Categorical Measures Research Articles

Protocol for Transcranial Direct Current Stimulation for Obsessive-Compulsive Disorder

Obsessive-compulsive disorder (OCD) is a debilitating disorder with an approximate lifetime prevalence of 1–3%. Despite advances in leading treatment modalities, including pharmacotherapy and psychotherapy, some cases remain treatment resistant. Non-invasive brain stimulation has been explored in this treatment-resistant population with some promising findings; however, a lack of methodological rigor has reduced the quality of the findings. The current paper presents the protocol for conducting research into the efficacy of transcranial direct current stimulation (tDCS) in the treatment of OCD. A double-blind randomised controlled trial (RCT) will be conducted involving active tDCS vs. sham tDCS on 40 general OCD patients. The intervention consists of 2 mA anodal stimulation over the pre-supplementary motor area (pre-SMA) with the cathode positioned over the orbitofrontal cortex (OFC). Participants will receive 10 sessions of 20 min of either sham- or active-tDCS over 4 weeks. Outcomes will be categorical and dimensional measures of OCD, as well as related secondary clinical measures (depression, anxiety, quality of life), and neurocognitive functions (inhibitory control, cognitive flexibility).

Frequency of Contact Lens Complications Between Contact Lens Wearers Using Multipurpose Solutions Versus Hydrogen Peroxide in the United States and Canada.

To retrospectively compare frequency of contact lens (CL) complications in soft CL users of hydrogen peroxide (H2O2) and multipurpose solutions (MPS). This was a multicenter, retrospective chart review of CL records from each patient's three most recent eye examinations at academic and private practices. Patients must have used the same solution type for at least 3 years. Univariate analyses were conducted using t tests, and chi-square or Fisher's exact test for categorical measures. There were 1,137 patients included, with 670 (59%) using MPS and 467 (41%) H2O2. In total, 706 (62%) experienced at least one complication; 409 used MPS and 297 used H2O2. There was no difference in the proportion of patients experiencing at least one complication between MPS (61%) and H2O2 (64%) (P=0.38). Multipurpose solutions users were more likely to report discomfort compared with H2O2 users (P=0.04). Presumed microbial keratitis was experienced by 16 MPS and nine H2O2 users (P=0.60). No significant differences were found in the frequency of CL complications between MPS and H2O2. H2O2 users were less likely to report discomfort and thus switching to a H2O2 system may be an alternative in CL users with discomfort.

Clinico-Radiological Outcome of Single-Level and Hybrid Total Disc Replacement with Spineart Baguera®-C for Cervical Myeloradiculopathy: Minimum 2-Year Follow-Up Study in Indian Population.

Context:Cervical radiculopathy and myelopathy is one of the most frequent ailments encountered by spine surgeon. Motion-preserving surgeries in cervical spine is a standard of care due to its certain advantages such as biomechanical anatomical conformity, reduced chances of adjacent segment degeneration, and revision surgeries. While there is abundant data from some centers, data from developing countries are still limited.Aims:The aim was to study the clinico-radiological outcome of single-level and hybrid total disc replacement (TDR) with Spineart Baguera®-C cervical prosthesis for cervical myeloradiculopathy.Settings and Design:Retrospective study.Materials and Methods:Retrospective analysis of the 29 consecutive patient undergoing single level TDR and hybrid fixation (i.e., TDR with anterior cervical discectomy and fusion) with Spineart Baguera®-C cervical prosthesis for myeloradiculopathy from January 1, 2014 to December 31, 2017, was done. Radiological features and outcome were studied from data collected on Insta-picture archiving and communication system.Statistical Analysis Used:SAS 9.4 was used for all computations. Results on continuous measurements were presented as mean and standard deviation (min-max) and results on categorical measurements were presented as numbers (n) and percentages.Results:Twenty-nine patients were included in the study. The mean age was 43.31 ± 9.04 years with 14 males and 15 females. The most common level of TDR was C5-C6 (72.41%). The mean follow-up duration was 3.14 years ± 1.13 years (2–5 years). The mean hospital stay was 4.93 ± 2.12 days. The mean neck disability index (NDI) at admission was 27.24 ± 7.66 which decreased to 6.41 ± 4.29 at final follow-up.Conclusions:Two-year data on treatment with Spineart Baguera®-C cervical prosthesis shows significantly improved NDI, visual analog scale (arm) with maintenance of movement of the prosthesis.

