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Cardiovascular II, 10:30 AM, Saturday February 24, 2018
609 Takotsubo cardiomyopathy in setting of acute coronary syndrome
University of Florida College of Medicine, Jacksonville, FL
Background Takotsubo cardiomyopathy is usually a diagnosis of exclusion with angiographically normal coronary arteries. Stress induced cardiomyopathy with concomitant acute coronary syndrome(ACS) is uncommon.
Case 57 years old male with history of hypertension presented with complaint of atypical chest pain after argument with his landlord. Nuclear stress test one month prior to presentation showed no inducible ischemia with preserved ejection fraction. In ED, his Troponin I was 0.34 initially and trended up to 0.60. ECG did not show any ischaemic changes and he was admitted to coronary care unit for Non ST elevation myocardial infarction (NSTEMI) treatment. His chest pain initially resolved with nitrates, however 4 hours after admission his pain acutely worsened.
A repeat ECG showed ST-segment elevation in V1-V4, AVR. Patient was taken for left heart catheterization which revealed a 90% stenosis of the mid left anterior descending artery (LAD) and 80% stenosis of the proximal diagonal branch. Left ventriculogram showed ejection fraction of 25%–30% with inferior, anterior, septal and lateral mid to distal wall hypokinesis, with hyperdynamic bases and apical ballooning. He received a drug eluding stent to LAD and diagonal branch. His troponin T peaked a 0.27 and trended down. EKG developed dynamic changes (figure). Transthoracic echocardiogram (TTE) done after re-vascularisation showed EF of 30%–35%, with same wall motion abnormalities as on Left ventriculogram. He was discharged in stable condition on aspirin, ticagrelor, atorvastatin and carvedilol. His TTE 3 months after showed complete recovery of LVEF and normal wall motion.
Conclusion Wall dysfunction in setting of myocardial injury in CAD should be limited to the region supplied by culprit artery. There may be possible additional stress induced cathecholamine surge leading to a Takotsubo cardiomyopathy with concomitant ACS.
610 Neurogenic cardiomyopathy in patients with intracranial haemorrhage
UTHSC Memphis, Collierville, TN
Purpose of study Cardiac pathology can accompany intracranial haemorrhage (ICH). Several reports have described neurogenic stunned myocardium in patients with ICH. However, the incidence, predictors and outcomes of neurogenic cardiomyopathy in ICH are not known. Herein, we hypothesise catecholamine surge accompanying intracranial haemorrhage may lead to cardiomyopathy (CM).
Methods used We analysed patients in the Nationwide Inpatient Sample (NIS) from the year 2012. ICH patients were identified and those with a discharge diagnosis of neurogenic CM were compared to those without neurogenic CM. Incidence and outcomes with predictors of neurogenic CM were identified using a multivariate regression model.
Summary of results A total of 7,296,968 (mean age 48.6±27.6, whites 62.4%, blacks 13.9%, males 57.7%) hospital discharges were analysed. We identified 24, 088 patients (0.3%) with a discharge diagnosis of ICH. These patients had a higher incidence of neurogenic CM compared to those without ICH (0.3% VS 0.1%, p<0.001). After adjusting for potential confounders on multivariate regression analysis female sex (OR 3.5; CI: 1.8 to 6.5; p<0.001), congestive heart failure (OR 4.6; CI: 2.5 to 8.4; p<0.001), hypertension (OR 0.43; CI: 0.24 to 0.78; p=0.005) and electrolyte abnormalities (OR 3.2; CI: 1.7 to 6.1; p<0.001) were positive predictors of neurogenic CM. Length of hospital stay was significantly longer in the cardiomyopathy group (24±19 days’ vs 9±12 days; p<0.001). Finally, no significant difference in mortality was seen among patients with neurogenic CM compared to those without cardiomyopathy (78.3% vs 76.6%; p=0.868).
Conclusions ICH is associated with a threefold increase in incidence of neurogenic CM together with an increased length of hospital stay, but without higher mortality.
611 Stress induced cardiomyopathy in the setting of neuroleptic malignant syndrome
University of Florida Health, Jacksonville, FL
Case report Neuroleptic malignant syndrome (NMS) is a rare, life-threatening condition associated with altered mental status, muscular rigidity, pyrexia, and autonomic dysfunction. Acute cardiomyopathy as a result of NMS has rarely been reported. Here we present a case of stress-induced cardiomyopathy (SCM) in a patient with NMS.
A 55 year-old female with a history of multiple system atrophy and depression treated with amantadine, carbidopa-levodopa, and sertraline, was initially brought to an outside hospital for fever and muscular rigidity. The patient was febrile to 107 °F and was treated with acetaminophen and ice packs. She was transferred to our facility for ST-segment elevations in anterior leads on electrocardiogram. On our exam she was afebrile at 98.4 °F with a pulse of 80 beats per minute and blood pressure of 102/77 mmHg. She exhibited muscular rigidity, tremor in her right hand, and hyper-reflexia of patellar and achilles tendons. Laboratory studies were significant for troponin of 0.09, CK-MB 8.4, CK 809, and NT-proBNP 2,118. Initial echocardiogram showed a left ventricular ejection fraction (LVEF) of 25%–30% with akinesis of the distal anterior-inferior septum, apex, anterolateral wall, and distal inferior wall. Coronary angiography showed normal coronary arteries. Repeat echocardiogram one hour later showed improved LVEF to 55%–60% with no regional wall motion abnormalities. On further questioning, patient reported stopping carbidopa-levodopa a few days prior to presentation. She was thought to have SCM secondary to NMS from antiparkinson medication withdrawal. Neurologic medications were restarted and she was transferred to Neurology service for further management.
SCM is defined as a transient reduction in left ventricular function in the absence of coronary artery disease, often associated with physical or emotional stress. The aetiology is unknown but is believed to be associated with catecholamine surge. It has rarely been described in cases of NMS, as was the case with our patient. Fortunately, this condition carries a good prognosis with complete reversal of the cardiomyopathy typically in seven days to two months.
612 Percutaneous intervention in takotsubo cardiomyopathy with septal rupture
1University of Mississippi Medical Centre, Jackson, MS
2Forest General Hospital, Hattiesburg, MS
Case report Here, an 83-year-old female presents with Takotsubo cardiomyopathy (TC) complicated by septal wall rupture discovered 7 days after admission on transthoracic echocardiogram (TTE). She was too high risk for surgery and thus medically managed for 2 weeks with beta blockade and diuresis. This allowed myocardial healing prior to percutaneous closure. Intraoperative transesophageal echocardiogram revealed dissection of the interventricular septum which was also successfully treated percutaneously. TTEs at 2 and 26 months showed a normal ejection fraction and no intracardiac shunting.
TC with cardiac wall rupture is a rare phenomenon. To our knowledge, one other case of percutaneous closure has been reported in this setting. Early surgical correction is indicated in post-myocardial infarction VSDs. With appropriate medical management and rapid improvement seen in TC, we postulate that time for myocardial healing can be afforded in post-TC VSDs, allowing percutaneous repair to be a safe and successful treatment option.
Adolescent medicine and paediatrics, Concurrent session, 1:00 PM, Saturday February 24, 2018
613 Education gaps in lesbian, gay, bisexual, transgender, plus (lgbtq+) health among medical residents
University of Florida College of Medicine, Jacksonville, FL
Purpose of study
To evaluate knowledge, learner attitudes, and satisfaction from current resident education in regards to the healthcare of LGBTQ+ youth.
Inform future educational interventions and curriculum development in the area of LGBTQ+ health for trainees.
Methods used An anonymous survey platform (Qualtrics) was used to create a survey to assess residents’ perceptions of knowledge, skill, learner attitudes, and already existing learning opportunities related to LGBTQ+health issues. This survey has been sent via chief residents to both the paediatric and psychiatric residents at UF Health in Jacksonville, Florida.
The results will be used as a needs assessment to help develop future educational opportunities for residents. The study is still in process with plans to disseminate the survey to programs across the country.
Summary of results 27 residents have completed the survey to date. 30% of respondents were PGY-1, 48% PGY-2, 15% PGY-3, and 7% PGY-4. Of these, there were 20 (74%) paediatric residents, 6 (22%) psychiatric residents and 1 (4%) MedPeds resident. Almost all agreed that it is important to know a patient’s sexual orientation and gender identity and indicated awareness that unique needs exist in regards to the healthcare of LGBTQ+youth. Residents reported minimal training, knowledge, and competence in providing care to this population regardless of training level. Additionally, residents are not familiar with some of the most common and easily available resources for LGBTQ+youth and parents. There was a change noted in residents’ comfort in providing care to LGBTQ+patients from intern year to later residency years. Data collection from this survey is ongoing.
Conclusions While this educational project is still in process, the data suggests a few key issues. Residents become more comfortable in taking histories and discussing sexual and gender specific concerns with LGBTQ +youth after intern year. However, self-perception of knowledge and skill level about providing care to LGBTQ +youth does not improve further into residency. Residents do not report feeling adequately trained in LGBTQ +healthcare, however do believe this training is important. There is a need for increased education in the care of LGBTQ +patients during residency and specific education should be developed based on residents’ perceived needs.
614 Improving the education of sports-related concussion for residents and medical students in paediatrics
University of Oklahoma Health Sciences Centre, Oklahoma City, OK
Purpose of study Sports-related concussion is an evolving injury and ongoing research has led to advancements in diagnosis and management. Keeping up-to-date with the latest guidelines is imperative for physicians evaluating and managing a sports-related concussion. This study sought to measure the effectiveness of an educational program about paediatric sports-related concussions
Methods used Paediatric residents and third and fourth year medical students completed an anonymous pre-lecture survey including 4-questions about comfort level in caring for patients with a concussion and 8- board prep style questions over sports-related concussion. After hearing a presentation over current concussion guidelines, the same residents and medical students completed an identical post-lecture survey. Analyses were performed using SPSS and were appropriate for matched data.
Summary of results 28 residents and medical students were present at the educational program. 21 trainees completed the pre-survey and 20 trainees completed the post-survey. 57% of the participants reported increased confidence in taking care of paediatric patients with sports-related concussions on the post-survey as compared to the pre-survey (p=0.0001). Knowledge increases were also noted with 79% of trainees choosing the correct response on the post survey as compared with 73% on the pre-survey (p=0.004).
Conclusions Overall, the formal teaching over sports-related concussion improved the comfort level of residents and medical students on concussion management and also improved quiz scores on basic knowledge of sport-related concussion. This remains an effective way to educate trainees about concussion management.
615 Descriptive study of invasive bacterial infections in young infants in the emergency department
University of Alabama at Birmingham, Birmingham, AL
Purpose of study Invasive bacterial infections (IBI) in young infants are associated with high morbidity and mortality. Considerable ED practice variation exists in the evaluation of IBI for this age group. We describe the demographic and microbiologic characteristics of infants with IBI.
Methods used Microbiology logs were analysed for positive blood or cerebrospinal fluid (CSF) cultures drawn in a tertiary paediatric ED from infants≤60 days from December 2011 – May 2016. Contaminants were classified a priori according to previously published parameters, with chart review ensuring that contaminant bacteria were treated as such. Descriptive statistics were performed on demographic and clinical variables.
Summary of results 59 infants had positive cultures. Four (6.7%) of these cultures were contaminants. Of the remaining 55 infants, 35 (63.6%) had bacteremia and 9 (16.4%) had both bacteremia and bacterial meningitis (table 1). Group B Streptococcus (GBS) was most frequently isolated, followed by Staphylococcus aureus (table 2). Of 19 infants (34.5%) with GBS disease, only 1 was <7 days of age, and 14 (73.7%) were African-American.
Conclusions GBS remains a primary cause of IBI in infants. Late-onset GBS is more common than early disease in the ED. The independent risk factor of African-American race for GBS proved consistent in our cohort.
616 Determinants of low birth weight and premature births in escambia county, highlighting significant geographic disparities
1University of Florida, Pensacola, FL
2University Alabama, Birmingham, AL
Purpose of study Birth outcomes such as low birth weight (LBW) <2500 grams and preterm birth (PT) <37 weeks gestation have profound sequelae.
Purpose To determine if there are geographic regions in Escambia County that have higher rates of LBW and PT and whether health determinants of LBW and PT will be identified in these regions.
Methods used Birth data on 11 311 births in Escambia County, including LBW, PT, health determinants, from 2012 to 2014 was extracted from Floridacharts.com. Health determinants including maternal age <20 years, black race, no high school graduation, obesity, smoking, prenatal care information and births outside level III NICU were included. Escambia County was divided into five regions for comparative analysis of birth outcome and health determinant rates.
Summary of results Statistically significant findings: LBW correlated with black race, maternal age <20 years and maternal education <HS; LBW negatively correlated with prenatal care in 1 st trimester. Preterm births correlated with maternal age <20 years and maternal BMI >30 and negatively correlated with PNC beginning in 1 st trimester. There were regional variations with higher rates of LBW, PT and health determinants in the central region (see table).
Conclusions This study demonstrates the central Region of Escambia County had higher rates of LBW, PT and negative risk determinants. This region currently has no prenatal services. Preventative interventions should especially target this region.
617 Distribution and correlation of c-reactive protein and erythrocyte sedimentation rate in the paediatric emergency department
University of Alabama, Birmingham, AL
Purpose of study Accurate understanding of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in paediatric emergency department (PED) populations and the interrelation of these values will inform clinical decision-making. We describe distributions and correlation between CRP and ESR, and their potential correlations with age.
Methods used This is sub-analysis of a large retrospective study of patients who had both CRP and ESR performed during a visit to a tertiary PED from 2014–2017. Values are reported as medians and interquartile ranges (IQR), as well as percentiles. Pearson’s test was performed to determine correlations, with p<0.05 considered statistically significant.
Summary of results The ED visits of 3204 patients were analysed. Table displays overall representative values, as well as values by percentile and age. There was moderate correlation between ESR and CRP (R=0.46; p<0.0001). There was mild correlation between decreasing age and higher ESR values (R=0.1; p<0.0001), but no significant correlation between CRP and age.
Conclusions For PED patients, inflammatory markers fall within traditional ranges of normal. A lack of strong correlation between CRP and ESR indicates that there may be clinical scenarios in which one test may be preferable, but further investigation is necessary to delineate these specific scenarios.
618 Asthma severity and obesity: examining the relationship among west alabama children
1University of Alabama at Birmingham School of Medicine, Birmingham, AL
2The University of Alabama, Tuscaloosa, AL
Purpose of study The relationship between obesity and asthma severity has been defined in adults, but fewer studies have been conducted in children. Asthma and obesity have a higher prevalence in the state of Alabama and Tuscaloosa County than nationally. We sought to investigate the relationship between the two in our unique patient population. The purpose of this study is to examine the relationship of asthma severity and obesity defined as greater than 95th percentile BMI among West Alabama children seen at the University Medical Centre (UMC) between ages 2–18.
Methods used This was a retrospective chart review conducted of children with an asthma diagnosis seen at a community medical centre from January 1 st, 2016 to January 1 st, 2017. The primary endpoint was to determine how increased asthma severity, by ICD-10 diagnoses, is associated with obesity in our unique patient population.
Summary of results There were 785 children included in the study. Our sampled patient population has higher rates of obesity than the state and national average. When compared with mild intermittent asthma, neither patients with mild persistent asthma (OR=1.45, 95% CI: 0.96 to 2.18) nor moderate persistent asthma (OR=1.04, 95% CI: 0.58 to 1.84) showed statistically significant increased odds of being obese. Patients assigned an ICD-10 code of Unspecified Asthma had the highest mean BMI percentile when compared with other asthma classifications (Mean=73.1%, n=170).
Conclusions In this study, we found no significant relationship between obesity and the asthma severity. Limitations of this study are small number of patients with severe persistent asthma (5) and large percentage of patients with no asthma severity specification (21.7%). Subsequently, this study highlights the need for better provider documentation of appropriate asthma severity for patients.
619 A prospective study on the association between second hand smoke exposure and hospital admission rates for asthmatics presenting with an acute exacerbation
1University of Florida, Pensacola, FL
2University of West Florida, Pensacola, FL
Purpose of study To determine if there is an association between second hand smoke exposure and higher hospital admission rates for children presenting to ER with an asthma exacerbation.
Methods used An IRB-approved prospective 6 month observational study was conducted. Questionnaires were given to asthmatics presenting with an exacerbation to the Paediatric ER.
Nine risk factors were assessed for a relationship to admission to inpatient, and the clinical respiratory score (CRS) on presentation. Risk factors included second hand smoke exposure, active smoking, moulds, pets, carpets, dust, mattress cover, URI, noncompliance to controller medication.
Summary of results Among 65 patients who were seen for asthma exacerbation, 18 (27.7%) were admitted. Statistically higher rates of admission were seen for patients with SHS exposure: (48.3% vs 11.1%, Chi-Square p=0.001). The following were not found to have statistical relationship to admission rate: age, sex, race, insurance, pets, carpets, active smoking, mattress cover, dust, medication compliance. On backward logistic regression analysis including all variables, exposure to second hand smoke was the only variable that remained statistically related to admission.
(p=0.002; Odds Ratio of 7.47). Additionally, the mean CRS on ER admission, for those exposed to second-hand smoke was higher (2.8 vs 1.8; Mann Whitney p<0.001).
Conclusions Second hand smoke exposure is associated with higher hospital admission rates in asthmatics who present to the ED with an exacerbation. Smoking cessation interventions for parents should be should be implemented to prevent these admissions with resulting cost savings.
620 Modified checklist for autism in toddlers, revised, with follow-up (mchat-r/f) and language development in extremely preterm children
University of South Alabama, Mobile, AL
Purpose of study To study the association of High-Risk results on M-CHAT-R/F with language development, as assessed by Bayley Scales of Infant and Toddler Development, 3rd Edition (Bayley III)
Methods used We reviewed medical records of children seen at a Developmental Follow-up Clinic from February 2016 to April 2017. Inclusion criteria included:
age 16 to 30 months, with M–CHAT–R/F and Bayley III done at the same visit,
birth weight less than or equal1000 g or gestational age less than 28 weeks, and
no prior diagnosis of autism spectrum disorder.
Data collected included demographic data; MCHAT-R/F results, including responses to each question; and Bayley III language composite score and receptive and expressive language scaled scores. Complete data were available for 40 subjects. Language composite scores were dichotomized, with scores less than 70 considered language delay.
