Risk Strata Research Articles

986-P: Evaluation of Cardiovascular Risk and All-Cause Mortality in Type 1 Diabetes: Comparison of Risk Engines in a 10-Year Follow-up

Type 1 diabetes (T1D) has higher risk of death and CVD compared with general population. Effective risk stratification is essential to implement preventive strategies. We compare the performance of Steno Type 1 Risk Engine (ST1RE) and EURODIAB PCS Risk Engine (EURO-RE) in 733 T1D (M 52%; age 39.3±11.1; DD 18.5±11.6; A1c 7.8±1.2%) with no prior CVD over a 11-yr follow-up (IQR: 9.9-13.0). Both models include age, A1c and albuminuria; ST1RE includes 7 more variables (sex, DD, SBP, LDL-C, eGFR, smoking and exercise), EURO-RE only 2 more variables (WHR, HDL-C). By ST1RE, 453 T1D (61.8%) had low- (<10%), 179 (24.4%) moderate- (10-20%) and 101 (13.8%) high-risk (≥20%); for EURO-RE, estimates were 496 (67.7%), 161 (22.0%) and 76 (10.4%). Regression between 10-yr risks was 0.921 (p<0.0001); concordance of risk strata attribution was 82.5% (n = 605); 98 (13.4%); 30 (4.1%) T1D had higher and, respectively, lower risk by ST1RE vs. EURO-RE. C-statistic for all-cause death (n = 46) was 0.810 (95% CI 0.738-0.882) for ST1RE and 0.802 (0.729-0.875) for EURO-RE. Incidence of CVD was available for 697 T1D (95%). C-statistics for all CVD (n = 32) were 0.770 (0.699-0.841) and 0.777 (0.706-0.849) for ST1RE and EURO-RE, respectively; for coronary events (n = 23) 0.739 (0.650-0.828) and 0.765 (0.683-0.847); for coronary revascularization (n = 14) 0.802 (0.707-0.897) and 0.824 (0.742-0.905). With the limitation of low number of events, C-statistics for stroke (n = 8) were 0.764 (0.596-0.931) and 0.805 (0.654-0.955) for ST1RE and EURO-RE; for peripheral disease (n = 5) 0.794 (0.658-0.931) and 0.733 (0.518-0.948); for ESRD (n = 8) 0.719 (0.544-0.893) and 0.723 (0.529-0.917). Cox regression with backward variable processing selects EURO-RE as covariate for CVD and all other vascular events including ESRD, with ST1RE selected as the strongest covariate for all-cause death. Both ST1RE and the less-demanding EURO-RE are validated and widely available tools to identify high risk T1D individuals. Disclosure M. Garofolo: Consultant; Self; Eli Lilly and Company. E. Gualdani: None. D. Lucchesi: None. P. Falcetta: None. P. Francesconi: None. S. Del prato: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Speaker’s Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Sanofi. G. Penno: Advisory Panel; Self; Eli Lilly and Company.

Clarifying the Trade-Offs of Risk-Stratified Screening for Prostate Cancer: A Cost-Effectiveness Study.

Cancer risk prediction is necessary for precision early detection, which matches screening intensity to risk. However, practical steps for translating risk predictions to risk-stratified screening policies are not well established. We used a validated population prostate-cancer model to simulate the outcomes of strategies that increase intensity for men at high risk and reduce intensity for men at low risk. We defined risk by the Prompt Prostate Genetic Score (PGS) (Stratify Genomics, San Diego, California), a germline genetic test. We first recalibrated the model to reflect the disease incidence observed within risk strata using data from a large prevention trial where some participants were tested with Prompt PGS. We then simulated risk-stratified strategies in a population with the same risk distribution as the trial and evaluated the cost-effectiveness of risk-stratified screening versus universal (risk-agnostic) screening. Prompt PGS risk-adapted screening was more cost-effective when universal screening was conservative. Risk-stratified strategies improved outcomes at a cost of less than $100,000 per quality-adjusted life year compared with biennial screening starting at age 55 years, but risk stratification was not cost-effective compared with biennial screening starting at age 45. Heterogeneity of risk and fraction of the population within each stratum were also important determinants of cost-effectiveness.

The national impact of the COVID-19 pandemic on U.S. prostate cancer community care.

