Attitudes towards deprescribing and the influence of health literacy among older Australians

Aim This study aimed to explore attitudes, beliefs and experiences regarding polypharmacy and discontinuing medications, or deprescribing, among community living older adults aged ≥65 years, using ≥5 medications. It also aimed to investigate if health literacy capabilities influenced attitudes and beliefs towards deprescribing. Background Polypharmacy use is common among Australian older adults. However, little is known about their attitudes towards polypharmacy use or towards stopping medications. Previous studies indicate that health literacy levels tend to be lower in older adults, resulting in poor knowledge about medications. Methods A self-administered survey was conducted using two previously validated tools; the Patients’ Attitude Towards Deprescribing (PATD) tool to measure attitudes towards polypharmacy use and deprescribing and the All Aspects of Health Literacy Scale (AAHLS) to measure functional, communicative and critical health literacy. Descriptive statistical analysis was conducted. Findings The 137 responses showed that 80% thought all their medications were necessary and were comfortable with the number taken. Wanting to reduce the number of medications taken was associated with concerns about the amount taken (P\u3c0.001), experiencing side effects (P\u3c0.001), or believing that one or more medications were no longer needed (P\u3c0.000). Those who were using ten or more medications were more likely to want to reduce the number taken (P=0.019). Most (88%) respondents would be willing to stop medication/s in the context of receiving this advice from their doctor. Willingness to consider stopping correlated with higher scores on the critical health literacy subscale (P\u3c0.021) and overall AAHLS score (P\u3c0.009). Those with higher scores on the overall AAHLS measure were more likely to report that they understood why their medications were prescribed (P\u3c0.000) and were more likely to participate in decision-making (P=0.027). Opportunities to proactively consider deprescribing may be missed, as one third of the respondents could not recall a recent review of their medications

Medication Management for People Living with Dementia: Development and Evaluation of a Multilingual Information Resource for Family Caregivers of People Living with Dementia

The aim of this chapter is to describe the development and evaluation of an online multilingual information resource focused on medication management, targeting people living with dementia and their family caregivers. Maintaining effective medication management is important to allow ongoing quality of life within the community setting and avoiding medication-related preventable hospitalisations for the person living with dementia. Family caregivers are likely to assume the role of medication management on behalf of the person in their care as dementia progresses. Little training or information is available to family caregivers to assist them with this role. A pilot online information resource was developed and evaluated. Responding to the evaluation, this resource was improved, and a more extensive evaluation process was undertaken. The development and evaluation process are outlined with a view to guiding the development of similar resources, especially those targeting linguistically diverse family caregivers and those with dementia. This is especially important given that many older adults will migrate during their lifetime, often to a country where they are not familiar with the language or health services. Extra support is needed to assist older immigrants who are themselves at risk or are caring for someone with dementia

A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses

ABSTRACT Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Developing a medication management resource for ethnic minority informal caregivers of people living with dementia

This paper outlines the motivation for and the development of a medication management information resource for Australian ethnic minority informal caregivers of people living with dementia. The aim of this project is to enable ethnic minority informal caregivers to safely and effectively manage medications for their care recipient living with dementia in the community setting. A large number of Australian informal caregivers of people living with dementia are from ethnic minority backgrounds. Medication management is a common, but often times complex, daily task undertaken by many informal caregivers. Since many of the caregiver\u27s medication management responsibilities increase as the cognitive capabilities of their care recipients\u27 decline with advancing dementia and no comprehensive dementia specific medication management information resource currently exists we felt it important to develop a useful, accessible information resource for informal caregivers in this role. The development of this medication management information resource occurred in two stages; the first stage involved a qualitative study to gain insight into the perspectives and the information needs of these ethnic minority informal caregivers as they manage medications for their care recipient. The results and main themes identified in this first stage were then used to inform the second stage of the study which involved the development of the medication management information resource, to be available online in both English and Italian. These are nearing completion and will be evaluated before becoming generally available online. It is anticipated that this information resource will provide family caregivers of people with dementia information and support in this role

Managing medications: the role of informal caregivers of older adults and people living with dementia. A review of the literature

Aims and objectives To explore published literature that describes what is known about the role of informal caregivers as they manage medications for older adults and/or people living with dementia residing in the community. Background The number of informal caregivers of older adults, including people living with dementia, is growing worldwide. Good medication management by informal caregivers contributes to improved health outcomes and reduced institutionalisations for the care recipient; however, little is known about this domain of care. Design Narrative review. Methods A literature search was conducted to identify relevant research articles written in English between January 2000-April 2013, sourced from online database searches using multiple keywords, reviewing reference lists and citations of key articles and Internet searches. Articles were included if they described informal caregiver medication management for older adults and/or people living with dementia. Results Ten articles were found that described this role from the perspective of the informal caregiver. The evidence suggests that this role is complex and is often made more difficult because of increasing medication regimen complexities, aspects of the relationship between the caregiver and the care recipient, healthcare system practices and a lack of information and/or training available to the informal caregiver, especially when caring for people living with dementia. Conclusion Responsibility for managing medications for older adults and/or people living with dementia in the community often falls to informal caregivers. More information resources are required for this role, which requires specific medication management skills and knowledge and is further complicated by the cognitive decline of the care recipient

Medication management concerns of ethnic minority family caregivers of people living with dementia

This qualitative study explored the medication management experiences of Australian ethnic minority family caregivers of people living with dementia. From the perspective of this group of caregivers, medication management was a source of stress resulting from the progressive loss of ability of care recipients to manage their own medications; the complexity of the medication regime and the caregiver\u27s lack of trust of the care recipient to safely and effectively manage medications. Caregivers used various strategies to manage medications and avoid conflict with care recipients including being watchful and involving other family members in medication management tasks. Family caregivers indicated that a lack of information and access to support to inform their medication management role added to their stress, which was exacerbated in some cases by limited English proficiency. Supportive factors noted by caregivers included a well-established relationship with a community pharmacist, involvement of a geriatrician, family support and caregiver support group participation