Usefulness of an early warning score as an early predictor of clinical deterioration in hospitalized children.

The early detection of clinical deterioration in hospitalized patients helps to improve the quality of care. The pediatric early warning score (PEWS) system predicts such deterioration in the first 24 hours of administration. Prior studies support the use of these tools. To assess the usefulness of the Brighton PEWS (B-PEWS) for the prediction of clinical deterioration among hospitalized children at a children's hospital in the Autonomous City of Buenos Aires. Cross-sectional study. The medical records of all patients aged 1 month to 18 years admitted to any hospitalization ward between March 1st and August 31st, 2018 were included. Predictive outcome measure: B-PEWS score (≤ 3 and ≥ 4 points). Outcome variable: clinical deterioration in the first 24 hours. Categorical outcome measures were analyzed with the χ² test and screening values were estimated. The relative risk was used as a measure of association. A ROC curve analysis and an optimal cut-point analysis according to the Youden index were done considering the score in a continuous manner. A total of 518 medical records were reviewed. Forty patients had clinical deterioration; the B-PEWS score was ≥ 4 in 37 patients and ≤ 3 in 3 (relative risk: 56.36; 95 % confidence interval: 17.76-178.89; p < 0.01). Sensitivity: 92.5 %; specificity: 88.3 %; positive predictive value: 39.8 %; negative predictive value: 99.3 %; positive likelihood ratio: 7.91; negative likelihood ratio: 0.08. AUC: 0.94 (95 % confidence interval: 0.89-0.98). The B-PEWS demonstrated to be useful to predict clinical deterioration in hospitalized children.

Accuracy of Smoking Status Reporting: Proxy Information in a Rapidly Fatal Cancer Setting.

ObjectiveTo assess whether patients and relatives can serve as reliable proxy reporters of other family members’ cigarette-smoking history.Patients and MethodsTwo samples (325 patients, 707 relatives) were identified from the Mayo Clinic Biospecimen Resource for Pancreas Research, enrolled from November, 6, 2000, to March 15, 2018. Smoking-history data, including categorical (ever/never) and quantitative (packs per day and years smoked) smoking measures, were obtained from self-completed questionnaires by patients and relatives. Relative reports were compared with patient reports on self; patient reports were compared with relative reports on self.ResultsOverall, spouses and first-degree relatives (FDRs) were accurate (94.5%) when reporting patient ever smoking; spouse reports were 98.6% sensitive and 97.7% accurate. Accuracy of patient reports was 97.8% for spouse smoking and 85.5% for FDR smoking; accuracy varied by relationship of FDR. When not concordant, patients generally over-reported daily packs smoked by relatives and under-reported years smoked. Within a 25% agreement range, spouse reports about patients’ daily packs smoked was 46.7%, and years smoked was 69.6%, whereas FDRs were 50% and 64.6%, respectively. When not concordant, relatives generally over-reported daily packs smoked by patients, but no consistent pattern was observed of over- or under-reporting years smoked by patients.ConclusionsPatients and relatives can be reliable proxies for smoking history (ever/never) in their family members, especially spouses. An accurate reporting of smoking status will help physicians to better gauge performance status and family smoking exposures to inform disease management.

Sex-Related Differences in Symptoms and Psychosocial Outcomes in Patients With Fibromyalgia: A Prospective Questionnaire Study.

ObjectiveTo investigate sex-related differences in patients with fibromyalgia (FM) in terms of demographic characteristics and clinical features, including tender point count (TPC), mood disorders, sleep problems, FM symptom severity, fatigue, cognitive dysfunction, and quality of life (QOL).Patients and MethodsWe studied 668 consecutive patients with FM (606 women) from May 1, 2012, to November 30, 2013. Validated questionnaires assessed outcomes of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), sleep problems (Medical Outcomes Study Sleep Scale), FM symptom severity (Revised Fibromyalgia Impact Questionnaire), fatigue (Multidimensional Fatigue Inventory), cognitive dysfunction (Multiple Ability Self-report Questionnaire), and QOL (36-Item Short Form Health Survey). Nonparametric Mann-Whitney U and Pearson χ2 tests were used to compare continuous and categorical outcome measures, respectively, between men and women. Linear regression models were performed for all continuous dependent variables, adjusting for age, body mass index, ethnicity, marital status, and highest education level completed. P<.05 was considered statistically significant. The Benjamini-Hochberg procedure was used to adjust for multiple comparisons.ResultsMultiple linear regression analysis revealed a significant association of female sex and greater TPC (P<.001), lower overall FM symptom severity (lower overall Revised Fibromyalgia Impact Questionnaire score; P=.03), and higher QOL subscale score for vitality (36-Item Short Form Health Survey vitality subscale score; P=.02). After adjustment for multiple comparisons, only the association between female sex and greater TPC remained significant. There were no sex-related differences in demographic characteristics, depression, anxiety, sleep problems, FM symptom severity, cognitive dysfunction, and QOL.ConclusionA higher TPC may be associated with female sex in patients with FM. The assumption of other sex-based differences in the clinical presentation of FM was not supported in our study.