5061 Background: We used data from a specialty-wide, community-based urology registry to determine trends in outpatient prostate cancer (PCa) care during the COVID-19 pandemic. Methods: 3,165 (̃ 25%) of US urology providers, representing 48 states and territories, participate in the American Urological Association Quality (AQUA) Registry, which collects data via automated extraction from electronic health record systems. We analyzed trends in PCa care delivery from 156 practices contributing data in 2019 and 2020. Risk stratification was based on prostate-specific antigen (PSA) at diagnosis, biopsy Gleason, and clinical T-stage, and we used a natural language processing algorithm to determine Gleason and T-stage from unstructured clinical notes. The primary outcome was mean weekly visit volume by PCa patients per practice (visits defined as all MD and mid-level visits, telehealth and face-to-face), and we compared each week in 2020 through week 44 (November 1) to the corresponding week in 2019. Results: There were 267,691 PCa patients in AQUA who received care between 2019 and 2020. From mid-March to early November, 2020 (week 10 – week 44) the magnitude of the decline and recovery varied by risk stratum, with the steepest drops for low-risk PCa (Table). For 2020, overall mean visits per day (averaged weekly) were similar to 2019 for the first 9 weeks (̃25). Visits declined to week 14 (18.19; a 31% drop from 2019), recovered to 2019 levels by week 23, and declined steadily to 11.89 (a 58% drop from 2019) as of week 44, the cut off of this analysis. Conclusions: Access to care for men with PCa was sharply curtailed by the COVID-19 pandemic, and while the impact was less for men with high-risk disease compared to those with low-risk disease, visits even for high-risk individuals were down nearly one-third and continued to fall through November. This study provides real-world evidence on the magnitude of decline in PCa care across risk groups. The impact of this decline on cancer outcomes should be followed closely.[Table: see text]

Laboratory Reporting Parameters of Microhematuria: Implications for Interpreting the 2020 AUA Guideline

ObjectiveTo explore how laboratories in the United States (U.S.) report red blood cell per high powered field (RBC/HPF) counts on urinalysis and to evaluate whether this methodology permits effective risk stratification in accordance with the 2020 AUA/SUFU microhematuria guidelines. Materials and MethodsReporting methods for RBC/HPF counts (ranges, or actual counts) were collected by querying urologists in U.S. academic medical institutions or commercial laboratories. We explore whether (1) the reporting schemes were concordant with the risk strata in the new microhematuria guideline (3-10 [low risk], 11-25 [intermediate risk], and more than 25 [high risk]), and (2) evaluate the potential for risk group misclassification based on reporting methodology. ResultsData were available for 141 laboratories. Seventy-two (51%) use RBC/HPF ranges, while the remainder use actual counts (or counts to a threshold). Sixty (42%) report range cutoffs which are not concordant with the microhematuria guidelines risk groups. Furthermore, fifty-six (40%) do not include the cutoff of 25 RBC/HPF which could potentially misclassify intermediate and high risk groups. Finally, sixteen (11%) do not include the cut-off of 3 RBC/HPF that defines the presence of microhematuria. ConclusionA significant number of laboratories report RBC/HPF counts in ranges that differ from thresholds in the 2020 AUA/SUFU guideline. The implication is potential misclassification of microhematuria both at minimum threshold diagnosis (3 RBC/HPF), and additionally between intermediate and high risk groups. Standardization of reporting schemes to actual RBC/HPF counts may allow improved adherence to guidelines while providing data for future guideline development.

Risk prediction in medically treated chronic thromboembolic pulmonary hypertension

BackgroundAt present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients.MethodsConsecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance.ResultsA total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score).ConclusionsA novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients.Trial registration: ClinicalTrials.gov (Identifier: NCT01417338).

Urinary-based tumor markers enhance microhematuria risk stratification according to baseline bladder cancer prevalence

IntroductionThe 2020 AUA microhematuria (MH) guideline stratifies patients into low, intermediate and high-risk for urologic malignancy based on established risk-factors for urothelial carcinoma. Notably, urine-based tumor markers (UBTMs) were not included in the risk classification. We evaluated the impact of incorporating UBTMs (cytology and multiple commercially available UBTMs) into this risk stratification. MethodsWe performed a systematic review of performance characteristics of UBTMs for the detection of bladder cancer during hematuria evaluation, pooled the reported sensitivity and specificity, and calculated positive and negative likelihood ratios (LR). These were then applied to the estimated pre-test probability for the diagnosis for each AUA risk strata: low-risk 0.5%, intermediate-risk 1.0%, and high-risk (2%-3%) in order to calculate a post-test probability of bladder cancer in the event of a positive or negative test. ResultsThe pooled sensitivity for urinary cytology and commercially available UBTMs was 68% and 58%-95%, respectively while the specificity was estimated at 91% and 34%-90%, respectively. The positive LRs of UBTMs ranged from 2.1-7.67 and negative LRs ranged from 0.07-0.48. A negative UBTM was associated with a post-test probability of cancer for low, intermediate, and high-risk patients of 0-0.2%, 0.2%-0.5%, and 0.4%-1.1%, respectively. In the setting of a positive UBTM, the post-test probability of cancer for low, intermediate, and high-risk patients was 1.1%-3.7%, 2.1%-7.8%, 4.2%-19.2%, respectively. ConclusionPending prospective validation, UBTMs may be able to enhance risk stratification and inform shared decision-making over clinical factors alone and allow for re-classification of patients into higher or lower risk categories.

