[Show abstract][Hide abstract] ABSTRACT: Background
Elderly people, particularly those with dementia, are sensitive to adverse anticholinergic drug effects. This study examines the prevalence of anticholinergic medication, and anticholinergic load and its predictors, in community-dwelling elderly patients (aged 75 years and older) in Australia.
A research nurse visited the home of each participant (n = 1,044), compiled a list of current medications, and assessed participants’ cognitive status using a subsection of the revised Cambridge Examination for Mental Disorders of the Elderly (CAMCOG-R). Anticholinergic load was determined for each patient using the Anticholinergic Drug Scale (ADS).
Multivariate analysis identified several patient factors that were associated with higher anticholinergic burden, including polypharmacy (i.e. taking five or more medications) (p
[Show abstract][Hide abstract] ABSTRACT: Spreading the word about science and inspiring people to connect with the processes and outcomes of science, whether as researchers, educators, students, industry professionals or consumers, is essential in forging stronger links among scientists and with the communities that stand to benefit from their work. How do we nurture inspirational scientific communication in the context of university undergraduate science education, particularly in large cohort settings that are often more mind-numbing than soul-stirring? Communicating your own discoveries effectively is the zenith of scientific endeavour. We have developed a large-scale original research experience for second or third year undergraduate biomedical science students. The students undertake ‘mini’ projects and present their research outcomes verbally, visually and in a written format suitable for journal publication. This helps students understand how science works and develops their ability to explain scientific concepts to their peers and others. To promote ‘original research’ to students in ways that inspire and motivate participation, we have also evolved strategies to help instructors and researchers communicate successfully with large student cohorts, including a wiki for secure data storage, FAQ sheets and databases of bioinformatics tools. Introduction of the research experience has improved survey scores overall and on items relating to communication. These strategies are applicable to any course seeking to introduce students to the practice of research and communication of research outcomes. Our experience suggests optimal multidimensional communication may be best achieved through instructors, researchers and students working together to develop effective stratagems for surviving and thriving in the information-dense, digital world.
[Show abstract][Hide abstract] ABSTRACT: What is known and objectiveThe elderly are at increased risk of adverse effects resulting from drug interactions due to decreased drug clearance and polypharmacy. This study examines the prevalence of the co-administration of clinically relevant cytochrome P450 (CYP) enzyme inhibitors with drugs that are substrates for these enzymes, in the community-dwelling elderly in Australia.Methods
Participants aged 75 years or older (n = 1045) were recruited via their general practitioners at four Australian sites (Newcastle, Sydney, Melbourne and Adelaide). A research nurse visited the home of each patient to compile a list of all prescription medications (including doses) currently used by the patient, and to complete assessments for depression, quality of life and cognitive status. The medication data were searched for the co-prescription of clinically relevant CYP inhibitor and corresponding substrate drugs.Results and discussionPotentially inappropriate CYP inhibitor–substrate combinations were found in 6·2% (65/1045) of patients. These patients were on significantly more medications (6·1 ± 3·0 vs. 3·9 ± 2·5; P = 0·001) and had a significantly lower physical quality of life (P = 0·047) than those who were not on any CYP inhibitor–substrate combinations. The most commonly prescribed inhibitor–substrate combinations involved the CYP 3A4 inhibitors, diltiazem and verapamil, with the substrates simvastatin or atorvastatin. Only 1 of 41 patients on a CYP3A4 inhibitor and a statin was prescribed a non-CYP 3A4 metabolized statin. Metoprolol was another substrate commonly co-prescribed with a CYP2D6 inhibitor. In many cases, the risks and benefits of potential interactions may have been considered by the GP as the prescribed doses of both the inhibitor and substrate were relatively low. There were, however, some notable exceptions, also involving the substrates simvastatin, atorvastatin and metoprolol. There were no GP factors that were associated with co-prescription of CYP inhibitors and substrates.What is new and conclusionThere is not a particular GP demographic that should be targeted for education regarding CYP interactions, but a focus on particular medications such as the statins may reduce the potential for clinically significant drug–drug interactions. As CYP drug–drug interactions are more common in patients on higher number of medications, particular vigilance is required at the time of prescribing and dispensing medications for elderly patients with multiple conditions.