Summary of results Analysis using a Chi-square test and Fisher s exact test showed no significant association between High-Risk results on M-CHAT-R/F and Language Delay (composite score <70), with a p-value 0.16 for Chi-square test and 0.17 for Fisher s exact test. Further analysis comparing mean scores on the Bayley III revealed significantly lower mean receptive language scaled scores (p-value 0.0022) and mean composite language scores (pvalue 0.0062) in the High-Risk M-CHAT-R/F group, compared to the Low-Risk group. Item analysis showed significant differences in responses to certain M-CHAT-R/F questions, depending on M-CHAT-R/F risk group and presence of Language Delay.
Conclusions Based on our limited data, a high-risk result on the M-CHAT-R/F in extremely preterm children may be associated with language delay. Interpreting the M-CHAT-R/F results in this population should be done with caution. The study is ongoing, and additional data should help clarify this association.
621 Knowledge of nightime driving restrictions in state graduated driver licensing laws
1University of Alabama, Birmingham, AL
2Childrens of Alabama, Bham, AL
Purpose of study Graduated Drivers’ Licensing (GDL) laws place limitations on newly licensed drivers. Fifty-six percent of teen crash deaths occur between 6 pm and 6 am. Most states include a nighttime driving restriction in GDL laws. Studies show that curfew laws reduce motor vehicle related deaths among 16- and 17-year-old drivers by 10 percent. Since there is no nationwide GDL system, the laws vary among states. Prior research has shown that states with the strongest laws enjoy the biggest reductions in fatal crashes among 15–17 year-old drivers and the biggest reductions in collisions reported to insurers among 16–17 year-old drivers, compared with states with weaker laws.
Methods used Adolescents were surveyed in a paediatric urban emergency department (ED) and at an area high school teen driving event. Parents were also surveyed in the ED. The survey questions were ‘what is the current state GDL law curfew?’ and ‘what is your age?’ Surveys were anonymous and voluntary. Data were entered into Excel database.
Summary of results There were a total of ninety adolescents (41 in ED and 49 at teen driving event) and 40 parents.
Only 7 (8%) of the teens and one (2.5%) of the adults knew the correct answer of midnight. The majority of teens thought the curfew is earlier than it is (46/90 (51%)) with 6 (6%)reporting they did not know the answer. 30 adults (75%) thought the curfew was earlier with 14 (35%)admitting they did not know the correct answer.
Conclusions Very few adolescents and parents know the state GDL curfew law. The majority of individuals think the curfew is earlier. This suggests that the state law could be strengthened to enact an earlier curfew.
622 Paediatric obesity: clinic follow-up rates and impact on bmi
The University of Tennessee Health Science Centre, LBonheur Children’s Hospital, Memphis, TN
Purpose of study Paediatric obesity is a growing epidemic, with the national childhood obesity rate at 17 percent. Thirty-seven percent of children ages 10–17 in Tennessee are overweight or obese, the highest rate in the nation. The purpose of our study was to track trends in BMI and clinic follow-up rates for overweight and obese children in a general paediatric resident clinic in Memphis, Tennessee.
Methods used We performed a retrospective chart review assessing overweight and obese patients under 18 years of age within our general paediatrics clinic. We recorded BMI and BMI percentile at the initial well child checks, as well as at any additional clinic visits the patients had in the following 12 months. We also collected data on whether dedicated follow-up weight visits were scheduled and attended.
Summary of results Data for 125 qualifying patients has been reviewed to date. Our study population was 92% Medicaid insured and 53% female. The average initial BMI percentile was 94.73. Thirty-two percent of patients had dedicated weight visits scheduled, with an average show rate of 42.5%. Of the patients who showed for at least one dedicated weight visit, the average change in BMI percentile over a 12 month period was +0.33. Of the patients who scheduled a dedicated weight visit but did not keep their appointment, the average change in BMI percentile was +0.27. Patients who never scheduled a dedicated weight visit but were seen again in clinic for an acute visit had an average change in BMI percentile of −0.73.
Conclusions Our results indicate that the majority of overweight and obese patients who attended well child checks were not scheduled for dedicated weight visits. Additionally, there is not a significant difference in BMI percentile change between those who attended dedicated weight management visits compared to those who did not, and overall BMI percentile trended up despite these visits. Children who only returned for acute visits averaged a decreased BMI percentile, although this could be attributed to an acute illness. These results indicate a need to reevaluate the general paediatrician’s approach to weight management. Further investigation will be needed to determine a more impactful method primary care physicians can use to curb this epidemic.
623 Herpes simplex virus testing in young infants: are we doing it right?
University of Alabama, Birmingham, AL
Purpose of study The clinical presentation of herpes simplex virus (HSV) infection in young infants can range from a single vesicle to fulminant sepsis. Despite the infant’s condition, comprehensive testing is essential to guide antiviral therapy and prevent morbidity and mortality. Our primary objective was to determine if, for infants for whom HSV disease is suspected, comprehensive testing (as recommended by the American Academy of Paediatrics,) is performed. We hypothesised that viral cultures and polymerase chain reaction (PCR) assays of skin and mucosal surfaces would not be performed in most cases, in contrast with published guidelines.
Methods used Using an electronic database query, records were reviewed for infants 0–60 days old in the emergency department (ED) at Children’s of Alabama from January 2005 – July 2007. The study population was defined as infants who underwent lumbar puncture (LP) and received acyclovir in the ED. Our study is part of a large, multicenter study of HSV disease in infants.
Summary of results During the study period, 104 infants received an LP and were prescribed acyclovir in the ED. Mean age was 25 days, and 57 (55%) were male. Cerebrospinal fluid HSV polymerase chain reaction (PCR) was conducted on 99 patients (95.2%). Viral surface cultures were done on 25 subjects (24.0%). PCR assays of mucosal surfaces were performed on 4 infants (3.8%), with no skin/vesicle PCRs ordered. Two patients (1.9%) had blood PCRs.
Conclusions In contrast to established guidelines, infants in the ED who are treated for HSV disease do not often receive the comprehensive battery of tests for HSV as recommended. If our single-centre findings prove generalizable, our study represents an educational opportunity that could considerably impact the care for young infants with this potentially devastating infection.
Allergy, immunology, and rheumatology II, Concurrent session, 1:00 PM, Saturday February 24, 2018
624 Analysis of prevalence/outcomes of pulmonary embolism in systemic lupus erythematosus discharges from nationwide inpatient sample database
University of Mississippi Medical Centre, Jackson, MS
Purpose of study To study the risk and relationship of acute pulmonary embolism (PE) and Systemic Lupus Erythematosus (SLE) in hospitalised patients using analysis of Nationwide Inpatient Sample (NIS) database.
Methods used NIS database (2003–2011) was queried to identify all adults (age >18 years) with SLE and PE using appropriate ICD-9 codes. Various characteristics and outcomes were compared between SLE patients with and without a PE. Multivariate logistic regression analysis was used to obtain adjusted odds ratio (OR). A comparison was performed to 10 year analysis of National Hospital Discharge Survey (NHDS) database.
Summary of results In NIS database, of 2 99 595 hospitalizations with SLE from 2003–2011, 3839 (1.28%) had PE [1.83 times of baseline prevalence, OR 1.85*]. After adjusting for potential confounders, compared to those without PE, SLE patients with PE had significantly higher inpatient mortality [6% vs 2.0%, OR 2.99*], greater disability at discharge [31% vs 26%, OR 1.26*], longer length of stay(LOS) by 2.91* days and higher cost of hospitalisation by $19400* [tables 1 and 2,*=p<0.001].The results were similar when compared to (NHDS) database, except males vs females ratio.
Conclusions SLE significantly increases the risk of developing PE in hospitalised patients which is further associated with significantly higher mortality, LOS, cost, and greater disability. This analysis highlights these risks and suggests that thromboembolism prophylaxis may be of value in these patients.
625 Relapsing pyoderma gangrenosum associated with levamisole
University Mississippi Medical Centre, Jackson, MS
Case report Pyoderma gangrenosum (PG) is a inflammatory skin condition. We present a case of severe relapsing PG in a patient with levamisole-positive cocaine abuse.
A 46-year-old African-American female with no significant past medical history presented to rheumatology clinic with painful ulcerative lesions on her bilateral lower extremities and symmetric joint pain in her hands. The lesions were present for months and had not responded to antibiotics and wound care. The rash started as a pustule and progressed to an enlarging painful ulceration. Her associated symptoms included fever,decreased appetite, pain, swelling, and stiffness of her hands and elbows.
On exam the ulcer on her right leg extended from the ankle to the knee. The left leg ulcer was circular and five centimetres. The lesions had a violaceous undermined border and a purulent, haemorrhagic base. She had warm, swollen, and tender wrists, multiple metacarpophalangeal joints, and elbows. She had non-reducible swan neck deformity of multiple digits and fixed flexion deformity of the elbows. Differential diagnosis included vasculitis, rheumatoid arthritis, inflammatory bowel disease. She was admitted to the hospital and was started on antibiotics and intravenous solumedrol 1 g for 3 days. A microscopic exam of tissue from an excisional biopsy showed interstitial chronic inflammation with dermal oedema and fibrosis. In the eroded area, acute and chronic interstitial inflammation was present without evidence of leukocytoclastic vasculitis. These findings were consistent with PG. Lab studies were notable for positive p-ANCA, proteinase 3 antibody, anti-myeloperoxidase antibody, and negative rheumatoid factor, cyclic citrullinated peptide. Urine toxicology was positive for cocaine and levamisole. The patient was negative for viral hepatitis and HIV. We educated her on the relationship between the skin lesions and joint pain in relation to cocaine. She was discharged on an oral prednisone taper and was advised to abstain from cocaine. She returned to clinic with new lesions, again tested positive for levamisole, and was started on cyclosporine 4 mg/kg. The lesions improved within two weeks, and prednisone was completely tapered off.
When dealing with a non-healing ulcer, clinicians should keep drug reactions in mind, specifically levamisole-induced lesions.
626 Intussusception in an infant with food protein-induced enterocolitis syndrome
Tulane University School of Medicine, New Orleans, LA
Case report A two month-old boy presented to the emergency department with projectile vomiting and pallor three hours after his second exposure to cow’s milk formula. He had leukocytosis with a left shift, and underwent x-ray and ultrasound that revealed intussusception. He underwent successful reduction with barium enema. At six months of age, he was again exposed to a cow’s milk formula, and had similar symptoms two hours later. We suspect that he has FPIES (Food Protein-Induced Enterocolitis Syndrome) triggered by cow’s milk, although this has not been proven by formal challenge.
Discussion FPIES is a severe form of non-IgE-mediated food allergy. Cow’s milk is the most common trigger, however, other foods have also been implicated. There is often a delay in diagnosis of this syndrome, perhaps due to the delayed timing of symptoms after ingestion and the associated non-specific lab findings of leukocytosis and left shift. FPIES is frequently mistaken for viral gastroenteritis, and is sometimes mistaken for more severe conditions requiring invasive procedures, such as intussusception and intestinal obstruction. There is no known co-occurrence of intussusception and FPIES found in the literature. There is one documented case in the literature of a child who underwent laparotomy for suspected intussusception, but was ultimately diagnosed with FPIES instead. Diagnosis of FPIES is clinical and imaging is not indicated. Here, we report the first case of a patient with suspected FPIES who also had intussusception. Our patient had two risk factors to develop intussusception: maternal gastroenteritis (which is why he was offered formula) and recent rotavirus vaccine. It is unlikely that FPIES alone would result in intussusception, but it is unusual that FPIES and intussusception occurred simultaneously.
627 Behcet’s flare masquerading as sepsis
SUNY Upstate Medical University, Syracuse, NY
Case report Behçet’s Syndrome is a vasculitis that causes both oral and genital ulcerations as well as skin involvement (80%), which includes folliculitis, erythema nodosum (EN), and acne-like exanthema. We describe a patient with active Behçet’s disease causing systemic organ dysfunction mimicking sepsis.
29-year-old male with history of Behçet’s syndrome, deep venous thrombosis, left femoral artery aneurysm status post graft placement presented with fever and erythematous swollen left lower extremity. Vitals signed showed temperature of 102.8, HR of 119 and BP of 104/59. Labs showed WBC of 14,000, C-reactive protein of 93, ESR >130. Physical exam showed acneiform lesions involving face, chest, and back. Left lower extremity was diffusely erythematous and swollen with a large circular, flat lesion. MRI of the extremity showed diffuse inflammatory changes. Broad-spectrum antibiotics were started for suspected sepsis secondary to abscess formation around the femoral graft site. But, patient continued to have leukocytosis, high fever, tachycardia, and hypotension. Small amount of serosanguinous fluid was aspirated which did not grow any organism. Antibiotics were stopped and methylprednisolone and colchicine were started. Patient improved clinically with above measures and was started on Azthioprine. Patient had complete resolution of his symptoms and skin lesion with solumedrol, colchicine and azathioprine. Thus his presentation was most consistent erythema nodosum and acne-like exanthema due to active Behçet’s flare rather than due to sepsis.
In Behçet’s flare, there is an increase in pro-inflammatory response seen by increased interferon-gamma, and tumour necrosis factor-alpha which is biochemically identical to the cytokine response seen in sepsis. As a result, both conditions can result in leukocytosis, elevated CRP, ESR, fever, tachycardia and hypotension making it difficult to differentiate between the two. Despite overlapping clinical presentations and inflammatory markers, skin lesions like EN and acne-like exanthema provide specific diagnostic value for Behcet’s disease. Research has shown that apart from skin lesions, Interleukin −2 (IL-2) might show a diagnostic value as this is increased in Behçets and decreased in sepsis. Future practice might consider IL-2 biomarker to differentiate Behcets and sepsis.
628 Levamizole vasculitis
Purpose of study Levamisole vasculitis (LV) has been recognised since it was first reported in 2010. Levamisole was FDA-approved but, withdrawn from use in humans in 1999. Presently it is seen in cocaine. Due its impact on health care, more aggressive action should be taken to curb its use.
Methods used A 35-year-old female who actively use cocaine, presented with a 3 day history of a painful skin rash on her thighs. On examination, the rash was erythematous with a large necrotic centre (figures 1 and 2). She had positive dsDNA and SSA antibodies. Skin biopsy showed perivascular lymphocytic infiltrate (figure 3). She was treated with 2 weeks of tapered prednisone and advised on cocaine cessation. There was improvement after 3 weeks (figure 4), and resolution after 2 months (figure 5).
Summary of results Two million people use cocaine in the United States with 70% of it now contaminated with levamisole. The vasculopathic purpura typically characterised by a bright erythematous border and necrotic centre. Levamisole’s immune stimulating effect leads to the production of autoantibodies, especially antineutrophil cytoplasmic antibodies. There are some cases with anti SSA, and dsDNA positivity. The mainstay of treatment is cessation of the drug.
Conclusions LV can manifest with extensive skin necrosis. Patient awarenes of the adverse effects is needed to help curb the use of cocaine in the United States.
629 A masquerading case of eosinophilia
University of Mississippi Medical Centre, Brandon, MS
Case report Eosinophilia is often challenging to diagnose as the differential is broad. Hypersensitivity reactions, such as drug reaction with eosinophilia and systemic symptoms (DRESS), are within the differential but can also be challenging as the symptoms typically begin 2–6 weeks following exposure to the medication. It is important to recognise the wide diversity in which hypersensitivity reactions may present.
A 22 yo female with history of mild asthma presented after recent hospitalisation for methicillin-resistant Staphyloccous aureus pneumonia requiring thoracotomy and chest tube. She was treated with vancomycin and ceftriaxone and developed a rash and peripheral eosinophilia concerning for drug hypersensitivity. She developed diffuse erythema, oedema to face, trunk and extremities, and mild elevation in creatinine but no change in transaminases. The clinical diagnosis of DRESS was confirmed using the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system, with a score of 7. (>6 is defined as definite DRESS) She continued to have progression of her non-painful, pruritic rash and an extensive reevaluation for sepsis was performed. She developed respiratory failure, was intubated, and a bronchoscopy showed eosinophils and histopathologic findings consistent with Langerhans cell histiocytosis (LCH). Systemic glucocorticoids were started with improvement in eosinophilia, rash and respiratory status. Her absolute eosinophil count improved from 4723 to 60, and repeat imaging of her lungs also improved. She was discharged on a long steroid taper and upon follow-up three months later, continued to improve.
This patient’s history demonstrates the necessity of an extensively large differential diagnosis in patients with eosinophilia and clinical symptoms. Her pneumonia was complicated with regimens of multiple antibiotics. Her clinical course was consistent with DRESS but her respiratory failure appears related to a second condition, LCH, the diagnosis of which would have been missed without lung biopsy. On the basis of our experience with this patient and a single other report with similar findings, we suggest that patients with pulmonary symptoms associated with DRESS may have a pulmonary vasculitic syndrome induced by eosinophil activation from the drug hypersensitivity reaction associated with DRESS.
630 Focus score zero sjÖgren’s syndrome
University of Oklahoma Health Sciences Centre, Oklahoma City, OK
Purpose of study Focus score and anti-Ro (or SSA) antibodies are the cardinal features of Sjogren’s syndrome (SS). There exists a subgroup of Sjogren’s patients who have a focus score of zero and are diagnosed with SS on the bases of anti-Ro positivity. We conducted this study to analyse the differences (if any) between the SS subgroups defined by their focus scores.
Methods used All subjects were examined in a comprehensive clinic for evaluation of sicca, comprised of medical/rheumatological, dental, ophthalmology, laboratory and pathological examinations. Subjects were classified according to the AECG SS Classification Criteria. We assessed subjects according to the SS Disease Activity Index (SSDIA), and compared the subgroup with focus score zero with focus scores of less than one and greater than one, in terms of classification criteria and extraglandular manifestations. We used Statistical Analysis System software for data analysis. We used chi-square or Fisher’s exact test for comparison between the groups. Understanding the need for correction for multiple comparisons we agreed upon an alpha of 0.005 for statistical significance, and p values less than 0.005 were considered statistically significant. Due to low representation of patients in subgroup with focus score between zero to one, they were not included in the analysis.
