Faculty Bibliography

BACKGROUND:A computerized physician order entry (CPOE) system provides opportunity for real-time alerts to prescribers. Winthrop University Hospital began using CPOE in 2009. OBJECTIVE:We sought to improve prescribing among older hospitalized patients by adding alerts to the CPOE system for potentially inappropriate medications. METHODS:In January 2011, informational alerts were integrated into the CPOE system for selected high-risk medications: diphenhydramine, metoclopramide, and all antipsychotics. We evaluated the effect of these alerts on prescribing frequency by comparing the number of prescriptions during the second quarters of 2010 ("pre-alert") with the second quarters of 2011 through 2013 ("post-alert"). Prescribing patterns were evaluated through a pharmacy database of medication orders. Frequency of prescribing was adjusted for total discharges. A comparison was made to ages 18-64 years, and comparing "as needed" vs standing orders. RESULTS:In the 65 years of age and older group, there were significant reductions in prescription rates pre-alert vs post-alert for diphenhydramine (p < 0.001) and metoclopramide (p < 0.001). There was no decrease in prescription rates for antipsychotics in older patients (p = 0.80). In the younger comparison group, no decreases in prescription rates for those drugs were observed. Our analysis is based on numbers of written prescriptions and not actual doses administered; therefore, no conclusions concerning the effect of these alerts on communication or documentation of risk/benefits of these medications can be ascertained. CONCLUSION/CONCLUSIONS:The data suggest that prescribing rates for drugs with the least efficacy and potential for harm and with alternative agents (i.e., diphenhydramine and metoclopramide) can be modified by CPOE alerts for older patients.

CONTEXT: African Americans have a lower total serum 25-hydroxyvitamin D [25(OH)D] but superior bone health. This has been referred to as a paradox. A recent publication found that free serum 25(OH)D is the same in black and white individuals. However, the study was criticized because an indirect method was used to measure free 25(OH)D. A direct method has recently been developed. OBJECTIVE: We hypothesized that although total serum 25(OH)D is lower in African Americans, free serum 25(OH)D measured directly would not differ between races. DESIGN: White and black healthy postmenopausal women were matched for age and body mass index. Serum total 25(OH)D, PTH, 1,25-dihydroxyvitamin D, vitamin D binding protein (VDBP), and bone density were measured. Measurement of free 25(OH)D was carried out using an ELISA. SETTING: The study was conducted at an ambulatory research unit in a teaching hospital. OUTCOME: A cross-racial comparison of serum free 25(OH)D was performed. RESULTS: A propensity match resulted in the selection of a total of 164 women. Total 25(OH)D was lower in black women (19.5 +/- 4.7 vs 26.9 +/- 6.4 ng/mL), but a direct measurement of free 25(OH)D revealed almost identical values (5.25 +/- 1.2 vs 5.25 +/- 1.3 ng/mL) between races. VDBP was significantly lower in blacks when using a monoclonal-based ELISA but higher with a polyclonal-based ELISA. Serum PTH, 1,25-dihydroxyvitamin D, and bone density were higher in African Americans. CONCLUSIONS: Free serum 25(OH)D is the same across races despite the lower total serum 25(OH)D in black women. Results comparing VDBP between races using a monoclonal vs a polyclonal assay were discordant.

AIM: The objective of this study was to develop a reference range for urine calcium excretion (both 24-hour and fasting) for African American women compared to White women. In addition, the variables that determine urine calcium excretion were identified. MATERIAL: Data were analyzed for baseline studies of healthy postmenopausal volunteers who participated in seven separate studies conducted at one site. METHODS: Some studies included fasting urine Ca/Cr and others 24-hour urine calcium excretion. 24-hour urine calcium was considered with and without correction for urinary creatinine excretion. Calcium was measured initially by atomic absorption spectrophotometry and more recently by an automated method (ADVIA 2400 Chemistry System). RESULTS: Participants were considered healthy based on history and physical and routine laboratory studies. Those screened who had a history of nephrolithiasis were excluded. A reference range for 24-hour urine calcium and fasting urine calcium/ creatinine was developed. Reference intervals of 11 - 197 mg/24-hour urine calcium excretion and of 0.007 - 0.222 of fasting Ca/Cr were found for African American women compared to 21 - 221 mg/24 hours and 0.019 - 0.264 in White women, respectively. Urine creatinine excretion was higher in African Americans consistent with their higher muscle mass. CONCLUSION: Urine calcium excretion is lower in postmenopausal African American than White women. The reference range developed should be considered in the diagnosis of hypocalciuric states and may also be useful in the diagnosis of hypercalciuria.

