Faculty Bibliography

OBJECTIVE:Dasotraline is a potent inhibitor of presynaptic dopamine and norepinephrine reuptake with a pharmacokinetic profile characterized by slow absorption and a long elimination half-life. The aim of this study was to evaluate the efficacy and safety of dasotraline in children with attention-deficit/hyperactivity disorder (ADHD). METHODS:Children aged 6-12 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomized to 6 weeks of double-blind once-daily treatment with dasotraline (2 or 4 mg) or placebo. The primary efficacy endpoint was change from baseline in the ADHD Rating Scale Version IV-Home Version (ADHD RS-IV HV) total score at week 6. RESULTS:A total of 342 patients were randomized to dasotraline or placebo (mean age 9.1 years, 66.7% male). Treatment with dasotraline was associated with significant improvement at study endpoint in the ADHD RS-IV HV total score for the 4 mg/day dose versus placebo (-17.5 vs. -11.4; p < 0.001; effect size [ES], 0.48), but not for the 2 mg/day dose (-11.8 vs. -11.4; ns; ES, 0.03). A regression analysis confirmed a significant linear dose-response relationship for dasotraline. Significant improvement for dasotraline 4 mg/day dose versus placebo was also observed across the majority of secondary efficacy endpoints, including the Clinical Global Impression (CGI)-Severity score, the Conners Parent Rating Scale-Revised scale (CPRS-R) ADHD index score, and subscale measures of hyperactivity and inattentiveness. Discontinuation rates due to adverse events (AEs) were higher in the dasotraline 4 mg/day group (12.2%) compared with the 2 mg/day group (6.3%) and placebo (1.7%). The most frequent AEs associated with dasotraline were insomnia, decreased appetite, decreased weight, and irritability. Psychosis-related symptoms were reported as AEs by 7/219 patients treated with dasotraline in this study. There were no serious AEs or clinically meaningful changes in blood pressure or heart rate on dasotraline. CONCLUSION/CONCLUSIONS:In this placebo-controlled study, treatment with dasotraline 4 mg/day significantly improved ADHD symptoms and behaviors, including attention and hyperactivity, in children aged 6-12 years. The most frequently reported AEs observed on dasotraline included insomnia, decreased appetite, decreased weight, and irritability.

PURPOSE/OBJECTIVE:Maintaining high water intake decreases kidney stone recurrence but is difficult to do. Strategies to reduce stone recurrence among adolescents are lacking. We conducted an ecological momentary assessment study to identify factors associated with water intake in adolescents with nephrolithiasis. MATERIALS AND METHODS/METHODS:The study population consisted of 15 female and 10 male patients 12 to 18 years old with at least 1 prior kidney stone. For 7 days participants used "smart" bottles to self-monitor water intake and received questionnaires randomly 4 times daily, which were completed in real time on mobile devices. The questionnaires ascertained awareness of water intake volume, awareness of water intake goals, perceived need to drink, access to water, alternative beverage consumption and attitudes toward bathrooms. Linear mixed effects models were fit to estimate the association between momentary responses and daily water intake. RESULTS:During 175 person-days 595 assessments (85%) were completed. Median daily water intake was 1,304 ml (IQR 848-1,832) and 20% of participants met their intake goal for 4 days or more. Unawareness of water intake volume was associated with drinking 690 ml less water per day (p = 0.04). A strong self-perceived need to drink more was associated with drinking 1,954 ml less water each day compared to no self-perceived need to drink more (p <0.01). Unawareness of intake goals was weakly associated with drinking 1,129 ml less water each day (p = 0.1). Access to water, alternative beverage consumption and bathroom aversion were not associated with water intake. CONCLUSIONS:Unawareness of water volume consumed and low responsiveness to perceived need to drink more were associated with low water intake. Interventions that help adolescents recognize when and identify how to increase water intake may be effective in decreasing stone recurrence.

Ascorbic acid better known as vitamin C, is a reducing carbohydrate needed for a variety of functions in the human body. The most important characteristic of ascorbic acid is the ability to donate two electrons, predestining it as a major player in balancing the physiological redox state and as a necessary cofactor in multiple enzymatic hydroxylation processes. Ascorbic acid can be reversibly oxidized in two steps, leading to semidehydroascorbic acid and dehydroascorbic acid, respectively. Further degradation is irreversible and generates highly reactive carbonyl-intermediates. These intermediates are able to induce glycation of proteins, a non-enzymatic and unspecific reaction of carbonyls with amino groups involved to several age-related diseases. In this study, we investigated the effect of ascorbic acid- and dehydroascorbic acid-induced glycation on PC12 cells, which represent a model for neuronal plasticity. We found that both applications of ascorbic acid or dehydroascorbic acid leads to glycation of cellular proteins, but that ascorbic acid interferes more with viability and neurite outgrowth compared with dehydroascorbic acid.

