Provision of a comprehensive medicines review is associated with lower mortality risk for residents of aged care facilities: a retrospective cohort study.

BACKGROUND: no studies have examined the impact of residential medication management review (RMMR, a 24-year government subsidised comprehensive medicines review program) in Australian residential aged care facilities (RACFs) on hospitalisation or mortality. OBJECTIVE: to examine associations between RMMR provision in the 6-12 months after RACF entry and the 12-month risk of hospitalisation and mortality among older Australians in RACFs. DESIGN: retrospective cohort study. SUBJECTS: individuals aged 65-105 years taking at least one medicine, who entered an RACF in three Australian states between 1 January 2012 and 31 December 2015 and spent at least 6 months in the RACF (n = 57,719). METHODS: Cox regression models estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for associations between RMMR provision and mortality. Adjusted subdistribution hazard ratios were estimated for associations between RMMR provision and next (i) emergency department (ED) presentation or unplanned hospitalisation or (ii) fall-related ED presentation or hospitalisation. RESULTS: there were 12,603 (21.8%) individuals who received an RMMR within 6-12 months of RACF entry, of whom 22.2% (95%CI 21.4-22.9) died during follow-up, compared with 23.3% (95%CI 22.9-23.7) of unexposed individuals. RMMR provision was associated with a lower risk of death due to any cause over 12-months (aHR 0.96, 95%CI 0.91-0.99), but was not associated with ED presentations or hospitalisations for unplanned events or falls. CONCLUSIONS: provision of an RMMR in the 6-12 months after RACF entry is associated with a 4.4% lower mortality risk over 12-months but was not associated with changes in hospitalisations for unplanned events or falls.

Medicines use before and after comprehensive medicines review among residents of long-term care facilities: a retrospective cohort study.

BACKGROUND: Residential Medication Management Review (RMMR) is a subsidized comprehensive medicines review program for individuals in Australian residential aged care facilities (RACFs). This study examined weekly trends in medicines use in the four months before and after an RMMR and among a comparison group of residents who did not receive an RMMR. METHODS: This retrospective cohort study included individuals aged 65 to 105 years who first entered permanent care between 1/1/2012 and 31/12/2016 in South Australia, Victoria, or New South Wales, and were taking at least one medicine. Individuals with an RMMR within 12 months of RACF entry were classified into one of three groups: (i) RMMR within 0 to 3 months, (ii) 3 to 6 months, or (iii) within 6 to 12 months of RACF entry. Individuals without RMMRs were included in the comparison group. Weekly trends in the number of defined daily doses per 1000 days were determined in the four months before and after the RMMR (or assigned index date in the comparison group) for 14 medicine classes. RESULTS: 113909 individuals from 1979 RACFs were included, of whom 55021 received an RMMR. Across all three periods examined, decreased use of statins and proton pump inhibitors was observed post-RMMR in comparison to those without RMMRs. Decreases in calcium channel blockers, benzodiazepines/zopiclone, and antidepressants were observed following RMMR provision in the 3-6 and 6-12 months after RACF entry. Negligible changes in antipsychotic use were also observed following an RMMR in the 6-12 months after RACF entry by comparison to those without RMMRs. No changes in use of opioids, ACE inhibitors/sartans, beta blockers, loop diuretics, oral anticoagulants, or medicines for osteoporosis, diabetes or the cognitive symptoms of dementia were observed post-RMMR. CONCLUSIONS: For six of the 14 medicine classes investigated, modest changes in weekly trends in use were observed after the provision of an RMMR in the 6-12 months after RACF entry compared to those without RMMRs. Findings suggest that activities such as medicines reconciliation may be prioritized when an RMMR is provided on RACF entry, with deprescribing more likely after an RMMR the longer a resident has been in the RACF.

Insights into the molecular basis of reduced vancomycin susceptibility among three prominent Staphylococcus aureus clonal complexes.

