tbuckley/cabot-search huggingface dataset:
Key Components of Effective Pediatric Integrated Mental Health Care Models
Authors: Juliet Yonek, Chuan-Mei Lee, Anna Harrison, Christina Mangurian, Marina Tolou-Shams
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Emerging evidence suggests that integrated care models are associated with improved mental health care access and outcomes for youths (children ≤12 years and adolescents 12-21 years) served in pediatric primary care settings. However, the key components of these complex models remain unexamined. <h3>Objective</h3> To identify and describe the key components of effective pediatric integrated mental health care models. <h3>Evidence Review</h3> The PubMed, Embase, PsycINFO, and Cochrane Controlled Register of Trials electronic databases were searched for relevant peer-reviewed articles published between January 1, 1985, and April 30, 2019. Articles were restricted to those published in the English language. Eligible articles reported original data on youths 17 years or younger, implemented an integrated mental health care model in a pediatric primary care setting, and assessed the model's association with primary outcomes (eg, mental health symptom severity) and secondary outcomes (eg, functional impairment and patient satisfaction). Articles that specified some degree of systematic coordination or collaboration between primary care and mental health professionals were included in the final review. Two independent reviewers extracted data on study design, model type, model components, level of integration, and outcomes. Study quality was assessed using the Jadad scale. Data were analyzed between January 1, 2018, and May 31, 2019. <h3>Findings</h3> Eleven randomized clinical trials involving 2190 participants were included. Three studies focused on youths with depression, 3 on youths with attention-deficit/hyperactivity disorder, and 5 on youths with behavioral disorders. Most studies (9 of 11) implemented either the collaborative care model (n = 3), a slightly modified version of the collaborative care model (n = 2), or colocated care (n = 4). The most commonly reported components of effective pediatric integrated mental health care models were population-based care, measurement-based care, and delivery of evidence-based mental health services; all 3 components were present in studies reporting clinical improvement of mental health symptoms. Other model components, such as treatment-to-target or team-based care, were common in studies reporting specific outcomes, such as functional impairment. <h3>Conclusions and Relevance</h3> This review is the first to date to systematically search and qualitatively synthesize information on the key components of effective pediatric integrated mental health care models. This knowledge may be especially useful for pediatric primary care administrators in the selection of an integrated care model for their setting.
The PI3-K/AKT/mTOR pathway as a target for breast cancer therapy
Authors: S. Di Cosimo, M. Scaltriti, D. Val, F. Rojo, M. Guzman, J. Jimenez, J. Seoane, J. Arribas, J. Baselga
Journal: Journal of Clinical Oncology (2007)

3511 Background: The PI3K/Akt/mTOR pathway is found dysregulated in multiple tumours, including breast cancer (BC). RAD001 is a recently developed drug which blocks mTOR. To study this compound’s anti-tumour effect and interactions with the aforementioned pathway, we set up a translational research program which integrates basic and clinical research data. Methods: The preclinal studies performed in BC cell lines and xenografts included the use of proliferation assays, western blot (WB), small interfering RNA and immunohistochemistry (IHC) analysis. The clinical studies consisted in a phase I study with escalating doses and collection of tumour biospies at different time points Results: Our first achievement was validating the antibodies used in WB and IHC and directed towards different components of the PI3K/Akt/mTOR pathway. We first reported that sensitivity to RAD001 correlated to basal levels of p-Akt. We then observed that RAD001 inhibits mTOR downstream, pS6 and eIF4G, but increases the levels of p-Akt, both in vitro and in patients’tumour biopsies. We demonstrated that knock down of the pS6 kinase mimics the effect of RAD001. Indeed, by combining the PI3K inhibitors and the genomic approch of p85 dominant negative vector, we demonstrated that RAD001 induced p-Akt is through PI3K. Besides the p-Akt induction we also found a RAD001 induction of IRS-1, the pivot mediator of the Insulin like Growth factor-1 Receptor (IGF-1R). We reported that RAD001 resulted in a prolonged activation of IRS-1 and in a sustained association with the p85 subunit of PI3K. Thus RAD001 disrupts an inhibitory mechanism impinging on the PI3K signalling, resulting in sustained activation of the IGF-1R pathway. Accordingly we demonstrated that combination of RAD001 with coumpounds directed against the IGF-1R, i.e. both IGF-1R tyrosine kinase inhibitors and monoclonal antibodies, prevented RAD001 induced p-Akt and resulted in a supradditive growth inhibitory effects both in vitro and in MCF-7 human BC derived xenografts.We are now conducting a phase I study with a monoclonal antibody directed at the IGF-1R that blocks IGF-1R signalling. Conclusions: Dual inhibition of mTOR and IGF-1R completely blocks the PI3K/Akt/mTOR pathway and provide a mechanistic-based combined approach. Clinical studies in BC patients are being planned. No significant financial relationships to disclose.
Abstract P337: Lifetime Burden of Traditional Cardiovascular Disease Risk Factors and Incidence of Cancer: The Bogalusa Heart Study
Authors: Alexander C Razavi, Tanika N Kelly, Jiang He, Camilo Fernandez, Tekada Ferguson, Xiaocheng Wu, Rupert Barshop, Lauren Maniscalco, Marie A Krousel-Wood, Seamus P Whelton, Roger S Blumenthal, Lydia A Bazzano
Journal: Circulation (2020)

