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Physician training on physical activity (PA) counseling in patient care is highly variable. The objective of this study was to improve PA counseling by pediatric residents through introduction of the four components of PA, called the FITT principle (frequency, intensity, time, type). Pediatric residents ( n=30) received lectures, curriculum content, and an electronic smart-phrase addressing PA in obesity, including the FITT principle. Surveys assessed resident attitudes, and chart reviews ( n = 423 over 16 months) identified evidence of PA counseling including FITT principle components preintervention and postintervention. Survey results showed positive attitudes and confidence regarding primary care provider roles in counseling on PA, with no differences postintervention. Chart reviews demonstrated increased documentation on PA frequency postintervention (pre 31.9% vs post 50.9%, P=.00006), but no significant changes in intensity, time or type. In conclusion, a focused PA curriculum promoted PA counseling by pediatric residents, with increased documentation of one component of the FITT principle.

PDF file - 59K, Amino acid and ammonia changes with ASNase treatment in media and cell supernatants.

Background/Aim: Hydration and hydroxyurea (HU) can modify sickle cell disease (SCD) severity. Optimal nutrition and L-glutamine (Gln) may provide further amelioration. Patients and Methods: Reviews of medical records and nutrition surveys were used to investigate severity of pediatric patients with SCD in relation to nutrition, growth, hematologic parameters, and disease-modifying agents. Results: Among 25 females and 25 males (9.1±7 years), beta-globin genotypes were: HbSS/Sβ(0), 60%; HbSC, 32%; HbSβ(+), 8%. The mean number of annual pain crises (APC) was 0.97±1.1. APCs increased ≥2-fold as HbF dropped to

Background Dimethandrolone (DMA) and 11β-methyl-19-nortestosterone (11β-MNT) are two novel compounds with both androgenic and progestational activity that are under investigation as potential male hormonal contraceptives. Their metabolic effects have never been compared in men. Objective Assess for changes in insulin sensitivity and adiponectin and compare the metabolic effects of these two novel androgens. Materials/methods In two clinical trials of DMA undecanoate (DMAU) and 11β-MNT dodecylcarbonate (11β-MNTDC), oral prodrugs of DMA and 11β-MNT, healthy men received drug, or placebo for 28 days. Insulin and adiponectin assays were performed on stored samples. Mixed model analyses were performed to compare the effects of the two drugs. Student's t test, or the non-parametric Kruskal-Wallis test as appropriate, was used to evaluate for an effect of active drug versus placebo. Results Class effects were seen, with decrease in HDL-C and SHBG, and increase in weight and hematocrit, with no statistically significant differences between the two compounds. No changes in fasting glucose, fasting insulin, or HOMA-IR were seen with either compound. There was a slight decrease in adiponectin with DMAU that was not seen with 11β-MNTDC. An increase in LDL-C was seen with 11β-MNTDC but not with DMAU. Discussion There were no significant changes in insulin resistance after 28 days of oral administration of these novel androgens despite a mild increase in weight. There may be subtle differences in their metabolic impacts that should be explored in future studies. Conclusion Changes in metabolic parameters should be carefully monitored when investigating androgenic compounds.

Background: The prevalence and clinical significance of de novo detection of anti-thyroglobulin antibodies (TgAbs) during the follow-up of patients with differentiated thyroid cancer (DTC) is unknown. Methods: We utilized the National Thyroid Cancer Treatment Cooperative Study registry (1987–2012). Patients registered after 1996 (n = 3318) were analyzed. We identified 1545 subjects who had available TgAb status (TgAb cohort) between years 1996 and 2012, of whom 1325 were TgAb negative at first postoperative follow-up testing. From this initial TgAb-negative group, we excluded 513 patients: 423 patients who had less than 3 years of follow-up and/or fewer than three follow-up visits, 86 patients with persistent disease after initial treatment, and 4 patients with data entry errors. The remaining 812 patients were included for analysis, comprising the TgAb persistently negative group (defined as TgAb negative for at least 3 consecutive follow-up visits and at least 3 years of follow-up) (n = 772) and the de novo TgAb-positive group in whom TgAbs became detectable (n = 40). We then assessed whether de novo appearance of TgAb was associated with DTC structural recurrence by using the Kaplan–Meier method. Results: The de novo detection of TgAb occurred in 5% of DTC patients. Recurrence of DTC in the TgAb persistently negative group compared with the de novo TgAb-positive group did not differ significantly (9.6% vs. 15.0%, p = 0.23). Baseline characteristics, histology, history of radiation exposure, staging, and median duration of follow-up were similar between the two groups. Interestingly, in all six patients who suffered a recurrence in the de novo TgAb-positive group, the TgAbs were negative at the time of recurrence detection and became positive at a median of 2.1 (0.7–8.7) years after the structural recurrence. Conclusions: Utilizing a large North American DTC registry, we found the prevalence of de novo TgAb detection to be 5% among initially TgAb-negative patients. We did not find a statistically significant association between de novo TgAb development and DTC structural recurrence. Larger prospective studies are required to confirm these findings and further assess the significance of de novo TgAb detection in the follow-up of DTC.