Plasma Aβ biomarker associated with cognitive decline in preclinical Alzheimer’s disease

AbstractBackgroundUsing immunoprecipitation‐mass spectrometry, we recently developed and validated a plasma composite biomarker for the assessment of Aβ levels. However, as yet, it’s utility to predict clinical and cognitive outcomes remains unclear. This study aimed to examine the relationship between this plasma Aβ composite biomarker and cognitive function in cognitively normal older adults in two independent cohorts.MethodThis is a longitudinal study conducted in two independent cohorts – the Australian imaging, Biomarkers and Lifestyle (AIBL) study and Japan’s National Centre for Geriatrics and Gerontology (NCGG) study. A series of linear mixed models were conducted to determine the relationships between plasma Aβ composite scores and cognitive decline. Cognitively normal (CN) older adults enrolled in the AIBL study (n=156) and the NCGG study (n=57) were included in this analysis. Participants had undergone Aβ neuroimaging using positron emission tomography (PET), cognitive assessments and provided blood samples. We derived a high‐performance plasma Aβ composite biomarker by immunoprecipitation with mass‐spectrometry. The main outcome measures were composites of episodic memory, executive function, language and attention.ResultBoth continuous and categorical measures of the plasma Aβ composite biomarker were significantly related to decline in episodic memory and executive function (Figure 1). The magnitude of effects of the plasma Aβ composite on episodic memory and executive function were comparable to that observed for the effects of PET Aβ levels on these same outcome measures.ConclusionSeveral plasma Aβ biomarkers have been developed, but none have yet been applied to investigate their relationship with cognitive outcomes. Our results have important implications for the use of this biomarker in the detection of at‐risk individuals.

Retrospective Assessment of Risk Factors for Head and Neck Cancer Among World Trade Center General Responders.

Objective: To assess the reliability of a questionnaire designed to reconstruct risk factors for head and neck cancer relative to the 9/11 World Trade Center (WTC) response and over the lifetime.Methods: As part of a nested case-control study, 200 WTC Health Program (WTCHP) General Responder Cohort (GRC) members completed a newly-developed study questionnaire via telephone (with a trained interviewer) or online (self-administered). We assessed agreement between measures of tobacco and alcohol use in our questionnaire results and data collected previously during WTCHP-GRC monitoring visits using Cohens Kappa (κ) and intraclass correlation coefficient (ICC) for categorical and continuous measures, respectively. We compared agreement by disease status, survey mode, and year of WTCHP enrollment.Results: We observed high agreement between measures of lifetime, pre-WTC, and post-WTC smoking prevalence (all κ > 0.85) and smoking duration (all ICC > 0.84). There was moderate agreement between measures of smoking frequency (ICC: 0.61–0.73). Agreement between measures of smoking frequency, but not duration, differed by disease status, and agreement between smoking measures was higher for participants who completed our survey by phone than by web. Among cases, there were no differences based on enrollment in the WTCHP before or after diagnosis.Conclusion: Agreement between measures was generally high, although potential reporting bias and a mode effect that should be considered when interpreting analyses of self-reported data in this population; however differential misclassification appears to be minimal. Our questionnaire may be useful for future studies examining similar behavioral risk factors among disaster-exposed populations.

Rapid Onset of Efficacy of Baricitinib in Chinese Patients with Moderate to Severe Rheumatoid Arthritis: Results from Study RA-BALANCE.

