Methotrexate polyglutamates as a potential marker of adherence to long-term therapy in children with juvenile idiopathic arthritis and juvenile dermatomyositis:an observational, cross-sectional study

Introduction: Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. The present study demonstrates the feasibility of using methotrexate polyglutamates (MTXPGs) as a biomarker to measure adherence to MTX treatment in children with JIA and JDM. Methods: Data were collected prospectively from a cohort of 48 children (median age 11.5 years) who received oral or subcutaneous (SC) MTX therapy for JIA or JDM. Dried blood spot samples were obtained from children by finger pick at the clinic or via self- or parent-led sampling at home, and they were analysed to determine the variability in MTXPG concentrations and assess adherence to MTX therapy. Results: Wide fluctuations in MTXPG total concentrations (>2.0-fold variations) were found in 17 patients receiving stable weekly doses of MTX, which is indicative of nonadherence or partial adherence to MTX therapy. Age (P = 0.026) and route of administration (P = 0.005) were the most important predictors of nonadherence to MTX treatment. In addition, the study showed that MTX dose and route of administration were significantly associated with variations in the distribution of MTXPG subtypes. Higher doses and SC administration of MTX produced higher levels of total MTXPGs and selective accumulation of longer-chain MTXPGs (P < 0.001 and P < 0.0001, respectively). Conclusions: Nonadherence to MTX therapy is a significant problem in children with JIA and JDM. The present study suggests that patients with inadequate adherence and/or intolerance to oral MTX may benefit from SC administration of the drug. The clinical utility of MTXPG levels to monitor and optimise adherence to MTX in children has been demonstrated. Trial registration: ISRCTN Registry identifier: ISRCTN93945409. Registered 2 December 2011.

Clinical characteristics of unilateral myopic anisometropia in a juvenile optometric practice population

Purpose: A retrospective study of longitudinal case histories, undertaken to establish the clinical and statistical characteristics of unilateral myopic anisometropia (UMA) amongst the juvenile and adolescent population at an optometric practice, is reported. UMA was defined as that specific refractive state where an unequivocally myopic eye is paired with a 'piano' [spherical equivalent refraction, (SER) = ±0.25 Dioptres (D)] companion eye. Methods: The clinical records of all patients aged <19 years on file at an established independent optometric practice were categorised as 'myopic' (SER ≤-0.50 D), 'hypermetropie' (≥+0.75 D) or 'emmetropic' (≥-0.37≤+0.62 D). Subsequently all juvenile patients matching the UMA criterion, together with a case-matched group of bilaterally myopic individuals, were selected as the comparative study populations. Results: A total of 14.4% (n = 21 of 146) of the juvenile myopic case histories were identified as cases of UMA. More than half of these UMA cases emerged between the ages of 11.5 and 13.5 years. There was a marked female gender bias. The linear gradient of the age-related mean refractive trend in the myopic eye of the UMA population was not statistically significantly different (p > 0.1) to that fitted to the ametropic progression recorded in either eye of the case-matched population of young bilateral myopes; uniquely the slope associated with the companion eye of UMA cases was statistically significantly (p < 0.025) less steep. Compared with bilateral myopes fewer cases of UMA required a refractive correction to relieve visual or asthenopic symptoms, and this initial correction was dispensed on average 1 year later (at age 12.7 years) in UMA patients. Conclusions: Individuals identified as demonstrating clinically-defined UMA can be considered as distinct but functionally normal cases on the continuum of human refractive error. However, any unilaterally-acting determining factor(s) underlying the genesis of the condition remain obscure. © 2004 The College of Optometrists.

Understanding the factors that affect the severity of juvenile stranger sex offenses

Understanding factors that affect the severity of a juvenile-stranger sexual assault has implications for crime prevention, and potentially, the assessment and treatment of juvenile sex offenders. This study investigated how victim characteristics and the number of suspects affected the use of physical violence and weapons and the occurrence of penetration in 495 allegations of sexual assault committed by juveniles against strangers. Statistically significant interactions between victim age and gender were found for occurrence of penetration and use of violence. Differences in offense characteristics were also found between offenses with varying victim-suspect age differences. When comparing the rate of penetration in the presence and absence of violence, little change was observed for lone suspects. However, the rate of penetration increased significantly for groups in the presence of physical violence, suggesting that violence in this context may be more expressive than instrumental. Theoretical explanations and practical implications are considered.

Medicines optimisation for young people with juvenile arthritis and other long-term conditions:system-level barriers to engagement

To explore the views of pharmacy and rheumatology stakeholders about system-related barriers to medicines optimisation activities with young people with long-term conditions. A three-phase consensus-building study comprising (1) focus groups with community and hospital pharmacists; (2) semi-structured telephone interviews with lay and professional adolescent rheumatology stakeholders and pharmacy policymakers, and (3) multidisciplinary discussion groups with community and hospital pharmacists and rheumatology staff. Qualitative verbatim transcripts from phases 1 and 2 were subjected to framework analysis. Themes from phase 1 underpinned a briefing for phase 2 interviewees. Themes from phases 1 and 2 generated elements of good pharmacy practice and current/future pharmacy roles for ranking in phase 3. Results from phase 3 prioritisation and ranking exercises were captured on self-completion data collection forms, entered into an Excel spreadsheet and subjected to descriptive statistical analysis. Institutional ethical approval was given by Aston University Health and Life Sciences Research Ethics Committee. Four focus groups were conducted with 18 pharmacists across England, Scotland and Wales (7 hospital, 10 community and 1 community/public health). Fifteen stakeholders took part in telephone interviews (3 pharmacist commissioners; 2 pharmacist policymakers; 2 pharmacy staff members (1 community and 1 hospital); 4 rheumatologists; 1 specialist nurse, and 3 lay juvenile arthritis advocates). Twenty-five participants took part in three discussion groups in adolescent rheumatology centres across England and Scotland (9 community pharmacists; 4 hospital pharmacists; 6 rheumatologists; 5 specialist nurses, and 1 physiotherapist). In all phases of the study, system-level issues were acknowledged as barriers to more engagement with young people and families. Community pharmacists in the focus groups reported that opportunities for engaging with young people were low if parents collected prescriptions alone, which was agreed by other stakeholders. Moreover, institutional/company prescription collection policies – an activity largely disallowed for a young person under 16 without an accompanying parent - were identified by hospital and community pharmacists as barriers to open discussion and engagement. Few community pharmacists reported using Medicines Use Review (England/Wales) or Chronic Medication Service (Scotland) as a medicines optimisation activity with young people; many were unsure about consent procedures. Despite these limitations, rheumatology stakeholders ranked highly the potential of pharmacists empowering young people with general health care skills, such as repeat prescription ordering. The pharmacy profession lacks vision for its role in the care of young people with long-term conditions. Pharmacists and rheumatology stakeholders identified system-level barriers to more engagement with young people who take medicines regularly. We acknowledge that the modest number of participants may have had a specific interest and thus bias for the topic, but this underscores their frank admission of the challenges. Professional guidance and policy, practice frameworks and institutional/company policies must promote flexibility for pharmacy staff to recognise and empower young people who are able to give consent and take responsibility for medicines activities. This will increase mutual confidence and trust, and foster pharmacy’s role in teaching general health care skills. In this way, pharmacists will be able to build long-term relationships with young people and families.