An assessment of intervention thresholds for very high fracture risk applied to the NOGG guidelines

The National Osteoporosis Guideline Group (NOGG) has developed intervention thresholds based on FRAX® to characterise patients at high and very high risk of fracture.Guidelines for the assessment of fracture risk have begun to categorise patients eligible for treatment into high and very high risk of fracture to inform choice of therapeutic approach. The aim of the present study was to develop intervention thresholds based on the hybrid assessment model of NOGG.We examined the impact of intervention thresholds in a simulated cross-sectional cohort of women age 50 years or more from the UK with the distribution of baseline characteristics based on that in the FRAX cohorts. The prevalence of very high risk using the hybrid model was compared with age-dependent thresholds used by the International Osteoporosis Foundation and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (IOF/ESCEO). The appropriateness of thresholds was tested based on the populations treated with anabolic agents.With an upper intervention threshold using the IOF/ESCEO criteria, 56% of women age 50 years or more would be characterised at very high risk. This compares with 36% using the IOF/ESCEO criteria and an age-specific intervention threshold over all ages. With an upper intervention threshold of 1.6 times the pre-existing intervention threshold, 10% of women age 50 years or more would be characterised at very high risk. The data from phase 3 studies indicate that most trial participants exposed to romosozumab or teriparatide would fall into the very high-risk category.Proposals for FRAX-based criteria for very high risk for the NOGG hybrid model categorise a small proportion of women age 50 years or more (10%) in this highest risk stratum. The level of risk identified was comparable to that of women enrolled in trials of anabolic agents.

POS-223 Clinical Utility of KidneyIntelX in Patients with Early Stages of Diabetic Kidney Disease in CANVAS Participants

Prediction of progression during early stages of diabetic kidney disease (DKD) and determination of those most likely to derive benefits from therapies a priori is challenging. KidneyIntelX is a new test that incorporates clinical data and three plasma biomarkers using machine learning into a composite risk score for DKD progression that has yet to be applied to a clinical trial cohort. We performed a post-hoc analysis of CANVAS Study participants with diabetes and prevalent DKD (defined by estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 or UACR > 30 mg/g at enrollment). Three circulating biomarkers in plasma, soluble Tumor Necrosis Factor Receptor 1 (sTNFR-1), soluble Tumor Necrosis Factor Receptor 2 (sTNFR-2), and Kidney Injury Molecule (KIM)-1, were measured with proprietary multiplex assays. We calculated chronic eGFR slope from 6 weeks in the canagliflozin arm and from baseline in the placebo arm and compared the proportion of individuals experiencing the composite kidney outcome of estimated glomerular filtration rate (eGFR) decline of ≥5 ml/min/year, ≥40% sustained decline in eGFR, or kidney failure within 5 years in CANVAS participants stratified by KidneyIntelX risk categories based on the existing model vs. the KDIGO risk strata. We also assessed clinical response to canagliflozin vs. placebo within KidneyIntelX and KDIGO risk strata. We included 1325 (31% of original cohort of 4330) CANVAS participants with prevalent DKD and available baseline plasma samples (mean age 64 years, 32% female, mean eGFR 65 mL/min/1.73 m2, median uACR 56 mg/g). During a mean follow-up of 5.6 years, 131 (9.9%) of this subgroup with baseline DKD experienced the composite kidney outcome. KDIGO categorization based on eGFR and uACR stratified 69%, 23% and 8% of the DKD population into “moderately increased risk,” “high risk,” and “very high risk,” with event rates of 7%, 17%, and 18% (relative risk [RR] of 2.3, 95% CI 1.3-4.2 for the “very high risk” vs. “moderately high risk” in the treatment arm and RR of 3.4, 95% CI 1.5-7.5 in the placebo arm). Using risk cutoffs from prior validation studies, KidneyIntelX stratified patients to low (40%), intermediate (45%), and high risk (15%) strata with event rates of 3%, 10%, and 26% (RR of 6.0 , 95% CI 3.2-11.3 for the high vs. low risk groups in the treatment arm and RR 15.2, 95% CI 4.8-37.8 in the placebo arm) (Figure). The treatment effects of canagliflozin vs. placebo varied by baseline strata of KidneyIntelX. In the low risk stratum, the RR was 1.65 (95% CI 0.54-5.08), in the intermediate stratum the RR was 0.59 (95% CI 0.36-0.98), and in the high-risk stratum the RR was 0.67 (95% CI 0.38-1.18). In the high-risk stratum, the absolute risk reduction (ARR) for canagliflozin vs. placebo for the composite kidney outcome was 8% vs. an ARR of 2.6% in the overall DKD population. KidneyIntelX successfully risk-stratified a large multi-national external cohort for risk of progression of DKD, with larger differences in observed events across KidneyIntelX risk strata compared to KDIGO risk strata. Moreover, individuals scored as high risk by KidneyIntelX have the potential to achieve greater absolute risk reductions for the outcome with canagliflozin treatment compared to non-stratified DKD participants.