Baricitinib is an oral, selective inhibitor of Janus kinase which demonstrates clinical efficacy in patients with rheumatoid arthritis (RA). This report aims to analyze the onset time of baricitinib in Chinese patients with moderately to severely active RA who had an inadequate response to methotrexate. This post hoc analysis evaluated clinical improvements of Chinese patients treated with baricitinib 4mg once daily compared with placebo, based on data from a phase3 study RA-BALANCE. Efficacy measures including American College of Rheumatology 20% (ACR20) response, ACR core set values, Disease Activity Score modified to include the 28 diarthrodial joint count (DAS28) using high-sensitivity C-reactive protein (hsCRP), DAS28-erythrocyte sedimentation rate, Simplified Disease Activity Index, Clinical Disease Activity Index, DAS28-hsCRP ≤ 3.2 response (low disease activity), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated at weeks1, 2, 4, 8, 12, 14, 16, 20, and 24 (except for FACIT-F evaluated every 4weeks). A logistic regression model and an analysis of covariance model were used to analyze treatment comparisons of categorical and continuous measures, respectively. Statistically significant (p ≤ 0.05) improvements were observed as early as week1 or 2 for the baricitinib group compared to placebo in almost all main efficacy measures. For other outcomes including 66 swollen joint count, 68 tender joint count, FACIT-F, and DAS28-hsCRP ≤ 3.2 response rate, differences were evident (p ≤ 0.05) by week4 in the baricitinib group compared with placebo. Significant improvements in all efficacy measures were sustained through 24weeks. Baricitinib demonstrated a rapid onset of efficacy on ACR20 response, ACR core set values, disease activity, and patient-reported outcome improvements in Chinese patients from RA-BALANCE. ClinicalTrials.gov identifier, NCT02265705.

Efficient Learning From Two-Class Categorical Imbalanced Healthcare Data

When data classes are differently represented in one v. other data segment to be mined, it generates the imbalanced two-class data challenge. Many health-related datasets comprising categorical data are faced with the class imbalance challenge. This paper aims to address the limitations of imbalanced two-class categorical data and presents a re-sampling solution known as ‘Syn_Gen_Min' (SGM) to improve the class imbalance ratio. SGM involves finding the greedy neighbors for a given minority sample. To the best of one's knowledge, the accepted approach for a classifier is to find the numeric equivalence for categorical attributes, resulting in the loss of information. The novelty of this contribution is that the categorical attributes are kept in their raw form. Five distinct categorical similarity measures are employed and tested against six real-world datasets derived within the healthcare sector. The application of these similarity methods leads to the generation of different synthetic samples, which has significantly improved the performance measures of the classifier. This work further proves that there is no generic similarity measure that fits all datasets.

Abstract 17284: Geographic Variation in Cardiovascular Health Among American Adults

Background: There are longstanding and pervasive geographic disparities in cardiovascular (CV) health in the US. We sought to evaluate the contemporary trends in CV risk factors by census regions from 2011-2017. The region-specific CV mortality for 2017 was evaluated to assess the geographic overlap between risk factors, CV mortality, and COVID-19 mortality. Methods: The age-adjusted prevalence (per 2010 US census proportions) of CV health index (CVHI) metrics (sum of ideal blood pressure, blood glucose, lipid levels, body mass index, smoking status, physical activity, and diet) (0-7 points), were estimated as both continuous and categorical (ideal, intermediate and poor CVHI) measures in the 2011-2017 BRFSS. Regional trends were evaluated with multivariable-adjusted logistic regression models. Age-adjusted CV mortality for 2017 was derived from the CDC WONDER database. COVID-19 crude mortality rates were ascertained from respective state public health departments. Results: Among 1,362,529 American adults, the CVHI score increased from 3.89±0.004 in 2011 to 3.96±0.01 in 2017 (P&lt;0.001), modestly improvements in all regions (P&lt;0.05 for all). Ideal CV health prevalence improved only in the northeastern (P=0.03) and southern regions (P=0.002). The CVHI score (3.81±0.01) and prevalence of ideal CV health [2017: 12.2% (95% CI: 11.7-12.7%)] was lowest in southern US. This corresponded with the distribution of CV mortality (per 100,000 persons), which was highest in southern region (233.0 [95% CI: 232.2-233.8]) and lowest in western region (197.5 [95% CI: 19.6-198.5]) ( Figure 1 ). State-level distribution of poor CV health did not track with COVID-19 mortality. Conclusion: Despite a modest improvement in CVHI, only one-in-six Americans have ideal CV health with significant regional and state-level differences that correlate with the geographical distribution of CV mortality but not COVID-19 mortality. These disparities may worsen after the COVID-19 pandemic.