Journal of Clinical Pharmacy and Therapeutics 04/2014; 39(4). DOI:10.1111/jcpt.12163 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Dementia is a complex and variable condition which makes recognition of it particularly difficult in a low prevalence primary care setting. This study examined the factors associated with agreement between an objective measure of cognitive function (the revised Cambridge Cognitive Assessment, CAMCOG-R) and general practitioner (GP) clinical judgment of dementia.
This was a cross-sectional study involving 165 GPs and 2,024 community-dwelling patients aged 75 years or older. GPs provided their clinical judgment in relation to each of their patient's dementia status. Each patient's cognitive function and depression status was measured by a research nurse using the CAMCOG-R and the 15-item Geriatric Depression Scale (GDS), respectively.
GPs correctly identified 44.5% of patients with CAMCOG-R dementia and 90% of patients without CAMCOG-R dementia. In those patients with CAMCOG-R dementia, two patient-dependent factors were most important for predicting agreement between the CAMCOG-R and GP judgment: the CAMCOG-R score (p = 0.006) and patient's mention of subjective memory complaints (SMC) to the GP (p = 0.040). A higher CAMCOG-R (p < 0.001) score, female gender (p = 0.005), and larger practice size (p < 0.001) were positively associated with GP agreement that the patient did not have dementia. Subjective memory complaints (p < 0.001) were more likely to result in a false-positive diagnosis of dementia.
Timely recognition of dementia is advocated for optimal dementia management, but early recognition of a possible dementia syndrome needs to be balanced with awareness of the likelihood of false positives in detection. Although GPs correctly agree with dimensions measured by the CAMCOG-R, improvements in sensitivity are required for earlier detection of dementia.
International Psychogeriatrics 06/2013; 25(10):1-9. DOI:10.1017/S1041610213000884 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Identification of factors associated with quality of life (QoL) in people having dementia will help develop strategies for maintenance and improvement of patient QoL. This study examined the predictors of QoL in a community-dwelling population aged 75 years and over, with or without dementia.
This was a cross-sectional study involving 169 GPs and 2,028 patients. Patients were interviewed to collect information on personal circumstances. Several instruments were administered including the WHOQOL-BREF (quality of life outcome measure), Geriatric Depression Scale, GPAQ (satisfaction with GP care), and the CAMCOG-R (cognitive function). Patients with a CAMCOG-R score < 80 were allocated to the dementia group. GPs provided an independent clinical judgment of cognitive function for each of their participating patients.
The dementia group had significantly lower QoL scores in all four domains of the WHOQOL-BREF (all p ≤ 0.002). The GDS score was negatively correlated with all four domains in the non-dementia group and with physical, psychological, and environmental QoL in the dementia group (all p < 0.001). Satisfaction with GP communication was positively associated with psychological QoL in the dementia group and all domains in the non-dementia group. Participants in the dementia group who had been given a diagnosis of a memory problem had significantly higher physical (2.05, 95% CI 0.36 to 3.74) and environmental (2.18, 95% CI 0.72 to 3.64) QoL.
Satisfaction with GP communication is associated with a higher QoL in their older patients. Diagnosis and disclosure of memory problems is associated with better QoL in people with dementia. Clinicians should not be deterred from discussing a memory diagnosis and plans for the future with patients.
International Psychogeriatrics 07/2012; 24(12):1962-71. DOI:10.1017/S1041610212001111 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dementia is increasing in prevalence as the population ages. An earlier rather than later diagnosis allows persons with dementia and their families to plan ahead and access appropriate management. However, most diagnoses are made by general practitioners (GPs) later in the course of the disease and are associated with management that is poorly adherent to recommended guidelines. This trial examines the effectiveness of a peer led dementia educational intervention for GPs.