Analysis of Risk Assessment Tools in the REPLACE Study

Purpose The REPLACE study showed that switching to riociguat (rio) can benefit pulmonary arterial hypertension (PAH) patients treated with phosphodiesterase type 5 inhibitors (PDE5i) but still at intermediate risk. Improvements to lower risk status with rio versus PDE5i were seen with all three risk assessment tools analyzed, although the difference was not statistically significant with the modified REVEAL risk score (mRRS). Here, we report changes in the components of the mRRS, COMPERA, and FPHN non-invasive risk assessment tools, and a post hoc analysis of RRS Lite 2 in REPLACE. Methods Individual components of mRRS, COMPERA, and FPHN non-invasive assessment tools, and RRS Lite 2 risk scores and risk strata were calculated for the rio group (n=111) and PDE5i group (n=113) at REPLACE baseline and Week 24. WHO/NYHA functional class (FC), 6MWD, and NT-proBNP were components of all risk scores. Vital signs (systolic blood pressure [SBP] and heart rate [HR]) and renal insufficiency were additional components for mRRS and RRS Lite 2. PAH etiology and demographics were also components of mRRS. Results For mRRS, COMPERA, and FPHN, 44% of patients in the rio group vs 23% in the PDE5i group improved their WHO/NYHA FC component score at Week 24. Similar results were found for the 6MWD component (1 point removed from mRRS: rio 41% vs PDE5i 27%; COMPERA grade 1/FPHN low risk at Week 24: rio 37% vs PDE5i 27%). The incidences of lowest-risk NT-proBNP component scores at Week 24 were rio 41% vs PDE5i 40% for mRRS, rio 21% vs PDE5i 12% for COMPERA, and rio 41% vs PDE5i 40% for FPHN. At baseline, mRRS vital sign scores were similar between the two groups. At Week 24, more patients in the rio group (50%) versus the PDE5i group (36%) had 1−2 points added to their mRRS score due to SBP 96 bpm. The overall result was similar for the mRRS and the RRS Lite 2. With RRS Lite 2, the proportion of patients achieving a low-risk stratum from baseline to Week 24 was 41% to 61% for rio and 37% to 50% for PDE5i. Conclusion Risk assessment tools showed similar trends in shared components between treatment groups at baseline and Week 24. Results with RRS Lite 2 were similar to mRRS. Differences in discrimination of the risk sores, weighting of components, and differences in the vital signs component of mRRS could explain between score differences at baseline and Week 24 in REPLACE. SBP and HR will be individually analyzed in future.

Application of the REVEAL risk score calculator 2.0 in the PATENT study

BackgroundRegular risk assessment is recommended in pulmonary arterial hypertension (PAH) management to improve patient outcomes. The REVEAL risk score (RRS) predicts survival in patients with PAH, including those from the PATENT study, which assessed riociguat, a soluble guanylate cyclase stimulator approved for PAH treatment. An updated version, RRS 2.0, has been developed to further refine risk prediction. MethodsThis post hoc analysis of PATENT-1 and its open-label extension PATENT-2 (n = 396) assessed RRS 2.0 score and risk stratum and their association with survival and clinical worsening-free survival (CWFS). ResultsAt PATENT-1 Week 12, riociguat improved RRS 2.0 versus placebo (least-squares mean difference versus placebo: −1.0 [95% confidence interval − 1.4 to −0.6; p < 0.0001]) and more patients improved risk stratum with riociguat (57%) versus placebo (42%). These improvements were maintained at PATENT-2 Week 12. RRS 2.0 score and risk strata at PATENT-1 baseline and Week 12 were significantly associated with survival and CWFS in PATENT-2 (p < 0.0001); change in RRS 2.0 score from PATENT-1 baseline to Week 12 was also significantly associated with outcomes. ConclusionsThese data suggest that RRS 2.0 has clinical utility in predicting long-term outcomes and monitoring treatment response in patients with PAH.

