Association Between Race and Usage of Pain Medications in Children With Long Bone Fractures in US Emergency Departments, 2011-2019.

OBJECTIVES: The purpose of this study was to determine the association between race and analgesic administration for children with long bone fracture (LBF) in US emergency departments. Previous studies have shown conflicting results regarding association between race and analgesic administration for pediatric LBFs. METHODS: We conducted a retrospective analysis of pediatric emergency department visits for LBF using the 2011-2019 National Hospital Ambulatory Medical Care Survey-Emergency Department. We investigated the diagnostic workup and analgesic prescription rate among White, Black, and other pediatric emergency department visits for LBF. RESULTS: Of the estimated 292 million pediatric visits to US emergency departments from 2011 to 2019, 3.1% were LBFs. Black children were less likely to be seen for a LBF than White or other children (1.8% vs 3.6% and 3.1%, P < 0.001). There was no association between race and subjective pain scale ( P = 0.998), triage severity ( P = 0.980), imaging (x-ray, P = 0.612; computed tomography scan, P = 0.291), or analgesic administration (opioids, P = 0.068; nonsteroidal antiinflammatory drugs/acetaminophen, P = 0.750). Trend analysis showed a significant decrease in opioid administration for pediatric LBF from 2011 to 2019 ( P < 0.001), with 33.0% receiving opioids. CONCLUSIONS: There was no association between race and analgesic administration, including opioids, or diagnostic workup in pediatric LBF. In addition, there was a significant downtrend in opioid administration for pediatric LBF from 2011 to 2019.

Integrated secure messaging to enhance medical education: a mixed methods study.

BACKGROUND: Instant messaging applications and texting are useful for educating and communicating with medical students; however, they present patient privacy concerns and do not address the challenge of student inclusion in patient care communication. EMR-integrated secure messaging offers an opportunity to include students on team communication, enhance their medical education, and ensure patient privacy. METHODS: Between July 2019 through March 2020, we performed a mixed method study to evaluate use of EPIC® Secure Chat as a means of enhancing student education and team communication. We promoted use of secure messaging in orientation, performed a pre- and post-rotation survey to assess perceptions of Secure Chat effect on communication, and directly reviewed and categorized messages. RESULTS: Twenty-four 3rd and 4th year students completed the pre-rotation survey, and 22 completed the post-rotation survey. Twelve (50%) students reported the quality of communication with faculty was either good or very good prior to internal medicine rotation, while 20 (91%) reported this post-rotation (p-value 0.001). There was a similar improvement in communication with ancillary staff. Nineteen (86%) students felt that secure messaging improved their communication with faculty. On message review, threads were frequently logistical, but also often included discussions of patient management. CONCLUSIONS: Students viewed Secure Chat as having a favorable effect on their communication with team members and reported communication on internal medicine to be improved compared to prior rotations. Messages included students on important patient care conversations. Secure messaging offers a novel medium to improve team communication, enhance student education, and maintain patient privacy.

Antibiotic utilization for adult acute respiratory tract infections in United States Emergency Departments.

BACKGROUND: Antibiotic stewardship programs have been a major focus in recent years to curtail antibiotic resistance. The purpose of this study was to evaluate antibiotic utilization for acute respiratory tract infections (ARTI) in the Emergency Department (ED) setting. MATERIAL AND METHODS: A retrospective analysis of adult ARTI visits to EDs utilizing 2011-2017 National Hospital Ambulatory Medical Care Survey- Emergency Department (NHAMCS-ED) datasets was conducted. Included were all visits of adults (≥18 years) diagnosed with ARTI. Antibiotics were determined based upon NHAMCS-ED use of the Multum Lexicon Drug Database coding system. All significance tests were two-sided, P-value <0.05 for significance. RESULTS: A total of 4632 unweighted ED visits, which represented more than 28 million US ED visits from 2011 to 2017, with 57.2% receiving a prescription for antibiotics. Antibiotic prescriptions for ARTI significantly declined from 65.8% in 2011 to 54.3% in 2017 (P = 0.046). Among all visits, patients were more likely to receive an antibiotic if they were over age 45 (33.0% vs 27.6%, P = 0.005), male (36.7% vs. 32.3%, P = 0.039), and presenting in a non-MSA ED (21.4% vs. 14.5%, P = 0.002). No association was found between antibiotic prescription and race (P = 0.076) insurance (P = 0.488), CBC (P = 0.148), x-ray (P = 0.278), and blood cultures (P = 0.182). CONCLUSION: We found a significant reduction in the utilization of antibiotics among adult ARTI visits to U.S. EDs from 2011 to 2017. This is an improvement from previous studies which showed no change, suggesting that antimicrobial stewardship efforts may be impacting overall antibiotic use and should continue to be practiced.

