Two-sample Wilcoxon Rank-sum Test Research Articles

0583 Obesity-Associated Sleep Hypoventilation Syndrome and Adverse Post-Operative Bariatric Surgery Outcomes

Abstract Introduction Although obesity hypoventilation syndrome (OHS) is associated with right ventricular dysfunction and increased mortality, its contribution to post-bariatric surgery risk remains unclear due to non-systematic OHS assessments. We hypothesize that patients with obesity-associated sleep hypoventilation (OASH) have increased adverse post-bariatric surgery outcomes than those without. Methods Patients undergoing polysomnography (PSG) prior to bariatric surgery at the Cleveland Clinic from 2011-2018 were retrospectively examined. OASH was defined by body mass index (BMI) ≥30kg/m2 and either PSG-based end-tidal CO2 ≥45mmHg or serum bicarbonate ≥27mEq/L. The following were considered individually and as a composite outcome: ICU stay, re-intubation, tracheostomy, discharge disposition or 30-day readmission. All-cause mortality was also examined. Outcomes were compared using two-sample t-test or Wilcoxon rank sum test and Chi-square or Fisher exact test. A multivariable logistic regression model included age, sex, BMI, apnea hypopnea index(AHI) and diabetes to examine OAHS and the composite outcome. All-cause mortality was compared using Kaplan-Meier estimation and hazard ratios from Cox proportional hazards models. SAS software (version 9.4) was used with overall significance level of 0.05. Results The sample comprised 1665 patients: age 45.2±12 years, 20.4% male, BMI=48.7±9 kg/m2, and 63.6% Caucasian. OASH prevalence was 68.5%. OAHS patients were older and more likely to be male with higher BMI, AHI and HbA1c. Although some individual outcomes were higher in OASH vs. non-OASH, findings were not statistically significant: re-intubation (1.5%vs.1.3%, p=0.81) and 30-day readmission (13.8% vs.11.3%, p=0.16). The composite outcome remained significantly associated with OAHS in the multivariable model: OR=1.36, 95%CI:1.005,1.845. Mortality was 2% in OASH and not significantly higher than non-OAHS (HR=1.39, 95%CI:0.56,3.42). Conclusion In this largest sample to date of systematically phenotyped OASH in patients undergoing bariatric surgery, we identify increased post-operative morbidity in those with OASH. Further study is needed to identify whether peri-operative treatment of OASH improves surgical outcomes. Support

The fetal/placental weight ratio is associated with the incidence of atopic dermatitis in female infants during the first 14 months: The Hamamatsu Birth Cohort for Mothers and Children (HBC Study).

BackgroundAmong atopic diseases, atopic dermatitis is the most common allergic disease in children and influences both infantile and parental quality of life.ObjectiveThe present study investigated the sex-specific relationship between the fetal/placental weight ratio and The incidence of atopic dermatitis in infants during the first 14 months of life.MethodsStudy participants were 922 infants (462 female and 460 male) from singleton pregnancies enrolled in the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) after the exclusion of 298 with missing data on atopic dermatitis. The enrollment of infants with atopic dermatitis was based on a positive response from parents regarding whether a physician had ever diagnosed their child with atopic dermatitis by 14 months of age. The two-sample Wilcoxon rank-sum test or χ2 test was adopted for descriptive analyses where appropriate. Unadjusted odds ratios and 95% confidence intervals for the infantile incidence of atopic dermatitis were compared using logistic regression analyses.ResultsMaternal and perinatal factors did not correlate with the incidence of infantile atopic dermatitis. Fetal/placental weight ratio, but not birth or placental weight, correlated with the incidence of atopic dermatitis in female, but not male, infants. A correlation was still observed after adjustments for maternal allergies, gestational age at birth, maternal smoking during pregnancy, and household income at birth (odds ratio: 1.57; 95% confidence interval, 1.05–2.33).ConclusionWe speculated that the intrauterine fetal environment, represented by a relatively small placenta, programs a predisposition in only female infants to atopic dermatitis during the first 14 months of life.