Summary of results We found 51 focus score zero subjects, 167 focus score positive subjects and 11 subjects with focus score between zero to one in our SS cohort. We found significantly higher prevalence of serum anti-La (or SSB) antibodies (p<0.0001, OR=5.82, 95% CIOR=2.7321 to 12.4117), abnormal Lissamine green corneal staining (p=0.002, OR=2.7, 95% CIOR=1.39 to 5.08) and hypergammaglobulinemia (p<0.0001, OR=6.44, 95% CIOR=2.45 to 17) in focus score positive subjects as compared to those with focus score zero.
Conclusions Focus score zero Sjögren’s syndrome subjects had a lower prevalence of anti-La antibodies, hypergammaglobulinemia and corneal staining with Lissamine green. These patients may represent a distinct subphenotype of the illness.
631 Infection unmasking life threatening vasculitis
Texas Tech University HSC Amarillo, Amarillo, TX
Case report A 19-year-old Guatemalan female presented with hypotension, SOB, cough, hemoptysis, intermittent fever with chills, diffuse abdominal pain with nausea and vomiting. Vitals on admission were T- 98.8 F, HR 72, RR 16, SBP/DBP 95/51. Her WBC was 12.9, neutrophil 87%, Hb 8.5, platelets 18,000, CRP 145, ESR 110, PCT 4, urinalyses showed few RBCs. CT chest showed diffuse infiltrates, dense consolidative changes and small bilateral posterior pleural effusions. CT abdomen showed small fluid collections near vaginal region and left common iliac thrombosis. On admission day 2, she developed new papules and pustules on the abdomen, chest and back. There was also new purulent vaginal and cervical discharge with cervical motion tenderness. Vaginal and skin biopsies were negative for infection or vasculitis. She was treated with appropiate antibiotics and showed significant clinical improvement. She was also started on anticoagulants for iliac vein thrombosis. On further evaluation for her thrombocytopenia and hypercoaguable state revealed: anticardiolipin, antiphospholipid, antiproteinase-3 (PR-3) and anti-myeloperoxidase (MPO) antibodies were positive. The patient was diagnosed with anti-neutrophil cytoplasmic antibody (ANCA)- associated vasculitis (AAV) and antiphospholipid syndrome. She was started on prednisone with further significant improvement.
Discussion Aetiology and pathophysiology of AAV is not fully elucidated and appears to be multifactorial. Genetic factors and characteristics of immune system, some environmental exposures such as silica and certain infections have been implicated in the pathogenesis of this form of vasculitis. Specifically, staphylococcus aureus and gram-negative bacteria have been described as possible triggers for ANCA development induction and expression of AAV. Molecular mimicry and cross-reactivity between ANCA and bacterial adhesion proteins as well as cytokines production during infections was proposed as a trigger for release of ANCA autoantigens on the surface of neutrophils. There is no established association of genital infections flaring AAV as in our case. So, it is important to recognise obscure infections as a possible trigger for life threatening vasculitis and appropriate antibiotic treatment for favourable vasculitis clinical course.
632 Granulomatosis with polyangiitis overlapping with behcet’s disease
Texas Tech Health Sciences Centre, Lubbock, TX
Case report Granulomatosis with polyangiitis (GPA) is a small vessel vasculitis that classically affects the upper respiratory tract, lungs and kidneys. Limited disease has been described. We observed a 60 y/o Caucasian man presenting with mucosal ulcer of the tongue, tender erythematous ulcers with purulent base and rolled borders in the inguinal folds and scrotum, as well as multiple petechial and haemorrhagic papules of the legs, palms and soles. He was systemically ill and in pain. A short bout of knee arthritis was observed. He manifested no respiratory symptoms. Evidence for previous retinal laser surgery suggested possible prior retinal vasculitis although the exact cause could not be determined due to the patient’s underlying intellectual disability.
Laboratory evaluation revealed leukocytosis (14.01 K/µl), anaemia (12 g/dl) and thrombocytosis 413 K/µl). The ESR was 80 mm/hr and CRP was 25.7 mg/dl. Complements were not depressed. Chest radiograph was normal. Microscopic hematuria was observed on two separate occasions while renal function remained normal. Histopathological examination of the inguinal ulcer biopsy revealed epidermal necrosis spanning the entire field with dense mixed inflammatory infiltrates of lymphocytes and eosinophils and a predominance of neutrophils and neutrophilic dusts, which is consistent with a neutrophilic dermatosis. Biopsy of the petechial and haemorrhagic lesions revealed leukocytoclasia and fibrinoid necrosis of small to medium sized blood vessels within the dermis consistent with leukocytoclastic vasculitis. Serological testing for cytomegalovirus, herpes simplex virus, varicella zoster virus, HIV and syphillis were negative. Blood culture and skin tissue culture were unremarkable. The above findings fulfil the International Criteria for Bechet’s Disease. Subsequent testing revealed antibodies to proteinase-3 in high titer. Since, he fulfilled the American College of Rheumatology Criteria for the diagnosis of GPA and the etanercept study group definition of limited GPA this patient expressed features that overlap with both conditions.
633 Unusual presentation of type i hypersensitivity reaction to cosmetic products
Univeristy of Mississippi Medical Centre, Jackson, MS
Background The immune system protects against disease, however undesirable allergic reactions can occur. There are four hypersensitivity classifications: Type I (IgE mediated), Type II (cytotoxic mediated), Type III (immune complex mediated) and Type IV (delayed T cell mediated). Type I hypersensitivity reactions are usually immediate and involve the release of mast cell mediators via IgE. Typical culprits include foods, insect stings and aeroallergens. The rash appreciated in this reaction is usually urticarial. Type IV hypersensitivity reactions are delayed and T cell mediated. These reactions usually involve the skin and are not typically urticarial. Common causes are metals, plants, and cosmetic products. We present an interesting case of cosmetic products causing a mixed Type I and Type IV mediated reaction.
Case A 21 year old Caucasian female presented with complaints of itching, rash, shortness of breath, palpitations and dizziness when using various brands of shampoos and soaps. She reported a red, pruritic rash on areas of her body shortly after exposure to her hygiene products. Along with her cutaneous reactions, she had other respiratory and cardiac manifestations which was concerning of an anaphylactic reaction. She had various patch testing of chemicals that provoked immediate local reactions. On skin biopsy of her rash, she had increased number of mast cells. However, she had an unremarkable work up for mast cell disorders as well as a normal IgE and absent eosinophilia. She was placed on scheduled antihistamines and a mast cell stabiliser for working diagnosis of contact urticaria, a type of contact dermatitis. The reason for her systemic IgE related symptoms and her final diagnosis still remains a mystery.
Discussion It is unusual to observe Type I Hypersensitivity reactions to chemical products. This patient’s symptoms of rash, shortness of breath and lightheadedness soon after exposure to her products points to an IgE mediated process of mast cell and basophil activation. Chemical products typically induce a Type IV hypersensitivity reaction, which is typically confined to the skin. This case showed a mixed response of Type I and Type IV response to products.
634 Statin-induced rhabdomyolysis without the statin?
LSUHSC, New Orleans, LA
Introduction Polymyositis and Dermatomyositis are inflammatory myopathies characterised by muscle inflammation and weakness in a proximal >distal distribution. It has an incidence of 1–2 per 1 00 000 persons annually in the US. Statin-induced myopathy is a well described side effect of statin therapy occurring in 2%–11% of all statin users. Both of these conditions can present similarly with rhabdomyolysis.
Case A 43 year old male with history of multiple GSWs to the abdomen and face 3 months prior awoke with diffuse body aches, constipation and weakness for 8 days. He had no functional limitations at baseline. He denied strenuous activity, dehydration or trauma. The physical exam was remarkable for 3/5 strength in the bilateral upper and lower extremities, which was more pronounced in the lower extremities and in proximal muscle groups. Initial labs revealed an elevated CK to 32,740 u/L with normal creatinine and potassium. Aggressive intravenous fluid was begun for treatment of rhabdomyolysis, but after several days without improvement, a rheumatologic workup was initiated. MRI of the lower extremity revealed diffuse myositis in all muscle compartments with surrounding oedema. Further studies included negative ANA, but positive Anti-Jo1 and Mi-2 which are highly specific for dermatomyositis. A muscle biopsy was performed and demonstrated degenerative muscle fibres without inflammation. The patient later reported similar symptoms of proximal weakness after lifting weights 5 months prior and underwent a muscle biopsy at an outside facility with unknown results. He was diagnosed with statin-induced rhabdomyolysis and his statin therapy was discontinued. His weakness improved following initiation of methotrexate and steroids, but he stopped taking this following his GSW 3 months prior without return of symptoms. During his hospitalisation, he was started on high dose methylprednisolone and methotrexate with rapid improvement of symptoms and CK levels.
Discussion Statin-Induced Myopathy is a commonly made diagnosis when a patient presents with rhabdomyolysis in the setting of statin therapy. It is important to consider other etiologies of diffuse myopathy especially when discontinuation of the statin does not yield expected improvement.
Endocrinology and metabolism, Concurrent session, 1:00 PM, Saturday February 24, 2018
635 Hypophosphatasia – defining the prevalence of an under-recognised disorder
Medical University of South Carolina, Charleston, SC
Purpose of study Hypophosphatasia (HPP) is rare inheritable disorder characterised by defective bone mineralization. HPP is caused by a defect in tissue non-specific alkaline phosphatase (TNSALP), an enzyme responsible for clearing inorganic phosphate. HPP has a heterogeneous presentation ranging from early dental loss, fractures or poor growth, to in utero death.1 Studies estimate severe forms of HPP to be present in 1:100,000–3 00 000 and moderate forms to be present in 1:6,370.2,3 Low alkaline phosphatase (ALP) can be used to screen for HPP and the degree of diminished ALP activity is proportionate to severity of the disease.1 Challenges in defining prevalence include varying symptomatology and non-HPP causes of transient low ALP. This study was performed to define the possible prevalence of HPP in the Medical University of South Carolina’s (MUSC) paediatric population.
Methods used A retrospective chart review was conducted on paediatric patients who had ALP levels taken between 2014–2017 at MUSC. ICD-10 criteria were applied to exclude non-HPP causes of low ALP. Patients with the consistently low ALP levels were reviewed for symptomatology suggesting possible HPP diagnosis.
Summary of results 2 74 642 paediatric patient encounters with ALP testing occurred between 2014–2017 at MUSC. Of the encounters, 679 patients had low ALP for age and gender. 63 of these patients were identified as having consistently low ALP, and were subsequently reviewed for symptomatology associated with the disorder. 8 patients were classified as ‘potential HPP patients’ due to low ALP and associated symptomatology. The average age of the potential HPP patients on the date of their lowest ALP test was 1.77±1.21 years. Of the potential HPP patients (n=8) exhibiting HPP-associated symptomatology, 60% (n=5) had skeletal issues, 50% (n=4) failure to thrive, 50% (n=4) neurological (50%), and 25% (n=2) muscular issues. The potential prevalence of the disorder is approximately 1:25 000.
Conclusions HPP is considered a rare disorder however less severe forms may be more common. Recognising persistent low ALP for age and gender in the setting of associated symptomatology is crucial for early evaluation for a diagnosis of HPP. In 2015, TNSALP enzyme replacement therapy for HPP was FDA approved and thus treatment may be considered.4
636 Novel type of autosomal recessive osteogenesis imperfecta linked with nbas gene
OU Medical Centre, Oklahoma City, OK
Purpose of study Osteogenesis Imperfecta (OI) is a heterogeneous group of connective tissue disorders characterised by fragile bones. Previously it was thought to be an autosomal dominant (AD) disorder with variants in the COLA1/A2 genes. New genetic variants are being discovered that are expressed in autosomal recessive (AR) fashion with atypical clinical features and bone fragility. We report a child with unique clinical features due to novel compound heterozygous variants in the NBAS gene.
Methods used This is a Caucasian female, born to healthy, non-consanguineous parents at 34 weeks gestation weighing 1740 grams. She had progeric appearance, frontal bossing, micrognathia, and blue sclera. Due to clinical signs of discomfort, a skeletal survey was ordered which showed fractures of clavicle, tibia, fibula, and right fifth and sixth ribs along with multiple wormian bones and osteopenia. Concern for OI was raised. A customised exome slice was obtained and was negative. She spent over a month in NICU for feeding and breathing difficulties and discharged home with nasogastric (NG) feeds and oxygen supplementation. Pamidronate infusions every 2 months started to prevent fractures and for pain management. She improved clinically (NG feeds and oxygen supplements were discontinued). Fractures have not been reported since. In the meantime, whole exome sequencing (WES) was performed which was diagnostic.
Summary of results Patient was found to be compound heterozygote for 2 variants of unknown significance (VUS) in NBAS (p.R517C and p.E151K), which were inherited from father and mother respectively. Patient’s asymptomatic sister was also tested and found to be a carrier of VUS p.R517C in NBAS.
Conclusions Molecular genetic classification of OI contains 15 types, which displays either AD or AR modes of inheritance and exhibit wide variations in clinical severity. Although the function is not clear, NBAS encodes for a peripheral protein involved in the Golgi/ER transport. Balasubramaniah et al reported variants in NBAS as a cause of atypical OI in two patients who have progeric appearance, as seen in our patient. Our case supports this hypothesis, that variants in NBAS cause a novel type of AR OI. Clinical application of WES is a powerful diagnostic tool. We implemented early treatment with pamidronate infusions that showed clinical improvement.
637 A novel mutation associated to albright’s hereditary osteodystrophy, type 1a pseudohypoparathyroidism
OU Tulsa Health Science Campus, Tulsa, OK
Case report Our patient is a female who presented at 2 years of age with decreased energy level, dry skin, constipation, short stature, delayed speech and delayed walking. She was diagnosed with hypothyroidism and started on thyroid replacement therapy. Her symptoms improved in growth and development, although height remained short, tracking along the first percentile isopleth. At 4 years of age, the patient experienced a hypocalcemic seizure. Parathyroid hormone level (PTH) was significantly elevated. The patient was noted to have physical findings of short stature, round facies, and brachydactyly. PCR and DNA sequencing of exons 1 through 13, confirmed a heterozygous, likley pathogenic, novel mutation in the adenylate cyclase stimulatory G protein (GNAS1) described as c.15A>G(p.Lys53Glu) in exon 2.This patient‘s clinical presentation and results of genetic testing make Albright hereditary osteodystrophy (AHO) the most likely unifying diagnosis. AHO is a genetically heterogeneous disorder characterised by short stature, brachydactyly, round face, obesity, and intellectual disability. It is associated with biochemical abnormalities involving end organ resistance to parathyroid hormone. Several subgroups of this condition, collectively termed pseudohypoparathyroidism (PHP), have been defined based on the absence or presence of AHO, with or without hormone resistance. Prompt identification is valuable in monitoring for complications. The goal of therapy is to normalise electrolyte imbalances mainly by fluid and calcium replacement and augmenting Vitamin D levels to maintain normocalcemia. This approach was adopted successfully in our case. Importantly, from this case we emphasise that other hormonal insensitivities (thyroid in this case), can present far sooner than the clinical signs of PTH insensitivity. As such, it is important to maintain a low threshold for suspicion and consider screening for pseudohypoparathyroidism when children present with signs of hormonal insufficiency such as hypothyroidism, short stature and developmental delay.
638 Effects of modified lipoproteins in first trimester trophoblast cells: a role in pre-eclampsia in pregnancies complicated by diabetes?
1Medical University of South Carolina, Charleston, SC
2Queen’s University Belfast, Belfast, UK
Purpose of study Pre-eclampsia (PE) complicates 2%–8% of pregnancies worldwide. In women with diabetes, the risk for PE is increased 4-fold. Trophoblast cells are involved in angiogenesis, producing growth factors to promote vascularisation of the developing placenta. In women destined to develop PE, trophoblast invasion is impaired, leading to incomplete spiral artery remodelling. Soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin (sEng) are anti-angiogenic factors, secreted from many cell types and tissues including placental trophoblast. Evidence suggests that increased release of these factors from the trophoblast into the maternal circulation may promote endothelial dysfunction associated with the development of PE. In this study, we investigated sFlt-1 and sEng release from the placental trophoblast cell line, HTR8/SVneo, in response to modified lipoproteins (which accumulate in vascular tissues of patients with diabetes) and/or elevated glucose.
Methods used HTR8/SVneo cells were exposed to highly-oxidised glycated low density lipoprotein (HOG-LDL) vs native LDL (N-LDL) (0–200 µg protein/ml) for 24 hour. To investigate the effect of hyperglycaemia, HTR8/svneo cells were pre-treated (72 hour) with 30 mM glucose followed by exposure to HOG-LDL vs N-LDL for 24 hour. Transcriptional expression of the sFlt-1 isoforms, i13 and e15a, endoglin and its major shedding protease, MMP-14, were measured by RT-PCR. sFlt-1 and sEng secretion in cell supernatants were measured by ELISA.
Summary of results HOG-LDL increased sFlt-1 mRNA expression (i13, p<0.05; e15a, p<0.01) and protein secretion (p<0.05). HOG-LDL increased mRNA expression of endoglin and MMP-14 (p<0.05) and secretion of sEng (p<0.01). N-LDL had no effect on HTR8/SVneo cells. High glucose potentiated the effects of HOG-LDL, but alone had no effect.
Conclusions Exposure of trophoblasts to modified lipoproteins may contribute to the development of PE in diabetes, and the presence of high glucose may amplify the effect. These findings may explain the increased risk of PE in women with diabetes.
639 Correlation of transcriptomes of islets of langerhans with parameters of interest from the pancreas of human donors with or without diabetes
1University of Tennessee Health Science Centre, Memphis, TN
2University of Florida, Gainesville, FL
Purpose of study The goal of our project was to compare islet gene expression in diabetic and non-diabetic organ donors in the context of age, BMI, cause of death and HLA genotypes to determine what environmental and heritable factors may play a role.
Methods used Laser-capture microdissection was used to isolate islets from 58 donor pancreas from the nPOD tissue bank. RNA was extracted and analysed on Affymetrix HTA 2.0 expression arrays. The genes most highly correlated with each of the parameters of interest were used in datamining.