Towards a better understanding of adult idiopathic epidermal necrolysis: a retrospective study of 19 cases.

BACKGROUND: Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]). OBJECTIVE: We sought to better describe adult IEN and understand the aetiology. METHODS: This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls. RESULTS: IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL. CONCLUSIONS: IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

Cholesterol-induced activation of TRPM7 regulates cell proliferation, migration, and viability of human prostate cells.

Cholesterol has been shown to promote cell proliferation/migration in many cells; however the mechanism(s) have not yet been fully identified. Here we demonstrate that cholesterol increases Ca(2+) entry via the TRPM7 channel, which promoted proliferation of prostate cells by inducing the activation of the AKT and/or the ERK pathway. Additionally, cholesterol mediated Ca(2+) entry induced calpain activity that showed a decrease in E-cadherin expression, which together could lead to migration of prostate cancer cells. An overexpression of TRPM7 significantly facilitated cholesterol dependent Ca(2+) entry, cell proliferation and tumor growth. Whereas, TRPM7 silencing or inhibition of cholesterol synthesis by statin showed a significant decrease in cholesterol-mediated activation of TRPM7, cell proliferation, and migration of prostate cancer cells. Consistent with these results, statin intake was inversely correlated with prostate cancer patients and increase in TRPM7 expression was observed in samples obtained from prostate cancer patients. Altogether, we provide evidence that cholesterol-mediated activation of TRPM7 is important for prostate cancer and have identified that TRPM7 could be essential for initiation and/or progression of prostate cancer.

Plasma vemurafenib concentrations in advanced BRAFV600mut melanoma patients: impact on tumour response and tolerance.

BACKGROUND: Vemurafenib improves survival in advanced BRAFV600(mut) melanoma patients, but tolerance is often poor and resistance frequently occurs, without predictive factor. Our aim was to investigate for the first time a relationship between plasma vemurafenib concentration (PVC) and efficacy or tolerance. METHODS: Plasma samples from unresectable metastatic BRAFV600(mut) melanoma patients treated with vemurafenib monotherapy were prospectively collected at each tumour response evaluation (RECIST 1.1) or when adverse event occurred (CTCAE 4.0). PVC was measured with liquid chromatography-tandem mass spectrometry. Herein, we report on PVC at steady state (≥14 days after vemurafenib introduction or dose modification). Samples collected after first melanoma progression were excluded from the response analysis. All samples were analysed in the tolerance analysis. We kept the closest collected sample from the onset of each adverse effect or the one with the highest PVC in the absence of this adverse effect. Comparisons of means (Student's t-tests and Wilcoxon rank sum tests) and of frequencies (χ(2) tests) were carried out. A logistic regression analysis identified predictors of progression. RESULTS: We included 105 plasma samples in 23 patients (10M/13F). Initial vemurafenib dose was 960 mg b.i.d., reduced by 25% (8 patients) or 50% (2 patients) for intolerance in 10 patients (44%). PVC displayed high inter-individual variability (13.0-109.8 µg/ml, median 54.0). Mean PVC was lower at time of first progression (38.8 ± 19.7 µg/ml) than mean PVC found when tumour was stable or in partial or complete response (56.4 ± 21.0 µg/ml, P = 0.013, 21 patients). Logistic regression revealed that having a low PVC (P = 0.01) or brain metastasis (P = 0.01) were both significantly and independently associated with tumour progression. High PVC was not statistically significantly associated with the occurrence of adverse effects. CONCLUSION: PVC at steady state is highly variable and low PVC was associated with tumour progression, suggesting a new path to melanoma resistance to vemurafenib.

