In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione ...depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations.
The study population was 3523 Australian Government Department of Veterans' Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used.
The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67-0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06-1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping.
Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
The aim of this study was to compare adherence and persistence in patients who add ezetimibe to statin therapy as a separate pill combination (SPC) or fixed dose combination (FDC).
Method
This ...is a retrospective cohort study of prescription data conducted in an Australian health dataset. Two cohorts were identified: those dispensed statins and subsequently ezetimibe as either SPC or FDC. We compared adherence to combination therapy using the medication possession ratio (MPR), multivariate linear and logistic regression. Persistence to initial combination medicines and any lipid‐lowering therapies were analysed using Kaplan Meyer survival and Cox proportional hazards models.
Results
A total of 3651 people initiated ezetimibe SPC and 5740 ezetimibe FDC. There was no significant difference in adherence with mean MPRs: ezetimibe SPC = 0.99 (95% confidence interval 0.98–1.01) and FDC = 0.97 (95% CI 0.95–0.99). One year persistence rates to initial combination medicines were ezetimibe SPC 49.1% vs. FDC 62.4%; hazard ratio (HR) = 1.81 (95% CI 1.76–1.90). However, persistence to any lipid‐lowering therapy was higher in those initiating ezetimibe SPC = 84.9% vs. FDC = 76%; HR = 0.62 (95% CI 0.55–0.72). One year persistence rates to any two lipid‐lowering medicines were similar: ezetimibe SPC 65.2% and FDC 65%.
Conclusion
In this study FDCs have little impact on either adherence or persistence to combination lipid‐lowering therapy in people who have been taking statins. The benefit of higher persistence to FDCs in first episode of treatment with initial medicines is debatable as persistence to dual therapy was similar in both cohorts.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Antipsychotics are frequently and increasingly prescribed to treat the behavioural symptoms associated with dementia despite their modest efficacy. Evidence regarding the potential adverse events of ...antipsychotics is limited and little is known about the longer-term safety of these medicines in the elderly. The aim of this review was to determine the impact of the choice of observational study design and methods used to control for confounding on the measurement of antipsychotic risks in elderly patients.
We searched PUBMED and the Cochrane controlled trials register for double-blind randomised controlled trials (RCTs), meta-analyses and published observational studies of antipsychotics.
Forty four studies were identified for the endpoints; death, cerebrovascular events, hip fracture and pneumonia. RCTs found a 20% to 30% increased risk of death, or an absolute increase of 1extra death per 100 patients with atypical antipsychotics compared to non-use. Cohort and instrumental variable analyses estimated between 2 to 7 extra deaths per 100 patients with conventional compared to atypical antipsychotics. RCTs found a 2 to 3 times increased risk of all cerebrovascular events with atypical antipsychotics compared to placebo and no association with serious stroke that required hospitalisation. Observational studies using cohort and self-controlled case-series designs reported similar results; no association where the endpoint was stroke causing hospitalisation and a doubling of risk when minor stroke was included. No RCTs were available for the outcome of hip fracture or pneumonia. Observational studies reported a 20% to 40% increased risk of hip fracture with both antipsychotic classes compared to non-use. The risk of pneumonia was a 2 to 3 times greater with both classes compared to non-use while a self-controlled case-series study estimated a 60% increased risk. Conventional antipsychotics were associated with a 50% greater hip fracture risk than atypical antipsychotics, while the risk of pneumonia was similar between the classes.
Choice of observational study design is critical in studying the adverse effects of antispychotics. Cohort and instrumental variable analyses gave more consistent results to clinical studies for mortality outcomes as have self-controlled case-series for the risk of cerebrovascular events and stroke. Observational evidence has highlighted the potential for antipsychotics to be associated with serious adverse events that were not reported in RCTs including hip fracture and pneumonia. Good quality observational studies are required, that employ appropriate study designs that are robust towards unmeasured confounding, to confirm the potential excess risk of hip fracture and pneumonia with antipsychotics.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective measures for screening, prioritizing, and planning care for frail individuals are essential for appropriate aged care provision. This study evaluates metrics derived from actigraphy ...measures (captured by wrist accelerometer) as a digital biomarker to identify frail individuals at risk of adverse outcomes, including death, hospitalization, and cognitive decline.
This was a secondary study using data from a randomized controlled trial assessing the effectiveness of an ongoing pharmacist service in residential aged care facilities. Three metrics are studied and compared: the Frailty Index, the daily time spent in light time activity, and the temporal correlation of the actigraphy signal, measured by detrended fluctuation analysis. The association between actigraphy-derived metrics at baseline and adverse events within 12 months (death, cognitive decline, and hospitalizations) was assessed using logistic regression.
Actigraphy records were available for 213 participants living in aged-care, median age of 85 years. Individuals with higher temporal correlation (activity is less random) were at lower risk of death (Standardized OR: 0.49; 95% CI 0.34, 0.7, p < 0.001) and hospitalization (Standardized OR: 0.57; 95% CI 0.42, 0.77, p < 0.001) in 12 months, but there was no difference in cognitive decline (Standardized OR: 1; 95% CI 0.74, 1.35, p = 0.98). The predictive model that included temporal correlation had an area under the curve of 0.70 (CI 0.60-0.80) for death and 0.64 (CI 0.54-0.72) for hospitalization.
