Significant Difference In Probability Research Articles

The Intersection of Socioeconomic Differences and Sex in the Management and Outcomes of Acute Myocardial Infarction: A Nationwide Cohort Study.

Patients with lower socioeconomic status (SES) have poorer outcomes following acute myocardial infarction (AMI) than patients with higher SES; however, how sex modifies socioeconomic differences is unclear. Using the United Kingdom (UK) Myocardial Ischaemia National Audit Project (MINAP) registry, alongside Office of National Statistics (ONS) mortality data, we analyzed 736,420 AMI patients between 2005 and 2018, stratified by Index of Multiple Deprivation (IMD) score Quintiles (most affluent [Q1] to most deprived [Q5]). There was no significant difference in probability of in-hospital mortality in our adjusted model according to sex. The probability of 30-day mortality in our adjusted model was similar between men and women throughout Quintiles, ((Q5; Men 7.6%; 95% CI 7.3-7.8% (P < .001), Women; 7.0%; 95% CI 6.8-7.3%, P < .001)) ((Q1; Men 7.1%; 95% CI 6.8-7.4%, P < .001, Women; 6.9%; 95% CI 6.6-7.1%, P < .001)). The probability of one-year mortality in our adjusted model was higher in men throughout all Quintiles (Q1; Men 15.0%; 95% CI 14.8-15.6%), P < .001, Women; 14.5%; 95% CI 14.2-14.9%, P < .001) (Q5; Men 16.9%; 95% CI 16.5-17.3%, P < .001, Women; 15.5%; 95% CI 15.1-15.9 by %, P < .001). Overall, female sex did not significantly influence the effect of deprivation on AMI processes of care and outcomes.

Similar pregnancy outcomes from fresh and frozen donor oocytes transferred to gestational carriers: a SART database analysis isolating the effects of oocyte vitrification.

This work aimed to study clinical and neonatal outcomes of embryos derived from frozen compared to fresh donor oocytes in gestational carrier cycles. This is a retrospective cohort study using the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database between 2014 and 2015, comprising of 1284 fresh transfer cycles to gestational carrier recipients of embryos resulting from fresh (n = 1119) and vitrified/thawed (n = 165) donor oocytes. Models were adjusted for gestational carrier age, preimplantation genetic testing (PGT-A), number of embryos transferred, multiple gestation, and fetal heart reduction. As our models were part of a larger analysis, intended parent BMI, smoking status, and parity were also adjusted for, but did not influence outcomes in this analysis. There was no significant difference in probability of live birth rates when comparing embryos derived from fresh and frozen donor oocytes in gestational carrier cycles. There were also no significant differences in biochemical pregnancy losses or clinical miscarriage. There were no significant differences noted in low birthweight or high birthweight infants derived from fresh versus frozen donor oocyte after transfer into a gestational carrier. The analysis of fresh and frozen donor oocytes in gestational carrier cycles provides the opportunity to assess for a possible effect of vitrification on the oocyte by controlling for differences in the uterine environment. We observed no significant differences in live birth, pregnancy loss, low birthweight or high birthweight infants when comparing fresh and frozen donor oocytes in gestational carrier cycles.

Association of Gender and Operative Feedback Quality in Surgical Residents

Feedback is critical for learning, however, gender differences exist in the quality of feedback that trainees receive. For example, narrative feedback on surgical trainees' end-of-block rotations differs based on trainee-faculty gender dyads, with female faculty giving higher quality feedback and male trainees receiving higher quality feedback. Though this represents evidence of gender bias in global evaluations, there is limited understanding of how much bias might be present in operative workplace-based assessments (WBAs). In this study, we explore the quality of narrative feedback among trainee-faculty gender dyads in an operative WBA. A previously validated natural language processing model was used to examine instances of narrative feedback and assign a probability of being characterized as high quality feedback (defined as feedback which was relevant as well as corrective and/or specific). A linear mixed model was performed, with probability of high quality feedback as the outcome, and resident gender, faculty gender, PGY, case complexity, autonomy rating, and operative performance rating as explanatory variables. Analyses included 67,434 SIMPL operative performance evaluations (2,319 general surgery residents, 70 institutions) collected from September 2015 through September 2021. Of 36.3% evaluations included narrative feedback. Male faculty were more likely to provide narrative feedback compared to female faculty. Mean probabilities of receiving high quality feedback ranged from 81.6 (female faculty-male resident) to 84.7 (male faculty-female resident). Model-based results demonstrated that female residents were more likely to receive high quality feedback (p < 0.01), however, there was no significant difference in probability of high quality narrative feedback based on faculty-resident gender dyad (p = 0.77). Our study revealed resident gender differences in the probability of receiving high-quality narrative feedback following a general surgery operation. However, we found no significant differences based on faculty-resident gender dyad. Male faculty were more likely to provide narrative feedback compared to their female colleagues. Further research using general surgery resident-specific feedback quality models may be warranted.

