The association between anticholinergic medication burden and health related outcomes in the ‘oldest old’: A systematic review of the literature

Background: Increased exposure to anticholinergic medication is problematic, particularly in those aged 80 years and older.

Objective: The aim of this systematic review was to identify tools used to quantify anticholinergic medication burden and determine the most appropriate tool for use in longitudinal research, conducted in those aged 80 years and older.

Methods: A systematic literature search was conducted across six electronic databases to identify existing tools. Data extraction was conducted independently by two researchers; studies describing the development of each tool were also retrieved and relevant data extracted. An assessment of quality was completed for all studies. Tools were assessed in terms of their measurement of the association between anticholinergic medication burden and a defined set of clinical outcomes, their development and their suitability for use in longitudinal research; the latter was evaluated on the basis of criteria defined as the key attributes of an ideal anticholinergic risk tool.

Results: In total, 807 papers were retrieved, 13 studies were eligible for inclusion and eight tools were identified. Included studies were classed as ‘very good’ or ‘good’ following the quality assessment analysis; one study was unclassified. Anticholinergic medication burden as measured in studies was associated with impaired cognitive and physical function, as well as an increased frequency of falls. The Drug Burden Index (DBI) exhibited most of the key attributes of an ideal anticholinergic risk tool.

Conclusion: This review identified the DBI as the most appropriate tool for use in longitudinal research focused on older people and their exposure to anticholinergic medication burden.

Chronic inflammation in CF airways - a persistent issue for A20

Cystic Fibrosis (CF) is characterised by prolonged and exaggerated airways inflammation. Despite recent developments to overcome the underlying functional defect in CFTR (cystic fibrosis transmembrane conductance regulator), there is still an unmet need to reduce the inflammatory response. The NF-kB regulator A20 is a key target to normalise the inflammatory response and is reduced in CF. Here, we describe the plethora of functions of A20 as they apply to innate immune function within the airways. Pharmacological compounds can enhance A20 mRNA and protein expression, but we observed a blunted effect in CF primary epithelial cells. In CF cells pre-treatment with gibberellic acid (GA3) shows anti-inflammatory effects only in some patients. We show that cells with higher basal p38 expression respond with an increase in pro-inflammatory cytokines. Furthermore, all CF PNECs show increased p38 mRNA when stimulated in the presence of GA3. Our results suggest that those patients may benefit from therapeutics targeting p38.

Phonic skills mediate improved literacy outcomes in at-risk primary school children: results from the Ready-to-Learn Programme

Background
Learning to read is a key goal during primary school: reading difficulties may curtail children’s learning trajectories. Controversy remains regarding what types of interventions are effective for children at risk for academic failure, such as children in disadvantaged areas. We present data from a complex intervention to test the hypothesis that phonic skills and word recognition abilities are a pivotal and specific causal mechanism for the development of reading skills in children at risk for poorer literacy outcomes.
Method
Over 500 pupils across 16 primary schools took part in a Cluster Randomised Controlled Trial from school year 1 to year 3. Schools were randomly allocated to the intervention or the control arm. The intervention involved a literacy-rich after-school programme. Children attending schools in the control arm of the study received the curriculum normally provided. Children in both arms completed batteries of language, phonic skills, and reading tests every year. We used multilevel mediation models to investigate mediating processes between intervention and outcomes.
Findings
Children who took part in the intervention displayed improvements in reading skills compared to those in the control arm. Results indicated a significant indirect effect of the intervention via phonics encoding.
Discussion
The results suggest that the intervention was effective in improving reading abilities of children at risk, and this effect was mediated by improving children’s phonic skills. This has relevance for designing interventions aimed at improving literacy skills of children exposed to socio-economic disadvantage. Results also highlight the importance of methods to investigate causal pathways from intervention to outcomes.

The impact of childhood residential mobility on mental health outcomes in adolescence and early adulthood: a record linkage study.

