NIOX VERO: Individualized Asthma Management in Clinical Practice

As we move toward an era of precision medicine, novel biomarkers of disease will enable the identification and personalized treatment of new endotypes. In asthma, fractional exhaled nitric oxide (FeNO) serves as a surrogate marker of airway inflammation that often correlates with the presence of sputum eosinophils. The increase in FeNO is driven by an upregulation of inducible nitric oxide synthase (iNOS) by cytokines, which are released as a result of type-2 airway inflammation. Scientific evidence supports using FeNO in routine clinical practice. In steroid-naive patients and in patients with mild asthma, FeNO levels decrease within days after corticosteroid treatment in a dose-dependent fashion and increase after steroid withdrawal. In difficult asthma, FeNO testing correlates with anti-inflammatory therapy compliance. Assessing adherence by FeNO testing can remove the confrontational aspect of questioning a patient about compliance and change the conversation to one of goal setting and ways to improve disease management. However, the most important aspect of incorporating FeNO in asthma management is the reduction in the risk of exacerbations. In a recent primary care study, reduction of exacerbation rates and improved symptom control without increasing overall inhaled corticosteroid (ICS) use were demonstrated when a FeNO-guided anti-inflammatory treatment algorithm was assessed and compared to the standard care. A truly personalized asthma management approach—showing reduction of exacerbation rates, overall use of ICS and neonatal hospitalizations—was demonstrated when FeNO testing was applied as part of the treatment algorithm that managed asthma during pregnancy. The aim of this article is to describe how FeNO and the NIOX VERO® analyzer can help to optimize diagnosis and treatment choices and to aid in the monitoring and improvement of clinical asthma outcomes in children and adults

The treatment of severe child aggression (TOSCA) study: Design challenges

<p>Abstract</p> <p>Background</p> <p>Polypharmacy (the concurrent use of more than one psychoactive drug) and other combination interventions are increasingly common for treatment of severe psychiatric problems only partly responsive to monotherapy. This practice and research on it raise scientific, clinical, and ethical issues such as additive side effects, interactions, threshold for adding second drug, appropriate target measures, and (for studies) timing of randomization. One challenging area for treatment is severe child aggression. Commonly-used medications, often in combination, include psychostimulants, antipsychotics, mood stabilizers, and alpha-2 agonists, which vary considerably in terms of perceived safety and efficacy.</p> <p>Results</p> <p>In designing our NIMH-funded trial of polypharmacy, we focused attention on the added benefit of a second drug (risperidone) to the effect of the first (stimulant). We selected these two drugs because their associated adverse events might neutralize each other (e.g., sleep delay and appetite decrease from stimulant versus sedation and appetite increase from antipsychotic). Moreover, there was considerable evidence of efficacy for each drug individually for the management of ADHD and child aggression. The study sample comprised children (ages 6-12 years) with both diagnosed ADHD and disruptive behavior disorder (oppositional-defiant or conduct disorder) accompanied by severe physical aggression. In a staged sequence, the medication with the least problematic adverse effects (stimulant) was openly titrated in 3 weeks to optimal effect. Participants whose behavioral symptoms were not normalized received additional double-blind medication, either risperidone or placebo, by random assignment. Thus children whose behavioral symptoms were normalized with stimulant medication were not exposed to an antipsychotic. All families participated in an empirically-supported parent training program for disruptive behavior, so that the actual comparison was stimulant+parent training versus stimulant+antipsychotic+parent training.</p> <p>Conclusions</p> <p>We hope that the resolutions of the challenges presented here will be useful to other investigators and facilitate much-needed research on child psychiatric polypharmacy.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00796302">NCT00796302</a></p

What contributes to patient and parent satisfaction with medication in the treatment of children with ADHD? A report on the development of a new rating scale