Cystoscopic urine obtained before the resection of low-grade urothelial carcinoma (LGUC), with adequate cytological sampling of the tumor, frequently revealed the presence of three-dimensional cell groups with disordered nuclei and cellular discohesion (3DDD). 936 cystoscopic urine specimens were categorized into five groups: Group 1 (80 specimens) with biopsy-proven LGUC within 6 months of cytologic examination, Group 2 (23 specimens) with biopsy proven LGUC within 6 to 36 months of cytologic examination, Group 3 (527 specimens) with a history of LGUC but no tumor for a period of greater than 3 years, Group 4 (300 specimens) with no association with LGUC, and Group 5 (6 specimens) with urinary lithiasis. Specimens with scant cellularity accounted for 20% of those in Group 1. For 3DDD in detecting LGUC in adequate cystoscopic urine, the sensitivity was 70%, specificity was 94%. Two- or three-dimensional cell groups with ordered nuclei and/or cellular non-discohesion were often seen in specimens from Groups 4 or 5. The 3DDD was present in a significant number of cases with concurrent negative cystoscopic findings but also positive LGUC in ensuing follow-up. In these cases, 3DDD with or without tumor identified at concurrent cystoscopy were found to be morphologically similar. Furthermore, the presence of 3DDD in 8% of Group 3 likely represents urothelial dysplasia that is not cystoscopically detectable. The high specificity and sensitivity of 3DDD is demonstrated. These findings are consistent with the decreased cell adhesion and disordered nuclear arrangement of low grade urothelial neoplasia.

OBJECTIVE:To determine factors associated with newborns having their first outpatient visit (FOV) beyond 3 days after postpartum hospital discharge. METHODS:Retrospective cohort analysis of all newborns born at a large urban university hospital during a 1-year period, discharged home within 96 hours of birth, and with an outpatient visit with an affiliated provider within 60 days after discharge. RESULTS:Of 3282 newborns, 1440 (44%) had their FOV beyond 3 days after discharge. Newborns born to first-time mothers, breast-feeding, at high risk for hyperbilirubinemia, or with a pathological diagnosis were significantly (P < .05) less likely to have FOV beyond 3 days in adjusted multivariable analysis, while newborns born via Caesarian section, of older gestational age, with Medicaid insurance, or discharged on a Thursday or Friday were more likely to have FOV beyond 3 days. Discharging provider characteristics independently associated with FOV beyond 3 days included family medicine providers, providers out of residency longer, and providers practicing at the institution longer. In addition, practice of outpatient follow-up had an independent impact on timing of FOV. Having an appointment date and time recorded on the nursery record or first appointment with a home nurse decreased the odds that time to FOV was beyond 3 days of discharge. CONCLUSIONS:Physician decisions regarding timing of outpatient visit after newborn discharge may take into account newborn medical and social characteristics, but certain patient, provider, and practice features associated with this timing may represent unrecognized barriers to care.

BACKGROUND:All cases reported to date of endometrioid endometrial adenocarcinoma (EEA) associated with pregnancy have been treated surgically or medically. We describe a case of EEA in pregnancy that was managed expectantly, allowing for observation of the natural course of the disease. CASE/METHODS:A 36-year-old woman, gravida 2 para 1, presented at eight weeks of pregnancy with heavy vaginal bleeding. Ultrasound assessment confirmed a missed abortion, and the patient underwent dilatation and curettage. Tissue pathology primarily suggested grade 1 EEA. The patient chose expectant management. Eight months later, she returned with vaginal bleeding. Hysterectomy was performed and the hysterectomy specimen showed FIGO grade 1 stage 1A EEA. CONCLUSION/CONCLUSIONS:Treating EEA associated with pregnancy is challenging. Our experience in the case described here suggests that expectant management should not be undertaken due to a high risk of recurrence.