Background. Hydration and hydroxyurea (HU) can modify sickle cell disease (SCD) severity. Optimal nutrition and L-glutamine (Gln) may provide further amelioration. Procedures. EMR reviews and nutrition surveys were used to investigate pediatric SCD severity in relation to nutrition, growth, hematologic parameters, and disease-modifying agents. Results. Among 25 females and 25 males, mean age was 9.1±7 years, and mean BMI percentile was 56.4±32.6. Hemoglobinopathies were: HbSS/Sß0, 60%; HbSC, 32%; HbSß+, 8%. Annual pain crises rose with age (APC mean, 0.97±1.1 hospital visits or admissions per patient). HbF dropped to

To determine whether a user-controlled sperm concentration test compared with standard semen analysis can effectively monitor spermatogenesis suppression for male contraception.Single center, prospective sub study of the ongoing clinical trial: "Study of daily application of Nestorone and testosterone combination gel for male contraception."Research institute at an academic medical center.Couples participating in the male contraceptive clinical trial.None.The ability by participants to monitor sperm suppression to a threshold compatible with contraceptive efficacy utilizing a user-controlled test verified by sperm concentration determined by standard laboratory methods.Thirty-eight men participating in a hormonal male contraceptive clinical trial provided multiple samples during spermatogenesis suppression for this substudy. Participants, employing a user-controlled test, correctly identified the absence of sperm (a negative test) in 100% of their laboratory-confirmed azoospermic samples (n = 122). Participants also identified 100% of samples (n = 73) with sperm0.2 million/mL as positive. Sperm counts between 0.01 and 0.2 million/mL were identified as negative in 96% of samples. Trial participants noted the overall ease of using the test with respect to sample preparation, test timing, and result interpretation, and that they could accurately use this test at home without difficulty.Participants undergoing spermatogenesis suppression in a hormonal male contraceptive trial performed user-controlled test to determine whether their semen sperm concentration was ≤ or0.2 million/mL. Compared with standard semen analyses, participants correctly identified 100% of samples with sperm counts0.2 million/mL as positive (Sensitivity 100%). A positive result when the couple is using a male contraceptive method triggers the need for semen analysis by a laboratory while the couple uses another method of contraception. Participants correctly diagnosed samples ≤0.2 million sperm/mL as negative in 99% of samples (specificity 99%). A negative result indicates a sperm concentration ≤0.2 million/mL, well below the threshold of ≤1 million/mL offering contraceptive efficacy demonstrated by prior studies. At-home sperm concentration test would minimize the need for users to return to the clinic to monitor suppression of spermatogenesis, decreasing cost and burden of male contraception trials and increasing practicality of the method.NCT: 03452111.

In the age of ever-increasing developments in targeted cancer treatments, new immune-based approaches for brain tumor therapy represent an attractive avenue. Despite encouraging pre-clinical data, results in patients have been sub-optimal, likely due to tumor-induced immune suppression and intrinsic resistance to immune attack. Chemotherapy and biologic agents may be able to disrupt these mechanisms and restore tumor sensitivity to immune attack. In this study, we explore whether a combination of gemcitabine and rapamycin can sensitize medulloblastoma cells to immunotherapy in vitro and in vivo.With the commercial medulloblastoma cell line, Daoy, we explored the concentrations of combinations of Gemcitabine with rapamycin needed to induce cytotoxicity. Next, we used flow cytometry to assess the cytotoxicity of chemotherapy-treated Daoy cells with the addition of anti-tumor T-cells, generated from naive T-cells stimulated in the presence of Daoy lysate-pulsed dendritic cells. Then, we examined the efficacy of chemotherapy alone versus chemotherapy plus immunotherapy in tumor growth inhibition of subcutaneous medulloblastoma xenografts.Rapamycin alone at1,000 nM had moderate activity against Daoy cells in vitro and ICCombining immunotherapy and chemo-biologic therapy inhibit medulloblastoma cell and xenograft growth, and may offer an effective treatment for patients with medulloblastoma.

Antimicrobial susceptibility testing (AST) is routinely used to establish predictive antibiotic resistance metrics to guide the treatment of bacterial pathogens. Recently, a novel phenotype termed “bicarbonate (NaHCO3)-responsiveness” was identified in a relatively high frequency of clinical MRSA strains, wherein isolates demonstrate in vitro “susceptibility” to standard β-lactams (oxacillin [OXA], cefazolin [CFZ]) in the presence of NaHCO3, and in vivo susceptibility to these β-lactams in experimental endocarditis models. We investigated whether a targeted phenotypic-genotypic screening of MRSA could rule in or rule out NaHCO3 susceptibility upfront. We studied 30 well-characterized clinical MRSA bloodstream isolates, including 15 MIC-susceptible to CFZ and OXA in NaHCO3-supplemented Mueller–Hinton Broth (MHB), and 15 MIC-resistant to both β-lactams in this media. Using a two-tiered strategy, isolates were first screened by standard disk diffusion for susceptibility to a combination of amoxicillin-clavulanate [AMC]. Isolates then underwent genomic sequence typing: MLST (clonal complex [CC]), agr, SCCmec, and mecA promoter and coding region. The combination of AMC disk susceptibility testing plus mecA and spa genotyping was able to predict MRSA strains that were more or less likely to be NaHCO3-responsive in vitro, with a high degree of sensitivity and specificity. Validation of this screening algorithm was performed in six strains from the overall cohort using an ex vivo model of endocarditis. This ex vivo model recapitulated the in vitro predictions of NaHCO3-responsiveness vs. nonresponsiveness above in five of the six strains.

Constant interruptions and continual data flow result in information overload for clinicians and become barriers to identification and extraction of relevant patient data and its correct interpretation. The aim of the study was to describe the types, frequencies, and impact of intensive care unit (ICU) interruptions on patient safety event occurrences and electronic health records (EHR) use.We conducted a live observational study for 6 weeks, observing critical care physicians' and other providers' communication while recording interruptions, patient safety events, and EHR use.Across 55 hours, the researchers observed 7515 ICU tasks, 15.7% of which were interrupted. We found that technological interruptions directly influences the occurrence of patient safety events: an increase in technological interruptions directly contributes to patient safety event occurrence (P = 0.004). Technological interruptions had a direct effect on human interruptions, as the frequency of technological interruptions increase, human interruptions also increase (P = 0.02).A prospective, observational study was conducted to understand the relationship between interruptions and patient safety events and EHR use, in a time-sensitive, activity-based study in a large academic medical center with a certified EHR system. We found that technological interruptions were statistically correlated to the occurrence of patient safety events, and human interruptions significantly affected the level of EHR use. This study recommends that ICUs adopt a safety culture that promotes minimizing unnecessary interruptions, such as side conversations during rounds, for improved quality of care.

