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Background Underrepresentation of older people in clinical trials remains. This study aimed to examine the inclusion of older people and associated safety and efficacy reports from clinical trials of new molecular entities for cardiovascular disease indications since commencement of the US Food and Drug Administration Drug Trial Snapshot (DTS) Program. The DTS provides concise information on participants included in clinical trials supporting US Food and Drug Administration approval of new drugs. Methods and Results A cross‐sectional analysis between January 1, 2015 and April 30, 2019 of DTS data including approval date, indication, number of trials and participants, age distribution, efficacy, and safety statements was conducted. Participation‐to‐prevalence ratio (PPR) was used to describe representation of older participants in trials relative to disease population. Efficacy and safety statements regarding age were compared with drug prescribing information. A total of 72 079 participants from 10 DTS reports were identified and 39 625 (55.0%) were aged ≥65 years old. Overall, 63.6% of cardiovascular disease DTS reports were representative of people aged ≥65 years old for specific cardiovascular disease conditions. Underrepresentation was observed in 4 DTS: 2 for heart failure (PPR 0.48 and 0.62), 1 for pulmonary arterial hypertension (PPR 0.72), and 1 for venous thromboembolism (PPR 0.38). Participants in clinical trials for new drugs for the treatment of atrial fibrillation (PPR 0.99 and 1.21) and hypercholesterolemia (PPR 0.84 and 0.97) were reflective of the older population for these diseases. An increased risk of adverse events in older participants was reported in 40% DTS safety statements but no differences were reported in the drug product information. Conclusions Despite the fact that >60% of cardiovascular disease trial participants for new molecular entities included in the DTS program were representative of the older population in real‐world clinical practice, concerns remain for conditions including heart failure or venous thromboembolism. Drug product information safety statements regarding age differences in adverse events were not reflective of trial findings. An increased directive is needed to facilitate the generation of real‐world evidence and appropriate reporting within drug product information for these potentially at‐risk patient populations.

Objective: To compare how frequently selected chronic diseases developed in women with breast cancer receiving endocrine therapy, and in women without cancer. Design, setting and participants: Retrospective, rolling cohort study, analysing a random 10% sample of Pharmaceutical Benefits Scheme (PBS) data for the period 1 January 2003 – 31 December 2014. Women with breast cancer who first commenced endocrine therapy between January 2004 and December 2011 were identified, and age- and sex-matched (1:10) by comorbidity with control groups of women who did not have a dispensing record for antineoplastic agents during the study period or the comorbidity of interest at baseline. Main outcome measures: Development of any of eight pre-selected comorbidities, identified in PBS claims data with the RxRisk-V model. Results: Women with hormone-dependent breast cancer were significantly more likely than women in the control group to develop depression (overall hazard ratio [HR], 1.36; 95% CI, 1.26–1.46), pain or pain–inflammation (HR, 1.30; 95% CI, 1.23–1.38), osteoporosis (overall HR, 1.27; 95% CI, 1.17–1.39), diabetes (HR, 1.24; 95% CI, 1.10–1.41), cardiovascular disorders (overall HR, 1.22; 95% CI, 1.13–1.32), and gastric acid disorders (HR, 1.20; 95% CI, 1.13–1.28). The hazard ratios for developing cardiovascular disorders, depression and osteoporosis were highest during the first year of endocrine therapy. The risk of hyperlipidaemia was lower among women with breast cancer than in the control group (HR, 0.88; 95% CI, 0.81–0.96). There was no significant difference between the two groups in the risk of reactive airway diseases (HR, 1.05; 95% CI, 0.98–1.13). Conclusion: Comorbid conditions are more likely to develop in women who have been diagnosed with hormone-dependent breast cancer than in women without cancer. Our results further support the need to develop appropriate models of care to manage the multiple chronic disorders of breast cancer survivors. Refereed/Peer-reviewed

Purpose To examine the prescribing of prochlorperazine secondary to the prescribing of a medicine which could lead to symptoms for which prochlorperazine is indicated and commonly used. Given the range of potential hypotensive, sedative, dystonic and other extra-pyramidal side effects associated with prochlorperazine, its association with hip fracture was also examined. Methods Prescription/event sequence symmetry analyses were undertaken from 1st January 2003 to 31st December 2006, using administrative claims data from the Department of Veterans' Affairs, Australia. This method assesses asymmetry in the distribution of an incident event (either prescription of another medicine or hospitalization) before and after the initiation of prochlorperazine. Crude and adjusted sequence ratios (ASR) with 95% confidence intervals (CI) were calculated. Results A total of 34 235 persons with incident use of prochlorperazine were identified during the study period. Statistically significant positive associations were found for a number of commonly used medicines, including cardiovascular medicines, NSAIDs, opioids and sedatives and the subsequent initiation of prochlorperazine that ranged from 1.07 (95%CI 1.01–1.14) for diuretics to 1.50 (95%CI 1.40–1.61) for statins. Prescription event analysis showed a 49% (95%CI 1.19–1.86) increased risk of hospitalisation for hip fracture following dispensing of prochlorperazine. Conclusions Prescribers should consider the possible contributing role of newly initiated medicines with the potential to cause of dizziness, and where possible address this through dose reduction or cessation of the medicine, rather than prescribing prochlorperazine. Copyright © 2010 John Wiley & Sons, Ltd.

