Clinical Risk Groups Research Articles

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: A GBECAM multicenter retrospective study.

e18822 Background: Oncotype DX (ODX) is a validated tool for the prediction of risk of recurrence and benefit of chemotherapy (CH) in both node negative (N0) and positive (N1), hormone receptor positive (HR+), HER2 negative (HER2-) early breast cancer (eBC). Due to limited access to novel genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective, but limited data is available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a large dataset of patients from various Brazilian institutions. Methods: Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CH indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! algorithm, as used in the MINDACT study. The ODX score was correlated with the indication of CH according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included the model. In the second model, only high clinical risk patients were included. The cost for ODX and CH (U$2,846 and U$14,464, respectively) were based on the Brazilian private medicine perspective. Uncertainty was assessed using deterministic and probabilistic sensitivity analyses. Results: Six hundred and forty-five patients were analyzed. 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (< 11), intermediate (11-25) and high (> 25) risk in 119 (18.4%), 415 (64.3%) and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, 234 (36.2%) had clinical and 198 (30.6%) had genomic indication for CH, respectively. In this model, ODX was modestly effective (5.6% reduction in CH indication) though with an incremental cost of US$ 2,040 per patient. Among 234 patients analyzed in the second model (high clinical risk only), 99 (42.3%) patients had genomic indication of CH. In this model, ODX led to a 57.7% reduction in CH indication and reduced costs by US$5,491 per patient (table). The results remained robust in the 1,000 probabilistic simulations. Conclusions: Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC in the perspective of the Brazilian private health system. Its incorporation into routine practice should be strongly considered by health care providers.[Table: see text]

Factors Related with Hospital Attendance and Mortality in Patients with COPD: A Case-Control Study in a Real-Life Setting.

IntroductionThe rising trend in hospital admissions among patients with chronic obstructive pulmonary disease (COPD) is worrying, not only because of the increasing costs, but also because of the worsening quality of life. We aimed to identify the predictive factors of hospital admission, re-admission and mortality of COPD patients through using information exclusively registered in electronic clinical records.MethodsWe conducted a population-based case–control study. All data were sourced from the different information systems comprising the Galician Health Service electronic record database. We included in the study patients diagnosed with COPD (code R95 in the medical record), ≥35 years old and with at least one spirometry performed ≤3 years prior inclusion. We fitted three logistic regression models, each one to ascertain the factors that influence the probability of admission, re-admission, and mortality, and calculated odds ratios (OR) with their 95% confidence intervals (95% CI).ResultsCOPD patients were admitted due to respiratory causes a mean of 1.51 times across the period December 2016–December 2017, with 55% requiring re-admission in the next 90 days. The factor most closely associated with the re-admission profile was home oxygen therapy (OR 3.06 95% CI 2.42–3.87), followed by male gender (OR 2.01 95% CI 1.48–2.72), a CHA2D-VASc scale score >2 (OR 1.28 95% CI 1.16–1.42), and severity by clinical risk group stratification (OR 1.14 95% CI 1.04–1.26). Male sex (OR 1.47 CI 95% 1.04–2.09), having been readmitted ≥2 times (OR 1.34 CI 95% 1.11–1.61) and being ≥70 years old (OR 1.05 CI 95% 1.03–1.08) increase the probability of dying from COPD during the study period.ConclusionThese results confirm the complexity of management of COPD exacerbations, and indicate the need to establish strategies that would ensure continuity of care after hospital admission, with the aim of preventing re-admissions and death.

Prevalence of inappropriate prescribing in complex chronic patients: Time trends in a health department of Valencia, Spain (2015–2019)