Impact of Geographical Distance from Quaternary Treatment Center on Clinical Trial Participation, Intensive Induction Chemotherapy, and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia

Introduction: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas. Methods: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada. Results: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy. The median distance was 33.1 km, with 29% of patients living more than 50 km away from the center. There was no significant difference in probability of intensive induction chemotherapy or clinical trial by distance from center, both in univariate and multivariable analysis adjusting for age, sex, cytogenetics and molecular testing, and performance status. There was no significant difference in overall survival by distance from center on univariate and multivariable analysis. Conclusion: In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, participation in clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single-payer environment.

A prospective cohort study of Plasmodium falciparum malaria in three sites of Western Kenya

BackgroundMalaria in western Kenya is currently characterized by sustained high Plasmodial transmission and infection resurgence, despite positive responses in some areas following intensified malaria control interventions since 2006. This study aimed to evaluate long-term changes in malaria transmission profiles and to assess patterns of asymptomatic malaria infections in school children aged 5–15 years at three sites in western Kenya with heterogeneous malaria transmission and simultaneous malaria control interventions.MethodsThe study was conducted from 2018 to 2019 and is based on data taken every third year from 2005 to 2014 during a longitudinal parasitological and mosquito adult surveillance and malaria control programme that was initiated in 2002 in the villages of Kombewa, Iguhu, and Marani. Plasmodium spp. infections were determined using microscopy. Mosquito samples were identified to species and host blood meal source and sporozoite infections were assayed using polymerase chain reaction.ResultsPlasmodium falciparum was the only malaria parasite evaluated during this study (2018–2019). Asymptomatic malaria parasite prevalence in school children decreased in all sites from 2005 to 2008. However, since 2011, parasite prevalence has resurged by > 40% in Kombewa and Marani. Malaria vector densities showed similar reductions from 2005 to 2008 in all sites, rose steadily until 2014, and decreased again. Overall, Kombewa had a higher risk of infection compared to Iguhu (χ2 = 552.52, df = 1, P < 0.0001) and Marani (χ2 = 1127.99, df = 1, P < 0.0001). There was a significant difference in probability of non-infection during malaria episodes (log-rank test, χ2 = 617.59, df = 2, P < 0.0001) in the study sites, with Kombewa having the least median time of non-infection during malaria episodes. Gender bias toward males in infection was observed (χ2 = 27.17, df = 1, P < 0.0001). The annual entomological inoculation rates were 5.12, 3.65, and 0.50 infective bites/person/year at Kombewa, Iguhu, and Marani, respectively, during 2018 to 2019.ConclusionsMalaria prevalence in western Kenya remains high and has resurged in some sites despite continuous intervention efforts. Targeting malaria interventions to those with asymptomatic infections who serve as human reservoirs might decrease malaria transmission and prevent resurgences. Longitudinal monitoring enables detection of changes in parasitological and entomological profiles and provides core baseline data for the evaluation of vector interventions and guidance for future planning of malaria control.Graphical abstract

Influence of illuminance on indication detectability during visual testing

Abstract Visually detecting irregularities on components is a complex process, influenced by physical, technical, and human factors. Current standards mainly focus on illuminance, demanding highest accuracy for it, without providing scientific justification. In this research, 63 inspectors visually inspected forgings, with and without crack-like indications. The influence of illuminance on probability of detection was investigated. Therefore, illuminance was varied in three steps (200 lx, 350 lx, 500 lx). Human factors (e.g., experience, motivation) were recorded by using questionnaires. The results show no significant difference in probability of detection between the three illuminance levels. Equal probability of detection rates could be achieved at illuminances below and at the required threshold (500 lx). A difference in illuminance was found between the measurement point and the test area of the respective participant. This leads to higher assumed illuminance than present on the component. Compared with the measurement accuracy of the used illuminance meter, none of these deviations could be used to explain the similar results at different illuminance. The fact that illuminance has a significant influence in detecting indications has been disproven for this case. Whether human factors can provide explanation for the results remains unclear. This will be investigated in further research.

Bisphosphonate Use for Glucocorticoid-Induced Osteoporosis in Elderly Patients with Immune Thrombocytopenia Receiving Prolonged Steroid Therapy: A Single Institute Retrospective Study.