Improvement of spinal alignment and quality of life after corrective surgery for spinal kyphosis in patients with osteoporosis: a comparative study with non-operated patients.

UNLABELLED: This study evaluated changes in spinal alignment and quality of life (QOL) after corrective spinal surgery for patients with postmenopausal osteoporosis and spinal kyphosis. Spinal global alignment and QOL were significantly improved after corrective spinal surgery but did not reach the level of non-operated controls. INTRODUCTION: With the increased aging of society, the demand for corrective spinal instrumentation for spinal kyphosis in osteoporotic patients is increasing. However, previous studies have not focused on the improvement of quality of life (QOL) after corrective spinal surgery in patients with osteoporosis, compared to non-operated control patients. The purposes of this study were thus to evaluate changes in spinal alignment and QOL after corrective spinal instrumentation for patients with osteoporosis and spinal kyphosis and to compare these results with non-operated patients. METHODS: Participants comprised 39 patients with postmenopausal osteoporosis ≥50 years old who underwent corrective spinal surgery using multilevel posterior lumbar interbody fusion (PLIF) for symptomatic thoracolumbar or lumbar kyphosis, and 82 age-matched patients with postmenopausal osteoporosis without prevalent vertebral fractures. Spinopelvic parameters were evaluated with standing lateral spine radiography, and QOL was evaluated with the Japanese Osteoporosis QOL Questionnaire (JOQOL), SF-36, and Roland-Morris Disability Questionnaire (RDQ). RESULTS: Lumbar kyphosis angle, sagittal vertical axis, and pelvic tilt were significantly improved postoperatively. QOL evaluated with all three questionnaires also significantly improved after 6 months postoperatively, particularly in domain and subscale scores for pain and general/mental health. However, these radiographic parameters, total JOQOL score, SF-36 physical component summary score, and RDQ score were significantly inferior compared with non-operated controls. CONCLUSIONS: The results indicate that spinal global alignment and QOL were significantly improved after corrective spinal surgery using multilevel PLIF for patients with osteoporosis and spinal kyphosis but did not reach the level of non-operated controls.

Increase in serum Ca2+/Mg2+ ratio promotes proliferation of prostate cancer cells by activating TRPM7 channels.

TRPM7 is a novel magnesium-nucleotide-regulated metal current (MagNuM) channel that is regulated by serum Mg(2+) concentrations. Changes in Mg(2+) concentration have been shown to alter cell proliferation in various cells; however, the mechanism and the ion channel(s) involved have not yet been identified. Here we demonstrate that TRPM7 is expressed in control and prostate cancer cells. Supplementation of intracellular Mg-ATP or addition of external 2-aminoethoxydiphenyl borate inhibited MagNuM currents. Furthermore, silencing of TRPM7 inhibited whereas overexpression of TRPM7 increased endogenous MagNuM currents, suggesting that these currents are dependent on TRPM7. Importantly, although an increase in the serum Ca(2+)/Mg(2+) ratio facilitated Ca(2+) influx in both control and prostate cancer cells, a significantly higher Ca(2+) influx was observed in prostate cancer cells. TRPM7 expression was also increased in cancer cells, but its expression was not dependent on the Ca(2+)/Mg(2+) ratio per se. Additionally, an increase in the extracellular Ca(2+)/Mg(2+) ratio led to a significant increase in cell proliferation of prostate cancer cells when compared with control cells. Consistent with these results, age-matched prostate cancer patients also showed a subsequent increase in the Ca(2+)/Mg(2+) ratio and TRPM7 expression. Altogether, we provide evidence that the TRPM7 channel has an important role in prostate cancer and have identified that the Ca(2+)/Mg(2+) ratio could be essential for the initiation/progression of prostate cancer.

Ovarian cancer incidence in the United States in relation to manufacturing industry.