Background and objectiveInappropriate prescribing (IP) is an important cause of health problems among elderly and complex chronic patients (CCPs). ObjectiveSurveillance of IP prevalence among elderly and CCPs in a health department. IP time trends across the period 2015–2019. MethodDescriptive population-based study. Setting: ‘València-Clínic-Malvarrosa’ Health Department, Valencia, Spain. Period: 2015–2019. Subjects: Complete set of CCPs in the department, defined by clinical risk groups. Number of CCPs (annual average in the period): 9102 (75% ≥65 years of age). IP was measured using an indicator consisting of 13 specific types of prescriptions defined as inappropriate. Analyses: frequencies and time trends, both overall and by specific type. ResultsOverall prevalence of IP ranged from 0.276 (2015) to 0.289 (2018) per patient, without time trend. The most frequent inappropriate prescription was type 1: “≥75 years of age with inappropriate medication”, which showed a stable rate across the period. Some types of inappropriate prescriptions displayed favourable decreasing time trends, while others showed no change or an unfavourable trend (i.e., joint prescription of absorbents and urinary antispasmodics). ConclusionsIP prevalence is a serious and persistent problem among the elderly and CCPs, especially in the oldest. It is therefore necessary its continuous surveillance (overall and by specific types of prescription). As well as interventions to optimise prescribing, thus improving the quality and efficiency of care for the elderly and CCPs.

Abstract P2-11-13: Distinctive clinicopathological features of premenopausal women with intermediate 21-gene recurrence score

Abstract Backgroud Since the results of TAILORx trial were published, it was shown that premenopausal young patients with intermediate Oncotype Dx(ODx) recurrence score(RS) (16-25) may benefit from adjuvant chemotherapy. In secondary analysis of the TAILORx trial, clinicopathological features can provide complementary information in addition to Oncotype Dx results. Although ambiguous benefit of adjuvant chemotherapy in premenopausal women with intermediate risk makes clinical decision difficult, the baseline characteristic may vary depending on menopausal status. This study intends to analyze whether the intermediate-risk group shows differences in characteristics by menopausal status. Materials and Methods 760 early breast cancer patients with ER positive, HER2 negative and lymph node negative patients who have been tested ODx from July 2013 to December 2020 at Severance Hospital were retrospectively reviewed. Results Of the 760 patients, 262 patients were postmenopausal status and 498 patients were premenopausal status. Among 262 postmenopausal patients, 152 patients were in low-risk group(RS 0-20), 43 patients were in intermediate-risk group(RS 21-25), 67 patients were in high-risk group(RS 26-100). Among 498 patients, 353 patients were in low-risk group(RS 0-20), 75 patients were in intermediate-risk group(RS 21-25), 70 patients were in high-risk group(RS 26-100), respectively. In premenopausal patients with intermediate risk, clinical risk group, PR score, and Ki-67 showed a significant difference from the low risk group(p-value 0.003, <0.001 and 0.005, respectively), but no significant difference from the high risk group(p-value 0.242, 0.085 and 0.729, respectively). However, in postmenopausal patients with the intermediate risk, clinical risk group and Ki-67 did not show a significant difference from the low risk group(p-value 1.000 and 0.120, respectively), but showed a significant difference from the high risk group.(p-value 0.009 and 0.001, respectively). Conclusion In this study, some of clinicopathological characteristics of premenopausal patients with intermediate risk were closer to those of high risk group than in the low risk group, unlike postmenopausal patients with intermediate risk. In premenopausal patients with intermediate risk, benefits from adjuvant chemotherapy may be unclear, but when considering the baseline characteristic itself, there is a significant difference with the low risk group when compared with postmenopausal patients. In that point of view, more aggressive treatment decision like adjuvant chemotherapy would be helpful to premenopausal patients with intermediate risk. Keywords: 21-gene recurrence score, premenopausal breast cancer, clinicopathological features Citation Format: Jung Min Park, Jee Hyun Ahn, Soon Bo Choi, Jieon Ko, Jee Ye Kim, Hyung Seok Park, Seung Il Kim, Byeong-Woo Park, Seho Park. Distinctive clinicopathological features of premenopausal women with intermediate 21-gene recurrence score [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-13.

