Treatment initiation for parkinson's disease in Australia 2013-2018 : a nation-wide study

Background Guidelines highlight the importance of an individualized approach to treatment initiation for Parkinson's disease. Our aim was to investigate initiation of anti-Parkinson medication in Australia from 2013-2018, and to determine factors predicting choice of initial treatment. Methods Cohort of new-users (N = 4,887) of anti-Parkinson medication aged >= 40 years were identified from a 10% random representative sample of national medication dispensing data from July-2013 to June-2018. Changes in treatment initiation were examined across the whole cohort and stratified by age and sex. Results Treatment initiation was most frequent with levodopa followed by non-ergot dopamine agonists (DAs) and anticholinergics. Two thirds initiated with levodopa across the study period. Initiation with non-ergot DAs increased from 22 to 27% (rate ratio, RR 1.23, 95% confidence interval, CI 1.02-1.47) and initiation with anticholinergics decreased from 6.9% to 2.4% (RR 0.34, 95% CI 0.21-0.55) from 2013-2018. Among persons aged >= 65 years, one third of women and one fourth of men initiated on levodopa. Among women aged = 65 years, consistent with current guidelines. Whilst the value of levodopa sparing strategies is unclear, treatment initiation with DA has become increasingly common relative to levodopa among women but not among men aged < 65 years.Peer reviewe

Impact of medication regimen simplification on medication incidents in residential aged care: Simpler randomized controlled trial

In the SImplification of Medications Prescribed to Long-tErm care Residents (SIMPLER) cluster-randomized controlled trial, we investigated the impact of a structured medication regimen simplification intervention on medication incidents in residential aged care facilities (RACFs) over a 12-month follow-up. A clinical pharmacist applied the validated 5-step Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) for 96 of the 99 participating residents in the four intervention RACFs. The 143 participating residents in the comparison RACFs received usual care. Over 12 months, medication incident rates were 95 and 66 per 100 resident-years in the intervention and comparison groups, respectively (adjusted incident rate ratio (IRR) 1.13; 95% confidence interval (CI) 0.53–2.38). The 12-month pre/post incident rate almost halved among participants in the intervention group (adjusted IRR 0.56; 95%CI 0.38–0.80). A significant reduction in 12-month pre/post incident rate was also observed in the comparison group (adjusted IRR 0.67, 95%CI 0.50–0.90). Medication incidents over 12 months were often minor in severity. Declines in 12-month pre/post incident rates were observed in both study arms; however, rates were not significantly different among residents who received and did not receive a one-off structured medication regimen simplification intervention

Implementing virtual collaborative inquiry practises in a middle-school context

The aim of the present study was to investigate the challenges that relate to the implementation of virtual inquiry practises in middle school. The case was a school course in which a group of Finnish students (N = 14) and teachers (N = 7) completed group inquiries through virtual collaboration, using a web-based learning environment. The task was to accomplish a cross-disciplinary inquiry into cultural issues. The students worked mainly at home and took much responsibility for their course achievements. The investigators analysed the pedagogical design of the course and the content of the participants' interaction patterns in the web-based environment, using qualitative content analysis and social network analysis. The findings suggest that the students succeeded in producing distinctive cultural products, and both the students and the teachers adopted novel roles during the inquiry. The web-based learning environment was used more as a coordination tool for organizing the collaborative work than as a forum for epistemic inquiry. The tension between the school curriculum and the inquiry practises was manifest in the participants' discussions of the assessment criteria of the course.The aim of the present study was to investigate the challenges that relate to the implementation of virtual inquiry practises in middle school. The case was a school course in which a group of Finnish students (N = 14) and teachers (N = 7) completed group inquiries through virtual collaboration, using a web-based learning environment. The task was to accomplish a cross-disciplinary inquiry into cultural issues. The students worked mainly at home and took much responsibility for their course achievements. The investigators analysed the pedagogical design of the course and the content of the participants' interaction patterns in the web-based environment, using qualitative content analysis and social network analysis. The findings suggest that the students succeeded in producing distinctive cultural products, and both the students and the teachers adopted novel roles during the inquiry. The web-based learning environment was used more as a coordination tool for organizing the collaborative work than as a forum for epistemic inquiry. The tension between the school curriculum and the inquiry practises was manifest in the participants' discussions of the assessment criteria of the course.The aim of the present study was to investigate the challenges that relate to the implementation of virtual inquiry practises in middle school. The case was a school course in which a group of Finnish students (N = 14) and teachers (N = 7) completed group inquiries through virtual collaboration, using a web-based learning environment. The task was to accomplish a cross-disciplinary inquiry into cultural issues. The students worked mainly at home and took much responsibility for their course achievements. The investigators analysed the pedagogical design of the course and the content of the participants' interaction patterns in the web-based environment, using qualitative content analysis and social network analysis. The findings suggest that the students succeeded in producing distinctive cultural products, and both the students and the teachers adopted novel roles during the inquiry. The web-based learning environment was used more as a coordination tool for organizing the collaborative work than as a forum for epistemic inquiry. The tension between the school curriculum and the inquiry practises was manifest in the participants' discussions of the assessment criteria of the course.Peer reviewe