OBJECTIVE: Ovarian cancer is primarily a disease of the industrialized world. However, few factors associated with industrialization that contribute to the etiology of ovarian cancer have been identified. We sought to explore factors potentially associated with ovarian cancer by correlating ovarian cancer incidence rates in US states with the distribution of US manufacturing. METHODS: Data on age-adjusted incidence rates for ovarian cancer per state in the United States and manufacturing rates per state were analyzed using multiple linear regression controlling for access to ovarian cancer care, fertility rate, and other potential confounders. RESULTS: In univariate analyses, ovarian cancer incidence rates were positively correlated with the extent of manufacturing, with dairy production, and with the manufacturing of pulp and paper. Using multiple linear regression, only the correlation of ovarian cancer with pulp and paper manufacturing industry was significant. The correlation of ovarian cancer with pulp and paper manufacturing industry remained significant after adjusting for access to ovarian cancer care, fertility rates, and other potential confounders (P < 0.05). CONCLUSIONS: Pulp and paper mills are associated with exposures to known ovarian carcinogens. Further epidemiological study of exposures involved in the manufacturing of pulp and paper in relation to risk of ovarian cancer is warranted.

HIV TESTING IN DENTAL PRACTICE: PERCEPTION AND ATTITUDE OF DENTISTS IN SOUTHWESTERN NIGERIA.

BACKGROUND: In recent times, the concept of routine HIV screening has been recommended to enhance early diagnosis and timely initiation of care thereby reducing morbidity and mortality among HIV infected persons. Dental practice has been identified as a unique venue of reaching at-risk individuals who may not otherwise access the conventional healthcare settings. AIM: To assess the perception and attitude of dentists in Southwestern Nigeria concerning integrating HIV testing into dental practice. METHODS: this descriptive cross- sectional study was conducted between January-March, 2014. Convenience sampling was used to select 113 practising dentists within Southwest Nigeria. Data collection was done using a self- administered questionnaire. RESULTS: Agreement to HIV testing in dental settings was in the order of 100% for private practitioners followed by 91.7% from teaching hospitals (91.7%) and least agreement was with state hospitals (76.5%). There was a strong association between participants' years of practice and support for HIV testing in dental settings with highest support among those between 7-9 years (p= 0.002). Significantly too (p= 0.013), all the specialists (100%) agreed to HIV testing in dental settings compared to general practitioners (84.0%). CONCLUSION: This study showed that most dentists in Southwest Nigeria acknowledged dental practice as being appropriate for expanded HIV testing and as well were willing to undergo training for HIV testing in their dental settings.

The Impact of Medicaid Expansion Under the Affordable Care Act on the Gap Between American Indians and Whites in Breast Cancer Management and Prognosis.

BACKGROUND: Breast cancer (BC) death rates in the USA have not significantly declined for American Indians (AIs) in comparison to Whites. Our objective was to determine whether Medicaid Expansion as part of the Affordable Care Act led to improved BC outcomes for AIs relative to Whites. PATIENTS AND METHODS: Using the National Cancer Database, we conducted a retrospective cohort study. Included were BC patients who were AI and White; 40 to 64 years of age; diagnosed in 2009 to 2016; lived in states that expanded Medicaid in January 2014, and states that did not expand Medicaid. Our outcomes were stage at diagnosis, insurance status, timely treatment, and 3-year mortality. RESULTS: There were 359,484 newly diagnosed BC patients, 99.49% White, 0.51% AI. Uninsured rates declined more in the expansion states than in the nonexpansion states (OR = 0.44, 95% CI: 0.15-0.97, P < 0.001). Lower rates of Stage I BC diagnosis was found in AIs compared to Whites (46.58% vs. 55.33%, P < .001); these differential rates did not change after Medicaid expansion. Rates of definitive treatment initiation within 30 days of diagnosis declined after Medicaid expansion (P < .001); there was a smaller decline in the expansion states (OR 1.118, 95% CI: 1.09, 1.15, P < .001). Three year mortality was not different between expansion and nonexpansion states post Medicaid expansion. CONCLUSIONS: In newly diagnosed BCs, uninsured rates declined more in the states that expanded Medicaid in January 2014. Timely treatment post Medicaid expansion declined less in states that expanded Medicaid. There was no differential benefit of Medicaid expansion in the 2 races.