Prednisolone, used as a standard initial treatment for immune thrombocytopenia (ITP), is an important risk factor for osteoporosis. To investigate the prevention of glucocorticoid-induced osteoporosis (GIO) in elderly ITP patients receiving prolonged steroid therapy, associations between GIO prevention and the real-world data of score changes of a dual-energy X-ray absorptiometry (DXA) scan, FRAX® and the Garvan tool during the initial loading of prednisolone were examined. In our institute, 22 ITP patients aged ≥ 70 years received 0.5–1.0 mg/kg prednisolone for 2–3 weeks as the initial ITP treatment between 2014 and 2021. The femoral neck bone mineral density (BMD) measured by DXA scan was entered into FRAX® to define the risk-adapted approach to bisphosphonate during the initial loading of prednisolone. Bisphosphonate was administered according to <−1.0 femoral neck BMD T-score measured by DXA scan. Worse scores of FRAX® and the Garvan tool were associated with bisphosphonate use for short-term fracture prevention in primary GIO; however, there were no incidents of fracture or significant differences in probabilities determined by FRAX® and the Garvan tool. During the initial loading of prednisolone, prescribing bisphosphonate might prevent the reduction in BMD in elderly patients with ITP receiving prolonged steroid therapy.

High pre-treatment neutrophil-to-lymphocyte ratio as a prognostic marker for worse survival in patients with recurrent/metastatic cervical cancer treated with immune checkpoint inhibitors

ObjectiveTo evaluate the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and survival outcomes among patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors. MethodsA retrospective analysis of patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors from 2016 to 2021 was conducted. Progression free survival (PFS) and overall survival (OS) outcomes were assessed for patients stratified by NLR (<8 vs ≥ 8) utilizing Kaplan-Meier method. Univariable analysis was performed to compare baseline characteristics between the two groups. ResultsA total of 49 patients were included in analysis. A majority of patients had squamous cell histology (57%), were PD-L1 positive (55%), received ≤ 1 prior lines of systemic therapy (57%), and had distant metastatic disease at the time of treatment (69%). The groups were well-balanced with respect to age, race, histology, smoking status, PD-L1 positivity, prior lines of treatment (≤1 vs > 1), prior radiation therapy, ECOG performance status, and disease distribution for patients with a NLR < 8 (n = 35) compared to those with a NLR ≥ 8 (n = 14). A pre-treatment NLR of < 8 was associated with improved survival (p < 0.01), with 57% (95% CI: 41%, 78%) probability of survival at one year compared to 26% (95% CI: 10%, 66%) for those with NLR ≥ 8. No statistically significant differences in probability of PFS at 1 year were seen between NLR < 8 compared to those with NLR ≥ 8 (p = 0.70). ConclusionsPre-treatment NLR may hold prognostic value for patients with metastatic/recurrent cervical cancer treated with PD-1/PD-L1 inhibitors, with NLR < 8 associated with improved survival.

P722: IS THE SECOND-GENERATION TYROSINE KINASE INHIBITOR A BETTER THERAPY THAN IMATINIB FOR PERSONS WITH CHRONIC MYELOID LEUKEMIA PRESENTING IN ACCELERATED-PHASE?

Background: Although most patients with chronic myeloid leukemia (CML) were presenting in the chronic phase at diagnosis, approximately 5% presented with features of accelerated phase. The features of accelerated phase were variably defined by different criteria, such as MD Anderson and European LeukemiaNet (ELN) criteria most often used. Regardless of these criteria used to defined accelerated phase, only scant data were available regarding the prognostic co-variates for outcome. Moreover, evidence that patients could benefit more from the second generation (2G-) tyrosine kinase inhibitor (TKI) than imatinib as initial therapy was still extremely limited. Aims: Explore whether patients with chronic myeloid leukemia (CML) presenting in accelerated-phase could benefit from initial second-generation tyrosine kinase inhibitor (2G-TKI) therapy. Methods: We interrogated data from consecutive patients with CML presenting in accelerated phase at diagnosis by the MD Anderson criteria (n = 325) or ELN criteria (n = 275). Propensity score matching (PSM) analysis was used to compare cytogenetic and molecular responses and outcomes in those receiving initial imatinib versus a 2G-TKI. COX multi-variable regression model was performed to identify the prognostic co-variates. Results: In the cohort defined by MD Anderson criteria, PSM analysis showed that patients receiving initial 2G-TKI (n = 89) had higher probability of achieving a CCyR (p = 0.01), MMR (p = 0.04) and MR4.5 (p = 0.004) than those receiving imatinib (n = 156), however, probabilities of FFS, PFS and survival were similar. Multi-variable analyses showed that lower platelets and higher blasts in blood or bone marrow were significantly-associated with poor FFS, PFS and/or survival (Figure A). In an attempt to determine whether choice of therapy contributed to the differences in responses and outcomes, platelets < 600 × 10E+9/L and blood / bone marrow blasts ≥ 5% were identified as the prognostic categorical co-variates by ROC analyses. The entire cohort were classified into low- (possessing none of these co-variates, n = 57), intermediate (possessing any 1 of these co-variates, n = 127) or high-risk (possessing all of these co-variates, n = 61) subgroups. There were significant differences in probabilities of outcomes among these risk subgroups (all p values < 0.001, Figure B). In each risk subgroup, patients receiving initial 2G-TKI had the similar outcomes to those receiving imatinib except higher incidences of responses including CCyR, MMR and MR4.5. The same results were observed in the cohort defined by ELN criteria. Image:Summary/Conclusion: Initial 2G-TKI lead to similar outcomes as imatinib in patients with CML presenting in accelerated-phase except higher therapy responses.