Staphylococcus aureus is a leading cause of healthcare-associated infections globally. Vancomycin-resistant S. aureus (VRSA), those with high-level resistance [minimum inhibitory concentration (MIC) of 16-32 µg/mL vancomycin], are uncommon, whereas vancomycin-intermediate S. aureus (VISA; MIC of 4-8 µg/mL), are isolated more frequently and develop during long-term and/or repeated use of the antibiotic. VISA can be difficult to eradicate and infections may persist. Our knowledge of mechanisms that underlie the development of VISA is incomplete. We used a genomics approach to investigate the VISA phenotype in three prominent S. aureus lineages. All VISA clinical isolates tested had increased cell wall thickness compared with vancomycin-susceptible S. aureus strains. Growth rates of clonal complex (CC) 5, CC8, and CC45 clinical isolates were reduced in 2 µg/mL vancomycin compared to media alone. Culture in 2 and 4 µg/mL vancomycin sequentially for two weeks reduced susceptibility to daptomycin, televancin, tigecycline, and vancomycin in a majority of CC5, CC8, and CC45 isolates tested. We identified alleles reported previously to contribute to the VISA phenotype, but unexpectedly, these alleles were unique to each CC. A subtherapeutic concentration of vancomycin elicited changes in the VISA transcriptome-common and unique-among the three CCs tested. Multiple genes, including those encoding a glycerate kinase, an M50 family metallopeptidase, and an uncharacterized membrane protein, were upregulated among all three lineages and not reported previously as associated with VISA. Although there are lineage-specific changes in DNA sequence, our findings suggest changes in the VISA transcriptome constitute a general response to stress that confers reduced susceptibility to multiple antibiotics. IMPORTANCE: Our understanding of the mechanisms that underlie the development of vancomycin-intermediate Staphylococcus aureus (VISA) is incomplete. To provide a more comprehensive view of this process, we compared genome sequences of clonal complex (CC) 5, CC8, and CC45 VISA clinical isolates and measured changes in the transcriptomes of these isolates during culture with a subtherapeutic concentration of vancomycin. Notably, we identified differentially expressed genes that were lineage-specific or common to the lineages tested, including genes that have not been previously reported to contribute to a VISA phenotype. Changes in gene expression were accompanied by reduced growth rate, increased cell wall thickness, and reduced susceptibility to daptomycin, televancin, tigecycline, and vancomycin. Our results provide support to the idea that changes in gene expression contribute to the development of VISA among three CCs that are a prominent cause of human infections.

Reproductive Ecology of the Invasive Alien Shrub Pyracantha angustifolia in the Grassland Biome, South Africa.

Knowledge on reproductive traits of problematic invasive alien plants, such as the woody invasive shrub Pyracantha angustifolia of temperate Chinese origin, can help better manage invasive species. To determine factors contributing to its invasion, we investigated floral visitors and pollen loads, self-compatibility, seed set, seed rain, soil seed banks, and seed longevity in the soil. Generalist insects were recorded visiting flowers and all carried pollen loads of high purity (>70%). Floral visitor exclusion experiments showed that P. angustifolia can set seed (66%) without pollen vectors, although natural pollination resulted in higher fruit set (91%). Fruit count surveys and seed set showed an exponentially increased relationship between seed set and plant size with high natural seed yield (±2 million seeds m-2). Soil core samples revealed a high seed density of 46,400 ± (SE) 8934 m-2 under shrubs, decreasing with distance away from the shrub. Bowl traps stationed under trees and fences confirmed that seeds were efficiently dispersed by animals. Buried seeds survived for less than six months in the soil. Due to high seed production, self-compatibility augmented by generalist pollen vectors, and effective seed dispersal by local frugivores, it is difficult to manage the spread manually. Management of this species should focus on the short life span of seeds.

Uncovering the phylogeography of Schinus terebinthifolia in South Africa to guide biological control.