Variations in Morning Serum Cortisol Levels Based on Sex and Pubertal Status

Introduction: Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency. Methods: A retrospective chart review was conducted using electronic medical records of patients seen at Children’s Mercy Kansas City from 11/01/2007 to 11/01/2017. Patients between 2 and 18 years of age who had pubertal staging assessed by a pediatric endocrinologist and confirmed adrenal sufficiency by high-dose ACTH stimulation testing were included. Two-sample Wilcoxon rank sum (Mann-Whitney) tests or t tests were used to compare morning cortisol levels between females and males – both independent of Tanner stage and by Tanner stage. Multivariable regression models were used to evaluate associations among covariates on two outcomes: morning cortisol levels and peak cortisol values with ACTH stimulation. Results: Morning cortisol levels were greater in females than males independent of Tanner staging (p = 0.0054) and also in Tanner stage 1 (p = 0.0042). No differences in mean morning cortisol levels between Tanner stage 2–5 females and males were found (p = 0.4652). Morning cortisol levels were not significantly different between Tanner 1 patients and Tanner 2–5 patients independent of sex (p = 0.0575). Sex was predictive of serum morning cortisol levels (p = 0.015), and morning cortisol levels were predictive of peak cortisol levels during ACTH stimulation testing (p < 0.001). Conclusions: These data suggest that different normative cortisol values may need to be established for pediatric females and males, and by pubertal status. Larger prospective studies are needed to evaluate the role of sex and pubertal status in identifying adrenal insufficiency in the ­pediatric population.

Body mass index and attitudes towards health behaviors among women with endometrial cancer before and after treatment

IntroductionSome experts have argued that obesity-related malignancies such as endometrial cancer are a “teachable moment” that lead to meaningful changes in health behaviors. It is unclear if endometrial cancer survivors...

Potent reduction of plasma lipoprotein (a) with an antisense oligonucleotide in human subjects does not affect ex vivo fibrinolysis

It is postulated that lipoprotein (a) [Lp(a)] inhibits fibrinolysis, but this hypothesis has not been tested in humans due to the lack of specific Lp(a) lowering agents. Patients with elevated Lp(a) were randomized to antisense oligonucleotide [IONIS-APO(a)Rx] directed to apo(a) (n = 7) or placebo (n = 10). Ex vivo plasma lysis times and antigen concentrations of plasminogen, factor XI, plasminogen activator inhibitor 1, thrombin activatable fibrinolysis inhibitor, and fibrinogen at baseline, day 85/92/99 (peak drug effect), and day 190 (3 months off drug) were measured. The mean ± SD baseline Lp(a) levels were 477.3 ± 55.9 nmol/l in IONIS-APO(a)Rx and 362.1 ± 89.9 nmol/l in placebo. The mean± SD percentage change in Lp(a) for IONIS-APO(a)Rx was -69.3 ± 12.2% versus -5.4 ± 6.9% placebo (P < 0.0010) at day 85/92/99 and -15.6 ± 8.9% versus 3.2 ± 12.2% (P = 0.003) at day 190. Clot lysis times and coagulation/fibrinolysis-related biomarkers showed no significant differences between IONIS-APO(a)Rx and placebo at all time points. Clot lysis times were not affected by exogenously added Lp(a) at concentrations up to 200 nmol/l to plasma with very low (12.5 nmol/l) Lp(a) levels, whereas recombinant apo(a) had a potent antifibrinolytic effect. In conclusion, potent reductions of Lp(a) in patients with highly elevated Lp(a) levels do not affect ex vivo measures of fibrinolysis; the relevance of any putative antifibrinolytic effects of Lp(a) in vivo needs further study.

Methylated DNA markers (MDMs) in primary (pCRC) and metastatic colorectal cancers (mCRC).