SPACECRAFT RELIABILITY CALCULATIONS USING STATISTICAL REGULARITIES IN OCCURRENCES OF FAILURES IN DEVICES, UNITS AND ASSEMBLIES DURING THEIR OPERATION

The paper addresses reliability analysis of manned spacecraft with the use of statistical regularities in in-flight failures of their devices, units and assemblies. It formulates validity criteria for using a device failure in reliability analysis, proposes a method for analyzing and classifying failures which enables factoring in different types of failures in reliability analyses. It considers a hypothesis of the absence of statistically significant differences in probabilities of individual valid failures and demonstrates the feasibility of its adoption with the use of dispersion analysis. A method is developed for evaluating product reliability using a functional relationship between reliability and the number of failures occurring in flight which makes it possible to significantly simplify reliability analysis for complex products, to establish the number of in-flight failures that is acceptable from the standpoint of the product reliability requirements, to study various product architectures from the standpoint of reliability criteria. It proposes a method for evaluating the lower boundary for the probability of manned spacecraft completing their missions based on the failure modes, effects and criticality analysis, and demonstrates the feasibility of optimizing the product redundancy scheme based on the fault tolerance requirements. Key words: manned spacecraft, flight, failure, fault tolerance, classification of failures, reliability, probability of failure-free operation, statistical analysis, dispersion analysis.

A Predictive Score for Failure-Free Survival in Persons with Chronic Myeloid Leukemia Receiving Imatinib

Background Initial tyrosine kinase inhibitor (TKI) therapy strategies in persons with newly-diagnosed chronic phase chronic myeloid leukaemia (CML) include the standard dose imatinib, a 2 nd generation TKI, staring with imatinib and then increasing the dose or switching to a 2 nd generation TKI if the 2020 European LeukemiaNet (ELN) response landmarks are not met. Which therapy strategy is best is still uncertain. There is no predictive score for failure-free survival in this setting to help physicians choose between these alternatives.Objective Develop and validate a predictive score for failure-free survival (FFS; FFS predictive score [FFSPS]) in persons with newly-diagnosed chronic phase CML receiving initial imatinib therapy.Methods Data from 1321 consecutive subjects receiving initial therapy with imatinib were interrogated to identify co-variates predicting FFS with failure defined according to the 2020 ELN criteria. Cut-offs for continuous variables were determined by analyzing receiver-operator characteristic (ROC) curves, and a Cox multi-variable regression model was used to identify predictive co-variates in a training dataset (n = 880). A weighted predictive score (FFSPS) was developed and validated in 441 other subjects.Results In the training dataset, WBC ≥ 120 × 10E+9 /L (Hazard Ratio [HR] = 1.7 [95% Confidence Interval (CI), 1.1, 2.2]), haemoglobin concentration ≤ 113.5 g/L (HR = 2.3 [1.7, 3.1]), blood basophils ≥ 11.5% (HR =1.6 [1.0, 2.3]) and EUTOS long-term survival (ELTS) risk score (intermediate-risk, HR = 1.9 [1.4, 2.6]; high-risk, HR = 3.7 [2.2, 5.0]) were significantly-associated with worse FFS and each assigned 1 point in the scoring system except ELTS high-risk which was assigned 2 points. According to the FFSPS, the training dataset were classified into 5 subgroups: the very low- (score = 0; n = 307, 35%), low- (score = 1; n = 176, 20%), intermediate- (score = 2; n = 183, 21%); high- (score = 3; n = 152, 17%) and the very high- (score ≥ 4; n = 62, 7%) risk subgroups. There were significant differences in the 7-year probabilities of FFS among the 5 subgroups (89% [84, 92%] vs. 76% [67, 83%] vs. 64% [56, 71%] vs. 52% [43, 60%] vs. 28% [17, 40%], p < 0.001, Figure A). The concordance statistic (C-statistic) based on the FFSPS was 0.75 (0.69, 0.78) in the training dataset. And in the validation dataset, 155 (35%), 88 (20%), 94 (21%), 70 (16%) and 34 (8%) subjects were classified as the very low-, low-, intermediate-, high-, and the very high-risk subgroups, among which there were significant differences in the probabilities of 7-year FFS (p < 0.001, Figure B). The C-statistic in the validation dataset was 0.74 (0.67, 0.80). Moreover, the FFSPS was also correlated with probabilities of major molecular response (MMR), MR 4.0 and MR 4.5, progression-free survival (PFS) and survival (all p-values < 0.001, Figure C-G).Conclusions We describe a predictive score for FFS in persons with newly-diagnosed chronic phase CML receiving initial imatinib therapy. The score identifies persons with different probabilities of success. These data should help physicians estimate the best TKI-therapy strategy in this setting. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Selection of Suitable Alternative Donor in the Absence of Matched Sibling Donor: A Retrospective Single-Center Study to Compare between Haploidentical, 10/10 and 9/10 Unrelated Donor Transplantation.