Population pharmacokinetics of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Interest in antifibrinolytic tranexamic acid (TA) has grown since the widespread removal of aprotinin, but its dosing during cardiac surgery is still debated. The objectives of this study were to investigate the population pharmacokinetics (PK) of TA given with either low- or high-dose continuous infusion schemes in adult cardiac surgery patients during cardiopulmonary bypass (CPB). METHODS: Patients were randomized to receive either low-dose (10 mg kg(-1) followed by an infusion of 1 mg kg(-1) h(-1) throughout the operation, and 1 mg kg(-1) into the CPB) or high-dose (30 mg kg(-1), then 16 mg kg(-1) h(-1), and 2 mg kg(-1) into the CPB) TA. Serum TA concentrations were measured in 61 patients and the data were modelled using Monolix. RESULTS: TA concentrations were 28-55 µg ml(-1) in the low-dose group and 114-209 µg ml(-1) in the high-dose group throughout surgery. TA PK was best described by a two-compartment open model. The main covariate effect was bodyweight, whereas the CPB did not influence the PK. Assuming a bodyweight of 70 kg, the population estimates were 4.8 litre h(-1) for clearance, 6.6 litre for the volume of the central compartment, 32.2 litre h(-1) for the diffusional clearance, and the peripheral volume of distribution was 10.8 litre. CONCLUSIONS: The PK of TA was satisfactorily described by an open two-compartmental model, which was used to propose a dosing scheme suitable for obtaining and maintaining the desired plasma concentration in a stable and narrow range in cardiac surgery patients.

Differences in Breast Cancers Among American Indian/Alaska Native and non-Hispanic Whites in the USA.

IMPORTANCE: Breast cancer (BC) death rates have not improved for American Indian/Alaska Native (AI/AN) women, whereas, it has significantly decreased for non-Hispanic White (White) women. OBJECTIVE: Delineate the differences in patient and tumor characteristics among AI/AN and Whites with BC, and its impact on age and stage at diagnosis as well as overall survival (OS). METHODS: Hospital-based, cohort study using the National Cancer Database to identify female AI/AN and Whites diagnosed with BC between the years 2004 and 2016. RESULTS: BC in 6866 AI/AN (0.3%) and 1,987,324 Whites (99.7%) were studied. The median age at diagnosis was 58 for AI/AN and 62 for Whites. AI BC patients traveled double the distance for treatment, lived in lower median income zip codes, had a higher percentage of uninsured, higher comorbidities, lower percentage of Stage 0/I, larger tumor size, greater number of positive lymph nodes, higher proportion of triple negative and HER2-positive BC than Whites. All the above comparisons were significant, p<0.001. Association between patient/tumor characteristics with age and stage at diagnosis was not significantly different between AI/AN and Whites. Unadjusted OS was worse for AI/AN as compared to Whites (HR=1.07, 95% CI=1.01-1.14, p=0.023). After adjustment of all covariates, OS was not different (HR=1.038, 95%CI=0.902-1.195, p=0.601). CONCLUSION: There were significant differences in patient/tumor characteristics among AI/AN and White BC which adversely impacted OS in AI/AN. However, when adjusted for various covariates, the survival was similar, suggesting that the worse survival in AI/AN is mostly the impact of known biological, socio-economic, and environmental determinants of health.

Trends and risk factors in the antibiotic management of skin and soft tissue infections in the United States.

OBJECTIVE: The aim of this study was to examine the trends and risk factors of antibiotic treatment for skin and soft tissue infections (SSTIs), in the United States. METHODS: We conducted a retrospective analysis of SSTIs visits utilizing the 2011-2016 National Ambulatory Medical Care Survey. RESULTS: There were over 43 million visits for SSTIs in the US. We found no association between antibiotic treatment and gender, age, race, insurance, region, and metropolitan statistical area. Methicillin-resistant Staphylococcus aureus (MRSA) antibiotics were prescribed at 34.8% of SSTI visits, methicillin-sensitive Staphylococcus aureus (MSSA) antibiotics at 27.5%, and other antibiotics at 21.7%. Among visits treated with an antibiotic, 40.4% (n = 378) received an antibiotic with MSSA coverage, while 59.6% (n = 558) received an antibiotic with MRSA coverage. Region where the visit occurred was associated with the use of MSSA versus MRSA antibiotics (p = .013). Mean age of visits receiving MSSA antibiotics was significantly older than visits receiving MRSA antibiotics, 53.8 ± 1.2 vs. 50.9 ± 0.9 (p = .045). CONCLUSIONS: This study found that providers more frequently utilize antibiotics with MRSA coverage for SSTIs. Antibiotic class chosen was associated with region, with MRSA coverage antibiotics more likely to be prescribed in the South. Additionally, individuals receiving antibiotics with MSSA coverage were older than those receiving antibiotics with MRSA coverage.