OBJECTIVES: Newborns hospitalized with unconjugated hyperbilirubinemia without critical comorbidities may receive intensive phototherapy (IP) in non-ICU levels of care, such as a mother-newborn unit, or ICU levels of care. Our aim was to compare outcomes between each level. METHODS: Using hospital discharge data from 2005 to 2011 in New York’s State Inpatient Database, we performed multivariate analyses to compare outcomes that included total cost of hospitalization, length of stay, 30-day readmission rate after IP, and the number of cases of death, exchange transfusion, and γ globulin infusion. We included term newborns treated with IP in their first 30 days of life and without diagnosis codes for other critical illnesses. Explanatory variables included level of care, sex, race, insurance type, presence or absence of hemolysis, hospital, volume of IP performed at each hospital, and year of hospitalization. RESULTS: Ninety-nine percent of IP was delivered in non-ICU levels of care. Incidence of major complications was rare (≤0.1%). After adjusting for confounders, ICU level of care was not associated with difference in length of stay (relative risk: 1.2; 95% confidence interval [CI]: 0.91 to 1.15) or 30-day readmission rate (odds ratio: 0.74; 95% CI: 0.50 to 1.09) but was associated with 1.51 (95% CI: 1.47 to 1.56) times higher costs. CONCLUSIONS: For otherwise healthy term newborns with jaundice requiring IP, most received treatment in a non-ICU level of care, and those in intensive care had no difference in outcomes but incurred higher costs. IP guideline authors may want to be more prescriptive about IP level of care to improve value.

4554 Background: Subgroup analyses have reported differences in clinical outcomes by ethnicity in patients (pts) receiving immune checkpoint inhibitors (Cheng et al Ann Oncol 2019; Peravali et al World J Clin Oncol 2021). We sought to compare real-world outcomes between Hispanic/Latinx and non-Hispanic/Latinx mRCC pts treated with first-line ipi/nivo within a safety-net healthcare system and at a tertiary care center in Southern California. Methods: We performed a retrospective analysis of mRCC pts who received ipi/nivo within the Los Angeles County Department of Health Services (a safety-net healthcare system) and the City of Hope Comprehensive Cancer Center (a tertiary oncology center) between Jan 1, 2015 and Dec 31, 2021. Pts were identified using institutional databases and clinical data were compiled from electronic health records. Pts with pathologic diagnosis of stage IV mRCC, age > 18 years and receipt of ipi/nivo as first-line therapy were included. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method and covariates were adjusted using multivariate Cox proportional hazards regression. Results: Of 96 pts, 67 (70%) were male, 90 (94%) had clear-cell histology, and 89 (93%) had intermediate/poor IMDC risk. Forty-two pts (44%) were Hispanic/Latinx while the remainder were non-Hispanic/Latinx (44 pts [46%] White, 7 pts [7%] Asian, and 3 pts [3%] Other). Fifty (52%) and 46 (48%) pts received their care at a tertiary care center and within a safety-net healthcare system, respectively. Median age, IMDC risk classification, BMI, and number of comorbidities were similar between both groups. Pooled analysis by ethnicity revealed significantly shorter PFS in Hispanic/Latinx vs non-Hispanic/Latinx pts (HR 1.60, 95% CI 1.04-2.48, p = 0.03). At 12 months, 19% of Hispanic/Latinx pts (95% CI, 9-32) and 35% of non-Hispanic/Latinx pts (95% CI, 23-48) were alive and progression-free. There was no difference in PFS between pts at the safety-net hospital system vs tertiary care center (HR 1.32, 95% CI 0.87-2.02, p = 0.19). Conclusions: Our real-world analysis of mRCC pts demonstrated poorer outcomes with ipi/nivo in Hispanic/Latinx pts. We are currently interrogating multiple social determinants of health that may contribute to these concerning disparities.

Background: While the metabolic effects of testosterone have been well studied, the effects of co-administration of an androgen and progestin are less established. Two novel compounds being investigated for male hormonal contraception, dimethandrolone undecanoate (DMAU) and 11β-methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC), have both androgenic and progestational activity. Aim: Characterize the effects of DMAU and 11β-MNTDC on metabolic parameters including weight, lipid parameters, insulin resistance, and adiponectin. Methods: Two randomized, double-blind, placebo-controlled studies in healthy men were previously performed to assess the safety and tolerability of DMAU and 11β-MNTDC taken orally for 28 days. Insulin and adiponectin assays were performed on a subset of banked samples. Changes in weight, LDL-C, HDL-C, fasting glucose, HOMA-IR, and adiponectin were assessed. Two way ANOVA with post hoc Tukey HSD was performed to assess for dosage (0, 200, or 400mg) and drug (DMAU or 11β-MNTDC) effects. Results: A total of 85 subjects were included in this secondary analysis. There was a statistically significant decrease in HDL-C (mean change -11 and -15 mg/dL) and increase in weight (3 and 2 kg) and LDL-C (18 and 23 mg/dL) in the DMAU and 11β-MNTDC 400mg groups respectively. There was no significant difference between the 200 and 400 mg groups nor differences between the two androgens. There were no statistically significant changes in fasting glucose, adiponectin or HOMA-IR. Conclusion: There were mild changes in weight, HDL-C, and LDL-C after 28 days of DMAU and 11β-MNTDC without significant changes in markers of insulin resistance or differences between the two compounds. Changes in metabolic parameters should be monitored and considered during further development of compounds for male hormonal contraception.

Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively., Addition of sodium bicarbonate (NaHCO3) to standard antimicrobial susceptibility testing medium reveals certain methicillin-resistant Staphylococcus aureus (MRSA) strains to be highly susceptible to β-lactams. We investigated the prevalence of this phenotype (NaHCO3 responsiveness) to two β-lactams among 58 clinical MRSA bloodstream isolates. Of note, ∼75% and ∼36% of isolates displayed the NaHCO3 responsiveness phenotype to cefazolin (CFZ) and oxacillin (OXA), respectively. Neither intrinsic β-lactam MICs in standard Mueller-Hinton broth (MHB) nor population analysis profiles were predictive of this phenotype. Several genotypic markers (clonal complex 8 [CC8]; agr I and spa t008) were associated with NaHCO3 responsiveness for OXA.

Methicillin-resistant Staphylococcus aureus (MRSA) poses significant therapeutic challenges related to its frequency in clinical infections, innate virulence properties, and propensity for multiantibiotic resistance. MRSA is among the most common causes of endovascular infections, including infective endocarditis (IE). Our objective was to employ transthoracic echocardiography (TTE) to evaluate the effect of exebacase, a novel direct lytic agent, in experimental aortic valve MRSA IE. TTE was utilized to evaluate the in vivo effect of exebacase on MRSA-infected vegetation progression when combined with daptomycin (versus daptomycin alone). Primary intravegetation outcomes were maximum size, weights at sacrifice, and MRSA counts at infection baseline versus after 4 days of daptomycin treatment (alone or in addition to exebacase administered once on treatment day 1). A single dose of exebacase in addition to daptomycin cleared significantly more intravegetation MRSA than daptomycin alone. This was associated with a statistical trend toward reduced maximum vegetation size in the exebacase plus daptomycin versus the daptomycin alone therapy groups (P = 0.07). Also, mean vegetation weights in the exebacase-treated group were significantly lower than those of the daptomycin alone group (P < 0.0001). Maximum vegetation size by TTE correlated with vegetation weight (P = 0.005). In addition, intravegetation MRSA counts in the combination group were significantly lower than those of untreated controls (P < 0.0001) and the daptomycin alone group (P < 0.0001). This study suggests that exebacase has a salutary impact on MRSA-infected vegetation progression when combined with daptomycin, especially in terms of vegetation MRSA burden, size, and weight. Moreover, TTE appears to be an efficient noninvasive tool to assess therapeutic efficacies in experimental MRSA IE.

Supplemental File

Short term Metabolic Effects of Two Novel Oral Androgens, Dimethandrolone Undecanoate and 11β-MNTDC Supplemental File

Background The current literature on determinants of behavior change in weight management lacks sufficient studies on type of motivation among children/adolescents, on perceived competence, and in relation to healthy eating. This study aimed to investigate type of motivation and levels of perceived competence for healthy diet and exercise, as well as general self efficacy among adolescents. We hypothesized that overweight/obese adolescents would demonstrate lower autonomous motivation and perceived competence regarding diet and exercise, and lower self-efficacy in general, and that the scores would be influenced by socioeconomic factors. Methods Normal weight (n = 40, body mass index

Rationale: A positive bronchodilator response (BDR) according to American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines require both 200 ml and 12% increase in forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) after bronchodilator inhalation. This dual criterion is insensitive in those with high or low FEV1. Objectives: To establish BDR criteria with volume or percentage FEV1 change. Methods: The largest FEV1 and FVC were identified fromthree pre- and three post-bronchodilator maneuvers in COPDGene (Genetic Epidemiology of COPD) participants. A total of 7,741 individuals with coefficient of variation less than 15% for both FEV1 and FVC formed bronchodilator categories of FEV1 response: negative (0.00% to 0.00 L to 9.00% to 16.00% to 0.16 L to 26.00% or >0.26 L). These response size categories are based on empirical limits considering average FEV1 increase of approximately 160 ml and the clinically important difference for FEV1. To compare flow and volume response characteristics, BDR-FEV1 category assignments were applied for the BDR-FVC response. Results: Twenty percent met mild and 31% met moderate or marked BDR-FEV1 criteria, whereas 12% met mild and 33% met moderate or marked BDR-FVC criteria. In contrast, only 20.6% met ATS/ERS positive criteria. Compared with the negative BDR-FEV1 category, the minimal, mild, moderate, and marked BDR-FEV1 categories were associated with greater 6-minute-walk distance and lower St. George's Respiratory Questionnaire and modified Medical Research Council dyspnea scale scores. Compared with negative BDR, moderate and marked BDR-FEV1 categories were associated with fewer exacerbations, and minimal BDR was associated with lower computed tomography airway wall thickness. Compared with the negative category, all BDR-FVC categories were associated with increasing emphysema percentage and gas trapping percentage. Moderate and marked BDR-FVC categories were associated with higher St. George's Respiratory Questionnaire scores but fewer exacerbations and lower dyspnea scores. Conclusions: BDR grading by FEV1 volume or percentage response identified subjects otherwise missed by ATS/ERS criteria. BDR grades were associated with functional exercise performance, quality of life, exacerbation frequency, dyspnea, and radiological airway measures. BDR grades in FEV1 and FVC indicate different clinical and radiological characteristics. United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Heart Lung & Blood Institute (NHLBI) National Center for Advancing Translational Sciences through UCLA CTSI Grant