Background: Finding a suitable donor at the optimal time is one of the most challenging issues in many transplant centers. We evaluated the clinical outcomes of 248 patients with acute leukemia and without matched sibling donors (MSD) who underwent alternative transplantation, including haploidentical (n=118), 10/10 matched unrelated (MUD, n=91), 9/10 mismatched unrelated (MMUD, n=21), and 9/10 mismatched related (MMRD, n=18) between January 2010 and November 2019 in our center. Materials and Methods: The myeloablative conditioning regimen was used in most of the patients. Both post-transplant cyclophosphamide (40mg/kg at +3, +4) and pre-transplant ATG were used in most of haploidentical transplantations. Patients with unrelated donors received ATG as a part of the conditioning regimen. Results: The median follow-up was 31.83 months. No significant difference in probability of 3-year leukemia- free survival (LFS) and overall survival (OS) as well as 3-year relapse incidence (RI) was noted among donor sources. A significant difference was found in the 3-year cumulative incidence (CI) of non-relapse mortality (NRM) among the donor sources: 37.89%, 24.20%, 24.30%, and 11.48%, for haplo, 9/10 MMUD, 10/10 MUD, and 9/10 MMRD (p=0.02). Using the multivariable Cox model, the advanced age of patients and Major-ABO mismatched were two risk factors independently associated with lower OS and DFS as well as higher NRM, whereas male donor and AML disease compared to ALL were associated with a better OS and DFS. Conclusion: No significant differences were observed in the overall outcome of haplo with other alternative transplantations, suggesting that haploidentical transplantation is a suitable, accessible, and inexpensive option.

Pharmacist Versus Physician Provider Management of Hydroxyurea Therapy for Polycythemia Vera (PERMANACE)

Background: Cytoreduction utilizing hydroxyurea to achieve a hematocrit (HCT) &amp;lt;45% has improved clinical outcomes for patients with Polycythemia Vera (PV). Pharmacists, through a collaborative practice agreement with hematologists, are uniquely posited to act as physician extenders and therapeutically dose adjust hydroxyurea (HU). Since 2013, HU therapeutic drug monitoring for PV patients has been transitioned to pharmacists in our oral chemotherapy clinic. We conducted a retrospective cohort cross-over study to evaluate pharmacist versus physician HU management to achieve a therapeutic HCT &amp;lt;45%. Methods: We retrospectively queried our institutional electronic medical record to identify patients diagnosed with PV with a documented ambulatory HU prescription. Additionally, patients' HU must have been managed by a physician (Phys) and subsequently crossed over to a pharmacist (PharmD) with at least two documented encounters by each clinician type. Hematological parameters for therapeutic drug monitoring are outlined in Table 1. Descriptive statistics were used for demographic information and a random effects model was used to evaluate HU management between Phys and PharmD. We fit a generalized linear regression model with random intercepts for each patient, using SAS's PROC GLIMMIX and Laplace approximation method t-test for a significant difference in probability of a therapeutic measurement between PharmD and Phys managed patients. Odd ratios were also calculated and adjusted for age and sex. Statistical analysis was performed using SAS (SAS9.4 SAS Institute, Cary, NC) and R software (The R Group, Vienna, Austria), with p&amp;lt;0.05 considered statistically significant. Results: Between 1/1/2003 and 1/20/2020, 104 patients meet the inclusion criteria. This cohort was primarily female (53%), white (97%), and aged 71 years during PharmD management vs 69 years during Phys management. The median time of a patient's HU management by PharmD was 2.4 years (IQR 1.2-3.8), Phys was 0.7 years (IQR 0.02-4.2), and overall was 3.6 years (IQR 2-6.6). 3154 complete blood count measurements were collected in the PharmD cohort and 2007 were collected in the Phys cohort. HU management by PharmD vs Phys resulted in statistically significant increases of therapeutic HCT measurements (p&amp;lt;0.0001) and platelet (PLT) measurements (p&amp;lt;0.0001) as shown in Figure 1. These outcomes remained significant when adjusted for both age and sex: HCT 87.8% vs 74.7% (p&amp;lt;0.0001) and PLT 78.4% vs 70.1% (p=0.0001). There was no difference white blood cell (WBC) therapeutic measurements between cohorts nor when adjusted for age and sex. Patients in the PharmD cohort had higher odds of achieving therapeutic HCT (OR 2.44; 95% CI [1.92 - 3.10], p&amp;lt;0.0001) and PLT (OR 1.55; 95% CI [1.25 - 1.92], p=0.0001) goals (Table 1). In terms of hematological safety parameters, there was no significant difference in neutropenia (OR 1.30; CI 95% [0.51-3.25]) with PharmD vs Phys HU management. All grade neutropenia occurred in 35 (1.1%) and 18 (0.9%) of patients between the PharmD vs Phys cohort, respectively. Grade 3 neutropenia occurred in 1.1% of patients in both cohorts with no instances of Grade 4 neutropenia. Conclusion: These findings support the efficacy of pharmacist therapeutic drug management of HU for patients with PV. Pharmacists managing HU achieve a target HCT and PLT count more often than physician management. By acting as a physician extender, pharmacist HU management for PV patients can help decrease the clinical burdens on physicians without compromising efficacy. Disclosures No relevant conflicts of interest to declare.

