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Gillian E Caughey,1,2 Kirsty Tait,3 Agnes I Vitry,3 Sepehr Shakib2,4 1Quality Use of Medicines and Pharmacy Research Centre, Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, 2Department of Clinical Pharmacology, Royal Adelaide Hospital, 3School of Pharmacy and Medical Sciences, University of South Australia, 4Discipline of Pharmacology, School of Medicine, University of Adelaide, North Terrace, Adelaide, SA, Australia Abstract: Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged ≥65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0–33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%–26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients’ prognosis and their preferences. The degree of benefit gained was not the driver of patients’ preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity. Keywords: multimorbidity, comorbidity, patient preference, patient decision-making, medicines, geriatrics

Abstract Background Pharmaceutical representatives provide medicines information on their promoted products to doctors. However, studies have shown that the quality of this information is often low. No study has assessed the medicines information provided by pharmaceutical representatives to doctors in Malaysia and no recent evidence in Australia is present. We aimed to compare the provision of medicines information by pharmaceutical representatives to doctors in Australia and Malaysia. Methods Following a pharmaceutical representative's visit, general practitioners in Australia and Malaysia who had agreed to participate, were asked to fill out a questionnaire on the main product and claims discussed during the encounter. The questionnaire focused on provision of product information including indications, adverse effects, precautions, contraindications and the provision of information on the Pharmaceutical Benefit Scheme (PBS) listings and restrictions (in Australia only). Descriptive statistics were produced. Chi-square analysis and clustered linear regression were used to assess differences in Australia and Malaysia. Results Significantly more approved product information sheets were provided in Malaysia (78%) than in Australia (53%) (P < 0.001). In both countries, general practitioners reported that indications (Australia, 90%, Malaysia, 93%) and dosages (Australia, 76%, Malaysia, 82%) were frequently provided by pharmaceutical representatives. Contraindications, precautions, drug interactions and adverse effects were often omitted in the presentations (range 25% - 41%). General practitioners in Australia and Malaysia indicated that in more than 90% of presentations, pharmaceutical representatives partly or fully answered their questions on contraindications, precautions, drug interactions and adverse effects. More general practitioners in Malaysia (85%) than in Australia (60%) reported that pharmaceutical representatives should have mentioned contraindications, precautions for use, drug interaction or adverse effects spontaneously (P < 0.001). In 48% of the Australian presentations, general practitioners reported the pharmaceutical representatives failed to mention information on PBS listings to general practitioners. Conclusions Information on indications and dosages were usually provided by pharmaceutical representatives in Australia and Malaysia. However, risk and harmful effects of medicines were often missing in their presentations. Effective control of medicines information provided by pharmaceutical representatives is needed.

Abstract Background Journal advertising is used by pharmaceutical companies to disseminate medicine information to doctors. The quality of claims, references and the presentation of risk results in Australia and the US has been questioned in several studies. No recent evidence is available on the quality of claims, references and the presentation of risk results in journal advertising in Australia and the US and no Malaysian data have been published. The aim of this study was to compare the quality of claims, references and the presentation of risk results in journal advertising in these three countries. Methods A consecutive sample of 85 unique advertisements from each country was selected from journal advertising published between January 2004 to December 2006. Claims, references and the presentation of risk results in medical journal advertising were compared between the three countries. Results Less than one-third of the claims were unambiguous claims (Australia, 30%, Malaysia 17%, US, 23%). In Malaysia significantly less unambiguous claims were provided than in Australia and the US (P < 0.001). However, the unambiguous claims were supported by more references than other claims (80%). Most evidence was obtained from at least one randomized controlled trial, a systematic review or meta-analysis (Australia, 84%, Malaysia, 81%, US, 76%) with journal articles being the most commonly cited references in all countries. Data on file were significantly more likely to be cited in the US (17%) than in Australia (2%) and Malaysia (4%) (P < 0.001). Advertisements that provided quantitative information reported risk results exclusively as a relative risk reduction Conclusions The majority of claims were vague suggesting poor quality of claims in journal advertising in these three countries. Evidence from a randomized controlled trial, systematic review or meta- analysis was commonly cited to support claims. However, the more frequent use of data that have not been published and independently reviewed in the US compared to Australia and Malaysia raises questions on the quality of references in the US. The use of relative rather than absolute benefits may overemphasize the benefit of medicines which may leave doctors susceptible to misinterpreting information.