Long-Term Effects on Preventing Frailty and Health Care Costs Associated with a Multifactorial Intervention in the Elderly: Three-Year Follow-Up Data from the Pre-Frail 80 Study

Introduction: Preventing or delaying frailty has important benefits. Studies show the effectiveness of multifactorial interventions in the frail and pre-frail elderly, but few have evaluated their long-term effectiveness. Frailty and its consequences have been shown to increase the use of health resources. The main aim was to evaluate the long-term effect of a multifactorial primary healthcare intervention in pre-frail elderly people at 36 months and determine the health resources used and their cost. Methods: A follow-up of a cohort study of patients who participated in a randomized clinical trial in an urban primary care centre in Barcelona was carried out. We included 200 non-institutionalized people aged ≥80 years who met the Fried pre-frailty criteria. The intervention group (IG) received a 6-month interdisciplinary intervention based on physical exercise, Mediterranean diet advice, assessment of inadequate prescribing in polypharmacy patients, and social assessment, while the control group (CG) received standard of care primary healthcare treatment. Sociodemographic variables were collected at baseline. The Fried criteria, comorbidities, and geriatric syndromes were collected at baseline and 12 and 36 months. For the analysis of health costs, data were collected on visits, complementary tests, hospital admissions, and surgical interventions in the last 36 months. Complexity, the rate of expected emergency admission, and the rate of expected mortality were collected at 36 months. Between-group characteristics were compared at baseline and 36 months using the χ2 test and the t test for independent samples. The post-intervention (12-month follow-up) versus longitudinal follow-up (36-month follow-up) comparison used McNemar’s test for each group. The nonparametric Mann-Whitney test was used to compare health costs. Results: Of the 200 patients initially included, we evaluated 135 (67.5%) patients who completed the 36-month follow-up. The mean age was 88.5 years and 64.4% were female. At 36 months, the transition to frailty was much lower in the IG than in the CG (22.1% vs. 32.8%, p = 0.013). The total mean health cost at 36 months was 3,110 EUR in the CG and 2,679 EUR in the IG. No significant between-group differences were observed according to Clinical Risk Groups. Conclusions: A multifactorial, interdisciplinary intervention carried out in primary care prevented frailty in pre-frail elderly people at 36-month follow-up. Although the IG was grouped into higher grade Clinical Risk Groups and therefore had greater morbidity, the cost was lower than that in the CG.

The Childhood Cancer Diagnosis (CCD) Study: a UK observational study to describe referral pathways and quantify diagnostic intervals in children and young people with cancer

IntroductionChildhood cancer is diagnosed in 400 000 children and young people (CYP) aged 0–19 years worldwide annually. In the UK, a child’s cumulative cancer risk increases from 1 in 4690...

Duration of Protection against Mild and Severe Disease by Covid-19 Vaccines

BackgroundVaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may wane over time since the receipt of the second dose of the ChAdOx1-S (ChAdOx1 nCoV-19) and BNT162b2 vaccines.MethodsWe used a test-negative case–control design to estimate vaccine effectiveness against symptomatic Covid-19 and related hospitalization and death in England. Effectiveness of the ChAdOx1-S and BNT162b2 vaccines was assessed according to participant age and status with regard to coexisting conditions and over time since receipt of the second vaccine dose to investigate waning of effectiveness separately for the B.1.1.7 (alpha) and B.1.617.2 (delta) variants.ResultsVaccine effectiveness against symptomatic Covid-19 with the delta variant peaked in the early weeks after receipt of the second dose and then decreased by 20 weeks to 44.3% (95% confidence interval [CI], 43.2 to 45.4) with the ChAdOx1-S vaccine and to 66.3% (95% CI, 65.7 to 66.9) with the BNT162b2 vaccine. Waning of vaccine effectiveness was greater in persons 65 years of age or older than in those 40 to 64 years of age. At 20 weeks or more after vaccination, vaccine effectiveness decreased less against both hospitalization, to 80.0% (95% CI, 76.8 to 82.7) with the ChAdOx1-S vaccine and 91.7% (95% CI, 90.2 to 93.0) with the BNT162b2 vaccine, and death, to 84.8% (95% CI, 76.2 to 90.3) and 91.9% (95% CI, 88.5 to 94.3), respectively. Greater waning in vaccine effectiveness against hospitalization was observed in persons 65 years of age or older in a clinically extremely vulnerable group and in persons 40 to 64 years of age with underlying medical conditions than in healthy adults.ConclusionsWe observed limited waning in vaccine effectiveness against Covid-19–related hospitalization and death at 20 weeks or more after vaccination with two doses of the ChAdOx1-S or BNT162b2 vaccine. Waning was greater in older adults and in those in a clinical risk group.

Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response amongst individuals in clinical risk groups

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited.Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs.Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0–80.1%; AstraZeneca 60.0%, 95%CI -63.6–90.2%).Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.

The impact of clinical risk conditions on influenza and pneumonia diagnoses in England: a nationally representative retrospective cohort study, 2010-2019.

The impact of influenza and pneumonia on individuals in clinical risk groups in England has not previously been well characterized. Using nationally representative linked databases (Clinical Practice Research Database (CPRD), Hospital Episode Statistics (HES) and Office for National Statistics (ONS)), we conducted a retrospective cohort study among adults (≥ 18 years) during the 2010/2011-2019/2020 influenza seasons to estimate the incidence of influenza- and pneumonia-diagnosed medical events (general practitioner (GP) diagnoses, hospitalisations and deaths), stratified by age and risk conditions. The study population included a seasonal average of 7.2 million individuals; approximately 32% had ≥1 risk condition, 42% of whom received seasonal influenza vaccines. Medical event incidence rates increased with age, with ~1% of adults aged ≥75 years hospitalized for influenza/pneumonia annually. Among individuals with vs. without risk conditions, GP diagnoses occurred 2-5-fold more frequently and hospitalisations were 7-10-fold more common. Among those with obesity, respiratory, kidney or cardiovascular disorders, hospitalisation were 5-40-fold more common than in individuals with no risk conditions. Though these findings likely underestimate the full burden of influenza, they emphasize the concentration of disease burden in specific age and risk groups and support existing recommendations for influenza vaccination.

Cost-effectiveness analysis of Oncotype DX from a Brazilian private medicine perspective: a GBECAM multicenter retrospective study.

Oncotype DX (ODX) is a validated assay for the prediction of risk of recurrence and benefit of chemotherapy (CT) in both node negative (N0) and 1-3 positive nodes (N1), hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer (eBC). Due to limited access to genomic assays in Brazil, treatment decisions remain largely driven by traditional clinicopathologic risk factors. ODX has been reported to be cost-effective in different health system, but limited data are available considering the reality of middle-income countries such as Brazil. We aim to evaluate the cost-effectiveness of ODX across strata of clinical risk groups using data from a dataset of patients from Brazilian institutions. Clinicopathologic and ODX information were analyzed for patients with T1-T3, N0-N1, HR+/HER2- eBC who had an ODX performed between 2005 and 2020. Projections of CT indication by clinicopathologic criteria were based on binary clinical risk categorization based on the Adjuvant! Algorithm. The ODX score was correlated with the indication of CT according to TAILORx and RxPONDER data. Two decision-tree models were developed. In the first model, low and high clinical risk patients were included while in the second, only high clinical risk patients were included. The cost for ODX and CT was based on the Brazilian private medicine perspective. In all, 645 patients were analyzed; 411 patients (63.7%) had low clinical risk and 234 patients (36.3%) had high clinical risk disease. The ODX indicated low (<11), intermediate (11-25), and high (>25) risk in 119 (18.4%), 415 (64.3%), and 111 (17.2%) patients, respectively. Among 645 patients analyzed in the first model, ODX was effective (5.6% reduction in CT indication) though with an incremental cost of United States Dollar (US$) 2288.87 per patient. Among 234 patients analyzed in the second model (high clinical risk only), ODX led to a 57.7% reduction in CT indication and reduced costs by US$ 4350.66 per patient. Our study suggests that ODX is cost-saving for patients with high clinical risk HR+/HER2- eBC and cost-attractive for the overall population in the Brazilian private medicine perspective. Its incorporation into routine practice should be strongly considered by healthcare providers.

Burden of Diabetic Retinopathy amongst People with Diabetes Attending Primary Care in Kerala: Nayanamritham Project.