The effect of donor and recipient race on outcomes of assisted reproduction

A growing literature suggests that minority races, particularly Black women, have a lower probability of live birth and higher risk of perinatal complications after autologous assisted reproductive technology. However, questions still remain as to whether these racial disparities have arisen because of associations between race and oocyte/embryo quality, the uterine environment, or a combination of the two. Oocyte donation assisted reproductive technology represents a unique approach to examine this question. This study aimed to evaluate the associations between the race of female oocyte donors and recipients and live birth rates following vitrified donor oocyte assisted reproductive technologies. This was a retrospective study conducted at a single, private fertility clinic that included 327 oocyte donors and 899 recipients who underwent 1601 embryo transfer cycles (2008-2015). Self-reported race of the donor and recipient were abstracted from medical records. Live birth was defined as the delivery of at least 1 live-born neonate. We used multivariable cluster weighted generalized estimating equations with binomial distribution and log link function to estimate the adjusted risk ratios of live birth, adjusting for donor age and body mass index, recipient age and body mass index, tubal and uterine factor infertility, and year of oocyte retrieval. The racial profile of our donors and recipients were similar: 73% white, 13% Black, 4% Hispanic, 8% Asian, and 2% other. Women who received oocytes from Hispanic donors had a significantly higher probability of live birth (adjusted risk ratio, 1.20; 95% confidence interval, 1.05-1.36) than women who received oocytes from white donors. Among Hispanic recipients, however, there was no significant difference in probability of live birth compared with white recipients (adjusted risk ratio, 1.07; 95% confidence interval, 0.90-1.26). Embryo transfer cycles using oocytes from Black donors (adjusted risk ratio, 0.86; 95% confidence interval, 0.72-1.03) and Black recipients (adjusted risk ratio, 0.84; 95% confidence interval, 0.71-0.99) had a lower probability of live birth than white donors and white recipients, respectively. There were no significant differences in the probability of live birth among Hispanic, Asian, and other race recipients compared with white recipients. Black female recipients had a lower probability of live birth following assisted reproductive technology, even when using vitrified oocytes from healthy donors. Female recipients who used vitrified oocytes from Hispanic donors had a higher probability of live birth regardless of their own race.

Local excision versus radical resection in patients with rectal neuroendocrine tumours: a propensity score match analysis.

The rectum is a common site for neuroendocrine tumours of the gastrointestinal tract. Diagnosis of these tumours has been increasing in recent years, highlighting the need to better define treatment options for patients with rectal neuroendocrine tumours (rNETs). We performed a retrospective analysis using the National Cancer Database (2004-2014) to compare overall survival (OS) between local excision (LE) and radical resection (RR). To minimize bias, we performed three propensity score-matched comparisons stratified by tumour size: <10 mm, 10-20 mm, >20 mm. We compared OS by Kaplan-Meier analysis. We also examined margin status and postoperative outcomes for each comparison. A total of 12 996 patients underwent surgical treatment for rNET. There was no significant difference in probability of 10-year OS between LE and RR for patients with tumours <10 mm (88.6% versus 83.8%, P = 0.631, respectively) and tumours 10-20 mm (69.5% versus 69.3%, P = 0.226, respectively). In patients with tumours >20 mm, probability of 10-year OS was significantly longer in the LE group (76.5% versus 37.0%, P < 0.001). For all tumour sizes <10 mm and >20 mm, RR had significantly higher rates of 30-day readmission and negative margins. In subset analysis, there was no difference in OS for patients with positive margins after LE versus negative margins after RR for all tumour size groups. Our findings suggest that LE is a reasonable treatment option in patients with rNETs, especially for patients with high perioperative risk. Limitations to this study include its retrospective nature and inability to analyse surgeon decision-making.

Influence of Rain on Highway Breakdown Probability

Capacity has been used to describe a deterministic value that represents the maximum volume of traffic supported by a road. Studies have pointed out the importance of not using a single value for capacity, but rather the concept of probability of occurrence of a traffic-flow breakdown. In this paper the probabilities of breakdown for a Brazilian highway under different weather conditions are compared. Data collected from inductive loop detectors and pluviometric data from automatic rain gauges are combined. Two methodologies of breakdown identification are then compared. The most consistent methodology for identifying breakdowns is used to generate breakdown probability distributions using the product limit and maximum-likelihood methods with the Weibull distribution. The results indicate significant differences in probability of breakdown for each studied climatic condition, including a maximum difference greater than 50% between dry and heavy rain conditions under the same traffic flow.

