correlated categories were: “testing” and “digital platforms” (r = 0.4157), “awareness” and “prevention” (r = 0.3088), “prevention” and “disease transmission” (r = 0.3025), “awareness” and “disease transmission” (r = 0.1685), “symptom” and “testing” (r = 0.1081), “awareness” and “symptom” (r = 0.0812), “symptom” and “digital platforms” (r = 0.0645), and “disease transmission” and “digital platforms” (r = 0.0450), p-values < 0.01. Several health behavior theoretical constructs were linked to our findings. ConclusionsIntegrating behavioral theories in the development of health risk communication should be taken seriously by government communication specialists who manage social media accounts, as these theories help underlining determinants of people's behaviors.

Activation of Investigator-Initiated Clinical Trials with a Pharmaceutical for Cancer Patients before and after Post-Millennial Changes of Regulations in Germany and Europe.

Simple SummaryThis opinion paper describes the regulatory hurdles for a clinical oncologist and physician scientist to activate an Investigator-Initiated Trial (IIT) before and after 2004 with German regulation as an example. Changes in legal framework with impacts on time and costs to activate a clinical trial are described. Evidence needed to reach the objective of higher patient safety and trial quality by European Union (EU) Clinical Trial Directive (CTD) 2001/20 is discussed.Shortly after the beginning of the year 2000, multiple legal changes with impacts on the regulatory framework of clinical trials became effective almost simultaneously. They included the European Union (EU) Clinical Trial Directive (CTD) 2001/20 followed by major changes in national drug laws, the change in the legal status of German University Hospitals (1998), and a new disease-related groups (DRG)-based reimbursement system for hospitals in Germany (2000). Together, these changes created enormous bureaucratic and financial inhibition of activation and conduct of academic investigator-initiated clinical trials (IIT). Examples for activating clinical trials in oncology before and after 2004 are outlined and discussed, focussing on extended time frames, the establishment of centralized responsibility structures and the exploding financial consequences. In addition, the evolution of trial numbers and the distribution of trial initiators between “commercial” and “academic” over time are discussed together with the occurrence of clinical registries. At the same time, progress in molecular biology led to a plethora of new targets for effective pharmacological therapy of life-threatening diseases such as cancer, and the overall number of clinical trials has not decreased. Yet, judging the regulatory and administrative hurdles between scientific study design and first-patient on trial before and after 2004 and weighing these against the lack of evidence that this regulation has achieved its goal to enhance patient safety and trial quality, the necessity to completely overhaul this CTD becomes obvious. A main goal of such an initiative should be to minimize bureaucracy. For the specific situation in Germany, relocation of responsibility and freedom to operate in University Hospitals and Medical Faculties back to the physician–scientists and reduction in interference by legal divisions should be a goal as well as increasing the public financial support for IITs.

Withdrawal.

Background Hepatoblastoma (HB) is the most common malignant embryonic liver tumor in children. In this study, we used the NGS method to detect the genotype characteristics of HB, summarized the correlation between common mutation genotypes of HB and clinical treatment and prognosis. Methods Firstly, DNA was extracted from tumor tissue specimens and peripheral blood of 19 children patients with HB. Then, DNA panel and NGS methods were used to detect tumor diagnosis and treatment-related genes, followed by summary of genotype characteristics. Thirdly, In order to further study the application of immunotherapy in HB, we performed programmed cell PDL1 immunohistochemical detection. Finally, the clinical treatment effect and prognosis of the children patients were statistically analyzed according to the characteristics of the genotype. Results In this study, some mutated genes including NFE2L2, CTNNB1, MYCN, TP53, AXIN1 and APC were related to the pathogenesis of HB. The immunohistochemical results showed lower expression of PDL1. The complete remission (CR) rate of children patients in the gene abnormality group was lower than that of the non-reported disease-related gene abnormality group. Conclusion The CR rate of the children patients with altered genotype was lower than those children patients without altered genotype. In addition, low expression of PDL1 limited the immunotherapy of children patients with HB.

Abdominal Aortic Screening Is a Priority for Health in Smoker Males: A Study on Central Italian Population.

Abdominal aortic aneurysm (AAA) is a major public health problem. In the last decade, in some European countries, abdominal aortic screening (AAS) is emerging as a potential prevention for the rupture of AAA. The goals of our study were to estimate AAA prevalence and risk factors in males and females in a central Italian population, also defining the cost-effectiveness of AAS programs. A pilot study screening was conducted between 1 January 2015 and 31 December 2019 in the municipality of Teramo (Abruzzo Region, Italy) in a group of men and women, ranging from the age of 65 to 79, who were not previously operated on for AAA. The ultrasound was performed by means of Acuson sequoia 512 Simens with a Convex probe. The anterior posterior of the infra-renal aorta was evaluated. The odds ratio values (ORs) were used to evaluate the risk of AAA, and the following determinants were taken into consideration: gender, smoke use, hypertension, and ischemic heart disease. We also estimated the direct costs coming from aneurysmectomy (surgical repair or endovascular aneurysms repair—EVAR). A total of 62 AAA (2.7%, mean age 73.8 ± 4.0) were diagnosed, of which 57 were in men (3.7%, mean age 73.6 ± 4.0) and 5 were in women (0.7%, mean age 74.3 ± 4.1). Male gender and smoke use are more important risk factors for AAA ≥ 3 cm, respectively: OR = 5.94 (2.37–14.99, p < 0.001) and OR = 5.21 (2.63–10.30, p < 0.000). A significant increase in OR was noted for AAA ≥ 3 cm and cardiac arrhythmia and ischemic heart disease, respectively: OR = 2.81 (1.53–5.15, p < 0.000) and OR = 2.76 (1.40–5.43, p = 0.006). Regarding the cost analysis, it appears that screening has contributed to the reduction in costs related to urgency. In fact, the synthetic indicator given by the ratio between the DRGs (disease related group) relating to the emergency and those of the elective activity went from 1.69 in the year prior to the activation of the screening to a median of 0.39 for the five-year period of activation of the screening. It is important to underline that the results of our work confirm that the screening activated in our territory has led to a reduction in the expenditure for AAA emergency interventions, having increased the planned interventions. This must be a warning for local stakeholders, especially in the post-pandemic period, in order to strengthen prevention.