One hallmark of molecular aging is glycation, better known as formation of so-called advanced glycation end products (AGEs), where reactive carbonyls react with amino-groups of proteins. AGEs accumulate over time and are responsible for various age-dependent diseases and impairments. Two very potent dicarbonyls to generate AGEs are glyoxal (GO) and methylglyoxal (MGO). The plasma level of such dicarbonyls is higher in aging and age-related diseases. Natural killer (NK) cells are cells of the innate immune system and provide a major defense against tumor cells and virus infected cells. They are able to kill modified or infected cells and produce different cytokines to modulate the function of other immune cells. Here we investigated the effect of GO- and MGO-induced glycation on the function of NK cells. Using the human NK cell line NK-92, we could demonstrate that both GO and MGO lead to glycation of cellular proteins, but that MGO interferes much stronger with NK cell function (cytotoxicity) than GO. In addition, glycation of NK cell targets, such as K562 tumor cells, also interferes with their lysis by NK cells. From this data we conclude that glycation acts negatively on NK cells function and reduces their cytotoxic potential towards tumor cells.

BACKGROUND:Asymptomatic blood pressure elevation is common in the inpatient setting. National guidelines recommend treating with oral agents to slowly decrease blood pressure; however, many clinicians use intravenous antihypertensive medications, which can lead to unpredictable changes in blood pressure. OBJECTIVE:To decrease the number of inappropriate orders (without symptoms of hypertensive emergency or order for NPO) of intravenous antihypertensives and adverse events associated with intravenous orders. DESIGN/METHODS:Quasi-experimental study with multidisciplinary intervention. PARTICIPANTS/METHODS:Inpatients with a one-time order for an intravenous antihypertensive agent from January 2016 to February 2018. MAIN MEASURES/METHODS:The main outcomes were the total numbers of orders and inappropriate orders, adverse events, and alternate etiologies per 1,000 patient-days. As a balancing measure, patients were monitored for adverse events when blood pressure was elevated and not treated. KEY RESULTS/RESULTS:There were a total of 260 one-time orders of intravenous antihypertensives on two medical units. Inappropriate orders decreased from 8.3 to 3.3 per 1,000 patient days (P = .0099). Adverse events associated with intravenous antihypertensives decreased from 3.7 to 0.8 per 1,000 patient days (P = .0072). CONCLUSION/CONCLUSIONS:This initiative demonstrated a significant reduction in inappropriate use of IV antihypertensives and an associated reduction in adverse events.

BACKGROUND:Lack of access to primary care physicians (PCPs) may be an important contributor to mortality differences attributed to race/ethnicity. This study examined the effects of primary care access on mortality of lung cancer patients in an underserved community. METHODS:Medical records of all newly diagnosed patients with primary lung cancer from 2012 to 2016 at a National Cancer Institute (NCI)-designated center in Bronx, New York were reviewed. Demographic data, PCP status, and residence in primary care shortage areas (PCSAs) were collected. Survival data from time of first imaging to death or the end of follow-up on January 1, 2018 were recorded. Survival analysis was performed using Kaplan-Meier and Cox hazards modeling. RESULTS:Among 1062 patients, 874 (82%) were PCSA residents, 314 (30%) were Hispanic, and 445 (42%) were African American. PCSA residents were likely Hispanics (P<0.001), African Americans (P<0.001), of lower income (P<0.001), and had advanced disease at diagnosis (P=0.01). Patients without established PCPs had more comorbidities (P=0.04), more advanced disease (P<0.001), and less in-network cancer treatment (P<0.001). PCSA residence (P=0.03, hazard ratio [HR]=1.27) and no established PCP (P<0.001, HR=1.50) were associated with increased mortality. In multivariable modeling, lack of established PCP remained a predictor of increased mortality (P=0.02, HR=1.25). DISCUSSION/CONCLUSIONS:Among newly diagnosed lung cancer patients, lack of established PCP is associated with increased mortality. Hispanics and African Americans increasingly resided in PCSAs, suggesting race/ethnicity mortality differences may be mediated by primary care shortage. Patients without PCPs had worse health outcomes. Effective health policy efforts to reduce mortality in lung cancer patients must include approaches to improve primary care access.