3599 Background: Existing tools for post-treatment CRC surveillance and monitoring are insensitive and expensive. MDMs are broadly informative for early detection of CRC but have not been extensively studied for disease monitoring. As a first step, we sought to assess the concordance of novel CRC-associated MDMs in pCRC and mCRC. Methods: A panel of 14 MDMs previously identified to be highly discriminant for pCRC was selected on the basis of high median fold-change of MDM levels relative to buffy coat (682 (IQR: 132-19347)). Surgically resected pCRC and paired mCRC were identified from institutional pathology databases. Quantitative methylation-specific PCR was used to assay MDMs. 30 paired samples per metastatic subtype were calculated to be sufficient. MDM levels were compared using two-sample and paired Wilcoxon rank sum tests. Results: 87 patients with paired pCRC and mCRC including 57 synchronous and 30 metachronous metastases were included. 41/87 (47%) had neoadjuvant and 59/87 (68%) had adjuvant chemotherapy. All synchronous metastases were to liver. Metachronous metastases were to liver in 19/30 (63%) and to lung in 11/30 (37%). The levels of 14 selected MDMs were remarkably similar between paired pCRC and mCRC (Table). Individual MDM levels and the average level of all MDMs combined were not significantly different ( p&gt; 0.0018 by Bonferroni correction). Conclusions: MDM levels are highly concordant in pCRC and mCRC. Thus, MDMs discovered from pCRC should be further studied for non-invasive surveillance after surgical resection and monitoring of treatment response in mCRC. [Table: see text]

195 Acne keloidalis nuchae: A population-based epidemiologic study in central and northeastern Pennsylvania

Acne keloidalis nuchae (AKN) is reported to mainly occur in adult men of African descent. However, it has been our clinical observation that a large portion of our patients with AKN is not African-American (AA). This study is the largest analysis of demographic and epidemiologic data in non-AA patients with AKN. A retrospective search of the Geisinger Health System EPIC database was performed to identify patients with AKN between 2011-2018. 110 patients were identified and their demographic and epidemiologic data were obtained and analyzed. Comparisons between AA and non-AA groups were performed using the Chi-square or Fisher’s exact test, and two-sample T-test or Wilcoxon rank sum test. Mean age at diagnosis was 36.1 years old, most patients were male (88.2%), Caucasian (59.1%), and had an average BMI of 33.5 kg/m2 (32.9 vs. 33.8 for AA and non-AA respectively, p=0.62). A subset of patients had diabetes (10% vs. 5.9% for AA and non-AA respectively, p=0.46), hyperlipidemia (10% vs. 20.6% for AA and non-AA respectively, p=0.15), were current or former smokers (31.6% vs. 34.3% for AA and non-AA respectively, p=0.66) and took anticonvulsants (10% and 19.1% of AA and non-AA respectively, p=0.21). The most common treatments used for AKN were oral tetracyclines (54.1%), topical corticosteroids (61.2%) and topical antibiotics (41.2%), with non-AAs more likely to be treated with topical antibiotics (p=0.0004). Most patients with AKN in central and northeastern Pennsylvania are Caucasian males. This study identifies similarities and differences between AAs and non-AAs with AKN. Our results serve as a reminder that AKN should be on the differential for chronic scarring folliculitis and perifolliculitis of the posterior scalp and neck in Caucasians and highlight the potential association between obesity and AKN.

Muscle fat quantification using magnetic resonance imaging: case-control study of Charcot-Marie-Tooth disease patients and volunteers.

BackgroundThis study aimed to evaluate the potential value of 3D multiple gradient echo Dixon‐based magnetic resonance imaging (MRI) sequence as a tool for thigh intramuscular fat quantification in Charcot–Marie–Tooth disease (CMT) patients.MethodsA prospective comparison study comprising 18 CMT patients and 18 age/sex‐matched volunteers was performed. MRI including 3D multiple gradient echo Dixon‐based imaging was performed for each subject. Region of interest analyses were performed at the upper and lower third of both thighs. The two‐sample t‐test or Wilcoxon rank sum test was used for intergroup comparison of the mean muscle fat fraction. Intraclass correlation coefficients were used to evaluate the interobserver agreement and test–retest reproducibility. Semiquantitive analysis using the Goutallier classification (Grades 0–4) was performed on T1‐weighted images in upper thigh muscles. For Goutallier Grade 0 muscles, comparison of the mean intramuscular fat fraction between volunteers and CMT patients was performed.ResultsThe interobserver agreements were excellent for all measurements (intraclass correlation coefficients > 0.8). Mean muscle fat fractions were significantly higher in all the measured muscles of CMT patients (P < 0.05) except in the adductor magnus in the upper thigh (P = 0.109). Goutallier Grade 0 muscles of the CMT patients showed a significantly higher mean fat fraction compared with that of the volunteers (P < 0.05).Conclusions3D multiple gradient echo Dixon‐based MRI is a reproducible and sensitive technique which can reveal a significant difference in the fat fraction of thigh muscle, including comparison between Goutallier Grade 0 muscles, between CMT patients and volunteers.