Background: The prevalence and clinical significance of de novo detection of anti-thyroglobulin antibodies (TgAb) during the follow up of patients with differentiated thyroid cancer (DTC), is unknown. Methods: We utilized the National Thyroid Cancer Treatment Cooperative Study registry (1987-2012). Of >5,000 registered DTC subjects, we identified 1,545 subjects who had available TgAb status (TgAb cohort), of whom 1,325 were TgAb negative at first post-operative follow-up testing. From this initial TgAb negative group, we excluded 513 patients: 423 patients who had less than three-years of follow-up and/or fewer than three follow-up visits, 86 patients with persistent disease after initial treatment, and 4 patients with data entry errors. The remaining 812 patients were included for analysis, comprising the TgAb persistently negative group [defined as TgAb negative for at least three consecutive follow-up visits and at least three-years of follow-up] (n = 772) and a de novo TgAb positive group in whom TgAbs became detectable (n = 40). We then assessed whether de novo appearance of TgAb was associated with DTC structural recurrence using the Kaplan-Meier method. Results: The de novo detection of TgAb occurred in 5% of DTC patients. Recurrence of DTC in the TgAb persistently negative group compared with the de novo TgAb positive group did not differ significantly (8.7% vs 13.3%, p = 0.2). Baseline characteristics, histology, history of radiation exposure, staging, and median duration of follow-up were similar between the two groups. Interestingly, in all 6 patients who suffered a recurrence in the de novo TgAb positive group, TgAbs were detected after the recurrence was detected radiologically [median 2.1, 0.7 - 8.7 years]. Conclusion: Utilizing a large North American DTC registry, we found the prevalence of de novo TgAb detection to be 5% among initially TgAb negative patients. We did not find a statistically significant association between de novo TgAb development and DTC structural recurrence. This study is limited by its retrospective design, institutional differences in TgAb assays, and the exclusion of large group of subjects due to lack of TgAb data or inadequate follow up. Furthermore, the small number of actual recurrences limits the power of the analysis to identify an association. Larger prospective studies are required to confirm these findings and further assess the significance of de novo TgAb detection in the follow up of DTC.

Background Chronic cough in children is a diagnostic challenge. Objective To discover the utility of nasal dipsticks and polymerase chain reaction (PCR)-DNA analysis in differentiating bacterial sinusitis from other causes of chronic cough and identifying pathogens from the nasal cavity. Method We recruited 22 patients under 15 years of age with cough lasting longer than 4 weeks (group 1), 7 controls with allergic rhinitis (group 2), and 10 controls without respiratory symptoms (group 3). Based on symptoms, the results of nasal secretion assays, and nasal endoscopy, a diagnosis of clinical bacterial sinusitis was made. We identified potential pathogens by quantitative PCR of nasal secretions. Results Group 1A (cough with clinical bacterial sinusitis n = 10): Eight (80%) patients had bacterial sinusitis associated with dominant potential pathogenic bacteria (PPB): Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Group 1B (cough without clinical bacterial sinusitis n = 12): None had dominant PPB. Group 2 (allergic rhinitis n = 7): None had dominant PPB. Group 3 (asymptomatic n = 10): None had dominant PPB. Twenty to 57% of all groups were colonized with Staphylococcus aureus. Fifty to 70% were colonized with Staphylococcus epidermidis, Corynebacterium pseudodiphtheriticum, and Dolosigranulum pigrum. Conclusion In children with chronic cough, clinicians can utilize a simple and inexpensive nasal secretion dipstick assay for rapid diagnosis of sinusitis and identify PPB by DNA-PCR test for specific antibiotic treatment.

Background.Sickle cell disease (SCD) affects millions of people worldwide, including >100,000 Americans, and is often complicated by acute crises. Complex pathophysiology makes it challenging to ameliorate SCD severity, which can be influenced by hydration and disease-modifying agents such as hydroxyurea (HU). Due to the increased metabolic demands of chronic illness, optimal nutrition and presumably antioxidant L-glutamine (Gln) may further contribute to disease control. Thus, we hypothesized that better nutrition and Gln adherence may reduce occurrences of pain crises in SCD. Methods.An IRB-approved retrospective review of pediatric patients with SCD ≥1 y of age was conducted at our institution, along with voluntary nutrition surveys. Evaluations were carried out for associations between disease severity and clinical/laboratory variables representing nutrition, growth, hematologic parameters [fetal hemoglobin (HbF), mean corpuscular volume (MCV)], and treatment compliance (with HU and/or Gln). Results.Preliminary analyses included data from 50 SCD patients (25 F/25 M), with a mean age of 9.1 ±7 y and a mean BMI of 56.4 ±32.6% (±SDEV). Sixty percent of the patients had HbSS/Sß0 (32%-HbSC and 8%-HbSß+). The average number of annual pain crises (APC, 0.97 ±1.14) requiring hospital visits or admissions per patient rose with age. HbF expectedly dropped with age. HbF levels - 0.87 ±1.1 for well hydrated/well nourished (n=14, 3.1 ±2.3 y) - 1.4 ±2 for well hydrated/poorly nourished (n=10, 11 ±6.4 y) - 1.97 ±2 for poorly hydrated/poorly nourished (n=8, 13 ±5.4 y). There were no correlations between caloric intake and BMI. However, 20% of surveyed patients (12 ±7.8 y) had Z-scores lower than -1 SD for both height and weight. Their mean APC was significantly higher (2.5 ±2.5vs.1 ±1.3,p=0.03 byt-test). Their prealbumin levels trended lower than normal for age, and were more diminished in older patients. Nearly 60% of our patients were on HU (80% with HbSS/Sß0, age 10.8 ±7.4 y). Good HU adherence was reported by 22 patients, typically ≥90%, which was associated with higher MCVs (92 ±9.6 vs. 74 ±10 f/L,p Conclusions.Well-nourished/hydrated patients were younger and had a milder disease phenotype, whereas more severe disease was seen in poorly nourished older patients, often with suboptimal compliance. L-Glutamine can be a clinically meaningful addition to HU and should be further studied in pediatric SCD. Disclosures No relevant conflicts of interest to declare.