Malaria risk stratification in Colombia 2010 to 2019.

BackgroundHeterogeneity and focalization are the most common epidemiological characteristics of endemic countries in the Americas, where malaria transmission is moderate and low. During malaria elimination, the first step is to perform a risk stratification exercise to prioritize interventions. This study aimed to identify malaria risk strata in the ecoepidemiological regions of Colombia.MethodsThis was a descriptive and retrospective study using cumulative malaria cases in 1,122 municipalities of Colombia from 2010 to 2019. To identify the strata, the criteria proposed by PAHO were adapted. To classify the receptive areas (strata 2, 3, and 4) and nonreceptive areas (stratum 1), 1,600 m above sea level, ecotypes, main malaria vector presence, Plasmodium species prevalence and occurrence of malaria cases were used. The area occupied by the receptive municipalities, the cumulative burden, and the at-risk population in the regions were calculated.ResultsNinety-one percent of the Colombian territory is receptive to the transmission of malaria and includes 749 municipalities with 9,734,271 (9,514,243–9,954,299) million at-risk inhabitants. Stratum 4 accounted for 96.7% of the malaria burden, and cases were concentrated primarily in the Pacific and Uraba-Bajo Cauca-Sinu-San Jorge regions. Plasmodium vivax predominates in most of the receptive municipalities, except in the municipalities of the Pacific region, where P. falciparum predominates. Anopheles albimanus, An. nuneztovari s.l., and An. darlingi were the main vectors in receptive areas.ConclusionsIn Colombia, 91.2% of the territory is receptive to the transmission of malaria and is characterized by being both heterogeneous and focused. Stratum 4 contains the greatest burden of disease, with a relatively greater proportion of municipalities with a predominance of P. vivax. However, there is a low proportion of municipalities with P. falciparum mainly in the Pacific region. These findings suggest that the latter be prioritized within the malaria elimination plan in Colombia.

Patient Risk Subgroups Predict Benefit of Adjuvant Chemotherapy in Stage II Rectal Cancer Patients Following Neoadjuvant Chemoradiation and Total Mesorectal Excision

BackgroundThe benefit of adjuvant chemotherapy (AC) is unclear in stage II (cT3-T4 N0) rectal adenocarcinoma (RAC) after neoadjuvant chemoradiation (NCRT) and total mesorectal excision (TME). We aim to identify pathologic factors that influence overall survival (OS) and stratify patients into risk profiles to assess the AC benefit within each profile. Patients and MethodsThe National Cancer Database for rectal cancer was utilized to identify patients with stage II RAC who completed NCRT and TME. Cox multivariable analysis was used to identify pathologic predictors of 5-year OS, which were then used to construct a nomogram and stratify patients into low-, intermediate-, and high-risk subgroups. Propensity score matching was applied for the receipt of AC within each risk stratum, and Kaplan–Meier analysis was used to measure 5-year OS. ResultsWe identified 3570 patients who met the inclusion criteria. Inadequate lymphadenectomy (<12), poor differentiation, involved distal margin, involved circumferential margin, perineural invasion, and absence of T-downstaging after NCRT were identified as unfavorable predictors of 5-year OS and were used to construct the nomogram. Kaplan–Meier analysis of the matched patients demonstrated the absolute 5-year survival benefits for each risk stratum as follows: 4% for low-risk patients (hazard ratio (HR) = 0.869; [0.651-1.021]; P = .062), 26% for intermediate-risk patients (HR, 0.249; [0.133-0.468]; P < .001), and 10% in high-risk patients (HR = 0.633 [0.427-0.940]; P = .024). ConclusionsThe survival benefit of AC for clinical stage II RAC following NCRT and TME is most pronounced among intermediate- and high-risk patients as determined by our nomogram. Risk-adaptive AC may be appropriate for selected patients by integrating standard reported pathologic elements into the treatment plan.