Schinus terebinthifolia is a problematic invasive alien plant (IAP) in South Africa that is a high priority target for biological control. Biological control has been implemented in the states of Florida and Hawaii (USA), where S. terebinthifolia is also an IAP. Phylogeographic work determined that there have been multiple introductions of two lineages (haplotype A and B) into the USA. Haplotype A was introduced to western Florida and Hawaii, while haplotype B was introduced to eastern Florida. Haplotypes A and B have subsequently hybridized in Florida, resulting in novel plant genotypes. Biological control agents in the USA are known to vary in efficacies on the two different haplotypes and hybrids. This study used molecular techniques to uncover the source populations of S. terebinthifolia in South Africa using chloroplast DNA and microsatellites. Populations from the introduced ranges in Florida (east, west and hybrids) and Hawaii were included (n = 95). All South Africa populations (n = 51) were found to be haplotype A. Microsatellite analysis determined shared alleles with western Florida and Hawaiian populations. The likely source of South African S. terebinthifolia was determined to be western Florida through the horticultural trade. These results will help guide a biological control programme to source agents that perform well on these populations in the USA. Furthermore, the presence of only one haplotype in South Africa highlights the need to ensure no further introductions of other haplotypes of the plant are made, in order to avoid similar hybridization events like those recorded in Florida.

An Advanced Pharmacy Practice Framework for Australia.

The need to develop An Advanced Pharmacy Practice Framework for Australia (the "APPF") was identified during the 2010 review of the competency standards for Australian pharmacists. The Advanced Pharmacy Practice Framework Steering Committee, a collaborative profession-wide committee comprised of representatives of ten pharmacy organisations, examined and adapted existing advanced practice frameworks, all of which were found to have been based on the Competency Development and Evaluation Group (CoDEG) Advanced and Consultant Level Framework (the "CoDEG Framework") from the United Kingdom. Its competency standards were also found to align well with the Domains of the National Competency Standards Framework for Pharmacists in Australia (the "National Framework"). Adaptation of the CoDEG Framework created an APPF that is complementary to the National Framework, sufficiently flexible to customise for recognising advanced practice in any area of professional practice and has been approved by the boards/councils of all participating organisations. The primary purpose of the APPF is to assist the development of the profession to meet the changing health care needs of the community. However, it is also a valuable tool for assuring members of the public of the competence of an advanced practice pharmacist and the quality and safety of the services they deliver.

APP intracellular domain-WAVE1 pathway reduces amyloid-ß production.

An increase in amyloid-ß (Aß) production is a major pathogenic mechanism associated with Alzheimer's disease (AD), but little is known about possible homeostatic control of the amyloidogenic pathway. Here we report that the amyloid precursor protein (APP) intracellular domain (AICD) downregulates Wiskott-Aldrich syndrome protein (WASP)-family verprolin homologous protein 1 (WAVE1 or WASF1) as part of a negative feedback mechanism to limit Aß production. The AICD binds to the Wasf1 promoter, negatively regulates its transcription and downregulates Wasf1 mRNA and protein expression in Neuro 2a (N2a) cells. WAVE1 interacts and colocalizes with APP in the Golgi apparatus. Experimentally reducing WAVE1 in N2a cells decreased the budding of APP-containing vesicles and reduced cell-surface APP, thereby reducing the production of Aß. WAVE1 downregulation was observed in mouse models of AD. Reduction of Wasf1 gene expression dramatically reduced Aß levels and restored memory deficits in a mouse model of AD. A decrease in amounts of WASF1 mRNA was also observed in human AD brains, suggesting clinical relevance of the negative feedback circuit involved in homeostatic regulation of Aß production.

The impact of visual distraction on episodic retrieval in older adults.

Impairment in long-term memory is one of the most salient alterations in cognitive aging. Findings of age-related deficits in source monitoring and recollection have revealed a selective decline in memory for detailed information. The underlying mechanism of this phenomenon is not well understood. We hypothesized that the influence of task-irrelevant visual stimuli present in our environment interferes with retrieval of detailed memories more for older than younger adults. We compared memory performance on a recall test for visual details when older adult participants' eyes were closed versus performance when their eyes were open and irrelevant visual stimuli were presented. The results showed that the presence of irrelevant visual information diminished long-term memory performance based on an objective measure of recollection for visual details. Comparison of the current results to findings from our earlier study using the same experimental paradigm with younger adults revealed that visual distraction disrupted recollection of relevant details to a greater degree in older than younger adults. This result suggests that visual distraction overwhelms older adults' declining cognitive control resources that are instrumental in the retrieval and selection of mnemonic details. More generally, these findings explicate a mechanistic basis for selective impairment of recollection in normal aging.