Clinical excellence in child and adolescent psychiatry: examples from the published literature.

There has been growing interest in the past century in improving understanding of the development and treatment of psychopathology of children, with increasing government funding of research in the past two decades. However, child and adolescent psychiatry excellence in clinical care has not been well-documented in the existing literature. This article provides examples of clinical excellence in paediatric mental health to supplement existing guidelines for the clinical practice of paediatric psychiatry. A review of the literature identified 204 unique peer-reviewed articles that were then further evaluated for applicability and relevance to the definition of clinical excellence as outlined by the Miller-Coulson Academy of Clinical Excellence (MCACE). Cases were then identified and selected for each domain of clinical excellence as they apply to child and adolescent psychiatry and to provide a model for patient care. KeypointsClinical excellence in child and adolescent psychiatry has not previously been defined or extensively documented.The Miller-Coulson Academy of Clinical Excellence (MCACE) has developed a systematic method to measuring excellence in clinical care and created a definition of clinical excellence.The MCACE defined the domains of clinical excellence as communication and interpersonal skills, professionalism and humanism, diagnostic acumen, skilful negotiation of the healthcare system, knowledge, scholarly approach to clinical practice, exhibiting a passion for patient care and modelling clinical excellence, and collaborating with investigators to advance science and discovery.There are numerous case examples in the literature that represent mastery in paediatric psychiatry in these areas.Clinicians in paediatric mental health will likely benefit from future research on evidence-based approaches to training and education in these domains of clinical excellence.

Safety considerations in the psychopharmacology of pediatric bipolar disorder.

Introduction: The standard of treatment of pediatric bipolar disorder (BPD) often requires life-long psychopharmacological management. Several pharmacological agents are approved by the US FDA for the treatment of pediatric BPD. However, each medication may cause adverse events (AEs). Provider awareness of AE profiles of common pharmacologic agents would serve to better inform patients and families in evaluating and selecting between treatment options. Areas covered: This review focuses on medications that, in our clinical experience, are commonly prescribed for youth with BPD and were evaluated in prospective clinical trials for the treatment of pediatric BPD. This paper highlights acute and long-term AEs described in these studies. Expert opinion: Most medications increase risk of AEs in youth with BPD. Treatment with lithium may lead to thyrotropin elevations, but generally does not cause significant weight gain. Divalproex may lead to weight gain; however, this finding was not consistent in comparison studies with lithium. Olanzapine, risperidone, quetiapine, and asenapine are associated with metabolic abnormalities and weight gain. Studies of ziprasidone, aripiprazole and lurasidone do not suggest significant metabolic AEs. More studies are needed to assess efficacy and safety of medications in managing pediatric BPD. Special focus on long-term maintenance trials is required to further identify long-term AEs in this population.

HEMERA Couples the Proteolysis and Transcriptional Activity of PHYTOCHROME INTERACTING FACTORs in Arabidopsis Photomorphogenesis.

Phytochromes (phys) are red and far-red photoreceptors that control plant development and growth by promoting the proteolysis of a family of antagonistically acting basic helix-loop-helix transcription factors, the PHYTOCHROME-INTERACTING FACTORs (PIFs). We have previously shown that the degradation of PIF1 and PIF3 requires HEMERA (HMR). However, the biochemical function of HMR and the mechanism by which it mediates PIF degradation remain unclear. Here, we provide genetic evidence that HMR acts upstream of PIFs in regulating hypocotyl growth. Surprisingly, genome-wide analysis of HMR- and PIF-dependent genes reveals that HMR is also required for the transactivation of a subset of PIF direct-target genes. We show that HMR interacts with all PIFs. The HMR-PIF interaction is mediated mainly by HMR's N-terminal half and PIFs' conserved active-phytochrome B binding motif. In addition, HMR possesses an acidic nine-amino-acid transcriptional activation domain (9aaTAD) and a loss-of-function mutation in this 9aaTAD impairs the expression of PIF target genes and the destruction of PIF1 and PIF3. Together, these in vivo results support a regulatory mechanism for PIFs in which HMR is a transcriptional coactivator binding directly to PIFs and the 9aaTAD of HMR couples the degradation of PIF1 and PIF3 with the transactivation of PIF target genes.

The importance of implementation strategy in scaling up Xpert MTB/RIF for diagnosis of tuberculosis in the Indian health-care system: a transmission model.

BACKGROUND: India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. METHODS AND FINDINGS: We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: -1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: -5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. CONCLUSIONS: The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary.

Modeling the impact of alternative strategies for rapid molecular diagnosis of tuberculosis in Southeast Asia.

Novel diagnostic tests hold promise for improving tuberculosis (TB) control, but their epidemiologic impact remains uncertain. Using data from the World Health Organization (2011-2012), we developed a transmission model to evaluate the deployment of 3 hypothetical TB diagnostic tests in Southeast Asia under idealized scenarios of implementation. We defined diagnostics by their sensitivity for smear-negative TB and proportion of patients testing positive who initiate therapy ("point-of-care amenability"), with tests of increasing point-of-care amenability having lower sensitivity. Implemented in the public sector (35% of care-seeking attempts), each novel test reduced TB incidence by 7%-9% (95% uncertainty range: 4%-13%) and mortality by 20%-22% (95% uncertainty range: 14%-27%) after 10 years. If also deployed in the private sector (65% of attempts), these tests reduced incidence by 13%-16%, whereas a perfect test (100% sensitivity and treatment initiation) reduced incidence by 20%. Annually detecting 20% of prevalent TB cases through targeted screening (70% smear-negative sensitivity, 85% treatment initiation) also reduced incidence by 19%. Sensitivity and point-of-care amenability are equally important considerations when developing novel diagnostic tests for TB. Novel diagnostics can substantially reduce TB incidence and mortality in Southeast Asia but are unlikely to transform TB control unless they are deployed actively and in the private sector.