Background: The burden of diabetic retinopathy (DR) in people attending the public health sector in India is unclear. Thirty percent of the population in India is reliant on public healthcare. This study aimed to estimate the prevalence of DR and its risk factors in people with diabetes in the non-communicable disease registers who were attending the family health centres (FHCs) in the Thiruvananthapuram district in Kerala. Methods: This cross-sectional study was conducted over 12 months in 2019 within the framework of a pilot district-wide teleophthalmology DR screening programme. The age- and gender-adjusted prevalence of any DR and sight-threatening DR (STDR) in the whole sample, considering socio-demography, lifestyle and known clinical risk groups, are reported. Results: A total of 4527 out of 5307 (85.3%) screened in the FHCs had gradable retinal images in at least one eye. The age and gender standardised prevalence for any DR was 17.4% (95% CI 15.1, 19.7), and STDR was 3.3% (95% CI 2.1, 4.5). Ages 41–70 years, males, longer diabetes duration, hyperglycaemia and hypertension, insulin users and lower socio-economic status were associated with both DR outcomes. Conclusions: The burden of DR and its risk factors in this study highlights the need to implement DR screening programs within primary care to reduce health inequality.

Development and validation of a nomogram for predicting survival in patients with surgically resected lung invasive mucinous adenocarcinoma.

BackgroundLung invasive mucinous adenocarcinoma (LIMA) is a unique and rare subtype of lung adenocarcinoma. We identified prognostic factors and developed a nomogram for predicting overall survival (OS) in LIMA patients after surgery.MethodsPatients diagnosed with LIMA between 2008 and 2016 from the Surveillance, Epidemiology, and End Results (SEER) database were randomized into training (n=1,254) and test (n=538) cohorts. A nomogram was established using the prognostic signature from the training cohort after multivariable Cox regression analysis. We externally validated the nomogram in a group of 369 patients from China. We separately tested for accuracy and clinical practicability using Harrell’s concordance-index (C-index), calibration plots, and decision curve analysis (DCA).ResultsWe included 2,161 patients in the analysis. Seven factors, all of which significantly affected OS, were incorporated into the final model, including age, sex, differentiation grade, the extent of surgery, lymphadenectomy, and T, N, and M stage. C-indexes for the training, test, and external validation cohorts were 0.735, 0.736, and 0.773, respectively. The areas under the time-dependent receiver operating characteristic curves at five years were 0.747, 0.798, and 0.777, respectively. The nomogram was discriminative and well-calibrated when applied to the test and external validation cohorts. Significant between-group differences in OS were observed when classifying groups by nomogram score (log-rank P<0.001). An online web server for clinical use was developed using the nomogram.ConclusionsThe nomogram facilitates accurate prediction of survival for patients with LIMA and can be used to stratify clinical risk groups for individualized treatment.

Abstract 9110: Use of a Genetic Risk Score to Predict Atrial Fibrillation in Patients With Cardiovascular Disease

Background: Early detection of atrial fibrillation (AF) could permit earlier anticoagulation and thus potentially reduce risk of embolic stroke. A validated genetic risk score (GRS) has been shown to predict AF risk but its clinical utility beyond established AF risk factors is unclear. Methods: We performed a prospective cohort analysis in pts w/o prior AF from 4 TIMI trials [SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, FOURIER (TIMI 59)]. Pts were divided into genetic risk quintiles using a validated 1,018 SNP GRS for AF. Clinical risk for AF was also calculated using the validated CHARGE-AF model (age, ht, wt, SBP, DBP, anti-HTN med, DM, CHF, MI, smoking). 3-year KM rates and adjusted HRs were calculated across clinical and genetic risk groups. C-index was used to determine if the addition of GRS improved AF prediction compared with clinical risk and NT-proBNP. Results: In 36,663 pts followed for a median of 2.3 yrs, 1,018 new AF cases (2.8%) were identified. AF GRS predicted a significant risk gradient for AF with a 33% increased risk per 1-SD increase in GRS (HR 1.33 [95%CI 1.26-1.41]; p&lt;0.001). Those in the top quintile of AF GRS were more than 2-fold more likely to develop AF (HR 2.26 [1.84-2.78], p&lt;0.001) compared with the bottom quintile. This risk prediction was on par with age and stronger than any other clinical risk factor. Further, GRS provided an additional gradient of risk stratification on top of the CHARGE-AF clinical risk score, such that pts with high GRS and CHARGE-AF score had an 8.1% 3-year AF risk (Fig) . The C-index for CHARGE-AF was 0.64 (0.63-0.66); addition of NT-proBNP raised the C-index to 0.67 (0.65-0.69), and inclusion of GRS increased it further to 0.69 (0.67-0.71) (p&lt;0.001). Conclusion: In pts with CV disease, AF GRS is a strong independent predictor of incident AF that provides complementary predictive value when added to a validated clinical risk score. AF GRS may be a clinically useful tool to identify very high-risk pts for consideration of AF screening.