Alcohol Consumption and Dietary Patterns: The FinDrink Study

The aim of this population-based study was to investigate differences in dietary patterns in relation to the level of alcohol consumption among Finnish adults. This study was part of the FinDrink project, an epidemiologic study on alcohol use among Finnish population. It utilized data from the Kuopio Ischaemic Heart Disease Risk Factor Study. A total of 1720 subjects comprising of 816 men and 904 women aged 53–73 years were included in the study in 1998–2001. Food intake was collected via a 4-day food diary method. Self-reported alcohol consumption was assessed with quantity-frequency method based on the Nordic Alcohol Consumption Inventory. Weekly alcohol consumption was categorized into three groups: non-drinkers (<12 grams), moderate drinkers (12–167.9 grams for men, 12–83.9 grams for women) and heavy drinkers (≥168 grams for men, ≥84 grams for women). Data were analyzed for men and women separately using multiple linear regression models, adjusted for age, occupational status, marital status, smoking, body mass index and leisure time physical activity. In women, moderate/heavy drinkers had lower fibre intake and moderate drinkers had higher vitamin D intake than non-drinkers. Male heavy drinkers had lower fibre, retinol, calcium and iron intake, and moderate/heavy drinkers had higher vitamin D intake than non-drinkers. Fish intake was higher among women moderate drinkers and men moderate/heavy drinkers than non-drinkers. In men, moderate drinkers had lower fruit intake and heavy drinkers had lower milk intake than non-drinkers. Moderate drinkers had higher energy intake from total fats and monosaturated fatty acids than non-drinkers. In contrast, energy intake from carbohydrates was lower among moderate/heavy drinkers than non-drinkers. In conclusion, especially male heavy drinkers had less favorable nutritional intake than moderate and non-drinkers. Further studies on the relationship between alcohol consumption and dietary habits are needed to plan a comprehensive dietary intervention programs in future

Targeted deletion of keratin 8 in intestinal epithelial cells disrupts tissue integrity and predisposes to tumorigenesis in the colon

Keratin 8 (K8) is the main intestinal epithelial intermediate filament protein with proposed roles for colonic epithelial cell integrity. Here, we used mice lacking K8 in intestinal epithelial cells (floxed K8 and Villin-Cre1000 and Villin-CreERt2) to investigate the cell-specific roles of intestinal epithelial K8 for colonocyte function and pathologies. Intestinal epithelial K8 deletion decreased K8 partner proteins, K18-K20, 75-95%, and the remaining keratin filaments were located at the colonocyte apical regions with type II K7, which decreased 30%. 2-Deoxy-2-[18F]-fluoroglucose positron emission tomography in vivo imaging identified a metabolic phenotype in the lower gut of the conditional K8 knockouts. These mice developed intestinal barrier leakiness, mild diarrhea, and epithelial damage, especially in the proximal colon. Mice exhibited shifted differentiation from enterocytes to goblet cells, displayed longer crypts and an increased number of Ki67 + transit-amplifying cells in the colon. Significant proproliferative and regenerative signaling occurred in the IL-22, STAT3, and pRb pathways, with minor effects on inflammatory parameters, which, however, increased in aging mice. Importantly, colonocyte K8 deletion induced a dramatically increased sensitivity to azoxymethane-induced tumorigenesis. In conclusion, intestinal epithelial K8 plays a significant role in colonocyte epithelial integrity maintenance, proliferation regulation and tumor suppression.</p