Categorical and gradational: alternative survey measures of sex and gender

Demands for recognition of gender diversity and transgender people are growing. We tested non-binary sex and gender measures using nationally representative samples of US adults to assess feasibility for general population surveys. We find more support for a two-step categorical approach, with separate questions about natal sex and gender identity, than for a single question assessing transgender status as the latter was less reliable within our online surveys and over time. We also consider the challenge of determining measurement reliability for fluid characteristics and argue that using categorical and gradational gender measures in combination should become standard practice.

English

BACKGROUND Road traffic accidents are the most common cause of thoracic and abdominal trauma. The role of point of care ultrasound especially in developing countries is gaining evidence in management of acutely ill. We wanted to test the reliability of Fast and E-Fast in blunt abdominal and thoracic trauma cases and evaluate their role in the management of RTAs. METHODS A cross sectional study was conducted over a 12-month period among patients presenting at Emergency Medicine Department at Government Medical College, Kannur (then known as Academy of Medical Sciences, Pariyaram). After clinical examination and recording details, fast and E-Fast was done in the emergency department by emergency physicians trained in ATLS using a standard curvilinear probe of 2 - 5 MHz using Sonosite M-Turbo portable ultrasound machine (Fujifilm Sonosite) and compared with the gold standard CT. The CT used was 16 slice Spiral CT scan machine by GE Healthcare (Chicago, Illinois, United States). Results on continuous measurements presented on mean + SD (min-max) and results on categorical measurements were presented in numbers (%). Sensitivity and specificity were computed for analysis. RESULTS The overall sensitivity of Fast is 72.8 % and the specificity is 92 %. The overall sensitivity and specificity of E-Fast are 87 % and 92.3 % respectively. The reliability of point of care ultrasound as a screening tool to triage patients with blunt abdominal and thoracic trauma is 100 %. CONCLUSIONS Fast and E-Fast are quite reliable as screening tools in the management of acutely ill blunt trauma abdomen and chest patients. KEYWORDS Point of Care, Ultrasound, Blunt Trauma, Sensitivity, Fast, E-Fast

Reactive attachment disorder and disinhibited social engagement disorder in adolescence: co-occurring psychopathology\xa0and psychosocial problems

Insufficient care is associated with most psychiatric disorders and psychosocial problems, and is part of the etiology of reactive attachment disorder (RAD) and disinhibited social engagement disorder (DSED). To minimize the risk of misdiagnosis, and aid treatment and care, clinicians need to know to which degree RAD and DSED co-occur with other psychopathology and psychosocial problems, a topic little researched in adolescence. In a national study of all adolescents (N = 381; 67% consent; 12–20 years old; 58% girls) in Norwegian residential youth care, the Child and Adolescent Psychiatric Assessment interview yielded information about psychiatric diagnoses and psychosocial problems categorized as present/absent, and the Child Behavior Check List questionnaire was applied for dimensional measures of psychopathology. Most adolescents with a RAD or DSED diagnosis had several cooccurring psychiatric disorders and psychosocial problems. Prevalence rates of both emotional and behavioral disorders were high in adolescent RAD and DSED, as were rates of suicidality, self-harm, victimization from bullying, contact with police, risky sexual behavior and alcohol or drug misuse. Although categorical measures of co-occurring disorders and psychosocial problems revealed few and weak associations with RAD and DSED, dimensional measures uncovered associations between both emotional and behavioral problems and RAD/DSED symptom loads, as well as DSED diagnosis. Given the high degree of comorbidity, adolescents with RAD or DSED—or symptoms thereof—should be assessed for co-occurring psychopathology and related psychosocial problems. Treatment plans should be adjusted accordingly.

The association of body mass index (BMI) with treatment outcomes in patients with major depressive disorder