Summary of results In our analysis T1D was highly correlated with synaptic transmission and CAM abnormalities in the context of age. Oct-1, enriched in this analysis, has been shown to be associated with the recruitment of the corepressor of IL-2 receptors of CD4 cells. NFkB was also enriched in the T1D group. In the case of BMI, T2D was associated with the Wnt, NK cell-mediated toxicity, and VEGF pathways. Additionally, transcription factors GATA-3 and SMAD3, which have been shown to promote Th2 differentiation and reduce beta cell replication, were enriched. Diabetic ketoacidotic (DKA) patients differed markedly from other causes of death. The non-DKA group was associated with TEF-1, a factor that has been implicated in complications associated with diabetes and can be induced by a high blood glucose concentration. GATA-6, associated with pancreatic agenesis, was also enriched.
Most notably in the HLA analysis, T1D and T2D were significantly enriched pathways. An enriched transcription factor, AP-2, has been shown to play an important role in metabolic syndrome and metabolic dysfunction in mice. In humans, a functionally significant SNP of the AP-2 genes has been shown to lower serum triglycerides and risk for T2D. The transcription factor MAZ was enriched across all HLA analyses and may modulate insulin transcription and may contribute to susceptibility to diabetes.
Conclusions A better understanding of the gene expression differences in islets of donors with different disease status and age/BMI/HLA/cause of death may provide more insight into the disease and potential targets for treatment.
640 Disordered eating behaviour and insulin omission in type 1 diabetes mellitus: mscoff as a screening tool
1University of Tennessee Health Science Centre, Memphis, TN
2Le Bonheur Children’s Hospital, Memphis, TN
3University of Memphis, Memphis, TN
Purpose of study Adolescents with type 1 diabetes mellitus (T1DM) are at a significantly increased risk for disordered eating behaviours including insulin misuse. These behaviours result in poor diabetes control, higher A1C’s and diabetes-related complications. Despite this, no universally accepted screening tool exists to assess risk for disordered eating behaviours in patients with T1DM. The SCOFF questionnaire is a brief (five yes/no questions) screening tool used for detecting restrictive eating disorders. It has been modified (mSCOFF) for use in a diabetic patient population. We conducted this study to evaluate the clinical utility of the mSCOFF to identify patients at risk for disordered eating behaviours and identify potential correlations with objective measures such as Haemoglobin A1C, BMI, and gender.
Methods used Patients≥10 years old who presented to our paediatric endocrinology clinic with T!DM completed the mSCOFF (n=133). In addition to demographic data, we obtained HbA1C levels, insulin omission reports, weight-adjusted basal insulin rates, and BMI z-scores by chart review. Independent sample t-test were used to determine differences between patients with positive disordered eating screens and those without positive disordered eating screens.
Summary of results The mSCOFF screening questionnaire identified 20 patients with ≥2 ‘yes’ questions, indicating positive results (15%) Individuals who screened positively for disordered eating omitted insulin more than individuals who did not screen positively for disordered eating (t (133)=−2.07; p=0.04). Results between the two groups were not significant for age, gender, ethnicity, duration of illness, BMI, haemoglobin A1C, insulin administration type, and weight-adjusted basal insulin.
Conclusions The current study suggests that the mSCOFF, a brief, diabetes-specific screening tool may help identify patients who are at risk for insulin omission as a form of disordered eating. Contrary to previous literature in eating disorders, we did not find a significant gender differential in those who screened positively. Further research is needed to determine ideal screening tools in this population.
641 Advanced glycation end products and glycosaminoglycan levels in patients with diabetic ketoacidosis
Texas Tech University Health Science Centre, Lubbock, TX
Purpose of study Diabetic ketoacidosis (DKA) causes acute inflammation associated with circulating cytokines and endothelial injury. These events contribute to the complications, such as cerebral oedema, associated with DKA. Changes in the levels of glycosaminoglycans (GAG) and advanced glycation end products (AGE) could provide additional information about the biochemical events associated with DKA.
Methods used 17 patients with DKA admitted to an ICU. Blood was obtained from these patients within 24 hours of admission, 24 hours following the first sample, and 72 hours following this first sample. ELISA based assays were used to measure glucose, haemoglobin A1c, AGE, glycated albumin, and GAG levels. One time blood sample from twenty healthy subjects represented a control group.
Summary of results The mean age of the control subjects was 36.3±12.1 years; 8 subjects were male. The mean age of the DKA patients was 34.7±19.1; 69% were male. Admission lab in DKA patients included mean glucose 529±333 mg/dL, mean bicarbonate 9.8±7.7 meq/L, mean anion gap 32.8±9.8 meq/L, and mean creatinine 1.2±0.8 mg/dL. Control subjects had significantly higher levels of AGE and glycated albumin. Patients with DKA had a higher GAG levels on admission, and these returned to control levels within 24 hours. There were no differences in soluble receptor for AGE in the control subjects and DKA patients.
Conclusions Patients with DKA had higher levels of GAG on admission than control subjects. This most likely reflects endothelial injury. DKA patients did not have higher levels of AGE. The explanation for this is uncertain and could reflect absorption to the damaged endothelial surfaces.
642 Hypoglycemic events in pump versus injection users in insulin dependent diabetics at diabetes camp
USA, Mobile, AL
Purpose of study Insulin pump therapy was introduced with the purpose of obtaining more stable BG levels in insulin-dependent diabetics. Clinical observation suggests higher predominance of hypoglycemia in patients on pump compared to injection therapy. Our objective was to identify and compare the frequency of hypoglycemic events in insulin-dependent diabetics, using pump vs injections, at diabetes camp in the Gulf Coast area, and analyse the statistical significance of the differences encountered.
Methods used We collected BG diaries from participants of diabetes camp in the Gulf Coast during 2015 and 2016. Prior approval from the diabetes camp board was obtained. During camp, participants were maintained at a controlled environment with standardised carbohydrate intake, activity level, BG check times and glucometers. Each participant had a diary with demographic information and BG levels. We combined data from the three summer camp events in the area (senior, junior and coastal). We included only complete camper diaries, and collected age, self-reported race, gender and most recent Hba1c. Total sample was 504 diaries. We defined hypoglycemia as BG≤60 mg/dl. Hypoglycemic events were counted and classified in day and nighttime. Stata performed statistical analysis. Per Shapiro-Wilk test, the variables did not show a normal distribution, so the Wilcoxon rank-sum test was applied.
Summary of results 57% of the sample was female and 43% was male. Calculated mean age was 12.6 years. 70% were Caucasian, 15% AA, 15% Hispanic and other. Calculated mean baseline Hba1c was 8.7. 54% of campers were on pump and 45% on injection therapy. 1093 hypoglycemic events were identified, 63% at daytime and 37% at nighttime. 56% of the hypoglycemic events occurred in pump users, compared to 43% in the injection users. 29% of the campers did not have any hypoglycemic events (53.7% on pump, 46.3% on injections). Applying Wilcoxon rank-sum test, no significant statistical difference was found in the mean of hypoglycemic events in pump vs injection users.
Conclusions No significant statistical difference was found in the mean of hypoglycemic episodes in pump users when compared to injection users at the studied population. Study design limitations, including broad list of confounding factors, were identified.
643 Determinants of paediatric type 2 diabetes recovery
UAB School of Medicine, Birmingham, AL
Purpose of study The primary purpose of this study is to evaluate the clinical and biochemical characteristics of children diagnosed with T2DM who then achieved HbA1C<6.5% at one year from diagnosis (i.e. ‘remission’ from T2DM) and at the end of three years (i.e. maintained remission). A secondary aim was to determine the characteristics of patients who had achieved HbA1C<8.5% (durable glycemic control) at these time points.
Methods used This was a cross sectional, retrospective electronic medical record chart review of paediatric patients with T2DM followed by Children’s of Alabama, UAB diagnosed between 1/1/2004 and 7/30/2016. Inclusion criteria were:
diagnosis of T2DM,
patients with a follow–up visit between 10–18 months after diagnosis,
for the secondary aim patients with a follow–up visit between 2.5–3.5 years after initial diagnosis.
Summary of results There were a total of 311 patients who had a follow-up at 1 year and 187 patients who also had a 3 year follow-up. Remission (HbA1C<6.5%) was seen in 35% at the end of 1 year and 26% at 3 year. Treatment: 62.1% initially received insulin and metformin, 15.8% received insulin only and 21.2% received metformin alone. Patients who achieved remission at 1 and 3 years had lower non-HDL cholesterol (p=0.04) and better total cholesterol/HDL ratio (p=0.008). Patients treated with insulin had significant lowering of HbA1C at the end of 3 years (11.36±2.17 to 9.17±2.3, p<0.00001), whereas non-insulin treated group did not have a significant change in HbA1C. Insulin treated patients had significant improvement in HDL, p=0.007, whereas non-insulin treated group did not.
Conclusions Only a minority of patients achieve remission at 1 and 3 year of follow-up. Patients who received insulin treatment achieved better glycemic and lipid outcomes.
644 Trends of peripheral arterial disease in hospitalised patients with type 1 or 2 diabetes
1University of Tennessee, Memphis, TN
2University of Tennessee Health Science Centre, Memphis, TN
Purpose of study Diabetes Mellitus (DM) is a major risk factor for Peripheral Arterial Disease (PAD). However, variation in outcomes with underlying type of DM is not well studied. We sought to review the trends and determine outcomes of PAD based on the type of DM: 1 and 2.
Methods used We analysed the 2003 to 2014 Nationwide Inpatient Sample database to examine the trends and in-hospital outcomes in DM adults presenting with a primary diagnosis of PAD.
Summary of results The number of patients admitted with PAD and co-existing diagnosis of DM increased from 45 465 (in 2003) to 46 490 (in 2014) (p trend <0.001). Differences in age,% of women, race and smokers are in table 1. Regionally, southern US showed decreased DM1-PAD but increase in DM2-PAD. Both groups showed increase in uninsured, hypertension, obesity and coronary disease. Further, the in-hospital mortality decreased from 3.6% to 2.3% for DM1 and from 3.6% to 2.6% for DM2. The mean hospital charges increased from $36 108 to $70 907 (DM1) and $32 129 to $69 816 (DM2), whereas the average length of stay (LOS) decreased from 5.8 to 5.3 days for combined groups (all ptrend <0.001).
Conclusions We found significant differences in patient demographics, regional differences, clinical comorbidities and in-hospital clinical outcomes between DM1 and DM2 in PAD patients.
Further research is warranted to better understand these differences and improve patient outcomes for diabetes related PAD hospitalizations.
645 Metformin has a positive effect in type 2 diabetes mellitus (t2dm) patients with squamous cell carcinoma (scc) of the larynx or oropharynx
1University of Tennesee, Memphis, TN
2Veteran’s Affairs Hospital, Memphis, TN
Purpose of study The five-year survival rate of patients with SCC of the head and neck continues to be under 50%. Reducing metastasis and recurrence is paramount in the future treatment of these cancers. The antidiabetic drug metformin modulates molecular pathways that are known to contribute to tumorigenesis, including activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) and increasing insulin sensitivity. Our study aimed to investigate if metformin produced a positive therapeutic effect on SCC of the larynx or oropharynx, whether through these or other mechanisms.
Methods used In a retrospective chart review using the computerised patient record system (CPRS) in the Memphis Veteran Affairs (VA) system, we compared patients with SCC of the larynx or oropharynx and T2DM on metformin to controls not on metformin. We investigated metastasis, recurrence, five-year survival rate, and other new malignancies in these T2DM patients with these cancers. There were 11 patients in the metformin group and 23 in the non-metformin group. These patients were matched for age, race, haemoglobin A1c (HbA1c), tumour stage, BMI and primary cancer therapy. Serum creatinine levels were also compared. Inclusion and exclusion criteria were identified. Statistical analysis included paired t-test, Chi-squared test, and ANOVA.
Summary of results Five-year survival rates were found to be significantly improved for larynx or oropharynx cancer patients on metformin (p<0.038), and patients on metformin had significantly lower metastases (p<0.001). While there was not a statistically significant difference in the reoccurrence of cancer or the presence of new malignancies, the metformin group had fewer of each.
Conclusions This retrospective study shows that metformin has a significantly positive effect on the outcome of SCC of the larynx or oropharynx in T2DM patients in conjunction with surgery, radiation, and chemotherapy. HbA1C levels were similar in both groups so any positive effects were not due to better diabetic control. The most significant conclusions from this study are that metformin reduces metastasis of these tumours and increases five-year survival rates of patients with SCC of the larynx or oropharynx.
Health care research, quality improvement and patient safety, Concurrent session, 1:00 PM, Saturday February 24, 2018
646 Identifying gaps in care of diabetic patients: a look at statins
Lenox Hill Hospital, New York, NY
Purpose of study The 2013 ACC/AHA Guidelines recommend statin therapy for all diabetics 40 to 75 years old, with LDL of 70–189. Statin intensity is guided by the 10 year ASCVD score and presence of cardiovascular disease (CVD). Despite the proven benefit of statins, disparities in prescription patterns exists with a marked underutilization/dosing of statins in diabetic women. We sought to measure our adherence to statin guidelines in diabetics and evaluate for gender disparities at our primary clinic, Lenox Hill Medicine (LHM).
Methods used We performed a retrospective chart review of Type 2 Diabetics, age 40–75, from January to March 2017. Those with statin allergy, transaminitis (3xUNL), LDL <70 and>189, and statin therapy refusal were excluded. Comorbid CVD was determined by chart review. Appropriateness of therapy was determined by statin intensity (those with CVD) or ASCVD score (those without CVD). Patients not on a statin when indicated or on an incorrect dose, were deemed inappropriately treated. Gender was then collected to allow for post-analysis of any gender disparity.
Summary of results 98 patients were included in this study, 70 of whom did not have CVD. Of those 70, 26 (37.15%) were not on a statin and 19 (27.14%) were underdosed; nearly 2/3 of diabetics without CVD were treated inappropriately. In comparison, 19/28 (67.86%) patients with CVD were duly on a high dose statin. Moreover, post analysis showed marked gender disparities. Of those without CVD, an alarming 31/44 (70.45%) women were treated inappropriately in contrast with 14/26 (53.85%) men. In fact, women without CVD were less likely to be on a statin (45.45%) than men (26.92%). Similarly, diabetic women with CVD were twice more likely to be treated inappropriately (42.86%) as opposed to their male counterparts (21.43%).
Conclusions Despite the benefits for primary and secondary prevention of CVD in diabetics, statin therapy remains suboptimal at our clinic. Disparities in prescription patterns exist, especially in female diabetics without CVD. Given the opportunity for improved morbidity/mortality, it is crucial to investigate barriers to guideline adherence and reasons for gender disparity in this population. The use of hospital/clinic based education to improve provider/patient knowledge regarding these gaps is an area that needs further exploration.
647 Knowledge, attitude and practices regarding noise in nicu
University of Tennessee Health Science Centre, Memphis, TN
Purpose of study To assess knowledge and attitude of health care providers regarding noise, its impact on VLBW infants and to identify practices associated with noise within NICU.
Methods used Health care providers were invited to participate in a survey regarding noise in NICU. The survey had 26 questions, including characteristics of participants, physiologic and developmental consequences of noise on neonates, and health care providers (Likert scale). Noise levels were continuously monitored in our open pod NICU at our Regional Medical Centre using ceiling and wall mounted Sound Indicating Metre of SONICU with cellular gateway modem.
Summary of results Total 87 healthcare providers participated in a survey, which includes 41% neonatal nurses, 12% physicians and physician extenders and 16% ancillary staff within NICU. Only 30% of participants were aware of current AAP recommendations of noise levels within NICU. Other important findings of the survey are listed in table. Total 20 328 noise data points were evaluated with Sound Indicating Metre over 14 days (from December 8 – December 22, 2016) with a median noise level of 62 (43–92) dBA. There was no significant diurnal variation in noise levels. The noise levels were significantly higher during physician bedside rounds (72dBA), new admission in NICU (77dBA), setting items on the top of isolette (80 dBA), closing incubator portholes fast (90 dBA).
Conclusions Majority of NICU staff were unaware of AAP recommendations and effect of noise levels on neonates. Some routine practices within NICU increase noise levels significantly and providers should be aware of its consequences.
648 Quality improvement: optimising antibiotic usage and screening for bacteriuria in patients with multiple sclerosis and other central demyelinating diseases
1Ochsner Medical Centre, New Orleans, LA
2Ochsner Medical Centre, Jefferson, LA
Purpose of study To reduce the number of unnecessary antibiotic prescriptions and urine cultures performed in persons with multiple sclerosis (MS) and other central nervous system (CNS) demyelinating diseases. This population is at high risk for urinary tract infections (UTIs) as a result of neurogenic bladder and frequent use of urinary catheters. UTIs increase the risk of MS flares and pseudoexacerbations. Consequently, there is a high rate of UTI screening and unnecessary treatment of asymptomatic bacteriuria in this population. Unnecessary urine cultures and antibiotics lead to increased healthcare costs, risk of adverse side effects, and antimicrobial resistance.
Methods used A single-centre quality improvement study, consisting of three phases, conducted in patients with MS and other CNS demyelinating diseases seen in the Ochsner Multiple Sclerosis clinic.
Phase one implements a urinalysis reflex (UAR) order that triggers a urine culture only when urinalysis (UA) reveals a white blood cell count >10 cells/high–power field to limit unnecessary urine cultures.
Phase two will provide patient education handouts and standardise urine collection supplies to limit sample contamination.
Phase three combines both interventions to reduce antibiotic prescriptions.
Summary of results Phase 1 of the study demonstrated a statistically significant decrease in the number of urine cultures ordered with implementation of the UAR order.
Conclusions Preliminary data from phase 1 demonstrate that the UAR order decreases the number of urine cultures ordered. Reducing unnecessary urine cultures and antibiotic prescriptions will reduce healthcare costs, minimise risk of adverse side effects and development of antimicrobial resistance, ultimately contributing to better patient outcomes.
649 Dextrose instillation as an alternative agent to observe ureteral efflux during pelvic reconstructive surgery
1Loma Linda University School of Medicine, Loma Linda, CA
2Loma Linda University Medical Centre, Loma Linda, CA
Purpose of study Various agents, such as indigo carmine, sodium fluorescein, and phenazopyridine, have been used to aid in the visualisation of ureteral efflux during cystoscopy but can be limited by cost, availability, and variability in renal excretion. Dextrose may be an alternative agent that can aid in visualisation of ureteral efflux. The purpose of this study was to evaluate the use, cost, postoperative UTI rates, and complications of dextrose instillation during cystoscopy.