Abstract 9061: Aortic Wall Stress Across Risk Groupings of Aortic Size and Height Indices in a Male Veteran Population With Ascending Thoracic Aortic Aneurysm

Introduction: Natural history studies of ascending thoracic aortic aneurysm (aTAA) identified maximum diameter as a predictor of aortic dissection, informing guidelines for prophylactic surgery. Studies have since challenged the biomechanical basis of diameter-based risk assessment. Indices of diameter with measures of body size were proposed to account for individual variation in diameter, including body surface area as aortic size index (ASI) or height as aortic height index (AHI). The goal of this study was to determine differences in aneurysm wall stresses across previously defined clinical risk groups for ASI and AHI. Methods: Height and weight measurements were retrospectively reviewed for 264 male veterans with aTAA. Wall stresses were previously simulated using finite element analyses on patient-specific geometries. Group differences in wall stress were assessed among ASI and AHI risk groups using the Kruskal-Wallis and Dunn tests. Results: Median ± interquartile range circumferential stresses among ASI risk groups were 486.5 ± 132.8, 510.7 ± 140.5, and 617.2 ± 201.6 kPa for groups 1-3 ( P = .19). Longitudinal stresses were 307.3 ± 70.8, 300.8 ± 67.9, and 359.1 ± 57.2 kPa ( P = .09). Among AHI risk groups, circumferential stresses were 476.9 ± 151.4, 503.3 ± 135.4, and 586.2 ± 102.6 kPa for groups 1-3 ( P = .008). Longitudinal stresses were 297.6 ± 80.7, 304.1 ± 64.7, and 361.2 ± 122.9 kPa ( P = .004). For both circumferential and longitudinal stresses, pairwise comparisons were significant between groups 1,3 and 2,3. No observations were classified as group 4 for ASI or AHI. Conclusions: Differences in wall stress were not significant across ASI risk groups and were significant between AHI groups 1,3 and 2,3. While both indices have been shown to stratify clinical outcomes, AHI-based risk groups may better reflect differences in biomechanical state. Prospective studies may further elucidate the relationship between biomechanical status and clinical outcomes.

Diffusion-Weighted Magnetic Resonance Imaging in the Evaluation of Wilms Tumors: Correlation with Histological Data. Pilot Study

The aim of the study is to assess the difference in apparent diffusion coefficient (ADC) values depending on the degrees of malignancy of Wilms’ tumor. The study includes 64 patients with verified Wilms tumor after a course of chemotherapy, before undergoing surgical treatment. The patients were examined using scanners with magnetic field induction of 3.0 and 1,5 T. ADC data collection (mm2/s) was carried out using specialized software. Statistical analysis was performed using the Graphpad Prism software package. Based on the results of this study, average ADC values were obtained for histological types of Wilms’ tumors distributed by clinical risk groups: 0.4 × 10-3 mm2/s — for the low grade of malignancy, 1.1 × 10-3 mm2/s — for the average grade of malignancy and 0.6 × 10-3 mm2/s — for the high grade. In addition, for the average grade of malignancy, the ADC values were divided into groups depending on the cellular composition — 1 ± 0.2 × 10-3 mm2/s — for the regressive and mixed type; 0.9 ± 0.2 × 10-3 mm2/s — for the epithelial type; 1.3 ± 0.4 × 10-3 mm2/s — for the stromal type. Thus, diffusion-weighted MRI can be a useful tool in the initial assessment and differential diagnosis of patients with Wilms tumor.