The study is a cluster randomised trial, conducted across three states and five sites. All GPs will complete an audit of their consenting patients aged 75 years or more at three time points - baseline, 12 and 24 months. GPs allocated to the intervention group will receive two educational sessions from a peer GP or nurse, and will administer the GPCOG to consenting patients at baseline and 12 months. The first education session will provide information about dementia and the second will provide individualised feedback on audit results. GPs in the waitlist group will receive the RACGP Guidelines by post following the 12 month auditOutcomes: Primary outcomes are carer and consumer quality of life and depression. Secondary outcomes include: rates of GP identification of dementia compared to a more detailed gold standard assessment conducted in the patient's home; GP identification of differential diagnoses including reversible causes of cognitive impairment; and GP referral to specialists, Alzheimers' Australia and support services. A "case finding" and a "screening" group will be compared and the psychometrics of the GPCOG will be examined.Sample size: Approximately 2,000 subjects aged 75 years and over will be recruited through approximately 160 GPs, to yield approximately 200 subjects with dementia (reducing to 168 by 24 months).
The trial outlined in this paper has been peer reviewed and supported by the Australian National Health and Medical Research Council. At the time of submission of this paper 2,034 subjects have been recruited and the intervention delivered to 114 GPs.
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000117415.
BMC Family Practice 03/2012; 13(1):12. DOI:10.1186/1471-2296-13-12 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the potential contraceptive effect of immunisation with zona pellucida antigens, 50 free-ranging koalas were immunised with either porcine zonae pellucidae (PZP), recombinant brushtail possum ZP3 (recBP-ZP3) or buffer, in complete Freund's adjuvant. A single booster immunisation in incomplete Freund's adjuvant was administered 3-5 months later. Where possible animals were recaptured, reproductive status was assessed and blood was collected at 1-3-month intervals for the next 33 months. Forty-three koalas were recaptured at least three times allowing reliable assessments of their fertility. Fourteen animals were observed never to have a pouch young. Of the remaining 29 animals the reproductive productivity of PZP treated females was reduced compared with control and recBP-ZP3 treated females, in terms of both total number of young produced, and failure to produce further young in females of proven fertility. One month after the initial immunisation, serum antigen-specific antibody titres were higher in animals immunised with PZP or recBP-ZP3 compared to controls, and reached a plateau by 4 months. Antibody against the relevant immunising antigen was also detected in ovarian follicular fluid, uterine fluid and vaginal secretions. Epitope analysis suggested that immune responses other than antibodies directed against the ZP3 amino acid sequence were responsible for mediating infertility. The results demonstrate that the fertility of female koalas can be compromised by immunisation against zona pellucida antigens. However, unlike in the eastern grey kangaroo and the brushtail possum, immunisation with bacterial recombinant brushtail possum ZP3 did not compromise fertility in the koala.
[Show abstract][Hide abstract] ABSTRACT: This study examined the potential of a recombinant marsupial zona pellucida 3 protein as a contraceptive vaccine for the Eastern Grey kangaroo, a marsupial that is locally overabundant in several regions of eastern Australia. First, a pilot study using porcine zona pellucidae (PZP) demonstrated that ZP proteins, primarily the ZP3 component of PZP, are highly immunogenic in the grey kangaroo and produce a long-lasting humoral response to a single immunisation, as found in other marsupials. Immunisation with 300 microg of a non-glycosylated recombinant brushtail possum ZP3 (recBP-ZP3) protein in complete Freund's adjuvant produced a similar, significant and sustained antibody response, and none of the immunised kangaroos (n=7) produced offspring during the following breeding season compared with four out of the six control animals. An epitope analysis of the B-cell response to recBP-ZP3 using a brushtail possum ZP3 identified numerous B-cell epitope regions clustered around the N- and C-terminal regions of the protein. Two regions of interest for further fertility vaccine development based on their immunogenicity and fertility trials and functional studies in other species were found to be immunogenic. These results suggest that immunocontraception based on targeting the ZP3 protein within the zona pellucida may be an effective strategy for fertility reduction in Eastern Grey kangaroos.