Satisfaction with medication is important in the evaluation of overall treatment outcome. There is a lack of consistent and validated rating scales for satisfaction with medication in ADHD, therefore comparison across studies is difficult. Here, we analyse the psychometric properties of the satisfaction with medication scale (SAMS), a new item-based questionnaire that assesses satisfaction with ADHD medication. Furthermore, we evaluate the predictive effect of ADHD symptoms and quality of life (QoL) on satisfaction. Data on satisfaction with Equasym XL® (methylphenidate) were collected in the OBSEER study using the parent (SAMS-P, n = 589) and patient (SAMS-S, n = 552) versions of the SAMS questionnaire. Internal consistency, item-total and cross-informant correlations, and the stability of satisfaction ratings over time were assessed. Satisfaction with medication scores were then correlated with ratings of ADHD symptoms and QoL. Rates of overall satisfaction with Equasym XL® among parents and children were high (>70%), as was internal consistency for both SAMS-P and SAMS-S (Cronbach’s alpha > 0.9). Similarly, item-total correlations were high (r = 0.71–0.90) for SAMS-P and medium–high (r = 0.57–0.77) for SAMS-S. Cross-informant correlations and the stability of satisfaction ratings were moderate (r = 0.54–0.59 and 0.48–0.60, respectively). ADHD symptom and QoL ratings were significantly negative and positive predictors of satisfaction, explaining 36–52% of satisfaction variance at the final visit. The results show that parent and patient satisfaction was high and could be assessed reliably with the new SAMS questionnaire. Parent and patient ratings were moderately correlated, and symptom severity, functional impairment and QoL were the most significant predictors of satisfaction

An observational study of once-daily modified-release methylphenidate in ADHD: quality of life, satisfaction with treatment and adherence

Attention deficit hyperactivity disorder (ADHD) impacts significantly on the quality of life (QoL) of patients and their families. Choice of therapy is increasingly influenced by treatment satisfaction and patient preference, with once-daily modified-release methylphenidate (MPH-MR) formulations offering clear benefits compared with immediate-release (IR) dosage forms. The effects of MPH-MR on QoL in ADHD have not been widely investigated and need more clarity in practice. The open-label OBSEER study evaluated the effectiveness and tolerability of Equasym XL®, a MPH-MR formulation, in routine practice. Children and adolescents (aged 6–17 years) with ADHD and attending school were included if Equasym XL® treatment was planned by the treating physician. Physicians, parents and patients completed questionnaires assessing QoL (KINDL; parent, child or adolescent versions), satisfaction with medication, adherence and treatment tolerability at baseline (Visit 1), 1–3 weeks (Visit 2) and 6–12 weeks (Visit 3) over a maximum 3-month observation period. Data from 822 consecutively referred patients were analysed. QoL and medication satisfaction increased from Visit 1 to Visit 3, with both patients and parents rating therapy with Equasym XL® as better than previous drug therapy. KINDL total score effect sizes were 0.67 (parents’ ratings), 0.52 (children’s ratings) and 0.51 (adolescents’ ratings; all p < 0.001). All KINDL subscores also increased: both parents and patients had the greatest improvement for school. Adherence to Equasym XL® was frequently rated as superior to prior treatment, particularly compared with MPH-IR repeated dosing. Treatment was generally well tolerated; approximately 3% of the patients discontinued treatment due to adverse events. Equasym XL® improved QoL compared with prior therapy, and resulted in good medication satisfaction and adherence in drug-naïve and previously treated patients

Fab five: pioneering sociocultural influence within the culture of basketball and American society

Dating back to when the inventor of the game, James Naismith, developed a mentoring relationship with John McClendon one of the African American pioneers in basketball (founder of the “fast-break”), there are countless examples of these intersections. Entering the college basketball culture as the most decorated recruiting class in National Collegiate Athletic Association basketball history, the University of Michigan Fab Five's legacy catalyzes a new era of American basketball culture. Gracefully talented, the Fab Five abruptly disrupted the institution of basketball, the National Collegiate Athletic Association, and the identity of basketball athletes globally. This paper presents a sociocultural exploration of the residual impact of the Fab Five's legacy. As authentic, confident, and culturally competent, the five young men intentionally resisted and acknowledged the intersections of race, culture, and class within the college basketball culture. We critically assess the evolution of basketball culture, grounded by the sociocultural experiences of the Fab Five, imprinting upon contemporary generations of college basketball programs and their player. Through these experiences, the Fab Five's success through conflict, during their short stint in college basketball and beyond their professional careers trailblazed a path for the modern-day basketball athlete. Known for their style of play, their expression of fashion on and off the court, and eagerness to talk smack, the Fab Five backed up their talk with performance. Their performance on and off the court, revolutionized the culture of basketball; Even more, American society. The Fab Five's legacy is the cultural catalyst for basketball culture on all levels