Methods used The medical records of patients that underwent intraoperative cystoscopy during pelvic reconstructive surgery between June 2016 and June 2017 were reviewed. The patients were divided into two groups: patients that had dextrose 50% (D50) instilled and patients that did not have D50 instilled during cystoscopy. Prophylactic antibiotics were administered to all patients. When dextrose was used, one ampule of D50 was directly instilled through the cystoscope. Demographics, UTI rates, and postoperative complications were compared. Pharmaceutical cost and availability were reported by the pharmacy at our institution.
Summary of results Out of 63 patients identified, dextrose instillation was used in 20 patients and no dextrose was used in 43 patients. Patients of both groups were comparable in age, body mass index, parity, menopausal status, pelvic organ prolapse stage, and history of recurrent UTIs. Each ampule of D50 cost $2.18 and there were no problems with supply shortage. As D50 was directly instilled into the bladder, there was immediate visualisation of ureteral efflux in surgery. Three patients in the dextrose group and 10 patients in the non-dextrose group developed postoperative UTIs. There was no statistically significant difference in postoperative UTI rates between the two groups (p=0.52) and there were no differences in complication rates.
Conclusions Dextrose is a cost-effective, readily available agent that provides instantaneous visualisation of ureteral efflux without an increased risk of postoperative UTI.
651 Opioid prescribing and dispensing frequencies among children 0–18 years old from 2000–2015
1Medical University of South Carolina, Charleston, SC
2South Carolina College of Pharmacy, Charleston, SC
Purpose of study Previous efforts demonstrated a decrease in overall opioid prescribing and dispensing for children 0–5 years old. Adolescents typically have greater opioid prescribing/dispensing and may not have experienced the same decline over time.
Methods used Using 2010–2015 paid South Carolina (SC) Medicaid claims data, we identified dispensed prescriptions for opioids to children 0–18 years old. We evaluated whether the frequency of opioid prescriptions per 1000 enrollees per year decreased over the 16 year study period, comparing changes among age groups. Logistic regression assessed whether year was predictive of opioid frequency, controlling for age, gender, and race/ethnicity. The SC Revenue and Fiscal Affairs Office and the Institutional Review Board of MUSC approved this study.
Summary of results There were 6.2 million person-years represented in the data. Overall, 15.6% of the children received an opioid per year (frequency 156.3/1000 children/year). Opioid prescribing/dispensing declined for all ages from a rate of 192.2/1000 to 78.5/1000 during the study period (Cochran–Armitage test for trend, p<0.0001), a 59.2% decrease in frequency. The decline in prescribing/dispensing was lower for the age group 16–18 (22% decline) from 362.9/1000/year to 281.7/1000/year compared to a 44.7% decline among children 11–15 years old and a 60.9% decline among children 6–10 years old. In logistic regression, year had a significant inverse association with the opioid prescription/dispensing (aOR 0.936, 95% CI: 0.935 to 0.936), even after adjusting for age, gender, and race/ethnicity. Black children were less likely to receive an opioid (aOR 0.66), while increasing age (aOR 1.22) was positively associated with receipt of opioid.
Conclusions Opioid prescriptions to children 0–18 years old in SC have decreased over the past 16 years, but the decrease was much more pronounced for younger children than for teens. Evaluating the differences in why children of different age strata receive opioids is an important next step in devising strategies for further reduction in their prescription and dispensing.
652 Utilisation of evidence-based behavioural health practices in medicaid-eligibile paediatric patients in louisiana
Louisiana State University, New Orleans, LA
Purpose of study Children have particularly benefited from the Louisiana Medicaid expansion allowing for greater access to behavioural health services for a previously un/under insured population. Currently 65% of Louisiana’s 0 to 18 population are Medicaid-insured. However, providers serving this population do not always use evidence-based practices (EBPs).Thus, access to behavioural healthcare has increased but the quality of care varies greatly. This study sought to identify such gaps.
Methods used Medicaid providers were contacted between February and April 2017 and surveyed about EBP utilisation via REDCap, Behavioural health disorder prevalence calculations were determined based upon paid Medicaid claims data. Parish census data were taken from the U.S. Census Bureau’s estimates. This helped establish the behavioural health burden for which Medicaid contracted providers were responding. Statistical analyses were performed using SAS (v9.4) and Epi Info (v7.0).
Summary of results Of 772 identified providers, 222 (28.7%) responded, representing 146 programs. A median (IQR) of 60% (50, 67.5) of providers reported use of EBPs. EBP use varied significantly by geographic region within the state (p<0.0001) with greatest use being in the capitol region (77.8%) and lowest use observed in north-west Louisiana (47.1%). Slight differences were observed between regions with regard to total population (p=0.069), race (p=0.055), and percentage of the population using Medicaid (p=0.005). These three variables were not however, associated with EBP use (p=0.081, 0.314, and 0.902, respectively).
Conclusions Behavioural health disparities persist in Louisiana. Though regions have varying characteristics, geography itself remains the strongest predictor of EBP use for behavioural health disorders, suggesting the benefits associated with access to quality treatment differ regionally. Possible reasons for these differences could be that subsets of providers have limited awareness, workforce capacity, and/or resources needed to implement EBPs. Solutions to address the limited utilisation of EBPs could include a regionalized approach to encourage the sharing of information and resources needed to adopt EBPs in practices servicing Medicaid-eligible children.
653 Tuning up fast track: refinements in triage criteria in a paediatric emergency room
Children’s of Alabama – University of Alabama, Birmingham, AL
Purpose of study In the Paediatric Emergency Department (ED) at an urban Children’s hospital patients of lower acuity with specific chief complaints and of specific ages, are directed to the Fast Track (FT) area of the ED. The goal of FT is to see low acuity patients in an efficient manner, directing them away from and minimising the use of resources of the Main Paediatric ED. In March of 2016, the criteria used by ED Triage to direct patients to FT was modified to include and exclude certain specific ages and chief complaints. Our goal was to determine if and how the criteria changes affected the average FT length of stay, FT volume as a percent of overall ED volume, total number of FT patients, as well as the specific conditions seen in FT.
Methods used We examined FT Data obtained from ER electronic medical records for all FT patients seen during the 12 months prior to March of 2016, as well as during the12 months after the criteria changes from July 2016 to July 2017.
Summary of results Based on our data, FT volume increased 42% post FT criteria change (11 016 patients PRE vs 19 043 patients POST). FT volume as a percent of the total ER volume increased from 14% to 25%. Average FT length of stay increased from 118 min to 125 min, whereas average ED length of stay decreased from 190 min to 186 min. Post criteria change we saw a 65% increase in the number of lacerations repaired, 54% of head injuries evaluated, and a 53% increase in patients with chief complaint of vomiting. The number of patients seen in FT with respiratory complaints, musculoskeletal complaints, along with headaches increased by a minimum of 42%.
Conclusions Refining the criteria for FT allowed us to expand the scope of practice of this area of the ED, increasing our FT volume by 42% and minimising use of main ED resources for evaluation of these patients. This data allows us to further analyse and refine FT criteria in order to decrease FT length of stay while continuing to provide excellent healthcare to the children of our community.
654 Consensus guidelines for patent ductus arteriosus management decreases need for treatment: a 15 year experience
UT Southwestern Medical Centre, Dallas, TX
Purpose of study To determine the impact on the use of therapy for PDA (indomethacin and/or surgical ligation) for 5 years (2011–2015) after implementing consensus guidelines for PDA management in infants<30 wks gestational age (GA).
Methods used Retrospective cohort study of infants born between 23–29 wks GA, admitted to the NICU between 2001–2015, and who were identified from a validated prospective NICU database. Patients receiving indomethacin prophylaxis were excluded. Infants were grouped into 2 epochs, before (2001–2010) and after (2011–2015) implementation of consensus guidelines, and into 2 GA groups, 23–26 wks and 27–29 wks. χ2 analysis was used for univariate comparisons and logistic regression to determine (1) whether the odds of therapy for PDA was dependent on GA and changed in epoch 2 and if the change in the 2 GA groups differed and (2) the success of indomethacin treatment.
Summary of results Between 2001–2015, 541/1607 (34%) infants 23–29 wks GA received PDA treatment. PDA treatment was less frequent in 27–29 wks than in 23–26 wks GA infants (269/978 [28%] vs 272/629 [43%], respectively; (p<0.001). The overall frequency of PDA treatment decreased from 40% to 20% in epoch 2 (p<0.001), decreasing from 34% to 14% in 27–29 wks and 48% to 30% in 23–26 wks GA infants (p<0.001 in both groups) (figure 1). In the entire cohort, the odds of PDA therapy on binary logistic regression was lower in 27–29 wks GA infants (adjusted odds ratio [aOR] 0.44, 95% confidence interval [CI] 0.34,0.57) and decreased during epoch 2 (OR 0.38, CI 0.29, 0.49); the change in treatment did not differ between the 2 GA groups (p=0.13). Among 482 infants receiving indomethacin for PDA, 136 (28%) had subsequent PDA ligation; the odds of ligation was lower in 27–29 wks GA infants (aOR 0.43,CI 0.23, 0.83) and decreased during epoch 2 (aOR 0.45, CI 0.24,0.86). Notably, the change in treatment did not differ between the 2 GA groups (p=0.59).
Conclusions The frequency of PDA treatment and ligation post-indomethacin for PDA, decreased after implementing conservative evidence-based treatment guidelines. These changes occurred in 23–26 wks and 27–29 wks GA infants, and treatment was less frequent in the latter group.
655 Evaluation of the go sheet for neonatal transport during a disaster
1UAMS, Little Rock, AR
2Arkansas Children’s Hospital, Little Rock, AR
3University of Louisville, Louisville, KY
Purpose of study There is currently no available tool to help safely transport neonates during a disaster situation. This is a vulnerable population with the inability to relay any medical information about themselves. This study was done to develop and validate a tool for safely transporting neonates during a disaster.
Methods used The Go Sheet was developed by a physician team based on information needed to appropriately care for a patient on arrival to a new hospital assuming no prior knowledge of the patient or their conditions. One hundred patients were randomly selected from the level IV neonatal intensive care unit in our institution. Each patient had a Go Sheet filled out by an attending physician (considered gold standard), as well as a resident (A), bedside nurse (B) and patient care technician (C). The electronic medical record and the patient’s bedside information card were used to find the information needed to complete each sheet. Go sheets from documenters A, B and C were then analysed by a blinded review physician who decided if the information on the Go Sheets was sufficient for proper care of the patient when compared to the gold standard. The decision was binary (yes or no). Percentage of agreement (yes) was summarised for each category of the Go sheets.
Summary of results Overall, the resident physicians had the greatest percentage of agreement with the gold standard in all categories except emergency contacts, line access and nursing instructions. There was high agreement with all documenters in the vital signs and allergies category, and the greatest variability when reporting medications with dosage and timing.
Conclusions For our validated tool we recommend an attending or resident physician fill out the Go sheet prior to transport. Accuracy of the tool could be further increased by using an electronic medical record to pull information directly from the patient’s chart.
656 Evaluation of heathcare-associated infections and antibiotic susceptibility in a paediatric intensive care unit
1University of Arkansas for Medical Sciences, Little Rock, AR
2Arkansas Children’s Hospital, Little Rock, AR
Purpose of study Critical care patients are at increased risk for healthcare-associated infections (HAIs) due to invasive devices, increased length of stay, and increased antibiotic usage. The purpose of this study is to determine if there is a difference in antibiotic susceptibility between HAIs and non-HAIs in a Paediatric Intensive Care Unit (PICU).
Methods used A retrospective chart review was conducted to compare antibiotic susceptibility between HAIs and non-HAIs from July 2014 to June 2016. A list of HAIs was provided by our Hospital Infection Prevention department. HAIs were identified using the Centres for Disease Control and Prevention National Healthcare Safety Network definitions. Microbiological data was obtained by generating a BD Epicentre report. Duplicate isolates for a single patient were excluded. HAIs were removed from this report to finalise a list of non-HAIs. Antibiograms were created for comparison of HAIs and non-HAIs.
Summary of results There was a total of 378 bacterial infections; 38 HAIs and 340 non-HAIs. The HAIs included, urinary tract (15/39%), blood stream (7/18%), surgical site (7/18%) and other (9/24%). Staphylococcus aureus (93/24%) was the most common organism; however, only represented 1 HAI. No difference was found between HAIs and non-HAIs for Klebsiella pneumonia (20/5%) and Pseudomonas aeruginosa (71/18%). A difference was found in Enterobacter cloacae (18/4%) HAIs (3/17%) and non-HAIs (15/83%) for cefepime (33% vs 93%), ceftriaxone (33% vs 73%), and ceftazidime (33% vs 61%). A difference was also found in Escheria coli (44/11%) HAIs (3/7%) and non-HAIs (41/93%) for ciprofloxacin (67% vs 73%), ceftazidime (67% vs 85%), and ceftriaxone (67% vs 76%).
Conclusions Decreased susceptibility with some gram negative HAIs compared to non-HAIs was found in the PICU. Increased rates of resistance to cephalosporins and fluoroquinolones was seen. This data supports the hypothesis that antibiotic usage in the healthcare setting could be a driver of antibiotic resistant HAIs. Future antimicrobial stewardship research could utilise antibiotic susceptibility of HAIs as a measure of improvement in antibiotic usage.
Medical education/medical ethics/advocacy, Concurrent session, 1:00 PM, Saturday February 24, 2018
657 Initial success of a faculty burnout intervention initiative in an academic paediatric department
LSU Health Science Centre, Children’s Hospital, Kenner, LA
Purpose of study Physician wellness and burnout are increasingly recognised as key risk factors for a variety of negative consequences including poor patient satisfaction, increased medical errors and malpractice claims, poor physician quality of life, high rates of physician depression and suicide and high turnover of highly trained physicians in academic health centres. Although factors contributing to high rates of burnout are increasingly understood and often described as ‘death by a thousand papercuts’, the ideal approaches to decrease or ameliorate burnout are less well defined. Our goal was to determine the role and impact of a pro-active physician wellness initiative on the rate of measured physician faculty burnout in an academic paediatric medical centre.
Methods used A validated, two item modification of the Maslach Burnout Inventory was utilised to measure faculty burnout at baseline. Following the initial survey, a faculty taskforce was formed with the goal of developing and testing pre-emptive activities and initiatives to impact burnout. After one year of taskforce activity the survey was completed and burnout measures compared. Intervention activities included didactic presentations on physician burnout, training on physician resiliency, formation of special risk groups (such as women, mothers, young faculty), yoga and mindfulness training and a heal-the-healer week with a variety of measurable interventions.
Summary of results Prior to the intervention, seventy four percent of faculty (58 of 78 full time faculty members) completed the survey tool. Thirty six percent of faculty reported measures consistent with burnout on at least one of the two survey questions. Following the intervention sixty eight percent of faculty (50 of 73) completed the repeat survey tool. Eighteen percent of faculty reported burnout. Total expense for the burnout intervention measures was under $5000.
Conclusions With a limited and focused investment in pro-active education and intervention, measures of faculty burnout in an academic paediatric faculty decreased by fifty percent. Sustainability and focused improvement of the initiative will define the longer term utility of such interventions, but short term success is possible.
658 A 5 year follow up of doctors treating relatives
1Marshall University Joan C. Edwards School of Medicine, Huntington, WV
2University of Arizona, Tucson, AZ
Purpose of study The goal of our study is to examine the beliefs and practices of residents and faculty physicians regarding treating relatives and themselves, and to compare this data with that from a similar population five years ago.
Methods used We conducted surveys at Internal Medicine, Paediatrics, Family Medicine and OB/GYN grand rounds at an affiliated hospital. The study period was from August to September 2017. These surveys were compared to data from 81 surveys conducted in 2012.
Summary of results The 83 respondents in 2017 were similar to the 81 respondents in 2012 in age, gender, year of training and department. In the 2017 survey, significantly fewer respondents prescribed medications to relatives without an examination, 19% compared to 35% in 2012 (p=0.02). Forty percent of current residents and faculty believe they should treat their relatives, similar to 54% in 2012 (p=NS). Fifty-nine percent treated relatives for minor illnesses, a non-significant decrease from 75% in 2012. Forty-eight percent treated themselves for minor illnesses, similar to 57% in 2012. Importantly, although 73% of current respondents have a primary care physician (PCP), a significantly higher proportion of men have PCPs (p=0.04) in 2017 in contrast to a significantly higher proportion of women having PCPs (p=0.01) in 2012.
Conclusions Many residents and faculty physicians treat their relatives and themselves. Although the overall frequency of respondents who do so decreased in the past five years and less treat without examination, too many physicians continue this practice, despite the ethical admonitions of the AMA and ACP against treating relatives. Physicians who treat their family or themselves inadvertently risk injuring loved ones and enduring the guilt of a misadventure. More education of physicians at all levels is required to convince physicians not to treat relatives and themselves. Further research is needed to determine why men are now having PCPs more often than women.
659 Medical student and intern knowledge of and comfort in obtaining travel histories
University of Alabama, Birmingham, AL
Purpose of study To evaluate the knowledge of obtaining travel histories in medical students and paediatric interns.
Methods used Medical students and paediatric interns separately participated in a high-fidelity simulation case (malaria or typhoid fever) that hinged on asking a travel history. Simulation observers documented if and how a travel history was asked. After the simulation, education was provided on obtaining travel histories. Participants then completed a survey that included questions on their previous education and comfort with obtaining travel histories. Chi-square test was performed for categorical variables and Student’s t-test was performed for continuous variables.
Summary of results There were a total of 24 simulations, and 145 (107 medical students and 38 interns) participated from June 2016-June 2017. Participants asked a travel history in all but 2 simulations; however, in 9/24 simulations (38%) they required prompting by either a confederate in the simulation or laboratory results. Nearly half of all participants (44.8%) did not have previous training in obtaining travel histories. Participants were more likely to ask travel histories in the last 3 months if they had received previous training in obtaining travel histories (1.2 times per month vs 0.9 times per month, p=0.042). Participants also were more comfortable diagnosing and treating conditions acquired from travel within the U.S. than those acquired from international travel (32.9% vs 22.4%, p<0.0001). Previous education in obtaining travel histories and past international travel did not significantly influence the amount of comfort participants had with travel histories.
Conclusions This study highlights the lack of knowledge regarding the importance of travel histories as part of basic patient history taking. Furthermore, medical students and interns had low comfort in the components of an adequate travel history and diagnosing conditions acquired from international travel. More formal education is needed in these areas.