Introduction: Cardiovascular disease (CVD) and cancer remain the leading causes of death globally. While these diseases have traditionally been regarded as separate entities, recent evidence points towards shared biological pathways, underlying a need to study CVD and cancer conjointly. We examined the association between CVD risk factors and the incidence of cancer over the life course in a biracial community-based cohort. Methods: The analysis included 1,368 participants of the Bogalusa Heart Study who had at least 3 measurements of CVD risk factors throughout life (57.6% women, 32.8% black, baseline age=10.5 + 3.6 years, median follow-up=38.2 years). CVD risk factors assessed included systolic and diastolic blood pressure, LDL-C, HDL-C, plasma glucose, serum triglycerides, and body mass index (BMI). Cancer cases were ascertained via the Louisiana Tumor Registry. Cox proportional hazards regression assessed the association between CVD risk factors and cancer incidence, adjusting for race, sex, smoking, and blood pressure-, lipid-, and glucose-lowering medications. Results: There were 88 incident cases of cancer, with breast (22.7%), cervical (11.4%), and prostate (9.1%) being the most highly represented cancers. BMI (kg/m 2 ) had the most robust association with incident cancer (HR=5.83, 95% CI: 2.24, 15.19; p=3.0x10 -4 ). We observed a strong association between annualized change in blood pressure per mmHg and hazard of all cancers (for systolic, HR=2.24, 95% CI: 1.50, 3.35; p&lt;0.0001 and diastolic, HR=4.86, 95% CI: 2.86, 8.27; p&lt;0.0001). Race and sex significantly modified the relationship of incident cancer with lipids and blood pressure, respectively ( Figure ). Conclusion: Subclinical increases in adiposity and blood pressure associate with an increased cancer risk, while HDL-C inversely associates with cancer risk, more consistently in women versus men and in blacks versus whites. Control of CVD risk factors beginning in childhood may lead to improved overall cancer prevention in the general population.
Olive Oil Consumption and Cardiovascular Risk in U.S. Adults
Authors: Marta Guasch-Ferré, Gang Liu, Yanping Li, Laura Sampson, JoAnn E. Manson, Jordi Salas-Salvadó, Miguel A. Martínez-González, Meir J. Stampfer, Walter C. Willett, Qi Sun, Frank B. Hu
Journal: Journal of the American College of Cardiology (2020)
Abstract MP14: Lower Cardiovascular Fitness is Associated With Higher C-Reactive-Protein-Related Cardiovascular Risk in Healthy Adolescents and Young Adults
Authors: Gregory S Troutman, David M Shipon, Michele A Fiorella, Daniella H Wong, Luis H Eraso
Journal: Circulation (2020)

Introduction: Inflammatory markers, such as C-reaction protein (CRP), have been shown to be highly associated with cardiovascular disease. However, it is unclear if baseline levels of cardiovascular fitness in young, healthy persons are related to inflammatory biomarkers who have not yet manifested cardiovascular disease. Methods: Data was compiled from the National Health and Nutrition Examination Survey (NHANES). Cardiovascular fitness level (low, moderate, high) was categorized by estimated VO2 max (with age/sex adjustment cut points). Associations with CRP-based cardiovascular risk were analyzed using ANOVA/Kruskal-Wallis and Chi-squared. Ordered logistic regression was employed to identify predictors of increasing CRP-based cardiovascular risk. To account for the complex survey design, all analyses were conducted using appropriate estimated weights following NHANES analytic guidelines. Results: 2,201 participants from 1999-2004 from ages 12-49 completed cardiovascular fitness testing and had full laboratory analysis. A sensitivity analysis was performed grouping participants into CRP-based cardiovascular risk categories (low &lt;1mg/L, moderate 1-3 mg/L, high &gt;3 mg/L) based on the 2003 AHA/CDC Scientific Statement. Increase in cardiovascular fitness category was associated with decrease in CRP-based cardiovascular risk (OR 0.83, 95% CI 0.75 to 0.91, p&lt;0.001). The relationship was strengthened (OR 0.77, 95% CI 0.68 to 0.87, p&lt;0.001) when adjusting for age, sex, BMI, diabetes, and smoking. Conclusions: In a sample representative of the United States civilian non-institutionalized population, lower levels of cardiovascular fitness were associated with increased inflammatory biomarkers related to cardiovascular risk, even with adjustment for fitness-related covariates. Further studies will help us to understand the therapeutic role on VO2 max and cardiovascular fitness improvement in reducing atherosclerosis-related inflammation.
Abstract P287: The Rising Trend of Hypertension in Pediatric and Adolescent Patients
Authors: Rodrigo Aguilar, Kanaan Mansoor, Zachary Higginbotham, Colin McCorkle, Elizabeth Saunders
Journal: Circulation (2020)

Background: A concerning trend in society today is the development of lifelong diseases, such as hypertension, at an early age. The sequelae of prolonged uncontrolled hypertension are devastating and include the development of vascular disease, kidney disease, and ultimately increased mortality among other things. Though it is thought that today’s children are affected by chronic conditions such as hypertension more frequently than in previous generations, this has not been thoroughly analyzed. This study aimed to evaluate incidence of hypertension, as well as mortality rates in patients with a diagnosis of hypertension in 2 different hospitalized patient populations, children ages 0-12 and adolescents ages 13-18 over the course of a 7-year period from 2005-2012. Methods: An NIS database was queried from 2005-2012. Exclusion criteria included patients greater than &gt;18 years old and patients with secondary causes of hypertension, as this study was looking at essential hypertension only. Analysis was performed via chi square or t test with SAS 9.4, all values were significant when p&lt;0.05. Results: As per our analysis, the incidence of hypertension in the pediatric populations had a decline in 2006, but since then it has been on the rise while hypertension in the adolescent age group showed a consistent upward trend. Furthermore, our data also revealed that the incidence of hypertension was highest in the Caucasian race in comparison to the other races, with a p-value of &lt; 0.001. Lastly, the likelihood of mortality in hospitalized pediatric populations with a diagnosis of hypertension was 2.03 while in adolescents it was 0.84 with a p value of &lt;0.001. Discussion: It is thought that the increase in incidence of hypertension in these patient populations could potentially be due to the high sodium, high fat, and low fiber diets of most American citizens. It is well documented that obesity is an epidemic in the youth of America and we believe an analysis of the correlation between hypertension and obesity in these patient populations is warranted, as it is possible that dietary modification in these patients could result in a lower incidence of hypertension, and thus lower mortality and morbidity rates.
Abstract P413: Latent Class Trajectory Modeling Identifies Distinct Clinical Phenotypes in a Cohort of Patients With Elevated Troponin Levels
Authors: Michael C Wang, Lucia Petito, Anna Pawlowski, Daniel Schneider, Lowie Van Assche, Donald M Lloyd-jones, Matthew J Feinstein
Journal: Circulation (2020)

Introduction: Clinicians widely use cardiac troponins I and T, sensitive and specific biomarkers of myocardial damage, as diagnostic criteria for myocardial infarction (MI). A common approach, dichotomizing based on whether troponin levels meet thresholds for MI, may miss meaningful heterogeneity in degree and pattern of troponin elevation, with wider clinical implications. Hypothesis: Using latent class trajectory modeling (LCTM) with patients’ patterns of troponin elevations will yield trajectories that represent clinically and prognostically distinct groups of patients. Methods: We used Northwestern Medicine’s Enterprise Data Warehouse to identify patients with at least 3 troponin measurements of which at least one was elevated during their inpatient stay. We built a LCTM to capture troponin trajectories from 13,432 patients with 65,162 measurements since 2000, using Bayesian Information Criterion to select the final model (# of classes varied from 3-7). We then described the clinical and prognostic factors associated with trajectory class membership. Results: LCTM identified 3 troponin trajectories: stable low (77.3%), moderate rise (9.5%), and severe rise-fall (13.2%). The average posterior probability of assignment was &gt;0.95 for all classes. The low group had the most comorbidities vs moderate/severe groups, including cancer (21.9% vs 13.9%/11.3%), heart failure (12.6% vs 8.9%/7.5%), and COPD (15.0% vs 11.8%/10.1%). The moderate/severe rising trajectories had a greater rate of clinically-diagnosed MI than the stable group (34.5%/44.1% vs 5.6%), with relatively more ST-elevation MI in the severe group (19.8% vs 5.3%) and Non-ST-elevation MI in the moderate group (29.3% vs 24.3%). One-year mortality was greatest in the low group vs moderate/severe groups (25.5% vs 21.4%/18.8%). Conclusions: In a cohort of hospitalized patients with elevated troponins, LCTM identified 3 distinct, clinically interpretable troponin trajectories which were associated with differing clinical phenotypes.
Abstract MP28: Egg Consumption is Positively Associated With Ischemic Stroke: The Million Veteran Program
Authors: Luc Djousse, Yuk-lam HO, Timothy Treu, Hugo J Aparicio, Sudha Seshadri, Kelly Cho, Peter W Wilson, J. M Gaziano
Journal: Circulation (2020)

Background: While observational data suggest a higher risk of coronary artery disease with frequent egg consumption, only limited and inconsistent data are available on the relation of egg consumption with stroke. Objective: To test the hypothesis that egg consumption is positively associated with the incidence of ischemic stroke among Veterans. Methods: The Million Veteran Program is an ongoing observational study designed to study genetic determinants of chronic diseases among Veterans (2011 to now). Egg consumption was self-reported at baseline using validated Willett food questionnaires. We used ICD 9 codes 433, 434, 436, 437.0, and 437.6 and ICD 10 codes I63, I65, I66, I67.2, I67.6 and I67.8 to identify ischemic stroke using previously validated algorithm and multivariable Cox proportional hazard model to estimate relative risks. Results: A total of 234,032 Veterans provided data on egg consumption and were free of stroke at baseline. Mean age at baseline was 65.6 (SD: 11.7) years and 91.6% (214,373 of 234,032) were men. Median egg consumption was 2-4 eggs per week. During a mean follow up of 3.2 years, a total of 5,747 new cases of fatal or non-fatal acute ischemic stroke occurred. Crude incidence rates for acute ischemic stroke were 6.5, 7.2, 7.1, 7.4, 8.0, and 8.3 cases per 1000 person-years for egg consumption of &lt;1/month, 1-3/month, 1/week, 2-4/week, 5-6/week, and ≥ 1/day, respectively. Corresponding adjusted hazard ratios (95% CI) were 1.00 (ref), 1.10 (0.97-1.25), 1.10 (0.97-1.25), 1.13 (1.00 -1.27), 1.19 (1.04-1.37), and 1.25 (1.09-1.44) controlling for age, sex, ethnicity, body mass index, education, smoking, alcohol intake, and overall diet quality (p linear trend 0.0007). The egg-stroke relation was not modified by body mass index, sex, or diabetes status. Conclusion: Egg consumption is positively associated with incidence of acute ischemic stroke among Veterans.
Circulatory miRNAs as Novel Non-Invasive Biomarkers for the Diagnosis of Coronary Artery Disease in Patients with and Without Diabetes Mellitus
Authors: Dinesh Kumar, Rajiv Narang, Vishnubhatla Sreenivas, Vandana Rastogi, Jagriti Bhatia, Daman Saluja, Kamna Srivastava
Journal: Metabolism (2020)
Clinical characteristics of severe acute respiratory syndrome coronavirus 2 reactivation
Authors: Guangming Ye, Zhenyu Pan, Yunbao Pan, Qiaoling Deng, Liangjun Chen, Jin Li, Yirong Li, Xinghuan Wang
Journal: Journal of Infection (2020)

ObjectivesPrevious studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. However, limited data was available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reactivation. This study aimed to evaluate the clinical characteristics of the SARS-CoV-2 reactivation.MethodsClinical records, laboratory results, and chest CT scans were retrospectively reviewed for 55 patients with laboratory-confirmed COVID-19 pneumonia (i.e., with throat swab samples that were positive for SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan. 8 to Feb. 10, 2020.ResultsAll 55 patients had a history of epidemiological exposure to COVID-19, and 5 (9%) patients who discharged from hospital presented with SARS-CoV-2 reactivation. Among the 5 reactivated patients, other symptoms were also observed, including fever, cough, sore throat, and fatigue. One of the 5 patients had progressive lymphopenia (from 1.3 to 0.56 × 109 cells per L) and progressive neutrophilia (from 4.5 to 18.28 × 109 cells per L). All 5 reactivated patients presented normal aminotransferase levels. Throat swab samples from the 5 reactivated patients were tested for SARS-CoV-2, indicating all positive for the virus.ConclusionsFindings from this small group of cases suggested that there was currently evidence for reactivation of SARS-CoV-2 and there might be no specific clinical characteristics to distinguish them.
Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression
Authors: Susan Swindells, Jaime-Federico Andrade-Villanueva, Gary J. Richmond, Giuliano Rizzardini, Axel Baumgarten, Mar Masiá, Gulam Latiff, Vadim Pokrovsky, Fritz Bredeek, Graham Smith, Pedro Cahn, Yeon-Sook Kim, Susan L. Ford, Christine L. Talarico, Parul Patel, Vasiliki Chounta, Herta Crauwels, Wim Parys, Simon Vanveggel, Joseph Mrus, Jenny Huang, Conn M. Harrington, Krischan J. Hudson, David A. Margolis, Kimberly Y. Smith, Peter E. Williams, William R. Spreen
Journal: New England Journal of Medicine (2020)

Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence.In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm.Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group.Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).