Objectives: the study aimed to examine the prevalence of comorbidity, the prescribing of potentially inappropriate medications and treatment conflicts in a large sample of older people who have been dispensed an antidepressant medicine. Conclusion: we observed a high level of potentially inappropriate prescribing and treatment conflicts that may arise when caring for older patients dispensed an antidepressant with comorbidity. These have the potential to place a large number of older people with depression at increased risk for adverse events. Methods: a cross-sectional study of administrative claims data from the Department of Veterans' Affairs, Australia, 1 April-31 July 2007, of veterans aged =65 years was conducted. Comorbidities determined using the pharmaceutical-based comorbidity index, Rx-Risk-V. Concomitant medicines that may be potentially inappropriate for patients with depression and areas of treatment conflicts were determined from Australian clinical guidelines or reference compendia. Results: a total of 39,695 subjects were included, with a median of 5 comorbid conditions (inter-quartile range 3-6). Ninety percent of medicine use was attributed to the treatment of comorbid conditions. Eighty-seven percent of the study cohort was identified as having at least one comorbid condition that may cause a potential treatment conflict when an antidepressant is used. Those conditions of most concern included cardiovascular diseases, anxiety disorders, arthritis or pain management and osteoporosis. Refereed/Peer-reviewed

Background:Depression is one of the leading contributors to the burden of non-fatal diseases in Australia. Although there is an overall increasing trend in antidepressant use, the relationship between use of antidepressants and depressive symptomatology is not clear, particularly in the older population.Methods:Data for this study were obtained from the Australian Longitudinal Study of Ageing (ALSA), a cohort of 2087 people aged over 65 years at baseline. Four waves of home interviews were conducted between 1992 and 2004 to collect information on sociodemographic and health status. Depressive symptoms were measured by the Center for Epidemiologic Studies – Depression Scale. Use of antidepressants was based on self-report, with the interviewer able to check packaging details if available. Longitudinal analysis was performed using logistic generalized estimating equations to detect if there was any trend in the use of antidepressants, adjusting for potential confounding factors.Results:The prevalence of depressive symptoms was 15.2% in 1992 and 15.8% in 2004 (p> 0.05). The prevalence of antidepressant users increased from 6.5% to 10.9% (p< 0.01) over this period. Among people with depressive symptoms, less than 20% were taking antidepressants at any wave. Among people without depressive symptoms, the prevalence of antidepressant use was 5.2% in 1992 and 12.0% in 2004 (p< 0.01). Being female (OR = 1.67, 95%CI: 1.25–2.24), having poor self-perceived health status (OR = 1.17, 95%CI: 1.04–1.32), having physical impairment (OR = 1.48, 95%CI: 1.14–1.91) and having depressive symptoms (OR = 1.62, 95%CI: 1.24–2.13) significantly increased the use of antidepressants, while living in community (OR = 0.51, 95%CI: 0.37–0.71) reduced the risk of antidepressant use.Conclusions:Use of antidepressants increased, while depressive symptoms remained stable, in the ALSA over a 12-year period. Use of antidepressants was low for people with depressive symptoms.

Introduction: People living with dementia may experience and express pain in different ways to people without dementia. People with dementia are typically prescribed fewer analgesics than people without dementia indicating a potential difference in how pain is identified and treated in these populations. The objectives of this study are to (1) investigate the prevalence of analgesic load, pain and daytime sedation in people with and without dementia in Australian residential aged care facilities (RACFs), and (2) investigate the clinical and diagnostic associations between analgesic load, pain and daytime sedation in people with and without dementia in Australian RACFs. Methods/analysis: This will be a cross-sectional study of 300 permanent residents of up to 10 low-level and high-level RACFs in South Australia with and without dementia. Trained study nurses will administer validated and dementia-specific assessments of self-reported and clinician-observed pain, sedation and other clinical and humanistic outcomes. Medicine-use data will be extracted directly from each resident's medication administration chart. Binary and multinominal logistic regression will be used to compute unadjusted and adjusted ORs and 95% CIs for factors associated with pain, analgesic load and daytime sedation. These factors will include dementia severity, behavioural and psychological symptoms, quality of life, resident satisfaction, attitudes towards medicines, activities of daily living and nutritional status. Ethics and dissemination: Institutional ethics approval has been granted. The findings will be disseminated through public lectures, professional and scientific conferences and in peer-reviewed journal articles. The findings of this study will allow for a better understanding of the prevalence and factors associated with analgesic use, pain and other outcomes in residential care. The findings of this study will be used to inform the development and implementation of strategies to improve the quality of life of people with dementia Refereed/Peer-reviewed