BackgroundIn patients with major depressive disorder (MDD), poor antidepressant treatment response might be associated with an excessive body mass index (BMI). However, the impact of underweight on treatment response is unclear. Moreover, it has not been studied whether a continuous or categorical BMI measure should be used to predict of treatment response. MethodsPost-hoc analysis of data collected in a clinical trial including adults with MDD (n=202) reporting outcomes of antidepressant medication, i.e. paroxetine, mirtazapine or paroxetine+mirtazapine. Measures included baseline BMI (underweight=BMI <18.5, normal weight:=BMI:18.5-23.9, overweight=BMI≥24) and symptom severity (17-item-Hamilton Depression scale; HAMD-17) assessed at weeks 0, 2, 3, 4, 6 and 8.Univariate analyses were used to explore the effect of baseline BMI on HAMD-17 reduction, response (defined as ≥50% HAMD-17 reduction) and remission (defined as HAMD-17 ≤7) at endpoint. Pearson correlation were used to explore the relationship between body weight, BMI as continuous measure and HAMD-17 reduction. Logistic regression was used to determine the predictors for remission. Multiple linear regression was used to establish the correlation of BMI with change of HAMD-17. Results111 (55.0%) patients were normal weight, 20 (9.9%) were underweight, 71 (35.1%) were overweight. Underweight patients showed the best improvement to antidepressant treatment. Non-remitters had greater body weight and BMI than remitters (P<0.05). The reduction of HAMD-17 was correlated with baseline body weight (r=-0.16, P=0.032) and BMI (r=-0.19, P=0.012). Logistic regression found patients with BMI<24 to be 2 times (OR=1.958, 95%CI: 1.015, 3.774) remitters (P=0.045) than overweight patients. The multiple linear regression showed that the change of HAMD-17 total score decreased with increasing BMI (β=-0.32, P = 0.016). ConclusionWe confirmed that BMI can predict treatment outcomes in MDD. For the first time we found that underweight patients benefit most from antidepressant treatment. The findings may be useful to physicians in their decision regarding the choice of antidepressants according to BMI.

Testing a continuous measure of recreation specialization among birdwatchers

ABSTRACT Recreation specialization is a framework that can be used to explain the variation among outdoor recreationists’ preferences, attitudes, and behaviors. Recreation specialization has been operationalized using several approaches, including summative indices, cluster analysis, and self-classification categorical measures. Although these approaches measure the multiple dimensions of the framework, they may not reflect the relative contribution of the dimensions to individuals’ degree of engagement. We illustrate an approach that uses second-order confirmatory factor analysis (CFA) factor scores as weights to determine a person’s degree of recreation specialization and compares the CFA-based results to those derived from cluster analysis. This approach permits the use of a broader set of statistical tests when compared to categorical specialization measures and provides information about the distribution of responses. Data were collected from an online survey of eBird registrants from the United States.

Real World Outcomes of Liposomal Daunorubicin and Cytarabine Versus 7+3 in Patients with Secondary Acute Myeloid Leukemia

Introduction: Liposomal daunorubicin and cytarabine (CPX-351) was approved based on data which showed improved overall survival (9.56 v 5.95 months; p = .003) and remission rates (47.7% v 33.3%; p = .016) compared to conventional cytarabine and daunorubicin (7+3) chemotherapy in older patients with newly diagnosed secondary acute myeloid leukemia (sAML). Patients receiving CPX-351 had prolonged time to neutrophil and platelet count recovery compared to 7+3, which was not associated with adverse outcomes (Lancet et al, JCO 2018). Based on these data, our center adopted CPX-351 as a first-line agent in this patient population. Considering the significant cost differences and delays in count recovery, we conducted a comparison of outcomes in patients who received CPX-351 versus 7+3 at our center. Methods: The objective of this study was to compare efficacy and safety of CPX-351 versus 7+3 in patients with sAML. Primary outcome was response rate as defined by CR or CRi. Secondary outcomes included duration of neutropenia, incidence of invasive fungal infections (IFIs), and number of patients proceeding to allogeneic hematopoietic cell transplant (HCT). Patients with sAML receiving induction with 7+3 (daunorubicin dosed at 60 or 90 mg/m2 per treating physician's discretion) or CPX-351 from July 2014 to April 2020 were reviewed. Secondary AML was defined as: AML with a history of myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), AML with myelodysplasia-related changes, or therapy-related AML. Patients with prior myeloproliferative neoplasms, myelofibrosis, or FLT3 mutations were excluded. Patient characteristics were summarized using descriptive statistics (TABLE 1) including mean for continuous measures and proportions and frequencies for categorical measures. The association between continuous variables and patient groups were assessed using ANOVA or Student's t-test. The associations between categorical variables and patient groups were evaluated using Chi-square test. Results: Over the study period, 65 patients with sAML received induction therapy with either CPX-351 (n = 31) or 7+3 (n = 34). Of these, 61 patients had an evaluable bone marrow biopsy at count recovery. The data is summarized in Table 2. The response rates (CR or CRi) were no different (36% 7+3 vs 36% CPX-351, p = 0.958) among the study population. Longer duration of neutropenia was observed with CPX-351 (33 days 7+3 vs 47 days CPX-351, p = 0.026). More patients in the 7+3 arm proceeded to allogeneic HCT; however, this was not statistically significant (59% 7+3 vs 39% CPX-351, p = 0.105). In an efficacy subgroup analysis of patients with TP53 mutation, there was no difference in response rates (33% 7+3 vs 11% CPX-351, p = 0.224). There was no difference in IFI between the groups (38% 7+3 vs 42% CPX-351, p = 0.761). Upon further analysis of IFI characteristics, there was no difference in choice of mold-active vs non mold-active prophylaxis (ppx) and the incidence of IFIs (40% mold ppx vs 39% non-mold ppx, p = 0.91). Patients with baseline neutropenia prior to induction did not have increased risk of IFIs (65% 7+3 vs 74% CPX-351, p = 0.626). Additionally, there were no between group differences in incidence of IFIs in patients who were neutropenic prior to induction. Conclusions: In the evaluable dataset of patients receiving 7+3 or CPX-351, there was no difference in CR/CRi rate between the two subgroups. There was a longer duration of neutropenia in the CPX-351 group without increased incidence of IFI. However, we report a higher incidence of IFI compared to the study population in Lancet et al (18% Lancet vs 40% Miami) despite appropriate anti-fungal prophylaxis, which may be due to patient selection on the clinical trial, demographic differences (e.g., age, ethnicity), or locoregional environmental factors. In our population, a greater percentage of patients who received 7+3 proceeded to allogeneic HCT. While this study was not powered to detect a significant difference between the two regimens and these findings require validation in larger cohorts, they do not support superior outcomes in patients who receive CPX-351. Data on differences in hospital costs will also be presented. Future directions include a larger multi-center real-world analysis to evaluate patient outcomes, safety, and the financial implications of these two regimens. Disclosures Watts: Genentech: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Aptevo Therapeutics: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees.