[Show abstract][Hide abstract] ABSTRACT: The spermatozoa of most marsupials lack nuclear stabilising disulfide-bonded protamines found in eutherian mammals. However, disulfide stabilisation has been observed in the acrosome of macropodid (Macropus eugenii) and phalangerid (Trichosurus vulpecula) marsupials. As a result this organelle, which is normally fragile in eutherian mammals, is robust and able to withstand physical and chemical challenge in these marsupials. The present study examined acrosomal characteristics of the spermatozoa of three dasyurid marsupials; the fat-tailed dunnart (Sminthopsis crassicaudata), eastern quoll (Dasyurus viverrinus) and northern quoll (Dasyurus hallucatus). In all species examined Bryan's staining demonstrated that significant acrosomal loss occurred following physical challenge with osmotic stress, cryopreservation without cryoprotectant and exposure to detergent (Triton-X). Bromobimane staining indicated that the acrosomes of dasyurids lacked stabilising disulfide bonds. As reported for the wallaby and possum, calcium ionophore (A23187) did not induce the acrosome reaction-like exocytosis in dasyurid spermatozoa but treatment with diacylglycerol (DiC8) caused significant acrosome loss at concentrations similar to those effective for other marsupials. The present study found that the spermatozoa of dasyurids are more sensitive to physical challenge than the previously-studied marsupials and we suggest that this is due to the absence of acrosomal stabilising disulfide bonds.
Reproduction Fertility and Development 02/2008; 20(2):295-302. DOI:10.1071/RD07178 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fertility control in the form of a zona pellucida (ZP)-based immunocontraceptive has shown potential as a humane form of control for overabundant marsupials including the brushtail possum and macropods. Further refinement and development of a ZP-based vaccine requires detailed knowledge of the protein structure and expression in order to ensure maximum efficacy and specificity. Sequencing and comparative analysis of the ZP3 protein from three marsupial orders in this study found a high overall level of conservation; within order Diprotodontia, the ZP3 protein is 86.9-98.9% identical. ZP3 identity falls to 56.6-57.2%, when the grey, short-tailed opossum (a Didelphimorphian) is compared to dasyurid and diprotodontan marsupials. This is similar to its amino acid identity with ZP3 from eutherian species (50.7-52.8%). Comparison of a 21 amino acid epitope in marsupial ZP3 that has shown contraceptive effects, reveals 95-100% identity between the four macropodid species, 81-86% amino acid identity between brushtail possum and the macropods and 67-71% identity between the diprotodontans and the fat-tailed dunnart (a dasyurid). This is comparable to the level of identity between related eutherian mammals. The expression pattern of three ZP genes during brushtail possum and tammar wallaby pouch young development was examined by RT-PCR. This analysis of ZP gene expression has confirmed that ZP mRNA transcription begins in the ovary during pouch young development by about 51 days of age. The presence of ZP transcripts at this stage in pouch young development suggests that marsupial ZP gene transcription begins before the onset of follicular development.
Molecular Reproduction and Development 12/2007; 74(12):1581-9. DOI:10.1002/mrd.20707 · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although marsupial oocytes undergo nuclear maturation in vitro, there is, at present, no indication of their developmental potential, largely owing to the lack of in vitro fertilisation and related technologies for marsupials. Glucose metabolism has proven a useful indicator of oocyte cytoplasmic maturation and developmental potential in several eutherian species. Therefore, the aims of the present study were to compare: (1) the rates of glycolysis and glucose oxidation in immature, in vitro-matured and in vivo-matured tammar wallaby oocytes; and (2) the metabolic rate of individual oocytes with their ability to form pronuclei after intracytoplasmic sperm injection. The rates of glycolysis measured in immature (2.18 pmol oocyte(-1) h(-1)), in vitro- matured (0.93 pmol oocyte(-1) h(-1)) and in vivo-matured tammar wallaby oocytes (0.54 pmol oocyte(-1) h(-1)) were within a similar range to values obtained in eutherian species. However, unlike the trend observed in eutherian oocytes, the glycolytic rate was significantly higher in immature oocytes compared with either in vivo- or in vitro-matured oocytes (P < 0.001) and significantly higher in in vitro-matured oocytes compared with in vivo-matured oocytes (P < 0.001). No relationship was identified between glucose metabolism and the developmental capacity of oocytes after intracytoplasmic sperm injection when assessed after 17-19 h. Oocytes that became fertilised (two pronuclei) or activated (one or more pronucleus) were not distinguished from others by their metabolic rates. Longer culture after intracytoplasmic sperm injection (e.g. blastocyst stage) may show oocyte glucose metabolism to be predictive of developmental potential; however, culture to the single-cell stage did not reveal any significant differences in normally developing embryos.