A physics-informed neural network to model COVID-19 infection and hospitalization scenarios

In this paper, we replace the standard numerical approach of estimating parameters in a mathematical model using numerical solvers for differential equations with a physics-informed neural network (PINN). This neural network requires a sequence of time instances as direct input of the network and the numbers of susceptibles, vaccinated, infected, hospitalized, and recovered individuals per time instance to learn certain parameters of the underlying model, which are used for the loss calculations.The established model is an extended susceptible-infected-recovered (SIR) model in which the transitions between disease-related population groups, called compartments, and the physical laws of epidemic transmission dynamics are expressed by a system of ordinary differential equations (ODEs). The system of ODEs and its time derivative are included in the residual loss function of the PINN in addition to the data error between the current network output and the time series data of the compartment sizes. Further, we illustrate how this PINN approach can also be used for differential equation-based models such as the proposed extended SIR model, called SVIHR model.In a validation process, we compare the performance of the PINN with results obtained with the numerical technique of non-standard finite differences (NSFD) in generating future COVID-19 scenarios based on the parameters identified by the PINN. The used training data set covers the time between the outbreak of the pandemic in Germany and the last week of the year 2021.We obtain a two-step or hybrid approach, as the PINN is then used to generate a future COVID-19 outbreak scenario describing a possibly next pandemic wave. The week at which the prediction starts is chosen in mid-April 2022.

Headache disability, lifestyle factors, health perception, and mental disorder symptoms: a cross-sectional analysis of the 2013 National Health Survey in Brazil.

To evaluate the past 2-week headache disability and explore its association with lifestyle factors, health perception, and mental disorder symptoms in the PNS 2013 survey. The prevalence of headache disorders has been associated with lifestyle factors, mental disorders, and health perception. However, less is known regarding their influence on headache-related disability. In a cross-sectional analysis, chi-squared tests and logistic regression models computed the associations between headache-related disability (defined as days lost from work, school, or household chores in the past 2weeks) and the variables of interest, compared to other disease-related disabilities groups or no day lost group. The adjusted models controlled for the effects of age, sex, income, and educational levels. In the sample aged ≥ 18years (n = 145,580), 10,728 (7.4%) participants reported any disease-related disability in the past 2weeks (median interquartile range (IQR) for age = 47 (33-59) years, 62% women), with the median (IQR) days lost = 5 (2-14). Headache disability represented 5.3% (572/10,728) of all diseases, constituting the 4th most prevalent disease-related disability [median (IQR) days lost = 3 (3-4)]. Among people aged 18-25years, headache disorders ranked 2nd as the most prevalent disability (13%), headache-related disability positively associated with physical inactivity, poorer health perception, and frequent mental disorders symptoms, and negatively associated with overweight, obesity, and alcohol consumption. Headache disability represents a leading cause of disease-related disability in Brazil and associates with unhealthy lifestyle factors, poorer health perception, and frequent mental disorder symptoms.

Factors associated with early 14-day unplanned hospital readmission: a matched case\u2013control study

Background/PurposeEarly unplanned hospital readmissions are burdensome health care events and indicate low care quality. Identifying at-risk patients enables timely intervention. This study identified predictors for 14-day unplanned readmission.MethodsWe conducted a retrospective, matched, case–control study between September 1, 2018, and August 31, 2019, in an 1193-bed university hospital. Adult patients aged ≥ 20 years and readmitted for the same or related diagnosis within 14 days of discharge after initial admission (index admission) were included as cases. Cases were 1:1 matched for the disease-related group at index admission, age, and discharge date to controls. Variables were extracted from the hospital’s electronic health records.ResultsIn total, 300 cases and 300 controls were analyzed. Six factors were independently associated with unplanned readmission within 14 days: previous admissions within 6 months (OR = 3.09; 95 % CI = 1.79–5.34, p < 0.001), number of diagnoses in the past year (OR = 1.07; 95 % CI = 1.01–1.13, p = 0.019), Malnutrition Universal Screening Tool score (OR = 1.46; 95 % CI = 1.04–2.05, p = 0.03), systolic blood pressure (OR = 0.98; 95 % CI = 0.97–0.99, p = 0.01) and ear temperature within 24 h before discharge (OR = 2.49; 95 % CI = 1.34–4.64, p = 0.004), and discharge with a nasogastric tube (OR = 0.13; 95 % CI = 0.03–0.60, p = 0.009).ConclusionsFactors presented at admission (frequent prior hospitalizations, multimorbidity, and malnutrition) along with factors presented at discharge (clinical instability and the absence of a nasogastric tube) were associated with increased risk of early 14-day unplanned readmission.