CONTEXT: 11β-Methyl-19-nortestosterone-17β-dodecylcarbonate (11β-MNTDC) is an orally bioavailable prodrug of 11β-methyl-19-nortestosterone (11β-MNT) with androgenic and progestational activity. OBJECTIVES: (i) Quantify 11β-MNT binding to androgen and progesterone receptors. (ii) Evaluate safety, tolerability, and serum gonadotropin and testosterone suppression by 11β-MNTDC in men. DESIGN AND SETTING: (i) In vitro receptor binding and transactivation studies and (ii) randomized, double-blind, placebo-controlled single-dose, dose-escalating phase I study at two academic medical centers. PARTICIPANTS AND INTERVENTION: Twelve healthy male volunteers were randomized (five active, one placebo) to escalating single oral doses (100, 200, 400, and 800 mg) of 11β-MNTDC or placebo given with or without food. MAIN OUTCOME MEASURES: (i) In vitro 11β-MNT/11β-MNTDC human receptor binding and transactivation and (ii) safety and tolerability, pharmacokinetics, and quantification of serum gonadotropin and testosterone concentrations for 24 hours following dosing. RESULTS: 11β-MNT avidly binds and activates human androgen and progesterone receptors, but 11β-MNTDC has minimal activity. Single oral doses of 11β-MNTDC were well tolerated without serious adverse events. Administration of 11β-MNTDC with food markedly increased average 11β-MNTDC and 11β-MNT serum concentrations (P < 0.001 for all doses) compared with fasting with a significant dose-related effect on average serum drug concentrations (P < 0.0001). The 200-, 400-, and 800-mg doses significantly suppressed average serum testosterone concentrations (P < 0.05). CONCLUSIONS: A single, oral dose of 11β-MNTDC up to 800 mg administered with food is safe and well tolerated in healthy men. The active drug 11β-MNT has androgenic and progestational activity, rapidly suppresses serum testosterone, and is a promising candidate for an effective once-daily oral male hormonal contraceptive.

BACKGROUND The incidence of nonmelanoma skin cancer (NMSC) exceeds the incidence of all other types of cancers combined. Cumulative sun exposure and intermittent sun exposure are known risk factors for the development of NMSC. Because obesity has been shown to decrease the risk of NMSC incidence, this study investigated whether the risk of NMSC with sun exposure was consistent across different levels of body size. METHODS Body size was assessed with the body mass index (BMI) and the waist-to-hip ratio (WHR). Sun exposure was assessed in watts and langleys and by the amount of time spent outdoors per day in the summer during a person's 30s. RESULTS Among 71,645 postmenopausal women eligible for inclusion in this study, 13,351 participants (18.6%) developed NMSC. A BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 was associated with lower NMSC hazard rates (hazard ratio for BMI, 0.78; hazard ratio for WHR, 0.89); however, the association between higher levels of sun exposure and a higher risk of NMSC was more apparent among women with a BMI ≥ 25 kg/m2 or a WHR ≥ 0.80 in comparison with those of a normal weight (P for interaction for BMI < .001; P for interaction for WHR = .022). CONCLUSIONS Although most studies have considered sun exposure as a covariate, none have addressed the potential interaction of body size with sun exposure; therefore, the effect size of being overweight or obese may have been overestimated. In comparison to the normal-weight group, those in the overweight group had increasingly higher hazard rates with increasing sun exposure. Further studies are warranted to investigate how increased weight interacts with sun exposure to influence skin cancer pathogenesis.

Safety and Pharmacokinetics of Oral 11βMNTDC - supplemental data

Gamete and embryo manipulations can result in alterations to the epigenome, and are associated with altered gene expression. The initial objective of this study was to determine the transcript level of several epigenetic modifiers in embryos that had been cultured from the 2-cell stage until the late-blastocyst stage in four culture conditions. Cultured embryos were compared to control, in vivo-produced late blastocysts to ascertain if differences in gene expression existed among the culture conditions; none were observed. As all of the embryos used were produced in females that had undergone superovulation, we next compared the transcript level of the same epigenetic modifiers between superovulated, in vivo-produced embryos and embryos produced from natural ovulation. Following in vitro culturing, expression of the genes analyzed was increased in all superovulation groups. We therefore hypothesized that the superovulation procedure-used to increase the number of embryos obtained for experimentation-may have caused an inappropriate acquisition of epigenetic modifications in the maternal genome prior to ovulation, which in turn caused misexpression of genes at the blastocyst stage. To test this hypothesis, we compared the level of global DNA methylation and histone 3 lysine-9 or -14 acetylation in zygotes obtained by natural- or superovulation. Indeed, superovulation decreased global DNA methylation on the maternal pronucleus of zygotes, which inversely correlated with H3K9/14 acetylation. In conclusion, superovulation alters the epigenome of the oocyte, resulting in the dysregulation of gene expression at the blastocyst stage.