Risk Factors Associated With Transition From Acute to Chronic Low Back Pain in US Patients Seeking Primary Care

Acute low back pain (LBP) is highly prevalent, with a presumed favorable prognosis; however, once chronic, LBP becomes a disabling and expensive condition. Acute to chronic LBP transition rates vary widely owing to absence of standardized operational definitions, and it is unknown whether a standardized prognostic tool (ie, Subgroups for Targeted Treatment Back tool [SBT]) can estimate this transition or whether early non-guideline concordant treatment is associated with the transition to chronic LBP. To assess the associations between the transition from acute to chronic LBP with SBT risk strata; demographic, clinical, and practice characteristics; and guideline nonconcordant processes of care. This inception cohort study was conducted alongside a multisite, pragmatic cluster randomized trial. Adult patients with acute LBP stratified by SBT risk were enrolled in 77 primary care practices in 4 regions across the United States between May 2016 and June 2018 and followed up for 6 months, with final follow-up completed by March 2019. Data analysis was conducted from January to March 2020. SBT risk strata and early LBP guideline nonconcordant processes of care (eg, receipt of opioids, imaging, and subspecialty referral). Transition from acute to chronic LBP at 6 months using the National Institutes of Health Task Force on Research Standards consensus definition of chronic LBP. Patient demographic characteristics, clinical factors, and LBP process of care were obtained via electronic medical records. Overall, 5233 patients with acute LBP (3029 [58%] women; 4353 [83%] White individuals; mean [SD] age 50.6 [16.9] years; 1788 [34%] low risk; 2152 [41%] medium risk; and 1293 [25%] high risk) were included. Overall transition rate to chronic LBP at six months was 32% (1666 patients). In a multivariable model, SBT risk stratum was positively associated with transition to chronic LBP (eg, high-risk vs low-risk groups: adjusted odds ratio [aOR], 2.45; 95% CI, 2.00-2.98; P < .001). Patient and clinical characteristics associated with transition to chronic LBP included obesity (aOR, 1.52; 95% CI, 1.28-1.80; P < .001); smoking (aOR, 1.56; 95% CI, 1.29-1.89; P < .001); severe and very severe baseline disability (aOR, 1.82; 95% CI, 1.48-2.24; P < .001 and aOR, 2.08; 95% CI, 1.60-2.68; P < .001, respectively) and diagnosed depression/anxiety (aOR, 1.66; 95% CI, 1.28-2.15; P < .001). After controlling for all other variables, patients exposed to 1, 2, or 3 nonconcordant processes of care within the first 21 days were 1.39 (95% CI, 1.21-2.32), 1.88 (95% CI, 1.53-2.32), and 2.16 (95% CI, 1.10-4.25) times more likely to develop chronic LBP compared with those with no exposure (P < .001). In this cohort study, the transition rate to chronic LBP was substantial and increased correspondingly with SBT stratum and early exposure to guideline nonconcordant care.

COVID-19 incidence and mortality in Nigeria: gender based analysis.

BackgroundCoronavirus Disease 2019 (COVID-19) has been surging globally. Risk strata in medical attention are of dynamic significance for apposite assessment and supply distribution. Presently, no known cultured contrivance is available to fill this gap of this pandemic. The aim of this study is to develop a predictive model based on vector autoregressive moving average (VARMA) model of various orders for gender based daily COVID-19 incidence in Nigeria. This study also aims to proffer empirical evidence that compares incidence between male and female for COVID-19 risk factors.MethodsWilcoxon signed-rank test is employed to investigate the significance of the difference in the gender distributions of the daily incidence. A VARMA model of various orders is formulated for the gender based daily COVID-19 incidence in Nigeria. The optimal VARMA model is identified using Bayesian information criterion. Also, a predictive model based on univariate autoregressive moving average model is formulated for the daily death cases in Nigeria. Fold change is estimated based on crude case-fatality risk to investigate whether there is massive underreporting and under-testing of COVID-19 cases in Nigeria.ResultsDaily incidence is higher in males on most days from 11 April 2020 to 12 September 2020. Result of Wilcoxon signed-rank test shows that incidence among male is significantly higher than female (p-value < 2.22 × 10−16). White neural network test shows that daily female incidence is not linear in mean (p-value = 0.00058746) while daily male incidence is linear in mean (p-value = 0.4257). McLeod-Li test shows that there is autoregressive conditional heteroscedasticity in the female incidence (Maximum p-value = 1.4277 × 10−5) and male incidence (Maximum p-value = 9.0816 × 10−14) at 5% level of significance. Ljung-Box test (Tsay, 2014) shows that the daily incidence cases are not random (p-value=0.0000). The optimal VARMA model for male and female daily incidence is VARMA (0,1). The optimal model for the Nigeria’s daily COVID-19 death cases is identified to be ARIMA (0,1,1). There is no evidence of massive underreporting and under-testing of COVID-19 cases in Nigeria.ConclusionsComparison of the observed incidence with fitted data by gender shows that the optimal VARMA and ARIMA models fit the data well. Findings highlight the significant roles of gender on daily COVID-19 incidence in Nigeria.