PURPOSE:The extent of medical trainees' engagement in scholarly medical education publication is not well described. This study sought to quantify the prevalence of medical student- and resident-authored medical education publications over 15 years, a benchmark essential for understanding current and future trends in trainee scholarship. METHOD:Of 91 identified journals, 16 met inclusion criteria as indexed general medical education journals. Only Academic Medicine provided complete author role information, allowing identification of medical student and resident authors. The authors retrospectively compiled and analyzed citation records from Academic Medicine from 2002 to 2016, tracking trainee authorship, author position, and publication type. RESULTS:A total of 6,280 publications were identified, of which 4,635 publications, by 16,068 authors, met inclusion criteria. Trainees were 6.0% (966/16,068) of all authors and authored 14.5% (673/4,635) of all publications. Trainee authorship rates varied by publication type: Trainees authored 33.3% (160/480) of medical humanities publications versus 6.9% (27/392) of commentaries. From 2002-2004 to 2014-2016, the proportion of authors who were trainees increased from 3.9% (73/1,853) to 7.1% (330/4,632) (P < .001 for trend). Over the same period, the percentage of trainee-authored publications increased: 9.4% (58/620) to 18.8% (225/1,199) (P < .001 for trend), driven primarily by increased trainee first authorship. CONCLUSIONS:Trainees constitute a small but growing proportion of authors and authored publications in Academic Medicine. Further work is needed to understand what trainee-, institutional-, and journal-level factors contribute to this trend, and whether similar increases in trainee authorship are occurring in other journals and fields.

BACKGROUND:Race, ethnicity and socio-economic status impact clinical outcomes in inflammatory bowel disease (IBD) patients. However, their impact on disability has not been studied. AIM/OBJECTIVE:To determine the association between race, ethnicity and socio-economic factors with disability in IBD, using the validated IBD disability index (IBD-DI). METHODS:Ambulatory IBD patients were enrolled at five academic centres participating in the New York Crohn's and Colitis Organization. We assessed the IBD-DI, and collected clinical and socio-economic data. Factors associated with moderate-to-severe disability (IBD-DI score > 35) on univariable analysis were tested in multivariable models with adjusted odds ratios (aOR) and 95% confidence intervals (CI) reported. RESULTS:In this study, 323 patients (57.3% CD, 51.4% female) were enrolled; 17.7% were Hispanic, 17% were non-Hispanic black, 56.0% were non-Hispanic Caucasian and 9.3% belonged to non-Hispanic non-black minority races. However, 39.0% of patients were publicly insured and 38.4% of patients had low annual household income (<$50 000). 100 (31.0%) patients reported moderate-to-severe disability. On multivariable analysis, Hispanic ethnicity (aOR 2.7, 95% CI 1.3-5.6), non-Hispanic non-black minority race (aOR 3.5, 95% CI 1.3-8.9), public payer (aOR 2.1, 95% CI 1.1-4.0) and low annual household income (aOR 3.0, 95% CI 1.7-5.4) were associated with moderate-to-severe disability controlling for disease characteristics. CONCLUSIONS:IBD patients who are minorities, have public insurance, or low household income, are 2-3 times more likely to report moderate-to-severe disability independent of disease characteristics in the United States. Future studies are needed to study their complex relationship and to mitigate disability.

BACKGROUND:Insulin titration is typically done face-to-face with a clinician; however, this can be a burden for patients due to logistical issues associated with in-person clinical care. The Mobile Insulin Titration Intervention (MITI) used basic cell phone technology including text messages and phone calls to help patients with diabetes find their optimal basal insulin dose (OID). OBJECTIVE:To evaluate sociodemographic and clinical correlates of reaching OID, text message response rate, and days needed to reach OID. METHODS:Primary care providers referred patients to MITI and nurses delivered the program. Three multivariable regression models quantified relationships between various correlates and primary outcomes. RESULTS:The sample included 113 patients from 2 ambulatory clinics, with a mean age of 50 years (SD = 10), 45% female, 79% Hispanic, 43% unemployed, and 46% uninsured. In regression models, baseline fasting blood glucose (FBG) was negatively associated with odds of reaching OID and 100% text responses, and positively associated with days to reach OID, p < .05). CONCLUSIONS:Patients with higher baseline FBG levels were less successful across outcomes and may need additional supports in future mHealth diabetes programs. PRACTICAL IMPLICATIONS/CONCLUSIONS:Basic cell phone technology can be used to adjust patients' insulin remotely, thereby reducing logistical barriers to care.

To assess the possible clinical implication of Dragon's Blood in dermatology, a PubMed search was conducted using the keyword "Dragon's Blood," "Croton lechleri," and more. Dragon's Blood from C. lechleri is an Amazonian medicinal plant with a characteristic red sap. Its array of phytochemical action in preclinical studies include anti-inflammatory, antioxidant, antimicrobial, antifungal, and antineoplastic properties. Clinical studies reflect wound healing and antiviral properties. Although its popularity is rising in western medicine, C. lechleri offers limited use in dermatology and further investigation is necessary to gain further insight into its potential clinical implication.