Identification of Salivary Gland Tumors (SGT) at Risk for Local or Distant Recurrence After Postoperative Radiation Therapy (PORT) With or Without Systemic Therapy (ST) Using Clinical Risk Grouping

To identify risk groups and patterns of recurrence after curative treatment of primary SGT treated with PORT +/- ST.We retrospectively identified consecutive pts with stage I-IVA SGT, excluding adenoid cystic carcinoma (ca), treated with curative-intent surgery and postoperative IMRT with or without radiosensitizing chemotherapy from 12/2008-02/2020 at a tertiary care center. Pts were classified into clinical risk groups based on histologic diagnoses and pathologic features: (1) low-risk = morphologically low grade (LG) tumors (e.g. acinic cell, secretory, LG mucoepidermoid (MEC), epithelial-myoepithelial, basal cell adenocarcinoma), pN0, without lymphovascular invasion (LVI) or perineural invasion (PNI), including minimally invasive/non-invasive carcinoma ex-pleomorphic adenoma (CXPA); (2) intermediate-risk = intermediate grade morphology (e.g. grade 2 MEC) or LG morphology with PNI or LVI or pN+; (3) high-risk = high grade histology (e.g. salivary duct, high-grade MEC, poorly differentiated ca including invasive CXPA). Kaplan Meier estimates were used for recurrence-free survival (RFS) and univariable predictors.72 pts were included. Median age at surgery was 59.6 years [interquartile range (IQR) 49.7,67.7 yrs]. Sites were: 86% parotid (n = 62), 8% submandibular (n = 6), 4% minor salivary (n = 3), and 1% unknown primary. SGT were classified into clinical risk groups: 26% low (n = 19), 25% intermediate (n = 18), and 49% high-risk (n = 35). Concurrent chemotherapy (CRT) was given to 3% of low-risk (n = 1), 13% of intermediate risk (n = 4), and 71% of high-risk pts (n = 25). Regimens included carboplatin + paclitaxel, cisplatin, and concurrent/adjuvant trastuzumab (in 10 pts with HER2-positive SGT). With a median follow-up of 40.5 months, 2-year OS was 95% (85-98%); there were 11 recurrences (9 distant metastasis (DM), 2 in-field local failure (LF) both in pts with gross residual after surgery), with 82% (9 of 11) having received CRT. All recurrences were in the high-risk group with 2-year RFS of 73% (54%-85%) and 2-year cumulative incidence of DM 21% and LF 6%. Factors associated with RFS included positive margins (P = 0.004) and low-neck positive lymph nodes (level III/IV/V vs. level I/II, P = 0.04). Thirteen pts (18%) had targeted genomic sequencing (4 with recurrence); common mutations included TP53 (n = 4), HRAS (n = 3), NFKBIZ (n = 3), and PIK3CA (n = 3). Mutations in NF1 (n = 3) and HNFA1 (n = 2) were observed only in pts that recurred.DM are the primary mode of recurrence in pts with resected SGT treated with PORT +/- ST and occurred only in high-risk pts. After randomized trials like RTOG 1008 determine the added benefit of chemo to PORT, DM is likely to remain an unmet need. Further studies incorporating molecular characterization of high-grade SGT may identify potentially actionable targets to prevent distant recurrence.

Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.

Factorial Analysis Quantifies the Effects of Pediatric Discharge Bundle on Hospital Readmission.

Factorial design of a natural experiment was used to quantify the benefit of individual and combined bundle elements from a 4-element discharge transition bundle (checklist, teach-back, handoff to outpatient providers, and postdischarge phone call) on 30-day readmission rates (RRs). A 24 factorial design matrix of 4 bundle element combinations was developed by using patient data (N = 7725) collected from January 2014 to December 2017 from 4 hospitals. Patients were classified into 3 clinical risk groups (CRGs): no chronic disease (CRG1), single chronic condition (CRG2), and complex chronic condition (CRG3). Estimated main effects of each bundle element and their interactions were evaluated by using Study-It software. Because of variation in subgroup size, important effects from the factorial analysis were determined by using weighted effect estimates. RR in CRG1 was 3.5% (n = 4003), 4.1% in CRG2 (n = 1936), and 17.6% in CRG3 (n = 1786). Across the 3 CRGs, the number of subjects in the factorial groupings ranged from 16 to 674. The single most effective element in reducing RR was the checklist in CRG1 and CRG2 (reducing RR by 1.3% and 3.0%) and teach-back in CRG3 (by 4.7%) The combination of teach-back plus a checklist had the greatest effect on reducing RR in CRG3 by 5.3%. The effect of bundle elements varied across risk groups, indicating that transition needs may vary on the basis of population. The combined use of teach-back plus a checklist had the greatest impact on reducing RR for medically complex patients.