Machine-learning analysis of contrast-enhanced computed tomography radiomics predicts patients with hepatocellular carcinoma who are unsuitable for initial transarterial chemoembolization monotherapy: A multicenter study

IntroductionDue to the high heterogeneity of hepatocellular carcinoma (HCC), patients with non-advanced disease who are unsuitable for initial transarterial chemoembolization (TACE) monotherapy may have the potential to develop extrahepatic spread or vascular invasion. We aimed to develop and independently validate a radiomics-based model for predicting which patients will develop extrahepatic spread or vascular invasion after initial TACE monotherapy (EVIT). Materials and methodsThis retrospective study included 256 HCC patients (training set: n = 136; testing set: n = 120) who underwent TACE as initial therapy between April 2007 and June 2018. Clinicoradiological predictors were selected using multivariate logistic regression and a clinicoradiological model was constructed. The radiomic features were extracted from contrast-enhanced computed tomography (CT) images and a radiomics signature was constructed based on a machine learning algorithm. A combined model integrated clinicoradiological predictor and radiomics signature was developed. The predictive performance of the two models was evaluated and compared based on its discrimination, calibration, and clinical usefulness. ResultsIn the training set, 34 (25.0%) patients were confirmed to have EVIT, whereas 26 (21.7%) patients in the testing set had EVIT. When the radiomics signature was added, the combined model showed improved discrimination performance compared to the clinicoradiological model (area under the curves [AUCs] 0.911 vs. 0.772 in the training set; AUCs 0.847 vs. 0.746 in the testing set) and could divide HCC patients into three strata of low, intermediate, or high risk in the two sets. Decision curve analysis demonstrated that the two models were clinically useful, and the combined model provided greater benefits for discriminating patients than the clinicoradiological model. ConclusionsThis study presents a model that integrates clinicoradiological predictors and CT-based radiomics signature that could provide a preoperative individualized prediction of EVIT in patients with HCC.

816 Comparative analysis of obstetric hemorrhage risk prediction tools

Hemorrhage risk prediction tools were developed in response to rising rates of obstetric hemorrhage (OBH). The California Maternal Quality Care Collaborative (CMQCC) risk prediction tool classifies patients as low, medium, and high risk for OBH. At our institution, a unique OBH risk predictor tool was derived from the CMQCC tool by adding a weighted value to individual risk factors. Our objective is to compare an enhanced institution-specific (IS) OBH risk prediction tool to the CMQCC OBH risk prediction tool. Retrospective cohort of delivery admissions from 2018 to 2019 at our institution. Admission OBH risk scores were assigned to each patient using both the IS and CMQCC score. Cohen’s Kappa estimated agreement. Scoring systems and maternal outcomes were compared using Chi-square test. Composite morbidity included transfusion, hysterectomy, uterine artery embolization, and ICU admission. 25,957 delivery admissions were included. A moderate association was observed between scoring systems (Kappa 0.41, p<0.001). The IS score categorized patients as low (60%), medium (37%), and high (3%) risk. The CMQCC score categorized patients as low (74%), medium (22%), and high (4%) risk. Both the IS score and the CMQCC score were able to differentiate OBH related morbidity across risk strata (Table 1). The IS score re-categorized CMQCC low risk patients to a higher risk stratum 26% of the time. CMQCC high risk patients were re-categorized to a lower risk stratum 86% of the time. The IS score independently predicted risk of composite OBH related morbidity within each stratum of the CMQCC score (Table 2). Notably, a composite event occurred in 11.6% of women with a low CMQCC and high IS score compared to 1.1% with both a low CMQCC and IS score. Both the IS and CMQCC score independently distinguish risk of composite morbidity and are valid predictors of OBH. Adding weighted values to individual risk factors further discriminates risk of morbidity. This suggests it may be reasonable to adapt the CMQCC’s score to more effectively reflect institutional populations and resources.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease

Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).

Risk Prediction Models and Scores in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) has historically been linked with sudden cardiac death (SCD). Currently, it is well established that only a subset of patients is at the highest risk stratum for such a catastrophic event. Detection of patients belonging to this high-risk category can allow for timely defibrillator implantation, changing the natural history of HCM. Inversely, device implantation in patients deemed at low risk leads to an unnecessary burden of device complications with no apparent protective benefit. Previous studies have identified a series of markers, now considered established risk factors, with genetic testing and newer imaging allowing for the detection of novel, highly promising indices of increased risk for SCD. Despite the identification of a number of risk factors, there is noticeable discrepancy in the utility of such factors for risk stratification between the current American and European guidelines. We sought to systematically review the data available on these two approaches, presenting their rationale and respective predictive capacity, also discussing the potential of novel markers to augment the precision of currently used risk stratification models for SCD in HCM.