Reproduction Fertility and Development 02/2004; 16(6):617-23. DOI:10.1071/RD03062 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The phosphorylation of tyrosine residues in cellular proteins is a major signal transduction event during sperm capacitation. In this study protein phosphorylation was monitored using a fluorescein isothiocyanate (FITC)-labeled antiphosphotyrosine monoclonal antibody and a flow cytometric procedure optimized for sperm. Using this technique, the correlation between tyrosine phosphorylation and sperm capacitation was examined in two marsupial species, the brushtail possum and the tammar wallaby and compared with that of ram spermatozoa. The levels of tyrosine phosphorylation in sperm from all three species were increased by the addition of cyclic AMP (cAMP) and vandate, a phosphotyrosine phosphatase inhibitor and were decreased by the addition of the phosphotyrosine kinase inhibitor, staurosporine. Oviductal conditioned media (CM) induced a progressive increase in tyrosine phosphorylation in both marsupial species and also induced morphological transition from a streamlined to a 'T'-shape configuration in brushtail possum spermatozoa but not in tammar wallaby spermatozoa. Transition to the 'T'-shape orientation associated with capacitation in marsupial spermatozoa was observed by 2 h of incubation in both species when tyrosine phosphorylation was increased by higher levels of cAMP i.e. 5 mM dibutyryl cAMP plus 3 mM pentoxyphylline. Thus the tyrosine phosphorylation trigger with CM may differ in these two marsupial species. Ram sperm tyrosine phosphorylation could be increased by addition of lower levels of cAMP (1 mM). These results support the finding that tyrosine phosphorylation is associated with sperm capacitation in marsupials. Similar results were obtained by using SDS PAGE/Western blot analysis of tyrosine phosphorylation in the brushtail possum spermatozoa. The specificity, efficiency and sensitivity of the procedure described here make it applicable for routine assessment of capacitation in large numbers of samples and in other species.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to determine the timing of oocyte activation, sperm decondensation and pronucleus formation after intracytoplasmic sperm injection (ICSI) in the tammar wallaby and to determine the fate of sperm structures at an ultrastructural level. Metaphase II-stage tammar wallaby oocytes were injected with spermatozoa and cultured for 1 (n = 15), 2 (n = 24), 4 (n = 30), 6 (n = 14), 8 (n = 32), 10 (n = 25), 12 (n = 29) or 19 h (n = 12). Oocytes were assessed using light, fluorescence and electron microscopy. The timing of oocyte activation and sperm decondensation after ICSI in the tammar wallaby is relatively similar to that of some eutherian species. Resumption of meiosis II was observed from 1 h and the first female pronucleus was seen 6 h after ICSI. Most oocytes (88%) possessed a female pronucleus by 10 h. Intact acrosomes persisted with intact sperm heads up to 2 h after ICSI. At 10 h, 80% of oocytes possessed a male pronucleus. The sperm tail had undergone considerable degeneration by 10 h after ICSI, including breakdown of the fibrous sheath dense fibres. The identification of sperm tail and midpiece remnants adjacent to pronuclei confirms that the events observed in wallaby oocytes after ICSI are not due to parthenogenetic activation.
Reproduction Fertility and Development 02/2004; 15(7-8):397-406. DOI:10.1071/RD03033 · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gametes from the brushtail possum (Trichosurus vulpecula), an Australian marsupial, require exposure to oviductal cells and/or their secretions before sperm binding and penetration of the zona pellucida can occur. Sperm-egg fusion, the next critical step in fertilization has not previously been reported in vitro. Here we describe the refinement of an oviduct epithelial cell (OEC) explant culture system using two different media to obtain in vitro sperm-egg fusion in the brushtail possum for the first time. Conditioned media from OEC explant cultures were supplemented with either 1% fetal calf serum (FCS) or 1 mg/ml polyvinyl alcohol and used for co-culture of epididymal sperm and superovulated eggs. Under these conditions zona penetration rates varied from 0 to 46% and sperm-egg fusion from 0 to 20%. Analysis of explant conditioned media indicated that qualitative and quantitative differences between batches could account, at least partially, for the large variability in zona penetration rates. Conditioned media that contained approximately 1 mM of ionic calcium were most effective for achieving sperm capacitation, zona binding, and penetration and sperm-egg fusion. The reorientation of the sperm head to T-shape, an indicator of capacitation in the brushtail possum, was closely linked with the concentration of calcium present in vitro.