Effectiveness and safety of electroacupuncture for poststroke patients with shoulder pain: study protocol for a double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial

BackgroundPractitioners of complementary and alternative medicine have suggested that acupuncture could alleviate poststroke shoulder pain, based on the clinical evidence. This study protocol is aimed at showing the effectiveness and safety of electroacupuncture therapy for stroke survivors with shoulder pain.MethodsAfter assessing their eligibility, 60 stroke survivors with shoulder pain will be enrolled from two traditional Korean medicine hospitals and randomly divided into either the verum or the sham electroacupuncture (EA) group with a 1:1 ratio. The participants will receive 9 sessions of EA procedures for 3 weeks. The verum EA consists of needling on 6 unilateral acupoints (LI4, LI15, TE14, SI9, SI11, and GB21) with electronic stimulation. A non-penetrating Park sham device and fake electronic stimulation will be used in the sham group on the same acupoints. Patients and outcome assessors will be blinded throughout the entire study. A visual analog scale will be used primarily for the evaluation, and pain rating scale, Fugl-Meyer assessment for upper extremity, modified Ashworth scale, manual muscle test, passive range of motion test, Korean version of a modified Barthel index, and Korean version of the Beck depression inventory will be also be measured. A blinding index will be assessed. For safety, adverse events will be recorded. Data will be statistically analyzed by two-sample t-test or Wilcoxon rank sum test for efficacy and a chi-squared test or Fisher’s exact test for safety, at 5% of significance level.DiscussionWe expect this double-center, randomized, sham-controlled, patient- and assessor-blinded parallel trial to explore the effectiveness and safety of EA therapy, compared with sham EA, for poststroke shoulder pain.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03086863

Biomechanical effects of osteoplasty with or without Kirschner wire augmentation on long bone diaphyses undergoing bending stress: implications for percutaneous imaging-guided consolidation in cancer patients

BackgroundOsteoplasty has been discouraged in long bones. However, despite a substantial lack of pre-clinical biomechanical tests, multiple clinical studies have implemented a wide range of techniques to optimise long bone osteoplasty. The aim of the present study is to evaluate the biomechanical properties of osteoplasty alone and in combination with Kirschner wires (K-wires) in a cadaveric human diaphyseal model undergoing 3-point bending stress.MethodsThirty unpaired human cadaveric hemi-tibia specimens were randomly assigned to receive no consolidation (group 1, n = 10), osteoplasty alone (group 2, n = 10), or K-wires augmented osteoplasty (group 3, n = 10). Specimens were tested on a dedicated servo-hydraulic machine using a 3-point bending test. Fracture load was calculated for each specimen; two-sample Wilcoxon rank-sum tests were used to assess differences between groups.ResultsMedian volume of polymethyl methacrylate injected was 18 mL for group 2 (25th–50th percentile 15–21 mL) and 19 mL for group 3 (25th–50th percentile 17–21). There were no significant differences in fracture load between groups 1 and 2 (z = − 0.793; p = 0.430), between groups 1 and 3 (z = − 0.944; p = 0.347), and between groups 2 and 3 (z = − 0.454; p = 0.650). Fractures through the cement occurred in 4 of 30 cases (13.3%); there were no K-wires fractures.ConclusionsOsteoplasty with or without K-wires augmentation does not improve the resistance of diaphyseal bone to bending stresses.

Impact of Pharmacist-directed Counseling and Message Reminder Services on Medication Adherence and Clinical Outcomes in Type 2 Diabetes Mellitus.