660 Media and advocacy training in paediatric residents
1University of Alabama, Birmingham, AL
2Centennial of Tennessee, Nashville, AL
Purpose of study Advocacy education is required for paediatrics residency programs. Media, in particular social media, plays a large role in providing health knowledge and much more. Published recommendations for residency programs on this topic are to utilise social media for education. No study has addressed the utilisation of media and social media outlets for advocacy of children resident training. We propose that didactic education and simulation of media interviews will increase knowledge and improve comfort with utilising media and social media for child advocacy.
Methods used This is a descriptive ongoing study of all paediatrics and medicine/paediatrics residents at the study institution who complete the required time on Injury Prevention and Childhood Advocacy. Our residents are educated through media handouts, one-on-one time with hospital media staff, videotaping by the staff, and meeting with faculty who have a media focus. The residents submitted surveys before and after media training to determine their level of comfort and interest in providing medical information through media or social media.
Summary of results Our preliminary data of 21 residents suggest that most residents (82% (17/21)) are ‘not at all’ or ‘only somewhat comfortable’ with speaking publicly on a medical topic prior to this intervention. After the intervention, all residents are at least ‘a little comfortable’ with doing a medical interview. (z=2.2, pval=0.03, 95% CI: 2.0% to 36%) Only three have had prior experience in a public speaking course, but none have been interviewed on a medical topic before. All residents felt they were more prepared after the training and 81% of residents were interested in additional training. 68% (11/16) residents indicated they are very likely to participate in child advocacy through media outlets after the training compared to only 9.5% (2/21) before training (z=3.7. pval <0.005, 95% CI: 28% to 90%).
Conclusions Paediatrics residents have very limited experience in public speaking prior to residency, and the large majority are not comfortable interviewing on a medical topic. Providing didactic and simulated media training does improve their comfort with interviewing on a medical topic and many are interested in having more education.
661 Implementation of reach out and read by health departments improves rural access
The University of Oklahoma, Edmond, OK
Purpose of study Many children begin school without the necessary language skills to read. Reach Out and Read (ROR) is an evidence based literacy program in paediatric practices. The AAP recommends that paediatric providers promote early literacy development at health supervision visits for children beginning in infancy and continuing at least until the age of school entry. The purpose of this study is to evaluate if expanding the ROR program in Oklahoma to County Health Departments improves rural access to Reach Out and Read.
Methods used Reach Out and Read site records were reviewed to determine the date of initiation of the program within County Health Departments in the state of Oklahoma. Using census data, all Reach Out and Read sites were plotted on a map of Oklahoma. ROR sites were reviewed and classified as either rural or urban using Rural Urban Commuting Area Codes for individual census tracts. Proportion of rural sites participating in ROR were compared before and after County Health Department involvement.
Summary of results Prior to implementation of the ROR program in County Health Departments, there were 67 participating ROR sites in the state of Oklahoma, of which 14 sites were located in rural areas (20.90%). 18 new ROR locations were established through the implementation of ROR in County Health Departments. 72% of County Health Departments were located in rural locations. After implementation of ROR in County Health Departments, there are now 27 rural ROR sites, therefore, 31.76% of ROR sites in the state of Oklahoma are now in rural areas.
Conclusions Implementation of ROR in County Health Departments in Oklahoma increases rural access to the ROR program. Use of ROR in Health Departments is an acceptable way to expand the ROR program to better serve rural children. Other states could use this model to improve rural access to the evidence based ROR model.
662 A curriculum-driven journal club
1East Tennessee State University, Johnson City, TN
2Quillen College of Medicine/ETSU, Johnson City, TN
Purpose of study Among the attributes needed to assure graduates of residency and fellowship programs become astute, informed consumers of the clinical research literature is a fundamental understanding of the most common study designs used in published studies. No best practice has thus far been established.
Methods used A curriculum was developed consisting of the 18 most common study designs/investigational tools presently used in the clinical research literature: Cross-Sectional, Crossover, Case-Control, Outcomes/Retrospective Cohort, Prospective Observational Cohort, Data Adjustment Methods, Survey, Meta-analysis (study- and patient-level), Systematic Reviews, Cost-Efficacy, Comparative Effectiveness, Quality Improvement, Big Data, and 4 on Randomised Controlled Trials (sources of bias, blinding and controls, absent data and cross-overs, superiority/equivalence/non-inferiority). The journal club advisor assigns the design and provides 1–2 concise, level-appropriate ‘support articles’ on each design/tool. The presenter is then free to select an article of his/her interest that employed this assigned design. Both are sent to trainees and faculty ≥2 weekends before the conference. The presenter develops a short set of PowerPoint slides presenting the key points from the support article(s) (20–25 min), followed by a group presentation/discussion of the research article using a medium chosen by the presenting trainee. The 18 month curriculum allowed for each topic to be covered twice within a 3 year program.
Summary of results This approach has been employed by the author in 6 different programs (2 residency, 4 cardiology fellowship) at 4 different institutions since 2002. Improvements, topic additions/deletions, and use of better support articles were made annually as needed. After initial organisation and acquisition of support articles, each journal club requires 2–3 hours work for the advisor; there are no other costs associated with this model.
Conclusions Although trainees (particularly fellows) have consistently given this journal club model high praise in annual program surveys, no valid metric (using a control group) to explore the relative value and impact of this model versus others has been developed. We hope to engage other institutions in a more formalised, controlled evaluation of this model.
663 Assessment of burnout and its identifying factors in lsuhsc paediatrics and medicine-paediatric residents compared to residents across the country
LSU Health Science Centre, Children’s Hospital, Kenner, LA
Purpose of study Physician wellness has emerged as a critical issue in medicine as numerous studies reveal an alarming percentage of trainees and practicing physicians experiencing high levels of depression, exhaustion, and even suicide compared to the general population. The LSUHSC Department of Paediatrics initiated a program one year ago to create a culture of well-being and resilience to prevent and ameliorate these issues with a significant focus on our trainees. As a part of a national study, our goals are to determine the prevalence of burnout in our trainees, the potential impact of our wellness initiatives, and identify factors that contribute to burnout and resilience.
Methods used Paediatric and Medicine-Paediatric trainees were recruited to complete a cross-sectional survey about mindfulness, their perceived global health, self-compassion, empathy, spirituality, resilience, burnout and compassionate care in the Spring of 2017. LSUHSC New Orleans was one of 53 residency programs nationwide participating in the Paediatric Resident Burnout-Resilience Consortium Study. This is a multi-site study, with a lead site, a coordinating centre, and participating sites.
Summary of results A total of 1753 residents were surveyed, 64 from LSUHSC. Overall response rate nationally was 66%, with LSUHSC at 57.81%. Nationwide, residents reported experiencing burnout at a rate of 53% whereas LSUHSC residents reported 46%. Furthermore, nationwide Paediatric residents had a 54% burnout rate and LSUHSC Paediatric residents had a 37% burnout rate. However, 52% of nationwide Medicine-Paediatric residents reported experiencing burnout and 75% for LSUHSC Medicine-Paediatric. Residents experiencing burnout by training year: PY1 nationwide 52% and PY1 LSU program 30%, PY2 nationwide 59% and PY2 LSU program 44%, PY3 nationwide 50% and PY3 LSU program 38%.
Conclusions LSUHSC resident burnout percentage is lower than national percentages, but higher in Medicine-Paediatric residents. By level, PY2 residents had highest burnout at LSUHSC and nationwide. Our wellness program may have contributed to these findings and this data will guide future interventions. Future plans are to add mindfulness training and reassess the same cohort of residents in 2018 with additional comparison to the ACGME Milestone data.
664 Resident perception of continuity of care in longitudinal care clinics
OUHSC, Oklahoma City, OK
Purpose of study Multiple studies have shown improved patient care outcomes as a result of continuity, including decreased hospitalisation and ER visits. Continuity of care is an important component of paediatric residency programs and education. Residents are required to participate in a continuity clinic for 36 half days each year in an effort to create a longitudinal outpatient experience. An initial clinic assessment measured continuity of care at the three University of Oklahoma Health Sciences Centre (OUHSC) paediatric residency continuity clinics. The results identified differences in resident and clinic continuity that varied significantly between the three clinics. The purpose of this current study is to better understand the variations in continuity by utilising a survey to evaluate resident perception of continuity of care and to identify factors affecting continuity.
Methods used Current 2nd and 3rd year paediatric residents at OUHSC as well as graduated paediatric residents from the Class of 2017 will be asked to complete an anonymous online survey via Research Electronic Data Capture (REDCap). Results will be analysed by resident class as well as by continuity clinic.
Summary of results A clinic assessment from 2016–2017 identified ranges in the usual provider of care (UPC) continuity measure: UPC by clinic 9%–49%, and UPC by resident 5%–72%. Discussion of these results led to creation of this study. Survey responses will identify resident perception of the following: continuity of care in their clinic, satisfaction with continuity of care, benefits of continuity, barriers to continuity, and methods to improve continuity. Data from this study is currently being collected.
Conclusions The analysis of the survey results will help delineate the current educational impact of continuity of care. In addition, identification of factors perceived by residents to be affecting continuity and their outpatient longitudinal education experience will help guide future curriculum and clinic processes to maximise continuity of care and quality of education.
665 Use of simulation in paediatric resident understanding of neonatal conventional ventilation: a randomised trial
MGovern Medical School, Houston, TX
Purpose of study In the Neonatal Intensive Care Unit changes in mechanical ventilation management, the use of surfactant, and continuous positive airway pressure have decreased resident exposure to ventilated patients. Simulation increases diversity and number of learning experiences, and is known to improve procedural skills. We evaluated the use of an interactive simulation to improve clinical skills regarding conventional neonatal ventilation.
Methods used From July 2016 to June 2017 residents were stratified by post graduate year then randomised. All residents received pre- and post-questionnaires evaluating knowledge of conventional ventilator settings, blood gas interpretation, and corrective ventilation measures. The intervention cohort received a session of simulated patient cases on a unit ventilator. Knowledge measures were analysed for baseline differences between the groups. The main outcomes of percentage correct on the post-questionnaire and simulated case ventilator interpretation checklist were compared with a Wilcoxon rank sum test.
Summary of results 89 residents were eligible, 73 completed the study. Baseline knowledge and comfort levels with ventilation were equal between groups. Posttest comfort levels increased with the intervention in identifying ventilator settings (mean 4.13, 95% CI: 3.98 to 4.27 vs mean 3.6, 95% CI: 3.45 to 4.1, p 0.002) and optimising ventilation (mean 4.2, 95% CI: 3.99 to 4.41 vs 3.6, 95% CI: 3.28 to 3.92, p 0.003). Knowledge of ventilator settings, interpreting blood gases, and corrective ventilation was significantly increased in the intervention group (Mean 69%, 95% CI: 62% to 75% vs mean 55%, 95% CI: 49% to 61%, p<0.001). Practical application by correctly interpreting simulated case ventilator settings was significantly increased in those who received the simulation (mean 89%, 95% CI: 86% to 92% vs mean 72%, 95% CI: 67% to 77%, p<0.001).
Conclusions Residents who received a simulation session had increased comfort levels with ventilators and blood gases, as well as increased ability to interpret a blood gas and make changes to optimise ventilation. Importantly residents exposed to the simulation were more likely to correctly interpret ventilator settings and may make more sound clinical decisions.
666 Perceived barriers to medical student screening for food insecurity
UT Health MGovern Medical School, Houston, TX
Purpose of study To identify barriers that medical students encounter when screening patients for food insecurity in an outpatient paediatrics setting and identify potential areas for curriculum development on the social determinants of health care.
Methods used We invited 43 medical students who rotated at a county paediatric clinic during the 2016–2017 academic year to participate in a retrospective survey study. The survey was composed of a series of questions to identify challenges students encountered while screening their patients for food insecurity. 63% of students who rotated at the clinical site participated in the survey.
Summary of results 81.48% of survey respondents indicated that they believed routinely screening patients was important, and 81.48% reported that screening patients was a successful way to learn about their patients. When asked about whether the food insecurity screening led to conversations about other tangible insecurities like housing or clothing, 66.67% indicated less than half the time. 85.19% of participants felt that the screening was their responsibility and 55.56% survey participants indicated that when they become physicians, they will feel that it is their responsibility to screen for food insecurity. However, when asked if they plan to screen when they are physicians, only 40.74% indicated ‘yes.’ There was a statistically significant difference (p=0.05) in the populations of primary care vs non-primary care when asked whether they would continue screening as a physician. 17% of respondents reported a primary care field as their chosen specialty. 63% reported a subspecialty. Of those pursuing primary care, 70% reported yes to continue screening in their future career, and 30% reported maybe/no. Of those pursuing a sub-specialised field, 24% reported they would continue screening, and 76% reported maybe/no.
Qualitative themes that emerged included perceptions about limited amount of time to screen, student forgetfulness, language barriers, and patient embarrassment as challenges to routine screening.
Conclusions This study is one of the few to look at medical student perceptions surrounding screening for social determinates of health. The study elucidated barriers to screening and the need for undergraduate medical curriculum development to address practical ways to screen in different contexts of medicine.
667 Snuggle squad volunteers benefit infants and nursing staff in neonatal intensive care unit
University of Louisville, Louisville, KY
Purpose of study Kentucky is experiencing a major opioid abuse epidemic affecting a significant number of neonates. Fetuses exposed to opioids in utero may experience neonatal abstinence syndrome (NAS) after birth. Between 2009 and 2013, the national NAS rate doubled, with Kentucky incidence remaining twice the national average. There is increased need for non-pharmacological interventions for NAS infants and support for parents and staff. In 2015, The University of Louisville School of Medicine students created a volunteer group (‘Snuggle Squad’) serving the Norton Children’s Hospital NICU. The aim of this pilot study is to determine if this volunteer group is helpful to the nursing staff, and warrants continuation of the program and possible extension to other hospitals. We measured approval of the group with an anonymous survey for nursing staff.
Methods used An anonymous survey was administered to nursing staff at Norton Children’s Hospital NICU. The survey contained five multiple-choice questions, with the ability to leave additional comments.
Summary of results 24 nurses participated in the survey. 91% of them considered the student volunteers helpful to the NICU. Specific comments included: ‘Student volunteers significantly help the NICU…NAS population is where we utilise them the most. Without them we would struggle to console each baby during the shift. A big part of the babies healing process is providing positive stimulation. Volunteers ensure we meet that need’ 43% of responders asked for the volunteers to be present every day. They did not identify significant issues related to the student volunteers compared to other volunteers. Suggestions to improve the program: 53% of responders had none, and 29% requested more volunteers.
Conclusions We concluded that the nursing staff is in favour of the Snuggle Squad program and believe it positively impacts the care provided to patients. In the future, we plan to expand the program to other NICUs in the city. Additionally, our long-term goal is to design and perform a study to specifically measure the impact of student volunteers on neonatal health outcomes. Current literature data is not strong enough to recommend cuddler programs as evidence-based interventions. We hope to contribute to the existing data and create a template for other organisations in developing cuddler programs.
Perinatal medicine II, Concurrent session, 1:00 PM, Saturday February 24, 2018
668 Systematic review and meta-analysis of the timing of initiation and dose of caffeine on the risk of bronchopulmonary dysplasia
Emory University School of Medicine, Atlanta, GA
Purpose of study Caffeine decreases the risk of bronchopulmonary dysplasia (BPD) in extremely preterm infants. Optimising caffeine use could increase therapeutic benefit.
Methods used We performed a systematic review and meta-analysis of observational studies and randomised trials evaluating the comparative effectiveness of different timing of initiation (early vs late) and dose (high vs standard) of caffeine on the risk of BPD. English language publications were identified from a PubMed search using MESH terms Caffeine AND Infant and by review of study reference lists. We adhered to the PRISMA guidelines and used the GRADE framework to assess the quality of evidence. When applicable, we performed a meta-analysis using random effects.
Summary of results We identified 548 studies in the search. For timing of caffeine initiation, we identified 5 observational studies evaluating 63 049 infants. Earlier initiation of caffeine (before day of life 3), compared to later initiation (at or after day of life 3), was associated with a decreased risk of BPD (unadjusted OR 0.59; 95% CI: 0.39 to 0.90, I2=97%; adjusted OR 0.69; 95% CI: 0.64 to 0.75, I2=10%; GRADE quality of evidence: very low to moderate). For dose of caffeine, we identified 3 trials enrolling 432 infants. High-dose caffeine, compared to standard dose, was associated with a decreased risk of BPD (OR 0.65; 95% CI: 0.43 to 0.97; I2=0%; GRADE quality of evidence: low to moderate).
Conclusions Earlier initiation and higher doses of caffeine may increase its beneficial effect on the risk of BPD. However, higher quality studies are necessary to guide optimal caffeine use.
669 Endothelial adrenomedullin signalling is necessary to protect neonatal mice against experimental bronchopulmonary dysplasia
Baylor College of Medicine, Houston, TX
Purpose of study Interrupted pulmonary angiogenesis is a hallmark of bronchopulmonary dysplasia (BPD) in human preterm infants. Adrenomedullin (AM) is a multifunctional peptide that mediates its angiogenic effects via calcitonin receptor-like receptor (Calcrl) and receptor activity-modifying protein (RAMP) −2. We observed that global AM–deficient mice have an increased susceptibility to hyperoxic injury. However, the endothelial cell-specific contribution and mechanisms of AM-mediated effects on developing lungs is unknown. Therefore, we tested the hypothesis that endothelial AM signaling-deficient neonatal mice will display increased susceptibility to hyperoxia-induced experimental BPD compared to wild type mice.
Methods used In vivo studies: One-day-old endothelial Calcrl-sufficient (eCalcrl +/+) or –deficient (eCalcrl ±) mice were exposed to room air or hyperoxia (FiO270%) for up to 14 days, following which the mouse lungs were harvested to determine angiogenesis and alveolarization, and the expression of calcitonin receptor-like receptor (Calcrl).
In vitro studies: For mechanistic studies, we used human pulmonary microvascular endothelial cells (HPMEC) and determined the effects of Calcrl antagonist, Calcrl knockdown or AM on extracellular signal-regulated kinases (ERK)1/2 and endothelial nitric oxide synthase (eNOS) expression and angiogenesis.