Influenza vaccine uptake among at-risk adults (aged 16\u201364\u2009years) in the UK: a retrospective database analysis

BackgroundIn the UK, annual influenza vaccination is currently recommended for adults aged 16–64 years who are in a clinical at-risk group. Despite recommendations, rates of vaccine uptake in the UK have historically been low and below national and international targets. This study aims to analyse vaccine uptake among adults in clinical at-risk groups from the 2015–2016 influenza season to the present.MethodsA retrospective analysis of influenza vaccine coverage in the UK was conducted using data extracted from publicly available sources. Clinically at-risk individuals (as defined by Public Health England), including pregnant women, aged 16–64 years, were included in this study.ResultsInfluenza vaccination coverage rates across the UK in adults aged 16–64 years in a clinical at-risk group have been consistently low over the past 5 years, with only 48.0, 42.4, 44.1 and 52.4% of eligible patients in England, Scotland, Wales and Northern Ireland receiving their annual influenza vaccination during the 2018–2019 influenza season. Influenza vaccine coverage was lowest in patients with morbid obesity and highest in patients with diabetes in 2018–2019. Coverage rates were below current national ambitions of ≥75% in all clinical risk groups. In these clinical at-risk groups, influenza vaccine coverage decreased between 2015 and 2019, and there was considerable regional variation.ConclusionsUptake of the influenza vaccine by adults aged 16–64 years in a clinical at-risk group was substantially below the national ambitions. As a result, many individuals in the UK remain at high risk of developing severe influenza or complications. Given that people who are vulnerable to COVID-19 are also at increased risk of complications from influenza, during the 2020–2021 season, there is a heightened need for healthcare professionals across the UK to address suboptimal vaccine uptake, particularly in at-risk patients. Healthcare professionals and policymakers should consider measures targeted at increasing access to and awareness of the clinical benefits of the influenza vaccine.

Effects of different molecular subtypes and tumor biology on the prognosis of medulloblastoma.

Medulloblastoma is one ofthe most common malignant brain tumors in the pediatric population. Recent studies identified four distinct medulloblastoma subgroups with different molecular alterations and pathways, and natural courses and outcomes. To evaluate the results of surgical and medical treatments of patients with medulloblastoma and compare them among the medulloblastoma subgroups. The clinical and radiological features, medical and surgical management and treatment outcomes and their correlation with molecular subgroups of 58 patients treated for medulloblastoma in the last 20years were evaluated. Fifty-eight patients, of whom 35 were male and 23 were female, were evaluated. The median age was 6years (range, 1-19years). The most common symptoms were nausea and vomiting (60%). Forty-three percent of the patients had headache and 40% had ataxia. Previous pathology reports revealed that 43 (74%), eight (14%), five (8%), and two (3%) had classic, desmoplastic, desmoplastic/nodular, and anaplastic morphologies, respectively. After the subgroup analyses, five patients (12%) were attributed to the wingless subgroup (WNT) group; 14 (32.5%), to the sonic hedgehog subgroup (SHH) group; and 24 (56%), to the non-WNT non-SHH group. On the basis of immunohistochemical analysis results, 15 patients could not be attributed to any subgroups. The clinical risk groups (average vs high-risk) and age at diagnosis (≥ 3years vs < 3years of age) were significant for 5-year event free survival (86% vs 43%, p:0.011 and 59% vs 36%, p:0.039). There was no significant difference in survival or event free survival according to molecular subtypes in this cohort. In corporation of molecular features to the clinicopathologic classification leads to risk-adapted treatment. Although the molecular subgroups did not affect outcome significantly in this study, more studies with larger numbers of patients are needed to understand the tumor pathophysiology of medulloblastoma and design the future medical practice.