Application of Healthcare 'Big Data' in CNS Drug Research: The Example of the Neurological and mental health Global Epidemiology Network (NeuroGEN)

Neurological and psychiatric (mental health) disorders have a large impact on health burden globally. Cognitive disorders (including dementia) and stroke are leading causes of disability. Mental health disorders, including depression, contribute up to one-third of total years lived with disability. The Neurological and mental health Global Epidemiology Network (NeuroGEN) is an international multi-database network that harnesses administrative and electronic medical records from Australia, Asia, Europe and North America. Using these databases NeuroGEN will investigate medication use and health outcomes in neurological and mental health disorders. A key objective of NeuroGEN is to facilitate high-quality observational studies to address evidence-practice gaps where randomized controlled trials do not provide sufficient information on medication benefits and risks that is specific to vulnerable population groups. International multi-database research facilitates comparisons across geographical areas and jurisdictions, increases statistical power to investigate small subpopulations or rare outcomes, permits early post-approval assessment of safety and effectiveness, and increases generalisability of results. Through bringing together international researchers in pharmacoepidemiology, NeuroGEN has the potential to be paradigm-changing for observational research to inform evidence-based prescribing. The first focus of NeuroGEN will be to address evidence-gaps in the treatment of chronic comorbidities in people with dementia

Development and validation of the medication regimen simplification guide for residential aged CarE (MRS GRACE)

Background: Residents of aged care facilities use increasingly complex medication regimens. Reducing unnecessary medication regimen complexity (eg, by consolidating the number of administration times or using alternative formulations) may benefit residents and staff. Objective: To develop and validate an implicit tool to facilitate medication regimen simplification in aged care facilities. Method: A purposively selected multidisciplinary expert panel used modified nominal group technique to identify and prioritize factors important in determining whether a medication regimen can be simplified. The five prioritized factors were formulated as questions, pilot-tested using non-identifiable medication charts and refined by panel members. The final tool was validated by two clinical pharmacists who independently applied the tool to a random sample of 50 residents of aged care facilities to identify opportunities for medication regimen simplification. Inter-rater agreement was calculated using Cohen’s kappa. Results: The Medication Regimen Simplification Guide for Residential Aged CarE (MRS GRACE) was developed as an implicit tool comprising of five questions about 1) the resident; 2) regulatory and safety requirements; 3) drug interactions; 4) formulation; and 5) facility and follow-up considerations. Using MRS GRACE, two pharmacists independently simplified medication regimens for 29/50 and 30/50 residents (Cohen’s kappa=0.38, 95% CI 0.12–0.64), respectively. Simplification was possible for all residents with five or more administration times. Changing an administration time comprised 75% of the two pharmacists’ recommendations. Conclusions: Using MRS GRACE, two clinical pharmacists independently simplified over half of residents’ medication regimens with fair agreement. MRS GRACE is a promising new tool to guide medication regimen simplification in aged care.Esa YH Chen, Janet K Sluggett, Jenni Ilomäki, Sarah N Hilmer, Megan Corlis, Leonie J Picton, Laura Dean, Christopher P Alderman, Nicholas Farinola, Joy Gailer, Jane Grigson, Andrew R Kellie, Peter JC Putsey, Solomon Yu, J Simon Bel