Age-Related Changes in Dynamic Iris Behavior Assessed Using a Programmable Closed-Loop Iris Control System.

Purpose: The purpose of this study was to develop and test a programmable closed-loop system for tracking, modulating, and assessing dynamic iris behavior, including in the mid-dilated position. Methods: A programmable closed-loop iris control system was developed by customizing an ANTERION OCT device (Heidelberg Engineering, Heidelberg, Germany). Custom software was developed to store camera and optical coherence tomography (OCT) images, track pupillary diameter (PD), control a light-emitting diode (LED), and modulate ambient lighting to maintain the iris in a dilated, constricted, or mid-dilated position in real-time. Study participants underwent 3 consecutive 65-second scan sessions. Dynamic iris behavior in the form of peak constriction velocity (PCV) and mid-dilated iris activity (MDIA) were calculated and analyzed offline. Results: Among 58 participants, 56 (96.6%) were eligible for analysis based on achieving and maintaining mean PD within ±10% of the calculated mid-dilated PD. Mean participant age was 49.8 ± 18.9 years. Mean PCV was 3.92 ± 0.83 mm/s, and mean MDIA was 0.37 ± 0.15 mm. The mean difference between the calculated and achieved mid-dilated PD was 0.166 ± 0.192 mm. There were significant negative correlations between PCV and age (slope = -0.022, P < 0.001) and MDIA and age (slope = -0.004, P < 0.001). Success rates were lower (69.0%) but relationships between dynamic iris behavior and age were similar based on achieving and maintaining mean PD within ±5% of the calculated mid-dilated PD. Conclusions: A programmable closed-loop iris control system can modulate dynamic iris behavior and maintain the iris in a mid-dilated position. Pupillary constriction velocity and iris activity in the mid-dilated position decrease with age. Translational Relevance: This system can be applied to study dynamic disease processes involving the iris and establish novel biometric measures that could serve as risk factors for acute and chronic primary angle closure glaucoma (PACG).

Identification of transcriptional regulatory variants in pig duodenum, liver, and muscle tissues.

BACKGROUND: In humans and livestock species, genome-wide association studies (GWAS) have been applied to study the association between variants distributed across the genome and a phenotype of interest. To discover genetic polymorphisms affecting the duodenum, liver, and muscle transcriptomes of 300 pigs from 3 different breeds (Duroc, Landrace, and Large White), we performed expression GWAS between 25,315,878 polymorphisms and the expression of 13,891 genes in duodenum, 12,748 genes in liver, and 11,617 genes in muscle. RESULTS: More than 9.68 × 1011 association tests were performed, yielding 14,096,080 significantly associated variants, which were grouped in 26,414 expression quantitative trait locus (eQTL) regions. Over 56% of the variants were within 1 Mb of their associated gene. In addition to the 100-kb region upstream of the transcription start site, we identified the importance of the 100-kb region downstream of the 3'UTR for gene regulation, as most of the cis-regulatory variants were located within these 2 regions. We also observed 39,874 hotspot regulatory polymorphisms associated with the expression of 10 or more genes that could modify the protein structure or the expression of a regulator gene. In addition, 2 motifs (5'-GATCCNGYGTTGCYG-3' and a poly(A) sequence) were enriched across the 3 tissues within the neighboring sequences of the most significant single-nucleotide polymorphisms in each cis-eQTL region. CONCLUSIONS: The 14 million significant associations obtained in this study are publicly available and have enabled the identification of expression-associated cis-, trans-, and hotspot regulatory variants within and across tissues, thus shedding light on the molecular mechanisms of regulatory variations that shape end-trait phenotypes.

The efficacy of low dose short-term prednisone therapy for remission induction in newly diagnosed rheumatoid arthritis patients.

BACKGROUND: The ACR/EULAR recommendations endorse the use of glucocorticoids (GCs) for rheumatoid arthritis (RA) patients' flares and as a bridge to a DMARD. However, the recommendation of low dose short-term monotherapy with (GCs) remains open to the discretion of the clinician. The aim of this study was to assess whether a short-term use of low dose prednisone monotherapy was effective in inducing remission in newly diagnosed RA patients. METHODS: A retrospective analysis of patients newly diagnosed with RA at a Community Health Center in North Dakota was performed based on the ACR/EULAR RA classification criteria. Demographic and clinical data were abstracted from patients' medical charts. Patients treated with (< 10 mg/day) of prednisone up to 6 months were included. Response to prednisone was analyzed according to pre- and post-treatment DAS28-ESR score and EULAR response criteria. RESULTS: Data on 201 patients were analyzed. The mean prednisone dose was 8 mg/day (range: 5-10; SD = 1.2) and the mean treatment duration was 42.2 days (12-177; 16.9). Disease severity significantly improved from baseline to follow-up for: tender joint count (8.6 ± 4.8 vs. 1.5 ± 3.3; P < 0.001), swollen joint count (6.2 ± 5.0 vs. 1.4 ± 3.0; P < 0.001), and visual analog pain score (4.8 ± 2.6 vs. 2.1 ± 2.5; P < 0.001). DAS28-ESR disease severity significantly improved from baseline to follow-up: (5.1 ± 1.2 vs. 2.7 ± 1.3; P < 0.001). Per EULAR response criteria, 69.7% of patients showed good response to treatment and 20.4% showed moderate response. 54.2% of patients reached remission. CONCLUSION: Short-term use of low dose prednisone monotherapy induced disease remission and improved clinical severity of RA in the majority of newly diagnosed patients.

A cross-sectional analysis of infant-driven and traditional feeding outcomes for neonatal intensive care unit infants.

OBJECTIVE: The goal of this study was to assess the impact of infant-driven feeding (IDF) compared to traditional feeding protocols in promoting earlier successful feeding outcomes. STUDY DESIGN: We performed a cross-sectional analysis of infants admitted to a level three neonatal intensive care unit (NICU) over a 2-year period. We compared infants fed with the traditional protocol to those under the IDF protocol. RESULTS: Infants in the IDF group were younger at first feed (p < 0.001). There was no difference in age at nasogastric (NG) tube removal or at discharge, length of stay, or percentage breastfeeding at discharge. There were no differences in outcomes within two subgroups born at <35 and <32 weeks gestation, respectively. CONCLUSION: The IDF program led to earlier initiation of oral feeding. However, this did not lead to earlier NG tube removal or discharge, a shorter length of stay, or increase in the rates of breastfeeding.

Serum calcium levels are elevated among women with untreated postmenopausal breast cancer.

OBJECTIVE: Reports of an association between primary hyperparathyroidism in women and risk of breast cancer suggest an etiologic role for high serum calcium. However, data on the association between serum calcium levels and breast cancer in women without clinical hyperparathyroidism are limited. METHODS: We conducted a hospital-based case-control study among postmenopausal women in Fargo, ND. Cases were women aged 65 and older with newly diagnosed, histologically confirmed breast cancer. Controls were aged 65 and older without clinical cancer who were seen at the same hospital. RESULTS: We obtained data on 190 white cases and 172 white controls. Primary hyperparathyroidism (an abnormally high calcium level confirmed by an abnormally high serum PTH) was found in 3/190 cases and in 0/172 controls (p = 0.25). After excluding the women with primary hyperparathyroidism, the mean calcium levels among cases was 9.6 mg/dL (range, 7.5-11.0, SD = 0.47) vs. 9.4 mg/dL (7.7-10.5, 0.43) among the controls (p < 0.0001). Comparing women in the top with women in the bottom tertile of serum calcium, the multivariable-adjusted odds ratio (OR) for breast cancer was 5.21 (95% CI: 2.59-10.48). There was no relationship between serum calcium and tumor size or stage. CONCLUSION: The distribution of serum calcium levels among postmenopausal women with incident breast cancer was shifted significantly toward the right. These findings are consistent with an effect of early breast tumors on calcium homeostasis. However, the lack of association between serum calcium levels and tumor size or stage supports the hypothesis that subclinical hyperparathyroidism may increase the risk for breast cancer.