Context Autoimmune thyroid disease is more common in women than in men. Fetal microchimerism has been implicated as a potential explanation for this disparity. Objective The objective of this study was to evaluate the relationship between parity and thyroid autoimmunity in the US population. Design, Setting, Patients The National Health and Nutrition Examination Survey was used to identify females with antithyroperoxidase (TPOAb) and antithyroglobulin antibody (TgAb) measurements and parity data. Subjects (n = 4864) were categorized as never pregnant (n = 909) or previously pregnant (n = 3955). The association of parity with thyroid autoantibodies was examined both qualitatively and quantitatively. Thyroid autoimmunity was defined as TPOAb and/or TgAb titers above the reference limits. Results Previous pregnancy carried an odds ratio (OR) of 1.55 [95% confidence interval (CI): 1.26 to 1.91] for thyroid autoimmunity compared with never pregnant. Number of pregnancies was associated with thyroid autoimmunity: OR = 1.37 (95% CI: 1.02 to 1.84); 1.4 (95% CI: 1.08 to 1.81); 1.52 (95% CI: 1.18 to 1.96); and 1.73 (95% CI: 1.38 to 2.18) for 1, 2, 3, and ≥4 pregnancies, respectively. Because ever-pregnant women differed in several variables—age, race, smoking status, history of thyroid disease, and urinary iodine level—from never-pregnant women (P < 0.001), a multivariate regression analysis was performed, which showed no association of pregnancy with thyroid autoimmunity. The association was further examined utilizing an age-matched analysis, which confirmed the absence of an association between thyroid autoimmunity and parity. Conclusion Although we initially observed a strong association between parity and thyroid autoimmunity, after controlling for age and other variables, we were unable to identify an association.

Journal Article published 6 Aug 2016 in Research in Cardiovascular Medicine, volume Inpress, issue Inpress..

Background We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline’s biological effects. Methods Design: Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance > 30 mL/min; proteinuria ≥ 1.0 g/day; Age ≥30 years; BP

ObjectiveThe objective of this study was to compare the relative stability in lumbar spondylolysis (SP) of a rigid anterior plate (with a novel compression slot) versus traditional posterior pedicle screw (PS) fixation.Summary of Background DataArthrodesis has been a mainstay of treatment for symptomatic isthmic spondylolisthesis in adults. Posterior PS fixation has become a commonly used adjunct. Some have advocated anterior lumbar interbody fixation (ALIF) plate as an alternative. The relative stability afforded by ALIF in SP has not been well characterized, nor has the contribution afforded by a compression screw slot in an ALIF plate.MethodsCalf spine segments were characterized in the normal state, after sectioning the pars (SP model), then after reconstruction with an interbody spacer and either PS/rods, or an ALIF plate, or both.ResultsALIF plate conferred stability on the spondylolytic segment only comparable to that of the normal functional spinal unit (FSU). Posterior fixation was more stable than anterior fixation in all testing modes. Addition of an ALIF plate conferred a significant additional stability in those that already had posterior fixation. The utilization of an anterior compression screw conferred additional stability in extension testing only.ConclusionsALIF plate reconstruction in the setting of SP may not confer enough segmental stability to predictably encourage fusion beyond that of the uninstrumented intact FSU. The utilization of an integral compression screw in an ALIF plate may not confer clinically significant additional construct stability in SP.

Veterans' health care has shifted towards outpatient treatment, and because of the high prevalence of chronic illness in veterans, more caregiving has been required of their families. The purpose of this study was to identify predictors of caregiver (CG) strain and satisfaction associated with caring for veterans with chronic illness. Data were collected using telephone interviews of 120 dyads. Strain was associated with helping with instrumental activities of daily living, using counseling and prayer for coping, accompanying veteran to appointments, help/advice from friends, paid help, exercising, and depression. Satisfaction was associated with veteran health, CG social support, age, and depression. Innovative and easily accessible interventions are needed to mitigate sources of strain in CGs of chronically ill veterans.

Background: Effective non pharmacological interventions are needed to treat neuropsychiatric symptoms and to improve quality of life for the 5.3 million Americans affected by dementia. Objective: The purpose of this study was to test the effect of a storytelling program, TimeSlips, on communication, neuropsychiatric symptoms, and quality of life in long-term care residents with dementia. Methods: A quasi-experimental, two-group, repeated measures design was used to compare persons with dementia who were assigned to the twice-weekly, 6-week TimeSlips intervention group (n = 28) or usual care group (n = 28) at baseline and postintervention at Weeks 7 and 10. Outcome measures included the Cornell Scale for Depression in Dementia, the Neuropsychiatric Inventory—Nursing Home Version, the Functional Assessment of Communication Skills, the Quality of Life—Alzheimer's Disease, and the Observed Emotion Rating Scale (this last measure was collected also at Weeks 3 and 6 during TimeSlips for the treatment group and during mealtime for the control group). Results: Compared with the control group, the treatment group exhibited significantly higher pleasure at Week 3 (p < .001), Week 6 (p < .001), and Week 7 (p < .05). Small to moderate treatment effects were found for Week 7 social communication (d = .49) and basic needs communication (d = .43). A larger effect was found for pleasure at Week 7 (d = .58). Discussion: As expected, given the engaging nature of the TimeSlips creative storytelling intervention, analyses revealed increased positive affect during and at 1 week postintervention. In addition, perhaps associated with the intervention's reliance on positive social interactions and verbal communication, participants evidenced improved communication skills. However, more frequent dosing and booster sessions of TimeSlips may be needed to show significant differences between treatment and control groups on long-term effects and other outcomes.

Shoulder pain and loss of shoulder function are common complaints reported by a variety of patients. This article suggests that shoulder pain and loss of function are directly proportional to lifestyle choices, including smoking and obesity. To investigate possible relationships between lifestyle choices and shoulder health, the authors conducted an online survey combining the Oxford Shoulder Questionnaire, the Shoulder Rating Questionnaire, and the Subjective Shoulder Rating System. Data were collected from 166 respondents. Statistical significance was set at P < .05. The data show a statistically significant correlation between decreased shoulder function and cigarette smoking and a similar correlation between decreased shoulder function, elevated cholesterol, and obesity.