The impact of early administration of vasopressor agents for the resuscitation of severe hemorrhagic shock following blunt trauma

BackgroundWhen resuscitating patients with hemorrhagic shock following trauma, fluid volume restriction and permissive hypotension prior to bleeding control are emphasized along with the good outcome especially for penetrating trauma patients. However, evidence that these concepts apply well to the management of blunt trauma is lacking, and their use in blunt trauma remains controversial. This study aimed to assess the impact of vasopressor use in patients with blunt trauma in severe hemorrhagic shock.MethodsIn this single-center retrospective study, we reviewed records of blunt trauma patients with hemorrhagic shock and included patients with a probability of survival < 0.6. Vital signs on arrival, characteristics, examinations, concomitant injuries and severity, vasopressor use and dose, and volumes of crystalloids and blood infused were compared between survivors and non-survivors. Data are described as median (25–75% interquartile range) or number.ResultsForty patients admitted from April 2014 to September 2019 were included. Median Injury Severity Score in survivors vs non-survivors was 41 (36–48) vs 45 (34–51) (p = 0.48), with no significant difference in probability of survival between the two groups (0.22 [0.12–0.48] vs 0.21 [0.08–0.46]; p = 0.93). Despite no significant difference in patient characteristics and injury severity, non-survivors were administered vasopressors significantly earlier after admission and at significantly higher doses. Total blood transfusion amount administered within 24 h after admission was significantly higher in survivors (8430 [5680–9320] vs 6540 [4550–7880] mL; p = 0.03). Max catecholamine index was significantly higher in non-survivors (2 [0–4] vs 14 [10–18]; p = 0.008), and administered vasopressors were terminated significantly earlier (12 [4–26] vs 34 [10–74] hours; p = 0.026) in survivors.Although the variables of severity of the patients had no significant differences, vasopressor use (Odds ratio [OR] = 21.32, 95% confident interval [CI]: 3.71–121.6; p = 0.0001) and its early administration (OR = 10.56, 95%CI: 1.90–58.5; p = 0.005) indicated significant higher risk of death in this study.ConclusionVasopressor administration and high-dose use for resuscitation of hemorrhagic shock following severe blunt trauma are potentially associated with increased mortality. Although the transfused volume of blood products tends to be increased when resuscitating these patients, early termination of vasopressor had better to be considered.

The Role of Ciprofloxacin Resistance and Extended-spectrum beta-lactamase (ESBL) Positivity in Infective Complications Following Prostate Biopsy.

To evaluate ciprofloxacin resistance (CR) and extended-spectrum beta-lactamase (ESBL) positivity in the rectal flora, antibiotic prophylaxis received, and post-biopsy infectious complications in patients undergoing prostate biopsy. Rectal swab samples collected from 99 patients suspected of prostate cancer two days before prostate biopsy were tested for microbial susceptibility and ESBL production. All patients were given standard ciprofloxacin and ornidazole prophylaxis. Ten days post-biopsy, the patients were contacted by phone and asked about the presence of fever and/or symptoms of urinary tract infection. Escherichia coli (E.coli) was the most common isolate detected in 82 (75%) of the rectal swab samples. Ciprofloxacin resistance was detected in 33% and ESBL positivity in 22% of the isolated E.coli strains. No microorganisms other than E.coli were detected in blood, urine, and rectal swab cultures of patients who developed post-biopsy complications. CR E.coli strains also showed resistance to other antimicrobial agents. The lowest resistance rates were to amikacin (n = 2, 7.4%) and nitrofurantoin (n = 1, 3.7%). Seven patients (7.6%) developed infectious complications. There was no significant difference in probability of hospitalization between patients with CR strains (14.3%) and those with ciprofloxacin-susceptible strains (14.3% vs. 4.7%; p = 0.194). However, strains that were both CR and ESBL-positive were associated with significantly higher probability of hospitalization compared to ciprofloxacin-susceptible strains (28.6% vs. 3.8%; p = 0.009). The higher rate of infectious complications with CR and ESBL-positive strains suggests that the agents used for antibiotic prophylaxis should be reevaluated. It is important to consider local resistance data when using extended-spectrum agents to treat patients presenting with post-biopsy infectious complications.

Divorce and Credit

Does failure in a marriage foretell a failure to repay credit? Analyzing the retail loan portfolio of a representative bank, we find no significant difference in probability of default between divorcees and others, but do find evidence for taste-based discrimination. Divorcees pay 5.8 basis points more in interest than non-divorced peers. This discrimination is greater in regions where clan culture is more dominant, and among loan officers who are male, are older, and have been longer on the job. Such discrimination is reduced if the loan officers are better educated, and if competition in local banking market is fiercer.