Abstract Background A number of surveys have examined use of complementary and alternative medicines (CAM) in Australia. However, there are limited Australian data on use of CAM and over-the-counter (OTC) medicines in the elderly population. The main aims of this study were to examine self-medication practices with CAM and OTC medicines among older Australians and variables associated with their use. Methods The Australian Longitudinal Study of Ageing (ALSA) is an ongoing multidisciplinary prospective study of the older population which commenced in 1992 in South Australia. Data collected in 4 waves of ALSA between 1992 and 2004 were used in this study with a baseline sample of 2087 adults aged 65 years and over, living in the community or residential aged care. OTC medicines were classified according to the World Health Organization Anatomical Therapeutic Chemical (ATC) classification. CAM were classified according a modified version of the classification adopted by the Therapeutics Goods Administration (TGA) in Australia. Results The prevalence of CAM or OTC use ranged from 17.7% in 2000-2001 to 35.5% in 2003-2004. The top classes of CAM and OTC medicines used remained relatively constant over the study period. The most frequent classes of CAM used were vitamins and minerals, herbal medicines and nutritional supplements while the most commonly used OTC were analgesics, laxatives and low dose aspirin. Females and those of younger age were more likely to be CAM users but no variable was associated with OTC use. Conclusion Participants seemed to self-medicate in accordance with approved indications, suggesting they were informed consumers, actively looking after their own health. However, use of analgesics and aspirin are associated with an increased risk of adverse drug events in the elderly. Future work should examine how self-medication contributes to polypharmacy and increases the risk of adverse drug reactions.

Abstract Background Provision of consumer information and patient education are considered an essential part of chronic disease management programmes developed for patients with heart failure. This study aimed to review the quality and availability of consumer information materials for people with heart failure in Australia. Methods The availability of consumer information was assessed through a questionnaire-based survey of the major organisations in Australia known, or thought, to be producing or using consumer materials on heart failure, including hospitals. The questionnaire was designed to explore issues around the use, production and dissemination of consumer materials. Only groups that had produced consumer information on heart failure were asked to complete the totality of the questionnaire. The quality of information booklets was assessed by using a standardised checklist. Results Of 101 organisations which were sent a questionnaire, 33 had produced 61 consumer resources on heart failure including 21 information booklets, 3 videos, 5 reminder fridge magnets, 7 websites, 15 self-management diaries and 10 self-management plans. Questionnaires were completed for 40 separate information resources. Most had been produced by hospitals or health services. Two information booklets had been translated into other languages. There were major gaps in the availability of these resources as more than half of the resources were developed in 2 of the 8 Australian states and territories, New South Wales and Victoria. Quality assessment of 19 information booklets showed that most had good presentation and language. Overall eight high quality booklets were identified. There were gaps in terms of topics covered, provision of references, quantitative information about treatment outcomes and quality and level of scientific evidence to support medical recommendations. In only one case was there evidence that consumers had been involved in the production of the booklets. Conclusion Key findings arising from the study included the need to develop a nationally coordinated approach for increasing the dissemination of information resources on heart failure. While the more recent publication of a booklet by the National Heart Foundation may have improved the situation, dissemination of written information materials may remain sub-optimal, especially among patients who are not enrolled in chronic heart failure management programmes.

Abstract Background The prevalence of comorbidity is high, with 80% of the elderly population having three or more chronic conditions. Comorbidity is associated with a decline in many health outcomes and increases in mortality and use of health care resources. The aim of this study was to identify, review and summarise studies reporting the prevalence of comorbidity of chronic diseases in Australia. Methods A systematic review of Australian studies (1996 – May 2007) was conducted. The review focused specifically on the chronic diseases included as national health priorities; arthritis, asthma, cancer, cardiovascular disease (CVD), diabetes mellitus and mental health problems. Results A total of twenty five studies met our inclusion criteria. Over half of the elderly patients with arthritis also had hypertension, 20% had CVD, 14% diabetes and 12% mental health problem. Over 60% of patients with asthma reported arthritis as a comorbidity, 20% also had CVD and 16% diabetes. Of those with CVD, 60% also had arthritis, 20% diabetes and 10% had asthma or mental health problems. Conclusion There are comparatively few Australian studies that focused on comorbidity associated with chronic disease. However, they do show high prevalence of comorbidity across national health priority areas. This suggests integration and co-ordination of the national health priority areas is critical. A greater awareness of the importance of managing a patients' overall health status within the context of comorbidity is needed together with, increased research on comorbidity to provide an appropriate scientific basis on which to build evidence based care guidelines for these multimorbid patients.

The grain boundaries and dislocations play an important role in understanding the deformation behavior in polycrystalline materials. In this paper, the deformation mechanism of Cu, Ni, and equimolar Cu-Ni alloy was investigated using molecular dynamic simulation. The interaction between dislocations and grain boundary motion during the deformation was monitored using the dislocation extraction algorithm. Moreover, the effect of stacking fault formation and atomic band structure on the deformation behavior was discussed. Results indicate that dislocations nucleate around the grain boundary in copper, the deformation in nickel changes from planar slip bands to wavy bands, and high density of dislocation accumulation as well as numerous kink and jog formations were observed for the equimolar Cu-Ni alloy. The highest density of the Shockley dislocation and stacking faults was formed in the equimolar Cu-Ni alloy which results in the appearance of a huge gliding stage in the stress–strain curve. The grain boundaries act as a sinking source for vacancy annihilation in Ni and Cu; however, this effect was not observed in an equimolar Cu-Ni alloy. Finally, radial distribution function was used to evaluate atom segregation in grain boundaries.

Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH.