The SEARCH for Diabetes in Youth Study: Rationale, Findings, and Future Directions

The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions

Migration Status in Relation to Clinical Characteristics and Barriers to Care Among Youth with Diabetes in the US

Migration status and the accompanying diversity in culture, foods and family norms, may be an important consideration for practitioners providing individualized care to treat and prevent complications among youth with diabetes. Approximately 20% of youth in the US have ≥ 1 foreign-born parent. However, the proportion and characteristics of youth with diabetes and ≥ 1 foreign-born parent have yet to be described. Study participants (n = 3,086) were from SEARCH for Diabetes in Youth, a prospective multi-center study in the US. Primary outcomes of interest included HbA1c, body mass index and barriers to care. Multivariable analyses were carried out using logistic regression and analysis of covariance. Approximately 17% of participants with type 1 diabetes (T1D) and 22% with type 2 diabetes (T2D) had ≥ 1 foreign-born parent. Youth with T1D and ≥ 1 foreign-born parent were less likely to have poor glycemic control [adjusted odds ratio (OR) (95% confidence interval): 0.70 (0.53, 0.94)]. Among youth with T2D, those with ≥ 1 foreign-born parent had lower odds of obesity [adjusted OR (95% CI): 0.35 (0.17, 0.70)]. This is the first study to estimate the proportion and characteristics of youth with diabetes exposed to migration in the US. Research into potential mechanisms underlying the observed protective effects is warranted

Trends in Incidence of Type 1 Diabetes Among Non-Hispanic White Youth in the U.S., 2002–2009

The SEARCH for Diabetes in Youth Study prospectively identified youth aged <20 years with physician-diagnosed diabetes. Annual type 1 diabetes (T1D) incidence per 100,000 person-years (95% CI) overall, by age-group, and by sex were calculated for at-risk non-Hispanic white (NHW) youth from 2002 through 2009. Joinpoint and Poisson regression models were used to test for temporal trends. The age- and sex-adjusted incidence of T1D increased from 24.4/100,000 (95% CI 23.9–24.8) in 2002 to 27.4/100,000 (26.9–27.9) in 2009 (P for trend = 0.0008). The relative annual increase in T1D incidence was 2.72% (1.18–4.28) per year; 2.84% (1.12–4.58) per year for males and 2.57% (0.68–4.51) per year for females. After adjustment for sex, significant increases were found for youth aged 5–9 years (P = 0.0023), 10–14 years (P = 0.0008), and 15–19 years (P = 0.004) but not among 0–4-year-olds (P = 0.1862). Mean age at diagnosis did not change. The SEARCH study demonstrated a significant increase in the incidence of T1D among NHW youth from 2002 through 2009 overall and in all but the youngest age-group. Continued surveillance of T1D in U.S. youth to identify future trends in T1D incidence and to plan for health care delivery is warranted

6. The Arithmetic of Fair Dealing at the Supreme Court of Canada

In the 2012 Supreme Court of Canada copyright cases, the Court found an opportunity to redefine the law of fair dealing in Canada. While the Court acknowledged that fair dealing is a question of fact, and thereby properly adjudicated by triers of fact like the Copyright Board of Canada, the Court stepped in to revisit the facts all over again. When compared to its common law counterparts like the UK and the US, Canada stands alone in its willingness to rehear fair dealing cases, which are a m..

Allattamento materno in Terapia Intensiva Neonatale: descrizione di un cambiamento

In questo articolo vengono presentati i risultati di un progetto per promuovere l’allattamento al seno in una terapia intensiva neonatale. Nel primo semestre del 1998 e del 2000 sono stati raccolti i dati su tutti i neonati ammessi nei primi 3 giorni di vita. Dei 100 ammessi nel 1998 sono stati raccolti i dati su 76 e su 50/61 ammessi nel 2000. Le informazioni sul tipo di allattamento sono state raccolte tramite intervista telefonica alle madri, nei primi mesi dell’anno successivo. Il programma offerto consisteva in una stanza per la raccolta del latte, con tiralatte elettrici professionali, cuscini e poltrone per migliorare il comfort; un corso di formazione sulla promozione dell’allattamento al seno per le infermiere e la disponibilità di una consulenza prima del ricovero e dopo la dimissione. I neonati erano comparabili per le principali caratteristiche. Non ci sono stati cambiamenti nella percentuale di madri che hanno cominciato a raccogliere il latte nei primi 3 giorni (dal 72 all’80%). È aumentato il numero di raccolte al giorno: più di 4 volte per il 62% delle madri nel 2000, rispetto a meno del 35% nel 1998; e la durata della raccolta, da 21±24 giorni nel 1998 a 42±44 nel 2000 (p=0.01). Come anche è aumentato il numero di neonati allattati al seno e/o con latte materno, dal 21.2% nel 1998 al 64% nel 2000 (p=0.001). I cambiamenti osservati sono incoraggianti ma ancora non ottimali. Occorre continuare ad investire su questa area con differenti strategie (materiali informativi, nuove tecniche o per migliorare la raccolta del latte) per poter continuare a migliorare i risultati

Chimeric Antigen Receptor Immunotherapy for Solid Tumors: Choosing the Right Ingredients for the Perfect Recipe

Chimeric antigen receptor T cell therapies are revolutionizing the clinical practice of hematological tumors, whereas minimal progresses have been achieved in the solid tumor arena. Multiple reasons have been ascribed to this slower pace: The higher heterogeneity, the hurdles of defining reliable tumor antigens to target, and the broad repertoire of immune escape strategies developed by solid tumors are considered among the major ones. Currently, several CAR therapies are being investigated in preclinical and early clinical trials against solid tumors differing in the type of construct, the cells that are engineered, and the additional signals included with the CAR constructs to overcome solid tumor barriers. Additionally, novel approaches in development aim at overcoming some of the limitations that emerged with the approved therapies, such as large-scale manufacturing, duration of manufacturing, and logistical issues. In this review, we analyze the advantages and challenges of the different approaches under development, balancing the scientific evidences supporting specific choices with the manufacturing and regulatory issues that are essential for their further clinical development

Improvement of Resveratrol Permeation through Sublingual Mucosa: Chemical Permeation Enhancers versus Spray Drying Technique to Obtain Fast-Disintegrating Sublingual Mini-Tablets

Resveratrol (RSV) is a natural polyphenol with several interesting broad-spectrum pharmacological properties. However, it is characterized by poor oral bioavailability, extensive first-pass effect metabolism and low stability. Indeed, RSV could benefit from the advantage of the sublingual route of administration. In this view, RSV attitudes to crossing the porcine sublingual mucosa were evaluated and promoted both by six different chemical permeation enhancers (CPEs) as well as by preparing four innovative fast-disintegrating sublingual mini-tablets by spray drying followed by direct compression. Since RSV by itself exhibits a low permeation aptitude, this could be significantly enhanced by the use of CPEs as well as by embedding RSV in a spray-dried powder to be compressed in order to prepare fast-disintegrating mini-tablets. The most promising observed CPEs (menthol, lysine and urea) were then inserted into the most promising spray-dried excipients’ compositions (RSV-B and RSV-C), thus preparing CPE-loaded mini-tablets. However, this procedure leads to unsatisfactory results which preclude the possibility of merging the two proposed approaches. Finally, the best spray-dried composition (RSV-B) was further evaluated by SEM, FTIR, XRD and disintegration as well as dissolution behavior to prove its effectiveness as a sublingual fast-disintegrating formulation