Wheat bread-making quality is mainly determined by glutenin proteins in the grain, which exist in a wide range of variable alleles with differential influence on processing attributes. A recently identified allele, Bx7 over-expression (Bx7(oe) ), has been showing highly significant positive effects on wheat dough strength over the normally expressed Bx7 allele. SDS-PAGE and normal RP-HPLC procedures failed to separate the two alleles. In the current study, an extensively optimised MALDI-TOF based procedure and a refined DNA based marker for efficiently differentiating Bx7(oe) from normal Bx7 allele were established. Results indicated that the MALDI-TOF procedure is cost effective, high throughput, and proven reliable, while the refined PCR marker only amplifies Bx7(oe) allele, a clear advantage over the previously developed codominant marker.

OBJECTIVE:To identify morphometric features unique to flat epithelial atypia associated with cancer using digital image analysis. STUDY DESIGN/METHODS:Cases with diagnosis of flat epithelial atypia were retrieved and divided into 2 groups: flat epithelial atypia associated with invasive or in situ carcinoma (n = 31) and those without malignancy (n = 27). Slides were digitally scanned. Nuclear features were analyzed on representative images at 20x magnification using digital morphometric software. RESULTS:Parameters related to nuclear shape and size (diameter, perimeter) were similar in both groups. However, cases with malignancy had significantly higher densitometric green (p = 0.02), red (p = 0.03), and grey (p = 0.02) scale levels as compared to cases without cancer. A mean grey densitometric level > 119.45 had 71% sensitivity and 70.4% specificity in detecting cases with concomitant carcinoma. CONCLUSION/CONCLUSIONS:Morphometry of features related to nuclear staining appears to be useful in predicting risk of concurrent malignancy in patients with flat epithelial atypia, when added to a comprehensive histopathologic evaluation.

BACKGROUND:Although histologic chorioamnionitis (HCA) is known to be associated with poor outcomes in preterm infants, its clinical significance among term infants is not clearly known. OBJECTIVES/OBJECTIVE:To investigate the utility of HCA in determining early onset clinical sepsis (EOCS) among term newborns. METHODS:The incidence of HCA and EOCS in term infants born during 2008-2009 was evaluated in a single center retrospective study (n = 3417). The predictive value of HCA for determining EOCS in term infants admitted to the neonatal intensive care unit (NICU) for suspected sepsis (n = 388) was quantified. Outcome of otherwise healthy term infants in the nursery with HCA was also investigated. RESULTS:Overall, 11% of term infants with HCA also had EOCS. HCA was associated with increased risk for EOCS (OR 2.6, 95% confidence interval 1.6-4.2, P < 0.001) among term infants admitted to the NICU for suspected sepsis. No cases of EOCS were found among otherwise well-appearing infants in the nursery with HCA. Multiple logistic regression analysis indicated that addition of HCA does not increase the power of a model combining C-reactive protein (CRP) and immature to total neutrophil ratio in determining EOCS. CONCLUSION/CONCLUSIONS:Although HCA in term infants is associated with EOCS, it did not improve the ability of CRP and immature to total neutrophil ratio to predict EOCS. Routine placental examination may not contribute to the diagnosis of EOCS in term infants.

Postoperative cerebral hyperperfusion syndrome (CHS) in patients undergoing carotid intervention is thought to be related to the absence of cerebral reserve. Although hyperperfusion syndrome is rare, severe postoperative headache is common and is considered to be a prodromal sign. Cerebral reserve is measured by studying the response of cerebral vessels to a vasodilator such as hypercarbia. We produced hypercarbia by holding respiration for 60 seconds during carotid endarterectomy. We attempted to evaluate the relationship between intraoperatively evaluated cerebral reserve and the development of postoperative headache which was severe enough to require the patient to take an over the counter analgesic (e.g., ibuprofen, acetaminophen, aspirin). Internal carotid artery flow 1 (F1), Pco 2, and blood pressure 1 (BP1) were recorded before and after (F2, Pco 2, and BP2) 60 seconds of apnea. An increase in flow of > 20% was considered indicative of adequate cerebral reserve. Patients were evaluated before discharge and with follow-up calls at 2 to 5 days postdischarge. Fisher exact test was used to evaluate categorical predictors. Unpaired t test was used to compare continuous variables. Results were considered significant when p < 0.05. A total of 30 nonconsecutive patients were evaluated prospectively. Of the 30 patients, 4 (Group I) developed severe postoperative headache; 26 did not (Group II). Demographics were similar in both the groups. Three patients in Group I and 16 patients in Group II had > 20% increase in flow (p = 0.6315). Pco 2 rose in both groups and BP2 was unchanged from BP1 in both groups. Lack of cerebral reserve does not appear to be related to the development of severe postoperative headache.