Association of Race/Ethnicity and the 21-Gene Recurrence Score With Breast Cancer–Specific Mortality Among US Women

Given the widespread use of the 21-gene recurrence score for identifying candidates for adjuvant chemotherapy, it is important to examine the performance of the Oncotype DX Breast Recurrence Score test in diverse patient populations to validate this approach for tailoring treatment in women in racial/ethnic minority groups. To examine whether breast cancer-specific mortality for women with hormone-dependent breast cancer differs by race/ethnicity across risk categories defined by the Oncotype DX Breast Recurrence Score test and whether the prognostic accuracy of the 21-gene recurrence score differs by race/ethnicity. This retrospective, population-based cohort study used the Surveillance, Epidemiology, and End Results Oncotype DX 2004-2015 database to obtain breast cancer-specific survival data on US women 18 years and older who were diagnosed with first primary stage I to III, estrogen receptor-positive breast cancer between January 1, 2004, and December 31, 2015, and had tumor testing through the Genomic Health Clinical Laboratory. Data were analyzed from April 20 to September 27, 2020. The primary outcome was breast cancer-specific mortality among women from different racial/ethnic groups stratified by the 21-gene recurrence score risk categories. Secondary analyses compared the prognostic accuracy of the recurrence score among the different racial/ethnic groups. A total of 86 033 patients with breast cancer (mean [SD] age, 57.6 [10.6] years) with Oncotype DX Breast Recurrence Score test information were available for the analysis, including 64 069 non-Hispanic White women (74.4%), 6719 non-Hispanic Black women (7.8%), 7944 Hispanic women (9.2%), 6950 Asian/Pacific Islander women (8.0%), and 351 American Indian/Alaska Native women (0.4%). Black women were significantly more likely than non-Hispanic White women to have a recurrence score greater than 25 (17.7% vs 13.7%; P < .001). Among women with axillary node-negative tumors, competing risk models adjusted for age, tumor characteristics, and treatment found higher breast cancer-specific mortality for Black compared with non-Hispanic White women within each recurrence score risk stratum, with subdistribution hazard ratios of 2.54 (95% CI, 1.44-4.50) for Black women with recurrence scores of 0 to 10, 1.64 (95% CI, 1.23-2.18) for Black women with recurrence scores of 11 to 25, and 1.48 (95% CI, 1.10-1.98) for Black women with scores greater than 25. The prognostic accuracy of the recurrence score was significantly lower for Black women, with a C index of 0.656 (95% CI, 0.592-0.720) compared with 0.700 (95% CI, 0.677-0.722) (P = .002) for non-Hispanic Whites. In this cohort study, Black women in the US were more likely to have a high-risk recurrence score and to die of axillary node-negative breast cancer compared with non-Hispanic White women with comparable recurrence scores. The Oncotype DX Breast Recurrence Score test has lower prognostic accuracy in Black women, suggesting that genomic assays used to identify candidates for adjuvant chemotherapy may require model calibration in populations with greater racial/ethnic diversity.

Cardiovascular preventive pharmacotherapy stratified by predicted cardiovascular risk: a national data linkage study.

Cardiovascular disease (CVD) risk management guided by predicted CVD risk is widely recommended internationally. This is the first study to examine CVD preventive pharmacotherapy in a whole-of-country primary prevention population, stratified by CVD risk. Anonymized individual-level linkage of New Zealand administrative health and non-health data identified 2 250 201 individuals without atherosclerotic CVD, alive, and aged 30-74 years on 31 March 2013. We identified individuals with ≥1 dispensing by community pharmacies of blood pressure lowering (BPL) and/or lipid-lowering (LL) medications at baseline (1 October 2012-31 March 2013) and in 6-month periods between 1 April 2013 and 31 March 2016. Individuals were stratified using 5-year CVD risk equations specifically developed for application in administrative datasets. One-quarter of individuals had ≥5% 5-year risk (the current New Zealand guideline threshold for discussing preventive medications) and 5% met the ≥15% risk threshold for recommended dual therapy. By study end, dual therapy was dispensed to 2%, 18%, 34%, and 49% of individuals with <5%, 5-9%, 10-14%, and ≥15% 5-year risk, respectively. Among those dispensed baseline dual therapy, 83-89% across risk strata were still treated after 3 years. Dual therapy initiation during follow-up occurred among only 13% of high-risk individuals untreated at baseline. People without diabetes and those aged ≥65 years were more likely to remain untreated. Cardiovascular disease primary preventive pharmacotherapy was strongly associated with predicted CVD risk and, once commenced, was generally continued. However, only half of high-risk individuals received recommended dual therapy and treatment initiation was modest. Individually linked administrative datasets can identify clinically relevant quality improvement opportunities for entire populations.