Aims To identify clinicopathologic and treatment variables associated with long-term overall survival (OS) in soft tissue sarcoma (STS) patients with lung metastases undergoing pulmonary metastasectomy (PM). Methods Retrospective review of 94 STS PM patients with an actual follow-up ≥5 years. Data were collected on demographics, tumor features, treatment, and outcome. Results Most primary tumors were intermediate/high grade and the common histopathologies were evenly distributed. Half of the primary tumors were located on the extremities. The mean disease-free interval (DFI) from time of original diagnosis until metastases was 25 months (median 15 months). Eighteen patients had synchronous metastatic disease. Bilateral pulmonary metastases and >1 metastasis were common. The median number of metastases resected was 2.5. Thirty-four patients had extrapulmonary tumor at the time of PM; all extrapulmonary disease was resected. Negative margin resection (R0) PM was performed in 74 patients. Actual 5-year disease-free survival (DFS) and OS for all patients were 5% and 15%, respectively. For the R0 group, actual 5-year DFS and OS were 7% and 18%, respectively. R0 resection and a prolonged DFI were associated with improved OS. Patient characteristics, tumor features, local recurrence, and adjuvant therapy did not affect OS. Conclusions Less than 20% of STS PM patients will survive 5 years. Complete resection and DFI are the most predictive factors for prolonged survival.

The optimal frequency for on-treatment serum T measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance.The objectives of the study was to determine the variability of postgel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24 hours (Cavg0-24).This was a double-blinded, placebo-controlled randomized trial.The study was conducted at five academic centers.Forty-seven symptomatic men 65 years old or older with an average of two morning T concentration less than 275 ng/dL participated in the study.Transdermal T or placebo gel was applied for 120 ± 14 days. Monthly dose adjustments were made if necessary to target serum T between 400 and 500 to 800 ng/dL.Variability of serum T 2 hours after the gel application on two outpatient visits and at multiple time points over 24 hours during the inpatient day was measured.On-treatment T levels varied substantially on the 2 ambulatory days and over 24 hours during the inpatient day. Ambulatory 2-hour postapplication T levels did not correlate significantly with either 2-hour postapplication serum T or Cavg0-24 measured during the inpatient day. Only 22.2% of men receiving T had a Cavg0-24 within the target range of 500-800 ng/dL; 81.5% had a Cavg0-24 within the broader 300-1000 ng/dL range.Large within-individual variations in serum T after T gel application render ambulatory 2-hour postapplication T level a poor indicator of average serum T on another day. Our data point out the limitations of dose adjustments based on a single postapplication serum T measurement.

Background: Pulse oximetry is a key part of the clinical evaluation and management of neonates with congenital heart defects. In 2011, the US Department of Health and Human Services recommended use of routine pulse oximetry to screen for critical congenital heart disease (CCHD). Current studies suggest pulse oximetry overestimates arterial oxygen saturation in moderately hypoxemic pediatric patients. Based on variable hypoxemia in neonates with CCHD, concern exists that present pulse oximeter technology may overestimate measured oxyhemoglobin. Objectives: To compare pulse oximetry and oxyhemoglobin values in NICU patients with known CCHD to evaluate the ability of pulse oximetry to reliably predict oxyhemoglobin accounting for potential confounding variables such as heart lesion, saturation range, total hemoglobin concentration, peripheral perfusion, and timing of measurements. Methods: This is a single-center retrospective study. Inclusion criteria were AHA-defined CCHD and umbilical artery blood gas-derived oxyhemoglobin with concurrent pulse oximetry recording during hours of life 0-72. Bland-Altman analysis and the concordance correlation coefficient were used to measure the internal consistency (agreement) between the two measurements. Results: 89 patients were evaluated with 599 paired arterial oxyhemoglobin and pulse oximetry recordings. 47% of all pulse oximetry values were ≥95% - the cutoff for CCHD screening. Pulse oximetry overestimated arterial oxyhemoglobin by a mean of 5.4% over all levels of oxygen saturation. Pulse oximetry overestimation was >3 in 65.4% of measurements, >6 in 41.2% of measurements, and >10 in 15.3% of measurements. Hour of life, total hemoglobin, and peripheral perfusion did not significantly affect the degree of overestimation. Conclusions: Our results reinforce the concern that present pulse oximeters overestimate oxyhemoglobin values, contributing to some false-negative CCHD screens and potentially leading to unnecessary escalations in care of those patients with diagnosed CCHD. Improvements in pulse oximetry accuracy and precision in the neonate would benefit both screening and clinical care in the NICU.

One way to increase choice of healthy over unhealthy behaviors is to increase the cost of less healthy alternatives or reduce the cost of healthier alternatives. The influence of price on purchases of healthy and unhealthy foods was evaluated in two laboratory experiments. In Experiment 1, thirty-two 10- to 12-year-old youth were given $5.00 and allowed to purchase multiple portions of a healthy food (fruit or vegetable) and a less healthy food (higher-fat snack). The price of one type of food varied from $0.50 to $2.50, while the price of the other type was held at $1.00. Increasing the price of a type of food reduced purchases of that type of food, but did not lead to substitution with the alternative type of food. In Experiment 2, twenty 10- to 14-year-old youth were given $1.00, $3.00, and $5.00 to purchase healthy and unhealthy foods. The price of each food was raised and lowered by 25% and 50%. Raising the price of healthy or unhealthy foods resulted in decreased purchases of those foods, and income available interacted with price to predict the pattern of substitution of alternative foods. These results show the potential for controlled laboratory studies of price and food purchases, and show that the substitution of healthier for unhealthy food is related to available money.