Background Understanding the causes of poor mental health in early childhood and adolescence is important as this can be a significant determinant of mental well-being in later years. One potential and relatively unexplored factor is residential mobility in formative years. Previous studies have been relatively small and potentially limited due to methodological issues. The main aim of this study was to investigate the relationship between early residential instability and poor mental health among adolescents and young adults in Northern Ireland.

Methods A Census-based record linkage study of 28% of children aged 0–8 years in 2001 in Northern Ireland (n=49 762) was conducted, with six monthly address change assessments from health registration data and self-reported mental health status from the 2011 Census. Logistic regression models were built adjusting for socioeconomic status (SES), household composition and marital dissolution.

Results There was a graded relationship between the number of address changes and mental ill-health (adjusted OR 3.67, 95% CIs 2.11 to 6.39 for 5 or more moves). This relationship was not modified by SES or household composition. Marital dissolution was associated with poor mental health but did not modify the relationship between address change and mental health (p=0.206). There was some indication that movement after the age of five was associated with an increased likelihood of poor mental health.

Conclusions This large study clearly confirms the close relationship between address change in early years and later poor mental health. Residential mobility may be a useful marker for children at risk of poorer mental health in adolescence and early adulthood

Clinical Outcomes in 3343 Children and Adults with Rheumatic Heart Disease from 14 Low and Middle Income Countries: 2-Year Follow-up of the Global Rheumatic Heart Disease Registry (the REMEDY study)

BACKGROUND: -There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease (RHD) or information on their predictors. We report the two year follow-up of individuals with RHD from 14 low and middle income countries in Africa and Asia.

METHODS: -Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for two years to assess mortality, congestive heart failure (CHF), stroke or transient ischemic attack (TIA), recurrent acute rheumatic fever (ARF), and infective endocarditis (IE).

RESULTS: -Vital status at 24 months was known for 2960 (88.5%) patients. Two thirds were female. Although patients were young (median age 28 years, interquartile range 18 to 40), the two year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.80-3.11), CHF (HR 2.16, 95% CI 1.70-2.72), New York Heart Association functional class III/IV (HR 1.67, 95% CI 1.32-2.10), atrial fibrillation (AF) (HR 1.40, 95% CI 1.10-1.78) and older age (HR 1.02, 95% CI 1.01-1.02 per year increase) at enrolment. Post-primary education (HR 0.67, 95% CI 0.54-0.85) and female sex (HR 0.65, 95%CI 0.52-0.80) were associated with lower risk of death. 204 (6.9%) had new CHF (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or TIA (8.45/1000 patient-years), 19 (0.6%) had ARF (3.49/1000 patient-years), and 20 (0.7%) had IE (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/TIA or systemic embolism. Patients from low and lower-middle income countries had significantly higher age- and sex-adjusted mortality compared to patients from upper-middle income countries. Valve surgery was significantly more common in upper-middle income than in lower-middle- or low-income countries.

CONCLUSIONS: -Patients with clinical RHD have high mortality and morbidity despite being young; those from low and lower-middle income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and treatment of clinical RHD are required to improve outcomes.

Lack of Association Between Haptoglobin Phenotype and Cystic Fibrosis Outcomes

Haptoglobin (Hp), a heme-Iron chelator, has different isoforms which are associated with variable tendency toward infections: Hp 1-1, Hp 2-1, and Hp 2-2. Cystic fibrosis (CF) outcomes are variable and influenced by genetic and environmental factors. The aim of this study was to determine whether Hp phenotype influenced disease severity in CF. One hundred forty-two CF patients from two centers were analyzed for Haptoglobin phenotype using gel electrophoresis of hemoglobin enriched serum. Clinical and microbiological data including bacterial colonization status, lung function, presence of CF-related diabetes and liver disease, rate of exacerbation, and mortality were compared between Hp phenotype groups. We found a trend toward less mucoid PA among Hp 2-2 (20.4 %) compared with Hp 1-1 and Hp 2-1 individuals (33.3 %), p = 0.317. Hp 2-2 individuals also had less antibiotic courses, and lower inflammatory markers without statistical significance. Haptoglobin phenotype is unlikely to be an important modifier of CF phenotype.