Introduction:Medication nonadherence is the most common issue observed in the management of diabetes because of complex and lifelong therapy. The study aimed to assess the effect of pharmacist-directed counseling and daily text message reminder on medication adherence and clinical profile of patients with type II diabetes.Materials and Methods:This prospective, open-labeled, randomized control trial was carried out in outpatient medical department of a secondary care referral hospital. A total of 330 patients who met study criteria were enrolled and randomized into an intervention group (n = 165), received counseling and daily messages about medication intake and control group (n = 165), and usual care by physician. Medication adherence and clinical outcomes such as glycosylated hemoglobin (HbA1C), systolic blood pressure (SBP), low-density lipoprotein (LDL) cholesterol, triglyceride (TG) levels, and body mass index (BMI) were recorded at baseline and follow-up visits. Two-sample Wilcoxon rank sum test was used to compare the mean difference of medication adherence and paired t-test was used to compare clinical outcomes.Results and Discussion:The mean age of intervention and control groups were 57.1 ± 8.55 and 58.5 ± 8.53 years, respectively. The mean difference of medication adherence from baseline to second follow-up visit was significantly more in intervention group (12.2 ± 7.1%) compared to that in control group (0.75 ± 10.2 %) with a P < 0.001. From baseline to second follow-up visit, HbA1C (7.79 ± 0.67 to 6.91 ± 0.83 %), SBP (136.75 ± 20.09 to 126.23 ± 18.22 mm Hg), and LDL cholesterol (104.14 ± 26.23 to 98.29 ± 20.87 mg/dL) levels were significantly reduced in intervention group compared to that in control group with a P < 0.01. No significant improvement was observed in TG (169± 33.71 to 168 65 ± 33.90 mg/dL) and BMI (27.9 ± 4.21 to 27.1 ± 3.12 Kg/m2) levels from baseline to second follow-up visit.Conclusion:Pharmacist-directed patient counseling combined with message reminder showed a greater effect on the improvement of medication adherence and control of glycemia, blood pressure, and lipid profile in diabetes.

Hypoenhancing prostate cancers on dynamic contrast-enhanced MRI are associated with poor outcomes in high-risk patients: results of a hypothesis generating study.

To investigate the association of hypoenhancement on dynamic Contrast enhanced (DCE) with prostate cancer patient outcomes. This was a single-institution retrospective Institutional Review Board (IRB)-approved cohort study of 54 men who had prostate Magnetic Resonance Imaging (MRI) within 6months of cancer diagnosis between 01/2012 to 03/2014. Two readers independently identified the dominant MRI-lesions utilizing Prostate Imaging-Reporting and Data System-version2- guidelines. These lesions were classified as hypoenhancing or hyperenhancing, compared to normal peripheral zone using quantitative DCE analysis. The t test for unequal sample sizes and the two-sample Wilcoxon rank-sum tests were used to compare groups. Logistic regression determined if DCE characteristics predict the development of metastases or prostate cancer death. Time-to-progression was significantly shorter for hypoenhancing tumors (6.2 vs. 24.8months, p = 0.05). Men with these lesions had a higher odds of having poor outcome (univariate logistic regression, odds ratio (OR) 6.79, 95% confidence interval (CI) 1.45-31.72, p = 0.02; multivariate analysis, OR 2.05, 95% CI 0.30-13.72, p = 0.47). Hypoenhancing tumors were larger (33.1 vs. 19.1mm, p < 0.001) and more likely to be intermediate (Gleason scores 3 + 4 and 4 + 3) and high-grade (Gleason scores ≥ 4 + 4) prostate cancers (p = 0.05). Men in the hypoenhancing group had a higher mean prostate-specific antigen (PSA) value (87.6 vs. 24.8ng/dL, p = 0.01) and PSA density (1.54 vs. 0.72, p = 0.03). The mean Ktrans and kep of hypoenhancing lesion were lower when compared to hyperenhancing lesions (p = 0.03 and p = 0.04). Ve values did not differ (p = 0.25). Men with hypoenhancing prostate cancers may have a worse prognosis than men with hyperenhancing tumors.

PS01.242: HIATAL HERNIA AFTER MINIMALLY INVASIVE ESOPHAGECTOMY

Abstract Background Hiatal hernias (HH) are a known, yet poorly studied, post-surgical complication of esophagectomy. The aim of this study was to analyze in a retrospective fashion the MIE experience at our institution, in order to individuate factors associated with post-surgical HH development. Methods We reviewed data from MIE performed at University of Colorado from July 2013 to July 2017. Our most common approach of choice is Ivor Lewis MIE with circular stapled end to side anastomosis. We divided our patient population in two groups: those who developed a HH at any time post operatively and those who did not. We compared pre-, intra- and post-operative clinical variables of interest in the two groups using Pearson chi-squared and Fisher's exact test for binomial variables and Two-sample Wilcoxon rank-sum (Mann-Whitney) test for continuous variables. Results 91 patients underwent MIE in the study period: 11 developed HH in a time frame ranging from one week to two years post operatively. 8 patients had a HH involving one or more intra-abdominal organs other than the stomach; 3 patients had a HH interesting mostly the tubulized stomach. 7 patients required a reoperation. There were no statistically significant differences in the prevalence of pre-operative comorbidities between the two groups. Patient who developed a HH were significantly less likely to have had prior abdominal or thoracic surgery (Pr = 0.039). As expected, they were also significantly more likely to require a reoperation (Pr = 0.000). There were no statistically significant differences in intra-operative variables between the two groups, including operative time and anastomotic technique, nor where there differences in incidence of post operative complications other than HH. We did observe a trend towards higher rate of preoperative chemotherapy and radiation in the HH group. Of note, we did attempt to prevent HH by means of tacking abdominal organs to the abdominal wall, however this did not prove to significantly decrease HH incidence. Conclusion HH occurs in a non-negligible percentage of patients undergoing MIE. Lack of prior surgery appears to be significantly associated with HH, perhaps due to lesser adhesion burden acting as a mean of organ fixation. Disclosure All authors have declared no conflicts of interest.

Natural history of echocardiographic abnormalities in mucopolysaccharidosis III

BackgroundMucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. MethodsA single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. ResultsTwenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). ConclusionsIndividuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range.

By Default: The Effect of Prepopulated Prescription Quantities on Opioid Prescribing in the Emergency Department.

IntroductionOpioid prescribing patterns have come under increasing scrutiny with the recent rise in opioid prescriptions, opioid misuse and abuse, and opioid-related adverse events. To date, there have been limited studies on the effect of default tablet quantities as part of emergency department (ED) electronic order entry. Our goal was to evaluate opioid prescribing patterns before and after the removal of a default quantity of 20 tablets from ED electronic order entry.MethodsWe performed a retrospective observational study at a single academic, urban ED with 58,000 annual visits. We identified all adult patients (18 years or older) seen in the ED and discharged home with prescriptions for tablet forms of hydrocodone and oxycodone (including mixed formulations with acetaminophen). We compared the quantity of tablets prescribed per opioid prescription 12 months before and 10 months after the electronic order-entry prescription default quantity of 20 tablets was removed and replaced with no default quantity. No specific messaging was given to providers, to avoid influencing prescribing patterns. We used two-sample Wilcoxon rank-sum test, two-sample test of proportions, and Pearson’s chi-squared tests where appropriate for statistical analysis.ResultsA total of 4,104 adult patients received discharge prescriptions for opioids in the pre-intervention period (151.6 prescriptions per 1,000 discharged adult patients), and 2,464 post-intervention (106.69 prescriptions per 1,000 discharged adult patients). The median quantity of opioid tablets prescribed decreased from 20 (interquartile ration [IQR] 10–20) to 15 (IQR 10–20) (p<0.0001) after removal of the default quantity. While the most frequent quantity of tablets received in both groups was 20 tablets, the proportion of patients who received prescriptions on discharge that contained 20 tablets decreased from 0.5 (95% confidence interval [CI] [0.48–0.52]) to 0.23 (95% CI [0.21–0.24]) (p<0.001) after default quantity removal.ConclusionAlthough the median number of tablets differed significantly before and after the intervention, the clinical significance of this is unclear. An observed wider distribution of the quantity of tablets prescribed after removal of the default quantity of 20 may reflect more appropriate prescribing patterns (i.e., less severe indications receiving fewer tabs and more severe indications receiving more). A default value of 20 tablets for opioid prescriptions may be an example of the electronic medical record’s ability to reduce practice variability in medication orders actually counteracting optimal patient care.

Menarche, menopause, and pregnancy data in untreated females and females treated with agalsidase alfa in the Fabry Outcome Survey

Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials.A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables.Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3).Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only mild progression of abnormalities, none requiring intervention. Valvular disease prevalence is similar to MPS I and II, but appears less severe. These findings raise no specific concerns for gene transfer trials in patients in this age range.

Abstract 71: Circulating Inter-alpha Inhibitor Protein Levels Decline After Stroke in Humans: Exogenous Supplementation is Protective in Multiple Animal Models of Ischemic Stroke

Introduction: Inter-alpha Inhibitor Proteins (IAIP) are a family of endogenous plasma and extracellular matrix molecules. IAIPs have been shown to down-regulate inflammation, inhibit destructive serine proteases, and bind extracellular histones to neutralize cytotoxicity. Interestingly, many of these factors also regulate neuroprotection after stroke. In our initial studies, we found that IAIP treatment was neuroprotective in the middle cerebral artery occlusion model. Here, we analyzed if stroke alters IAIP using plasma samples from both mice and human stroke patients, and we investigated whether IAIP could provide neuroprotection using multiple stroke models. Methods: C57BL/6 mice were subjected to stroke with an autologous thromboembolic clot followed by reperfusion using t-PA. A separate cohort underwent the permanent occlusion model. Mice were randomized to receive IAIP or vehicle at 6h and 18h after stroke onset. Infarct was assessed 48h after reperfusion with t-PA, or 72h after permanent occlusion. Plasma samples from stroke patients and vascular risk factor matched controls were used for changes in IAIP levels using ELISA. Statistics were performed by two-sample t-test or Wilcoxon rank-sum test. P &lt;0.05 considered significant. Results: IAIP treatment significantly reduced total injury size (t-PA alone 22±2% vs. t-PA+IAIP 13±3%; n=4-5/grp). Protection was also seen after permanent occlusion (vehicle 59.4±3.9% vs IAIP 39.5±5.9%; n=6-8/gp, p&lt;.05), showing efficacy of IAIP in two different models. IAIP treatment improved survival rates (82% with IAIP vs 63% with vehicle) and neurological scores compared to vehicle group (p&lt;0.05). Mean IAIP levels were significantly lower (stroke patients 134.4 ug/ml; n=51 vs controls 157.5 ug/ml; n=40), in parallel, increased IAIP-Histone complexes were seen in these patients. Similar changes were identified in mouse samples. Conclusions: Our results show that delayed IAIP treatment can significantly reduce cell death in both permanent ischemia and/or in combination with t-PA. IAIP could potentially represent an important, novel treatment for stroke. Our studies in combination with t-PA further strengths this clinical translatability and to design personalized dosing based on IAIP levels.

Mitochondrial DNA copy number instability in ERBB2-amplified breast cancer tumors.

Increase in the copy number of ERBB2, a Tyrosine Kinase Receptor (TKR) leads to the overexpression of oncogene product and consequently uncontrolled cell proliferation which has been reported in different aggressive cancers with mitochondrial malfunctions. Although, amplification of ERBB2 has been reported in different studies; however, the association between changes in mitochondrial DNA content and the ERBB2 gene copy number is poorly understood. The relative mitochondrial DNA content of breast cancer tumor tissues of 70 patients who were referred to Imam Khomeini Hospital Complex was determined using quantitative Real-time PCR. Multiplex ligation-dependent probe amplification (MLPA) was conducted to evaluate the ERBB2 gene copy number variation and finally, two-sample Wilcoxon rank-sum (Mann-Whitney) test was used to investigate the possible association between mitochondrial DNA (mtDNA) content and the ERBB2 gene amplification. Seventeen out of 70 breast cancer tumor tissues were found with ERBB2 gene amplification. Comparison of the mitochondrial DNA content of the aforementioned samples with the rest of the cases showed a significant decrease in the mitochondrial DNA content of the ERBB2-amplified samples (P=0.01). Our data provided evidence that ERBB2 have the potential to have a regulatory role over mitochondrial activity by controlling the mtDNA content.