Purpose Warfarin management in the elderly population is complex as medicines prescribed for concomitant diseases may further increase the risk of major bleeding associated with warfarin use. We aimed to quantify the excess risk of bleeding-related hospitalisation when warfarin was co-dispensed with potentially interacting medicines. Methods A retrospective cohort study was undertaken over a 4-year period from July 2002 to June 2006 to examine bleeding risk associated with medications co-administered in patients taking warfarin using an administrative claims database from the Australian Department of Veterans and Affairs. All veterans aged 65 years and over who were new users of warfarin were followed until death or study end. Risk of bleeding was assessed using a Poisson GEE model adjusting for age, gender, socioeconomic status, co-morbidity index, previous bleeding related hospitalisations and indicators of health service use. Results Overall, 17661 veterans who used warfarin at any time during the study period were included. The overall incidence rate of bleeding-related hospitalisations was 4.1 (95% CI 3.7-4.6) per 100 person-years in veterans who were not receiving potentially interacting medicines. Bleeding-related hospitalisation rates were significantly increased when warfarin was co-prescribed with low-dose aspirin (Adjusted rate ratio (AdjRR) 1.44, 95% CI 1.00-2.07), clopidogrel (AdjRR 2.23, 95% CI 1.48-3.36), clopidogrel with aspirin (AdjRR 3.44, 95% CI 1.28-9.23), amiodarone (AdjRR 3.33, 95% CI 1.38-8.00) and antibiotics (AdjRR 2.34, 95% CI 1.55-3.54). Conclusions Models assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions. Refereed/Peer-reviewed

The aim of this study was to examine the effect of psychotropic medications (antipsychotics, antidepressants, anxiolytics, hypnotics and sedatives) on the risk of falls and fractures in a cohort of elderly people in South Australia. A retrospective cohort study was undertaken using the wave 1 (1992) and wave 3 (1994) data of the Australian Longitudinal Study of Ageing (ALSA). Persistent use of psychotropic medicines was defined as use of one or more psychotropic medications at both wave 1 and wave 3. A comprehensive list of potential confounding variables was individually entered into regression models to examine effects on risk ratios. The results showed that the use of psychotropic medications was associated with an increased risk of falls in females (IRR = 1.47, 95% CI = 1.31-1.64) but not in males (IRR = 1.03, 95% CI = 0.85-1.26). The use of psychotropic medications was also associated with an increased risk of a fracture in females (RR 2.54; CI 1.57-4.11; p < 0.0001) but not in males (RR = 0.66; p = 0.584; CI 0.15-2.86). In both analyses, the body mass index (BMI) was determined to be the only confounding variable. After adjusting for BMI, the IRR in females decreased to 1.22 (95% CI 1.02-1.45; p < 0.015) for falls and the RR decreased to 1.92 (p < 0.015, CI 1.13-3.24) for fractures. Refereed/Peer-reviewed

Background: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. Conclusions/significance: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities. Methodology/principal findings: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P

Objective: To compare the demographic, socioeconomic, and medical characteristics of patients who had a General Practitioner Management Plan (GPMP) with those for patients without GPMP. Methods: Cohort study of patients with chronic diseases during the time period 1 July 2006 to 30 June 2008 using the Australian Department of Veterans’ Affairs (DVA) claims database. Results: Of the 88 128 veterans with chronic diseases included in the study, 23 015 (26%) veterans had a GPMP and 11 089 (13%) had a Team Care Arrangement (TCA). Those with a GPMP had a higher number of comorbidities (P < 0.001), and a higher use of services such as health assessment and medicine review (P < 0.001) than did those without GPMP. Diabetes was associated with a significantly increased use of GPMP compared with all other chronic diseases except heart failure. Conclusions: GPMPs are used in a minority of patients with chronic diseases. Use is highest in people with diabetes. What is known about the topic?: Despite the fact that the Chronic Disease Management (CDM) program is appreciated by patients and allied health professionals, limited research has assessed how it is used in practice. What does this paper add?: In the Veteran population, use of a General Practitioner Management Plan (GPMP) was associated with a higher number of comorbidities and of prior hospitalisations. Across chronic diseases use of GPMPs was low but was higher in people with diabetes. What are the implications for practitioners?: Further research into the effect of CDM program on improvement of health outcomes is required. Refereed/Peer-reviewed

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.