Firm Life Cycle and Cost of Debt

This paper examines the relation between the corporate life cycle and lending spreads. Using a sample of 20,307 firm-loan observations spanning 5,076 publicly traded U.S. firms, we find that mature firms pay lower lending spreads. This reduction is incremental to the variation explained by financial controls that may have previously been thought to sufficiently account for variation in the corporate life cycle. In our multivariate analysis, continuous measures of maturity yield point elasticities with effects as large as 1.50 bps while categorical life cycle measures indicate that firms in the introduction and decline phases pay lending spreads that are greater than firms in the mature phase (6 percent and 12 percent, respectively). We explore omitted variables bias and instrumental variable estimation in robustness testing and find these patterns persist. Our findings are consistent with theoretical predictions regarding the relationship between the corporate life cycle and various lending risks.

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Long-term metformin treatment and risk of peripheral neuropathy in older Veterans

AimOur objective was to assess whether increased duration of metformin therapy is associated with incident peripheral neuropathy (PN) in older Veterans with diabetes. MethodsUsing national Veterans Affairs registry data from 2002 to 2015, we examined Veterans (50 + years) with diabetes. Long-term metformin therapy was defined as prescription ≥ 500 mg/day, filled for ≥ 6 consecutive months. Metformin therapy duration was examined both as continuous and categorical measures. Incident PN was defined by medical chart review. We estimated unadjusted and adjusted (variables selecteda priori)odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. ResultsThe study included n = 210,004 individuals (mean ± SD: age: 66.2 ± 8.4 yrs, 96% male) prescribed metformin for 47.0 ± 34.0 months. Nineteen percent developed PN during follow-up. After adjusting for age, body mass index, duration of time receiving health care within the VA, smoking status, alcohol abuse, and vitamin B12 testing and treatment, the number of months of metformin treatment was associated with elevated odds for incident PN (aOR (metformin treatment - continuous) = 1.009 (95% CI = 1.009, 1.010); aOR (metformin treatment – categorical (ref: 6-<18 months): 18-<44.1 months = 1.57 (1.51–1.63), 44.1-<61 months = 2.05 (1.97–2.14), 61 + months = 2.69 (2.58–2.79), all p-values < 0.0001). ConclusionOur study suggests that Veterans treated for at least 18 months with metformin are approximately 2–3 times more likely to develop PN than those treated at least six, but<18 months. Future studies are needed to determine whether the association we found may be due to a decline in vitamin B12 status following metformin initiation.