The Parametric, Psychological, Neuropsychological, and Neuroanatomical Properties of Self and World Evaluation

Background: As an individual moves from adolescence to adulthood, they need to form a new sense of self as their environment changes from a limited to a more expansive structure. During this critical stage in development the last dramatic steps of neural development occur and numerous psychiatric conditions begin to manifest. Currently, there is no measure that aids in the quantification of how the individual is adapting to, and conceptualizing their role in, these new structures. To fill this gap we created the Self and World Evaluation Expressions Test(SWEET). Method: Sixty-five young adults (20.6 years-old), 36 with a history of drug use, completed the SWEET. A factor analysis was performed on the SWEET and the resultant factors were correlated with psychological, neuropsychological, and neuroanatomical battery that included both T1-wieghted and diffusion tensor magnetic resonance imaging scans. Results: We derived four factors: Self, Social-Emotional, Financial-Intellectual, and Spirituality. While showing limited relationships to psychological and neuropsychological measures, both white matter integrity and gray matter density showed significant relationships with SWEET factors. Conclusions: These findings suggest that while individual responses may not be indicative of psychological or cognitive processes they may relate to changes in brain structure. Several of these structures, such as the negative correlation of the affective impact of world with the dorsal anterior corpus callosum white matter integrity have been observed in psychiatri

A common genetic network underlies substance use disorders and disruptive or externalizing disorders

Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders

Chiropractic care for paediatric and adolescent Attention-Deficit/Hyperactivity Disorder: A systematic review

<p>Abstract</p> <p>Background</p> <p>Psychostimulants are first line of therapy for paediatric and adolescent AD/HD. The evidence suggests that up to 30% of those prescribed stimulant medications do not show clinically significant outcomes. In addition, many children and adolescents experience side-effects from these medications. As a result, parents are seeking alternate interventions for their children. Complementary and alternative medicine therapies for behavioural disorders such as AD/HD are increasing with as many as 68% of parents having sought help from alternative practitioners, including chiropractors.</p> <p>Objective</p> <p>The review seeks to answer the question of whether chiropractic care can reduce symptoms of inattention, impulsivity and hyperactivity for paediatric and adolescent AD/HD.</p> <p>Methods</p> <p>Electronic databases (Cochrane CENTRAL register of Controlled Trials, Cochrane Database of Systematic reviews, MEDLINE, PsycINFO, CINAHL, Scopus, ISI Web of Science, Index to Chiropractic Literature) were searched from inception until July 2009 for English language studies for chiropractic care and AD/HD. Inclusion and exclusion criteria were applied to select studies. All randomised controlled trials were evaluated using the Jadad score and a checklist developed from the CONSORT (Consolidated Standards of Reporting Trials) guidelines.</p> <p>Results</p> <p>The search yielded 58 citations of which 22 were intervention studies. Of these, only three studies were identified for paediatric and adolescent AD/HD cohorts. The methodological quality was poor and none of the studies qualified using inclusion criteria.</p> <p>Conclusions</p> <p>To date there is insufficient evidence to evaluate the efficacy of chiropractic care for paediatric and adolescent AD/HD. The claim that chiropractic care improves paediatric and adolescent AD/HD, is only supported by low levels of scientific evidence. In the interest of paediatric and adolescent health, if chiropractic care for AD/HD is to continue, more rigorous scientific research needs to be undertaken to examine the efficacy and effectiveness of chiropractic treatment. Adequately-sized RCTs using clinically relevant outcomes and standardised measures to examine the effectiveness of chiropractic care verses no-treatment/placebo control or standard care (pharmacological and psychosocial care) are needed to determine whether chiropractic care is an effective alternative intervention for paediatric and adolescent AD/HD.</p