Spectrum and Clinical Significance of HLA Class I Alleles and Their Somatic Mutations in Immune Aplastic Anemia

Clonal hematopoiesis associated with loss of HLA class I alleles due to somatic mutations and/or 6p loss of heterozygosity (LOH) is frequent in immune aplastic anemia (AA). HLA-B*40:02 is more likely to be involved in HLA loss in Japanese AA patients, suggesting a role for this allele in immune pathophysiology (Zaimoku Y et al, Blood 2017). Mutations in non-B*40:02 HLA class I alleles have been reported in a limited number of patients from the United States (Babushok D et al, Blood Adv 2017) and Japan (Mizumaki H et al, 60th ASH meeting), but their prevalence and clinical significance are not well characterized. We investigated somatic mutations of HLA class I alleles, HLA allele frequencies, and their correlations with outcomes of therapy in a total of 532 AA patients, aged 2 years or older, treated on various Hematology Branch protocols (clinicaltrials.gov NCTs 00001964, 00061360, 00195624, 00260689, 00944749, 01193283, and 01623167). HLA allele-lacking (HLA-) monocytes from cryopreserved peripheral blood mononuclear cells were screened by flow cytometry after staining with allele-specific monoclonal antibodies for HLA-A and/or HLA-B (HLA-flow) in 172 AA patients. HLA- monocytes accounting for 0.5% to 100% (median 9.5%) of total monocytes were detected in 49 (28%) of the 172 patients and in 59 (15%) of 382 alleles analyzed (Figure 1). Loss of cell surface expression was frequent for HLA-B14 (46%), B27 (33%), B49 (33%), A68 (26%), A2 (23%), B40 (21%), and B8 (21%). One percent to 60% (median, 8.9%) of glycosylphosphatidylinositol-linked protein-negative (GPI-) monocytes were also present in 43% (21 of 49) of the patients with HLA- monocytes, but GPI- clones had normal HLA cell surface expression. Deep sequencing of HLA-A, HLA-B and HLA-C on sorted HLA- and HLA+GPI+ monocytes was performed in 42 of the 48 patients from whom adequate cells were available. Somatic mutations and/or LOH corresponding to the lacking alleles were detected in all 42 cases (Figure 1): 9 had both somatic mutations and LOH, 20 had somatic mutations only, and 13 had LOH only. Among the 13 patients who showed only LOH in the absent allele, 6 had somatic mutations in other alleles of HLA+ monocytes that was not analyzable of HLA expression, and 2 had a breakpoint of LOH between HLA-A and HLA-C, leading to loss of a single HLA-A allele. Somatic mutations or LOH involving only one allele were present in 37 patients among 6 HLA-A alleles (in 02:01 [7 patients], 02:05 [1], 02:06 [3], 02:11 [1], 68:01 [2], 68:02 [2]) and 10 HLA-B alleles (07:02 [1], 08:01 [4], 14:01 [1], 14:02 [7], 27:05 [1], 35:02 [1], 35:05 [1], 40:01 [1], 40:02 [3], 45:01 [1]), but were not found in HLA-C alleles. HLA allele frequencies in AA patients, including 271 white Americans, 120 African-Americans, and 99 Hispanics and Latinos, were compared with ethnicity-matched individuals in bone marrow donor datasets of the National Marrow Donor Program, and underwent random-effects meta-analyses. HLA-B*07, B*14, and B*40 were overrepresented in AA, while A*02, A*68, and B*08 frequencies were similar to those of healthy donors (Figure 2). In 164 severe AA patients who were initially treated with horse antithymocyte globulin (hATG), cyclosporine, and eltrombopag between 2012 and 2018, 36 and 79 were positive and negative for HLA- monocytes, respectively, and 49 were not tested by HLA-flow. There was no significant difference in overall and complete response rates at six months among the three groups (Figure 3). Clonal evolution, defined as acquisition of abnormal bone marrow cytogenetics or morphology, especially high-risk evolution to chromosome 7 abnormalities, complex cytogenetics, or morphological MDS/AML, tended to be more frequent in patients with HLA- monocytes, compared to the other two groups, but the difference did not reach statistical significance. Clinical outcomes were also assessed according to the presence of specific HLA alleles in 400 severe AA patients who were treated with hATG-based initial immunosuppressive therapy from 2000 to 2018: there was no significant differences in probabilities of response and clonal evolution according to the alleles associated with somatic mutations. Our study revealed that somatic mutations in HLA genes in AA are broadly distributed, but some alleles are preferentially affected. Inconsistent with previous studies, we found that outcomes of therapy did not significantly correlate with HLA gene mutations or with distinct HLA alleles. Disclosures No relevant conflicts of interest to declare.