The role of Mycobacterium tuberculosis antigen specific cytokines in determination of acid fast bacilli culture status in pulmonary tuberculosis patients co-infected with human immunodeficiency virus.

IntroductionThe interaction between Mycobacterium tuberculosis and HIV leads to rapid progression of tuberculosis (TB) and human immunodeficiency virus (HIV)-induced immunosuppression. Diagnosis of TB in these patients is more difficult due to its atypical presentations giving contradicting results. The overall aim of this study was to evaluate the ability of pro-inflammatory cytokine (Th1) and anti-inflammatory cytokine (Th2) to discriminate between culture-positive and -negative smear status in HIV-TB co-infected patients.MethodsIn a prospective cohort, a total of 86 study participants were recruited: 46 culture-negative and 40 culture-positive. Blood and sputum samples were collected from all participants. The blood was then analyzed using FACSCalibur flow cytometer to immunophenotype the cells and ELISA performed for cytokine profiles. Sputum samples were analyzed to determine smear status using direct microscopy and Lowenstein Jensen medium. Statistical analyses were performed using R software. Independent samples t-test was used to compare means between the two groups, while the medians were compared using two-sample Wilcoxon rank sum test. Pearson's Chi-square test was used to compare the proportion of male and female participants across the culture and AFB smear status. In order to determine the predictive power of Th1 and Th2 in discriminating Pulmonary Tuberculosis status (PTB) (culture status was used as a confirmatory test), binary logistic regression models were fitted for Th1 covariates [IFN-γ, TNF-α, IL-2 and IL-12(p70)] and Receiver Operating Characteristic (ROC) curves plotted.ResultsThe overall mean age of the participants was 39 years (SD=12), 42% being male. Although, lymphocytes counts were higher in culture-positive relative to culture-negative, the CD8, CD19, and CD16/CD56 were comparable in the two groups. The CD4 counts differed between the two groups (P=0.012). The Th1 showed a better discrimination between culture-positive and -negative PTB individuals; IFN-γ (P=0.001), TNF-α (P=0.001), IL-2 (P=0.001) and IL-12(p70) (P=0.016). The Th2 cytokines (IL-4, IL-6 and IL-10) were comparable between the culture-positive and -negative groups. However, when the combination of Th1 cytokines [IFN-γ, TNF-α, IL-2 and IL-12(p70)] was fitted in binary logistic regression models, the predictive power was high with area under curve (AUC) being 89.7% in discriminating PTB.ConclusionThis study provides evidence for the ability of a combination of Th1 cytokines in discriminating against culture-positive and culture-negative PTB.

High transverse skin incisions may reduce wound complications in obese women having cesarean sections: a pilot study

Objective: Women having cesarean section have a high risk of wound complications. Our objective was to determine whether high transverse skin incisions are associated with a reduced risk of cesarean wound complications in women with BMI greater than 40.Methods: A retrospective cohort study was undertaken of parturients ages 18–45 with BMI greater than 40 having high transverse skin incisions from January 2010 to April 2015 at a tertiary maternity hospital. Temporally matched controls had low transverse skin incisions along with a BMI greater than 40. The primary outcome, wound complication, was defined as any seroma, hematoma, dehiscence, or infection requiring opening and evacuating/debriding the wound. Secondary outcomes included rates of endometritis, number of hospital days, NICU admission, Apgar scores, birth weight, and gestational age at delivery. Analysis of outcomes was performed using two-sample t-test or Wilcoxon rank-sum test for continuous variables and Fisher’s exact test for categorical variables.Results: Thirty-two women had high transverse incisions and were temporally matched with 96 controls (low transverse incisions). The mean BMI was 49 for both groups. There was a trend toward reduced wound complications in those having high transverse skin incisions, but this did not reach statistical significance (15.63% versus 27.08%, p = .2379). Those having high transverse skin incisions had lower five minute median Apgar scores (8.0 versus 9.0, p = .0021), but no difference in umbilical artery pH values. The high transverse group also had increased NICU admissions (28.13% versus 5.21%, p = .0011), and early gestational age at delivery (36.8 versus 38.0, p = .0272).Conclusion: High transverse skin incisions may reduce the risk of wound complications in parturients with obesity. A study with more power should be considered.