Temporal correlation of the actigraphy signal from aged care residents was strongly associated with death and hospitalization, but not cognitive decline. Digital biomarkers may have a place as an objective, accurate, and low-cost patient metric to support risk stratification and clinical planning.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
IntroductionThis feasibility study aims to develop and test a new model of practice in Australia using digital technologies to enable pharmacists to monitor early signs and symptoms of ...medicine-induced harms in residential aged care.Methods and analysisThirty residents will be recruited from an aged care facility in South Australia. The study will be conducted in two phases. In phase I, the study team will work with aged care software providers and developers of digital technologies (a wearable activity tracker and a sleep tracking sensor) to gather physical activity and sleep data, as well as medication and clinical data from the electronic medication management system and aged care clinical software. Data will be centralised into a cloud-based monitoring platform (TeleClinical Care (TCC)). The TCC will be used to create dashboards that will include longitudinal visualisations of changes in residents’ health, function and medicine use over time. In phase II, the on-site pharmacist will use the centralised TCC platform to monitor each resident’s medicine, clinical, physical activity and sleep data to identify signs of medicine-induced harms over a 12-week period.A mixed methods process evaluation applying the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) evaluation framework will be used to assess the feasibility of the service. Outcome measures include service reach, changes in resident symptom scores (measured using the Edmonton Symptom Assessment System), number of medication adverse events detected, changes in physical activity and sleep, number of pharmacist recommendations provided, cost analysis and proportion of all pharmacists’ recommendations implemented at 4-week, 8-week and 12-week postbaseline period.Ethics and disseminationEthical approval has been obtained from the University of South Australia’s Human Research Ethics Committee (205098). Findings will be disseminated through published manuscripts, conference presentations and reporting to the study funder.Trial registration numberACTRN12623000506695.
It is not known if the medicines and services for COPD are used in Australia according to the COPD-X guideline. This study examined the use of medicines and health services for COPD among an ...Australian cohort to determine if they were consistent with recommendations.
The administrative claims data from the Australian Government Department of Veterans' Affairs were used and included persons aged ≥50 years who were using medicines for COPD in April 2016. Use of medicines was identified using the Anatomical, Therapeutic and Chemical Classification and Pharmaceutical Benefits Scheme. Use of services was identified using the Medicare Benefits Schedule and Australian Government Department of Veterans' Affairs Fee Schedule.
Of the 143,261 persons aged ≥50 years, 12,623 (8.8%) were on medicines for COPD. Of the total COPD population, 42% were managed on monotherapy, 36% on dual therapy, 21% on triple therapy, and 1.5% on more than three COPD medicines. Monotherapy comprised tiotropium (80%) predominantly. Services to practitioners who may provide pulmonary rehabilitation service showed less than 10% of the cohort had a claim for a visit to an exercise physiologist and less than a third had a claim for a physiotherapist visit in the prior 12 months. Services to assist with care coordination in the form of general practitioner management plans were only claimed by half of the cohort, while services supporting appropriate medicine use were claimed by less than one in six cases, despite high levels of inhaler use and multiple inhaler use.
More than three-quarters of COPD persons aged 50 years and above were managed on either monotherapy or dual therapy, consistent with the guideline recommendations. Almost one-quarter was on three or more therapies, which will create challenges for multiple device management. Many services that may benefit persons with COPD appear to be underutilized.
•The effects of medicines on physical function have not been quantified.•We studied the association between medicine changes and 24-hour activity composition.•As sedative/anticholinergic load ...increased, sedentary time increased.•Wearable accelerometry bands can be used to monitor the effects of medicines on physical function.
Studies have shown that use of medicines with sedative or anticholinergic properties is associated with a decline in physical function; however, the effects have not been quantified, and it is not known how and which specific physical movements are affected. This prospective study quantified the impact of a change in sedative or anticholinergic load over time on 24-hour activity composition.
This study used data collected from a randomised trial assessing an ongoing pharmacist service in residential aged care. The 24-hour activity composition of sleep, sedentary behaviour, light-intensity physical activity, and moderate to vigorous physical activity was derived from 24-hour accelerometry bands. Mixed effect linear models were used to regress the multivariate outcome of 24-hour activity composition on medication load at baseline and at 12 months. A fixed effect interaction between trial stage and medication load was included to test for differing sedative or anticholinergic load effects at the two trial stages.
Data for 183 and 85 participants were available at baseline and 12 months respectively. There was a statistically significant interaction between medication load and time point on the multivariate outcome of 24-hour activity composition (sedative F = 7.2, p < 0.001 and anticholinergic F = 3.2, p = 0.02). A sedative load increase from 2 to 4 over the 12-month period was associated with an average increase in daily sedentary behaviour by an estimated 24 min.
As sedative or anticholinergic load increased, there was an increase in sedentary time. Our findings suggest wearable accelerometry bands are a possible tool for monitoring the effects on physical function of sedative and anticholinergic medicines.
The ReMInDAR trial was registered on the Australian and New Zealand Trials Registry ACTRN12618000766213.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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