Summary of results Exposure of neonatal mice to 70% oxygen decreased the expression of endothelial Calcrl expression. Further, hyperoxia-induced alveolar and pulmonary vascular simplification was augmented in neonatal eCalcrl ±mice compared to eCalcrl +/+ mice. Mechanistically, Calcrl deficiency decreased eNOS expression and ERK1/2 activation in HPMEC. Further, inhibition of ERK1/2 and eNOS signalling in HPMEC decreased AM-mediated angiogenesis.
Conclusions We conclude that endothelial AM signalling protects against hyperoxia-induced experimental BPD in neonatal mice via ERK1/2 and eNOS pathways. Our results indicate that AM and Calcrl-RAMP2 interface are potential therapeutic targets for the management of BPD in human preterm infants.
670 Effects of umbilical cord-derived mesenchymal stem cells in an in-vitro model of bronchopulmonary dysplasia
University of Texas Health, San Antonio, TX
Purpose of study Bronchopulmonary Dysplasia is a debilitating respiratory disease that affects over 15 000 neonates annually. Oxidative stress has been shown to play a key role in disease manifestation. Therapeutic agents capable of mitigating oxidative damage should be investigated. Emerging evidence suggests that umbilical cord-derived mesenchymal stem cells (UC-MSCs) may be a novel treatment option for BPD. The purpose of this study was to investigate the effects of UC-MSCs in an in-vitro model of hydrogen peroxide-induced lung injury.
Methods used UC-MSCs, derived from human Wharton’s jelly tissue, were verified against criteria for MSCs per the International Society for Cellular Therapy. Rat lung epithelial cells (RLE-6TN) were used to model the lung epithelium in neonates. RLE-6TN cells were treated as follows: i) control (grown at standard cell culture conditions), ii) injured (100 µM H2O2 for 1 hour), and iii) treated (100 µM H2O2 for 1 hour +50% UC-MSC conditioned media). Cell proliferation, wound healing, production of reactive oxygen species, and RNA expression of caspase-6 and superoxide dismutase-2 were measured.
Summary of results Compared to the control, RLE-6TN proliferation after injury decreased by 51% versus a decrease of 4% in the treated group (p<0.05). Four hours after creating a wound across RLE-6TN cell monolayers, the control group had healed by 14% while the injured group reached 33% closure and the treated group had 48% closure (p<0.05). Hydrogen peroxide increased oxidant injury 1.7-fold whereas the treated group decreased oxidant injury to 0.5- fold of control (p<0.05). Caspase-6, a measure of cell apoptosis, increased after injury but did not demonstrate a significant decrease after UC-MSC conditioned media exposure. Superoxide dismutase-2 was similar in all groups.
Conclusions Our findings suggest that UC-MSCs may potentially improve alveolar epithelial cell proliferation and wound healing as well as reduce production of reactive oxygen species after oxidative stress injury. Further studies will optimise the concentration of UC-MSC conditioned media, remeasure it’s effects on apoptosis and anti-oxidants, and examine mitochondrial function.
671 Comparison of preterm versus term wharton’s jelly-derived mesenchymal stem cells in differing oxygen tensions
University of Texas Health, San Antonio, TX
Purpose of study Mesenchymal stem/stromal cells (MSCs) are integral in regenerative medicine with a promising potential in treating major neonatal morbidities. Specifically, MSCs derived from human umbilical cords are easily and humanely obtained, have robust properties, low immunogenicity, and offer the potential for autologous therapy. To date, there are no studies comparing the regenerative potential of preterm versus term Wharton’s jelly-derived (WJ) MSCs. Therefore, we aim to compare cell proliferation, motility, senescence, and viability in preterm WJ-MSCs compared to term WJ-MSCs in differing oxygen tensions.
Methods used WJ-MSCs were derived from 5 preterm and 5 term umbilical cords using the enzymatic digestion method. Our WJ-MSCs were isolated and characterised in adherence to the standards set forth by The International Society for Cellular Therapy. We examined four cellular aspects: i) proliferation, ii) motility, iii) cell viability and iv) senescence.
Summary of results WJ-MSCs were successfully isolated from all preterm and term umbilical cords. They demonstrated an adherence to plastic, had a spindle cell morphology, met the criteria for cell surface antigen markers, and differentiated into osteocytes, adipocytes, and chondrocytes. Under normoxia, the cells from preterm and term infants had similar functional properties. Exposure to hyperoxia (90%) and hypoxia (1%) for 24 hours increased cell motility in preterm WJ-MSCs (p<0.05). The term WJ-MSCs had increased proliferation when grown at 1% oxygen (p<0.05). There were no differences in cellular senescence or viability between the two groups. When all the samples were grouped, hyperoxia revealed a significant reduction in cell viability (p<0.05).
Conclusions In summary, our preliminary findings suggest that WJ-MSCs derived from full term versus preterm umbilical cords have similar functional characteristics. However, exposure to hyperoxia and hypoxia may impact the potential therapeutic efficacy of MSCs. For instance, preterm cells have better migratory properties in hyperoxia/hypoxia, and term WJ-MSCs proliferate more rapidly in hypoxia. Further studies will be needed to evaluate the characteristics of WJ-MSCs under different micro-environmental changes.
672 Thioredoxin reductase inhibition and bronchopulmonary dysplasia: a focus on glutathione in the neonatal lung
University of Alabama, Birmingham, AL
Purpose of study Bronchopulmonary dysplasia (BPD) is a lung disease with significant morbidity and mortality in preterm infants. A developing fetus exists in a hypoxic environment (~3%O2). Endogenous antioxidant systems, including the glutathione (GSH) and thioredoxin (Trx) systems, protect the lungs and mitigate O2 related injury. Previous work from our lab has shown that the Trx reductase-1 (TrxR1) inhibitor, aurothioglucose (ATG), attenuates hyperoxia-induced lung developmental abnormalities in a murine BPD model. This appears to be mediated via activation of nuclear factor E2-related factor 2 (Nrf2). Nrf2 is a regulator of endogenous antioxidant responses. We hypothesise that ATG treatment enhances pulmonary GSH-dependent responses in a murine BPD model.
Methods used Within 12 hour of birth, C3H/HEN pups received saline or 25 mg/kg ATG and were exposed to either room air (RA, 21%O2) or hyperoxia (HO, 85%O2). Lungs were collected at 1, 3, and 7 d. GSH levels (total and oxidised) were determined in whole homogenates. Data (n=4–6) were analysed by 2-way ANOVA with Tukey’s post hoc. Significance was accepted at p<0.05.
Summary of results At 1 d, there were no significant effects of ATG or HO on total GSH or GSSG levels. At 3 d, total GSH levels were 1.3 fold higher in HO+saline (p=0.0206) and 1.7 fold higher in HO+ATG (p=0.0002) when compared to RA +saline. Individual differences between HO+saline and HO+ATG were not detected, but two-way ANOVA indicated an independent effect of ATG on GSH levels at 3 d (p=0.0020). At 7 d, total GSH was 1.5 fold greater in lungs from HO+ATG treated pups (p=0.0447) vs RA +saline. There were no significant effects of HO or ATG on GSSG levels at 3 d or 7 d.
Conclusions Our results show that ATG enhances total GSH levels in the lungs of HO-exposed pups but has no effect on GSSG levels. Given the importance of GSH-mediated antioxidant responses in protection from hyperoxia, we speculate that ATG-mediated enhancement of GSH-dependent antioxidant responses contributes to the protective effects of TrxR1 inhibition in our murine BPD mode. This supports the rationale for TrxR1 inhibitors, which mitigate the effects of hyperoxia on the developing lung, to prevent the development of BPD in preterm infants.
673 Utilisation of spontaneous breathing tests for assessing extubation readiness in preterm infants: timing matters
University of Kentucky, Lexington, KY
Purpose of study Preterm neonates often require mechanical ventilation in the first days of life. Having such respiratory support is necessary for survival, but long term ventilator reliance is associated with pulmonary injury and chronic morbidities; thus, early extubation is highly desirable. A failure requiring re-intubation can also have major consequences (respiratory distress, lung parenchymal injury, etc). In the past few years our institution has implemented a spontaneous breathing test (SBT) to assess respiratory readiness in ventilated preterm infants; here, we investigated the value of various durations SBTs to predict respiratory success after extubation, with specific comparisons of 15,10, and 3 min.
Methods used Outcomes of first extubation cases that occurred in the first 30 days of life were evaluated from the EMR of our neonatology service line from Jan 2015-Sept 2017. First-extubation failure was defined as a requirement for reintubation within 72 hours post extubation. Success rates were compared across gestational ages<30 weeks, comparing SBT protocols that were 15,10, and 3 min in duration. Extubation success rates were compared among patients.
Summary of results A total of 69 patient extubation outcomes were investigated using successful SBT protocols of 15 min (n=15), 10 min (n=31), or 3 min (n=23) as entrance criteria. Infant birthweight ranged from 430 g to 1600 g, with gestational ages ranging from 23 to 29 6/7 weeks. Using a SBT duration of 15 min was associated with a 47% prediction of extubation success. Shortening the SBT duration to 10 or 3 min significantly improved the predictive value to 84% and 91% respectively (p<0.05). The longer duration SBTs were less predictive in the most premature infants.
Conclusions Assessment of extubation readiness is a major challenge in preterm infants and use of SBTs may help in clinical decision-making. Our findings suggest the duration of such tests is critical for predictiveness. We postulate that a longer duration SBT may induce physiological stress that complicates result interpretation (eg. skeletal muscle fatigue), and that could contribute to later respiratory failure, especially for the most premature patients. Further investigation of predictors of extubation readiness in preterm infants is clearly warranted.
674 Randomised trial of skin-to-skin contact to prevent hypothermia in preterm neonates
University of Alabama, Birmingham, AL
Purpose of study To prevent neonatal hypothermia, the World Health Organisation (WHO) recommends the thermoregulation care protocol that includes warm delivery rooms, immediate drying, skin-to-skin contact (SSC) as continuously as possible, breastfeeding, delayed bathing and weighing, appropriate bundling, mother and baby together, warm transportation, warm resuscitation, and training and awareness raising. However, SSC is not routinely practiced in preterm infants in many birth facilities around the world.
Objectives To test the hypothesis that SSC initiated either at birth or at 1 hour after birth reduces moderate or severe hypothermia in preterm neonates at (a) one hour after birth and (b) at discharge when compared to standard thermoregulation care.
Methods used Preterm neonates (≥32 to 366/7 weeks of gestational age) born at a tertiary delivery centre in Zambia were randomised in two phases (Phase 1: birth to 1 hour, Phase 2: 1 hour to discharge) to either as much SSC as possible in combination with standard thermoregulation care (SSC group) or to standard thermoregulation care (control group). The primary outcome was moderate or severe hypothermia (axillary temperature <36.0 o C) at (a) one hour after birth or (b) at discharge.
Summary of results The proportion of neonates with moderate or severe hypothermia did not differ between the SSC and control groups at 1 hour after birth (50% versus 52%, RR=0.96, CI: 0.7 to 1.3, p=0.78) or at discharge (18% versus 19%, RR=0.93, CI: 0.46 to 1.9, p=0.91). Ambient temperatures averaged 27.7oC±1.0°C or 82.0±1.9 F (mean ±SD) and did not differ between the groups. Duration of SSC in the SSC group in Phase 1 was 36±19 min (mean ±SD) and in Phase 2 was 58%±23% (mean ±SD) of the length of hospital stay.
Conclusions In facilities where ambient temperature is maintained appropriately, SSC practiced as much as possible in combination with standard thermoregulation care initiated either at birth or at 1 hour after birth did not reduce moderate or severe hypothermia in preterm infants compared to standard thermoregulation care.
675 Skin-to-skin care with a plastic bag to prevent neonatal hypothermia: a randomised controlled trial
1University of Alabama, Birmingham, AL
2University Teaching Hospital, Lusaka, Zambia
Purpose of study Skin-to-skin care (SSC) is recommended by the WHO to prevent neonatal hypothermia, reduce sepsis, and increase survival. Polyethylene bags (PB) reduce moderate hypothermia in term infants. This study tested the hypotheses that PB in addition to SSC reduces moderate hypothermia (<36.0°C) at 1 hour after birth and at discharge in term infants in resource-limited settings.
Methods used This study was conducted in the tertiary referral centre in Lusaka, Zambia. Term infants were randomised in two phases using sequentially-numbered sealed opaque envelopes after birth (phase 1) and again at 1 hour after birth (phase 2) to either SSC with PB or SSC alone. Infant and maternal temperature were recorded at birth, 1 hour, 4 hours, and then every 4 hours until discharge or 24 hours after birth. A sample size of 420 infants was required to detect a 25% relative risk reduction in phase 1 and 300 infants were required to detect a 33% relative risk reduction in phase 2.
Summary of results Four hundred and twenty three infants with a mean gestational age of 39 weeks and birth weight of 3220 g were studied. The rate of moderate hypothermia at 1 hour was 71/211 (33.6%) in the SSC-PB group compared with 100/212 (47.2%) in the SSC alone group (RR, 0.71; 95% CI: 0.56 to 0.90; p<0.01). The rate of moderate hypothermia at discharge was 10/152 (6.6%) in the SSC-PB group compared with 23/147 (15.6%) in the SSC alone group (RR, 0.42; 95% CI: 0.21 to 0.85; p=0.01). The mean temperature at 1 hour was 36.1°C±0.8 in the SSC-PB group compared with 35.9°C±0.6 (p=0.04) with SSC alone. The mean temperature at 1 hour for phase 2 participants did not differ between groups. The mean temperature at discharge was 36.5°C±0.4 in the SSC-PB group compared with 36.3°C±1.1 in the SSC alone group (p<0.01). The rates of severe hypothermia, hyperthermia, and other adverse events did not differ significantly.
Conclusions Polyethylene bags in combination with SSC reduced moderate hypothermia at one hour after birth and at discharge from hospital in term infants compared with SSC alone.
676 Continuous renal replacement therapy removes cytokines during neonatal extracorporeal life support
1Medical University of South Carolina, Charleston, SC
2University of Pittsburgh, Pittsburgh, PA
Purpose of study Continuous renal replacement therapy (CRRT) is used during extracorporeal life support (ECLS) to optimise fluid management but may result in removal of cytokines from the circulation. Studies in vitro, in animals, and in adults demonstrate hemofiltration of cytokines via CRRT; this has never been demonstrated in infants receiving ECLS. We hypothesised that CRRT during infant ECLS removes cytokines from the circulation resulting in quantifiable cytokines in the ultrafiltration fluid (UF), specifically interleukin 6 (IL-6), IL-10, IL-13, and TNF-alpha (TNF-α).
Methods used We prospectively enrolled infants receiving ECLS with concurrent CRRT. Whole blood was collected at cannulation and every 6 hours during the initial 24 hours of ECLS, then every 24 hours for the remainder of concurrent therapy; UF was sampled every 6 hours throughout concurrent therapy beginning 6 hours after CRRT initiation. ELISA was used to quantify cytokine concentrations.
Summary of results We analysed 92 UF and 8 blood samples from 8 patients. Quantifiable amounts of IL-6 and TNF-α were found in the UF and serum (figure 1). IL-10 and IL-13 were not found in the UF.
Conclusions CRRT use during neonatal ECLS results in cytokine clearance, particularly IL-6 and TNF-α. These can be quantified in the UF of infant ECLS patients suggesting that CRRT-mediated cytokine removal may modulate inflammatory responses in these infants.
677 Measuring bilirubin binding capacity in very low birthweight newborns
1University of Texas at Houston, McGovern Medical School, Houston, TX
2Stanford University, Palo Alto, CA
Purpose of study Although it is known that low bilirubin binding capacity (BBC) increases the risk of bilirubin neurotoxicity in very low birthweight (VLBW) newborns, the amount of blood required for measurement has made clinical application impractical. Our aim is to evaluate the reliability of a novel microassay method to measure BBC in VLBW newborns.
Methods used In a prospective cohort study of 60 VLBW newborns (30 ELBW and 30 1.0–1.5 kg birthweight), we quantified precision and reliability of a hematofluorometry microassay (20 µl blood). Blood samples were repeated daily as lipid infusions increased from 0 to 3 g/kg/day and again as rates decreased from 3 to 0 g/kg/day, with a maximum of 10 blood samples per patient. Precision was assessed by test-retest agreement, quantified by the standard deviation (SD) of 2 assays performed by the same tester on each blood sample. Reliability was assessed by comparing precision (variation within samples) to variation between blood samples from different patients, quantified as the intraclass correlation coefficient (ICC). ICC ranges from 0 (high precision and poor reliability) to 1.0 (low precision and excellent reliability). We hypothesised that the ICC for BBC in our population would be >0.80 and that the 95% CI would exclude values<0.70. We used multilevel regression to account for within-patient correlation.
Summary of results Preliminary results are reported from 244 blood samples from 35 patients. Based on 7.1±1.3 blood samples per patient, the mean BBC was 19.9±4.7 mg/dl (min 8.9, max 38.5). The SD for within blood sample test-retest was 1.23 (95% CI: 1.13 to 1.35) and was stable over the range of BBC values. Adjusting for clustering within patients, the between blood sample SD was 2.9, resulting in an ICC of 0.93 (95% CI: 0.91 to 0.95). Means are expressed with ±SD.
Conclusions Preliminary results suggest that hematofluorometry microassay can reliably detect changes in BBC in VLBW newborns and can be used to investigate factors beyond albumin levels that effect BBC. More research will be necessary to demonstrate clinical utility.
678 Neurofibromin deficiency induces endothelial cell proliferation and retinal neovascularization
Augusta University, Augusta, GA
Purpose of study Neurofibromatosis type 1 (NF1) is the result of inherited mutations in the NF1tumour suppressor gene, which encodes the protein neurofibromin. Eye manifestations are common in NF1 with recent reports describing a vascular dysplasia in the retina and choroid. Common features of NF1 retinopathy include tortuous and dilated feeder vessels that terminate in capillary tufts, increased endothelial permeability, and neovascularization. Given the retinal vascular phenotype observed in persons with NF1, we hypothesise that preserving neurofibromin may be a novel strategy to control pathological retinal neovascularization.
Methods used Nf1 expression in human endothelial cells (EC) was reduced using shRNA and EC proliferation, migration, and capacity to form vessel-like networks were assessed in response to vascular endothelial growth factor (VEGF) and hypoxia. Wild type (WT), Nf1 heterozygous (Nf1±), and Nf1flox/+ ;Tie2cre pups were subjected to hyperoxia/hypoxia using the oxygen-induced retinopathy model. Retinas were analysed quantitatively for extent of retinal vessel dropout, neovascularization, and capillary branching.
Summary of results Neurofibromin expression was suppressed in response to VEGF, which corresponded with activation of Mek-Erk and PI3-K-Akt signalling. Neurofibromin-deficient EC exhibited enhanced proliferation and network formation in response to VEGF and hypoxia via an Akt-dependent mechanism. In response to hyperoxia/hypoxia, Nf1 ±retinas exhibited increased vessel dropout and neovascularization when compared with WT retinas. Neovascularization was similar between Nf1 ±and Nf1flox/+ ;Tie2cre retinas, but capillary drop out in Nf1flox/+ ;Tie2cre retinas was significantly reduced when compared with Nf1 ±retinas.
Conclusions These data suggest that neurofibromin expression is essential for controlling endothelial cell proliferation and retinal neovascularization and therapies targeting neurofibromin-deficient EC may be beneficial for NF1 retinopathy.
Renal, electrolyte and hypertension II, Concurrent session, 1:00 PM, Saturday February 24, 2018
679 Impaired arterial baroreflex sensitivity in prehypertension
Emory University, Decatur, GA
Purpose of study Prehypertension is associated with increased risk of hypertension and cardiovascular disease (CVD), the mechanisms of which remain unclear. Prior studies have shown increased resting sympathetic nerve activity (SNA), and augmented blood pressure (BP) responses during mental stress, suggesting autonomic dysregulation at rest and during stress. We hypothesised that compared to normotensives (≤120/80 mmHg), prehypertensives (120/80–139/89 mmHg) have impaired arterial baroreflex sensitivity (BRS) leading to autonomic dysregulation, and increased neurocardiovascular reactivity to mental stress.
Methods used 22 participants were studied: 12 otherwise healthy prehypertensives (35±6 years) and 10 matched normotensive controls (32±6 years). We recorded muscle SNA (MSNA) using microneurography, beat-to-beat BP, and continuous EKG during 5 min of supine rest and 3 min of stress via mental arithmetic. Arterial baroreflex sensitivity (BRS) was measured via modified oxford technique using IV boluses of nitroprusside and phenylephrine to manipulate arterial BP. The slope of the linear relationship between diastolic BP and MSNA (sympathetic BRS), and systolic BP and R-R interval (cardiovagal BRS) were assessed.
Summary of results As expected, baseline systolic BP (130±7 vs 117±8 mmHg) and diastolic BP (87±7 vs 74±8 mmHg) were significantly higher in prehypertensives (p<0.001). Resting MSNA (25±12 vs 18±10 bursts/min) tended to be higher in prehypertensives (p=0.08). Sympathetic BRS was comparable between the groups, but cardiovagal BRS (13±10 vs 22±10 ms/mmHg) was significantly lower in prehypertensives (p=0.03). During mental arithmetic, minute by minute increases in BP and MSNA did not differ between the groups. However, there was a significant correlation between diastolic BP reactivity to mental stress and resting cardiovagal BRS (r=0.703, p=0.016), as well as with resting sympathetic BRS (r=0.795, p=0.010) in the prehypertensive group. In contrast, in normotensive controls, there was no correlation between BP responses to stress and cardiovagal (r=0.126, p=0.766) or sympathetic BRS (r=0.287, p=0.581).
Conclusions These findings suggest that early impairment of arterial BRS may be present in prehypertension and may modulate BP responses to stress, contributing to increased hypertension and CVD risk.
680 Role of prostaglandin e2 and the indoleamine 2,3 dioxygenase pathway in the modulation of rejection in experimental kidney transplantation
1Augusta University, Augusta, GA
2Charlie Norwood VA Medical Centre, Augusta, GA
Purpose of study The indoleamine 2,3-dioxygenase (IDO) transprotein prevents rejection (RJX) in rodent kidney transplants, but is increased in untreated RJX, suggesting that RJX blunts the expression of other, pro-tolerant cytokines. In this regard, prostaglandin E2 (PGE2), generated by COX2 and binding to the EP4 receptor, protects against renal fibrosis and is anti-apoptotic for tubular cells, suggesting possible benefit in RJX. On this basis, we theorised that RJX would blunt PGE2 activity from rejecting pig kidneys, offering a potential mechanism for the lack of immunosuppression associated with increased IDO in RJX. To address this, we utilised COX2 and EP4 expression as surrogate markers for PGE2 activity, and correlated with IDO expression in rejecting pig kidneys.
Methods used Thirteen pig kidneys were studied: allotransplants (Allo, n=4), autotransplants (Auto, n=4) and normal right kidneys (Control, n=5). RJX was assessed by Banff criteria. Renal function (serum creatinine), IDO gene (PCR) and enzyme (HPLC), and COX2 and EP4 expressions (western blotting), were assessed. All transplants utilised the left kidney followed by right nephrectomy. All pigs were sacrificed under live organ harvests 72 hours post-op.
Summary of results RJX (mean Banff rejection IIA) increased serum creatinine (10.3±2.7 vs 3.9±1.1 mg/dL mean ±SEM, for Allo vs Auto), and both kidney IDO gene (4.46±2.6 vs 0.75±0.32, p=0.2) and enzyme activity (1276±506 vs 54±3.5 pmol/hr/mg protein, p=0.1). Ischemia induced COX2 expression (2.06±0.74 vs 0.34±0.08 units for Auto vs Control, respectively, p=0.015), while RJX suppressed COX2 expression (0.15±0.07 vs 2.06±0.74 units for Allo vs Auto, p=0.015). EP4 expression was depressed in both Allo and Auto compared to Control (0.26±0.07 vs 0.74±0.17 vs 1.44±0.38 units, Allo vs Auto vs Control, p=0.037).
Conclusions In RJX, IDO is induced and COX2 is blunted. The differential expression of COX2 between Auto and Allo suggests ischemia induces COX2, but this induction appears to be mitigated by allogeneic responses to rejection. The loss of the pro-tolerant effect of PGE2 may promote rejection in allotransplants and may help explain the inability of elevated IDO levels to suppress rejection.
681 Protein expression of tumour necrosis factor-alpha receptor type 1 is reduced in renal cortical tissue of endothelial nitric oxide synthase knockout mice
Tulane University School of Medicine, New Orleans, LA
Purpose of study As tumour necrosis factor-alpha (TNF-α) induces natriuresis via activation of its receptor type 1 (TNFR1), its mechanistic role in the development of salt sensitive hypertension (SSH) is not yet clearly defined. We have shown earlier that chronic high salt (HS) intake increase, but non-specific pharmacological inhibition of nitric oxide synthase (NOS) isoforms decrease TNFR1 protein expression in the kidney. Here we examined the hypothesis that such decrease in TNFR1 protein expressions are specific to inhibition of the endothelial isoform of NOS (eNOS), which is the main isoform linked to the development of SSH
Methods used Experiments were performed in eNOSKO as well as in WT (C57BL6) mice (n=6–7 in each group; 8–9 weeks of age) chronically fed either normal (NS; 0.4% NaCl) or HS (4% NaCl) diet for 3 weeks. Systemic BP was measured using tail-cuff plethysmography at the start of the experiment and at the end of every week during the experimental period. At the end of the treatment period, the mice were sacrificed and the kidneys were isolated and processed for tissue analysis. Immuno-histochemical analysis of TNFR1 and TNFR2 protein expression using appropriate antibodies in renal cortical tissues was performed.
Summary of results In the basal condition, the mean BP in eNOSKO mice was higher (89±0.8 vs 76±2.1 mmHg) than that in WT mice. There is no change in BP after 3 wks of NS or HS intake in WT, but HS intake for similar period in eNOSKO increased BP (107±3.6 vs 88+0.9 mmHg) compared to the baseline value. As expressed in percent area of positive staining, it was observed that TNFR1 immunoreactivity is lower in eNOSKO mice compared to WT mice both in NS (1.4%±0.2% vs 2.7±0.6%; p<0.05) and HS (1.8%±0.2% vs 4.1±0.5%; p<0.01) intake conditions. The intensity of TNFR1 immunoreactivity also showed the similar results. However, TNFR2 immunoreactivity was minimal in both strains of mice.
Conclusions These data indicate that TNFR1 activity is downregulated in the kidney in the condition of eNOS deficiency which minimises sodium excretion during HS intake leading to the development of SSH.
682 High protein intake is associated with end stage renal disease progression and mortality in patients with chronic kidney disease
1University of Tennessee Health Science Centre, Memphis, TN
2Veteran Affairs Medical Centre, Memphis, TN
Purpose of study High protein intake is associated with worse progression of CKD in patients with non-dialysis dependent CKD (NDD-CKD), but its effects on renal death (mortality or ESRD) are less well characterised.
Methods used We examined 854 NDD-CKD US veterans followed at a tertiary medical centre. We estimated dietary protein intake (DPI) from urea nitrogen and creatinine measured from morning spot urine collections and using the Maroni formula. The associations of baseline DPI (analysed as a continuous variable using splines, and divided into quartiles) with the composite of all-cause mortality or ESRD was examined in Cox models adjusted for demographics, comorbidities, medication use, baseline estimated GFR and proteinuria.
Summary of results Patients were 66±11 years old, 96% were men, 59% were African American and 55% were diabetic. The baseline estimated GFR was 38±21 ml/min/1.73 m2. Higher DPI was associated with higher mortality or ESRD (figure). Compared to the second quartile, the hazard ratios (95% CI) of mortality associated with quartiles 1, 3 and 4 of DPI were 1.18 (0.82–1.69), 1.03 (0.71–1.49) and 1.47 (1.04–2.08), respectively.
Conclusions In patients with moderate and advanced NDD-CKD, high DPI is associated with higher all-cause mortality or ESRD progression. Further studies are needed to determine the amount of DPI providing optimal outcomes in this patient population.
683 Effect of rituximab on mortality in end stage renal disease secondary to lupus
1Augusta University, Augusta, GA
2VA Medical Centre, Augusta, GA
Purpose of study Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that may lead to dialysis. Rituximab (RTX) is a B-cell inhibitor used in refractory LN, but it is unknown if RTX therapy prior to dialysis influences mortality. This study examined the association between RTX therapy and mortality in patients with end stage renal disease secondary to lupus (ESRD SLE).
Methods used Incident dialysis cases in the United States Renal Data System from 2006–2010 were queried for a cause of ESRD SLE (code 7100) from CMS Form-2728. ICD-9 and CPT codes identified comorbid diagnoses and RTX infusion in hospital claims. The association of RTX and mortality, controlling demographic and other comorbidities, was examined using Cox proportional hazards (CPH).
Summary of results There were 3307 patients identified with ESRD SLE. Patient demographics included: mean ±SD age of 41±15 years, 82% female, 53% black and 40% white. RTX infusion was documented in 68 (2.1%) patients. RTX(+) patients were younger (37±15 years) but did not differ from RTX(-) in gender, race, or dialysis access type. There was a non-significant increase of bacteremia, septicemia, and herpes zoster in RTX(+) patients. In the final CPH model, among those who died ≥4 years after starting dialysis, RTX(+) patients had a significantly greater adjusted hazard ratio (aHR) for death (aHR=4.13, p=0.0021) than RTX(-) patients. However, for those who died <4 years of dialysis, the RTX(+) infusion showed no association with mortality compared to RTX(-). Other risk factors for mortality in ESRD SLE patients included catheter access vs AVF (aHR=1.61) or a diagnosis of septicemia (aHR=1.51). Decreased mortality was found for females (aHR=0.82), other vs white race (aHR=0.62), and Hispanic ethnicity (aHR=0.62).
Conclusions Among patients with ESRD SLE, RTX had no effect on survival for patients dying <4 years of dialysis, but significantly increased risk of death for patients after 4 years of dialysis. Initiating dialysis with a catheter or developing septicemia also have an increased risk for death. We speculate that the increase in mortality observed in RTX(+) patients after 4 years be may be a potential late complication of long term immunosuppression.
684 Utility of lung ultrasound b-lines in volume assessment of end stage renal disease patients on hemodialysis
Augusta University, Medical College of Georgia, Augusta, GA
Purpose of study Volume assessment in end stage renal disease (ESRD) patients on hemodialysis (HD) can be sometimes challenging. Lung ultrasound to look for B-lines, which indicate interstitial oedema, is an emerging tool in assessing bedside volume status, and may assist in setting ultrafiltration (UF) goals for dialysis. We performed a quality assurance project to assess the utility of lung ultrasound in determining UF goals.
Methods used ESRD patients were studied before and after HD. Clinical parameters of volume status including systolic blood pressure (SBP) and presence of oedema were recorded pre-dialysis, and target UF was set accordingly. We counted the number of B-lines pre and post HD using two portable ultrasound machines, GE V-scan and GE Sonosite. For each patient, the ultrasound probe was placed at the same mid-axillary or mid-clavicular intercostal space to visualise B-lines pre and post HD. Linear regression or ANOVA was used to examine the association between the number of B-lines and fluid removed by UF.
Summary of results 24 ESRD patients were studied for the number of lung B-lines pre and post HD. B-lines were categorised as 0, 1–2, and 3 or more. For all patients, UF removed trended with the number of B-lines, but there was no significant association. There was a non-significant decrease in the number of B-lines with UF from 3.4±2.1 to 0.7±1.0 (p=0.53). Patients with ≥3 B-lines tended to get more volume removal with mean UF volume of 2.4±0.9 L. Mean UF removal in patients with 1–2 B-lines was 1.3±0.9 L, and with 0 B-lines was 1.4±0.6 L. Interestingly, four patients who did not have any B-lines could not tolerate target UF set pre-HD on the basis of SBP and oedema.
Conclusions Lung ultrasound may be a useful tool for bedside volume assessment of hemodialysis patients and help in deciding UF goals to achieve dry weight. Our pilot project shows a trend that higher number of B-lines may correlate with higher UF tolerance but the data is non-significant. A larger sample size and more sophisticated portable ultrasound machines may give a better idea of any association between B-lines and the determination of UF goals in HD.
685 Association of mesangial igm deposits with rapidly progressive diabetic nephropathy
1Ochsner Clinic Foundation, Metairie, LA
2Vanderbilt, Nashville, TN
Purpose of study Classic diabetic nephropathy (DN) is characterised by progressive proteinuria and decline in kidney function over a period of 10–15 years. However, when the clinical course does not fit the norm, a kidney biopsy is often performed to confirm the diagnosis. Whether the tissue specimens of those who require kidney biopsy and are found to have DN disclose additional unique pathological findings is not well established.
Methods used We performed a retrospective review of clinical data and kidney biopsy results from patients with long-standing type 2 diabetes mellitus who underwent kidney biopsy for the following indications:
1) rapid onset or worsening of proteinuria uncharacteristic for DN (n=5) and
2) positive serum protein electrophoresis for monoclonal gammopathy (n=3) suspicious for plasma dyscrasia; and were found to have pathologic evidence of DN.
Summary of results Eight cases were identified. The mean age of the cohort was 62 years, predominantly African American (62%), with equal percentage of men and women. The mean serum creatinine, estimated glomerular filtration rate (eGFR) and urine protein-to-creatinine ratio values at the time of the biopsy were 2.39 mg/dL, 30.1 ml/min and 8.7 g/g, respectively. Glomerular findings consistent with DN and arterionephrosclerosis were present in all cases. In addition, varying degrees of mesangiopathic changes were noted by light microscopy, along with mesangial IgM deposition by immunofluorescence and electron microscopy. Five patients had a rapidly progressive course (decline in eGFR >10 ml/min/year) and three of them required renal replacement therapy within one year post biopsy. The median rate of decline of kidney function was estimated at −11 ml/min/year (range:+3.2 to −28.0).
Conclusions Although IgM mesangial deposition is often associated with minimal change disease or focal segmental glomerulosclerosis, evidence of its association with DN is sparse. Our results suggest that mesangial IgM deposition may be found in individuals with DN exhibiting an unusual clinical course and this finding could be associated with an accelerated course of DN. Further investigation is warranted to better characterise this entity.
686 a rare case of crescentic c3 nephritis
LSUHSC, New Orleans, LA0
Case report C3 nephritis is primarily a disease of children, though the age range may extend into adulthood. It affects 1–3 people in one million. It may present with acute nephritis (16% to 38%), isolated macroscopic hematuria (21%–36%), nephrotic syndrome (12%–55%) microscopic hematuria with subnephrotic range (15%) and isolated proteinuria.
A 35-year-old Caucasian male with no past medical history presented with emesis and general body aches. He was in his usual state of health until 3 days earlier when he developed nausea, vomiting, night sweats, tachycardia, and palpitations. He reported that these episodes started about a year ago, occurring every few months, and lasting for about a week. The symptoms would occur every night but he never sought medical attention. On physical examination, he appeared frail and volume depleted, but otherwise unremarkable. Lab results showed sCr 3.37 mg/dl, urinalysis with RBC 6–10, protein >500 mg/dl, blood >1+, urine protein/creat ratio 2,351 mg/g, serum albumin 2.8 g/dL, and subsequent renal biopsy was consistent with a crescentic glomerulonephritis with C3 mesangial staining on immunofluorescence. Small mesangial electron dense deposits were present. Electron microscopy was negative for large dense deposits ruling out Dense deposit disease.
Findings support the diagnosis of Crescentic C3 Glomerulonephritis (C3 GN). The patient was treated with lisinopril 5 mg QD, Prednisone 70 mg QD, and mycophenolate 1500 mg BID. A month later the proteinuria decreased to 852 mg/g, serum albumin increased to 4.1 g/dL, and eGFR improved from 22 mL/min to 42 mL/min (creatinine decreased to 2.0 mg/dL). Complement levels were in normal range. (C3 138 mg/dl, C 4 36 mg/dl). The patient reported previous symptoms had improved.
Conclusion The patient presented with an acute kidney injury with an unknown renal history. The biopsy was consistent with a rare case of crescentic C3 GN that responded well to treatment. This is a rare cause of glomerulonephritis with no large scale studies regarding therapy. This case is an example of a successful treatment for crescentic C3 GN. Physicians should be aware of this as a cause of rapidly progressive crescentic GN for appropriate diagnosis and treatment.
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