Uptake of osteoporosis treatment recommended by an orthogeriatrics service after hip fracture: Retrospective cohort study of prevalence and potential barriers and enablers at a tertiary referral hospital in Sydney.

OBJECTIVE: The primary aim was to determine the 12-month period prevalence of and time to osteoporosis treatment following minimal trauma hip fractures in patients who were recommended treatment by an orthogeriatrics service. The secondary aim was to determine the factors associated with receiving treatment including the impact of osteoporosis clinic follow-up. METHODS: A retrospective cohort study of patients with minimal trauma hip fractures admitted at a tertiary hospital in Sydney between 1 April 2017 and 31 March 2019 was performed. Baseline characteristics were collected from medical records. Osteoporosis treatment data were collected from patients and general practitioners. Univariate and multivariate logistic regression analyses were used to determine the factors associated with receiving osteoporosis treatment. RESULTS: There were 189 participants who consented to participate with a mean age of 84.6 years. Most (76.7%) were females, 18.5% were nursing home residents, 70.9% had normal cognition, 20.6% were taking osteoporosis treatment prior to admission, 61.9% had osteoporosis treatment recommendations documented on the discharge summary, and 10.1% were followed up in the osteoporosis clinic. Ninety-eight patients (51.9%) received treatment within the first 12 months after fracture with a median time to treatment of 90 days. Factors associated with receiving osteoporosis treatment within 12 months on multivariate analysis included normal cognition (p = 0.03), taking osteoporosis treatment prior to admission (p < 0.001), including treatment recommendations in the discharge summary (p = 0.006) and osteoporosis clinic follow-up (p < 0.001). CONCLUSIONS: Osteoporosis treatment after hip fracture remains suboptimal at this hospital. Patient and health service factors associated with treatment uptake could inform future quality improvement work.

Interactions Between the Aging Gut Microbiome and Common Geriatric Giants: Polypharmacy, Frailty, and Dementia.

The gut microbiome has pervasive bidirectional relationships with pharmacotherapy, chronic disease, and physical and cognitive function. We conducted a narrative review of the current literature to examine the relationships between the gut microbiome, medication use, sarcopenia and frailty, and cognitive impairment. Data from in vitro experiments, in vivo experiments in invertebrates and complex organisms, and humans indicate associations between the gut microbiome and geriatric syndromes. Better understanding of the direct and indirect roles of the microbiome may inform future prevention and management of geriatric syndromes.

Prevalence of adverse drug events and adverse drug reactions in hospital among older patients with dementia: A systematic review.

AIMS: This systematic review aimed to quantify the prevalence of adverse drug events (ADEs) and adverse drug reactions (ADRs) in older inpatients with dementia. METHODS: A systematic search of observational studies was performed in Embase, Medline, PsycINFO, International Pharmaceutical Abstracts, Scopus and Informit. Articles published in English that reported the prevalence of ADEs or ADRs in hospital patients aged 65 years or older with dementia were included. Two authors reviewed titles and abstracts and all eligible full-text articles. Relevant information relating to ADEs, ADRs and dementia was obtained from each article. RESULTS: In total, 5 articles were included. One study reported the prevalence of ADEs to be 81.5%, defined using the Naranjo algorithm. Four studies assessed the prevalence of ADRs, ranging from 12.7 to 24.0%, assessed using various methods. One study defined ADRs according to the World Health Organization-Uppsala Monitoring Centre criteria, 2 studies employed the World Health Organization definition and 1 study did not explicitly define ADRs. The most frequently reported drug classes implicated in ADEs and ADRs were psychotropic, antihypertensive and analgesic drugs. CONCLUSION: Our findings suggest a high prevalence of ADEs and ADRs in older inpatients with dementia. However, only 1 study documented ADEs and there was variability in approaches to ADR assessment. A greater understanding of ADEs and ADRs, as well as tailored assessment tools, will promote prevention of ADEs and ADRs in people with dementia.

Pain and Inflammation Management in Older Adults: A Brazilian Consensus of Potentially Inappropriate Medication and Their Alternative Therapies.

Purpose: The aim of the present study was to develop and validate a Potentially Inappropriate Medications (PIM) list and alternative therapies for treatment of pain and inflammation in older people adapted to the Brazilian context. Methods: A preliminary PIM list suitable for the Brazilian market was developed on the basis of three published international PIM lists [Beers 2015, Screening Tool of Older People's Potentially Inappropriate Prescriptions - 2015, European Union (7) PIM list]. We used the modified Delphi technique (two-round) to validate concerns of use and alternative therapies related to PIM for treatment of pain and inflammation in older adults ≥65 years in Brazil. The panel involved nine Brazilian experts in geriatric pharmacotherapy. All items with mean Likert scale score ≥4.0 (agree) and the lower limit of 95% confidence interval ≥4.0 were considered validated in this study. Results: At the end of the consensus process, 94 (65.3%) items of 144 were validated. In total, consensus was reached for 33/35 (94.3%) concerns about drugs that should be avoided in older patients regardless of diagnosis, for 22/23 (95.7%) concerns about drugs that should be avoided in older patients with specific conditions or diseases, for 11/23 (47.8%) with special considerations of use, and for 28/63 (44.4%) of therapeutic alternatives. Conclusion: Although these criteria are not designed to replace clinical judgement, PIM and alternative therapies lists can be useful to inform prescribers, pharmacists, and health care planners and may serve as a starting point for safe and effective use of medications in older people.

Potentially inappropriate medication in the elderly: a systematic review of validated explicit criteria.

PURPOSE: Potentially inappropriate medication (PIM) use causes preventable adverse drug reactions in older patients. Several assessment tools have been published to identify and avoid PIM use. In this systematic literature review, we aim to provide summaries and comparisons of validated PIMs lists published between 1991 and 2017 internationally. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA), we performed a systematic review of articles describing the development and validation of criteria for identification of PIMs among older people published between January 1991 and April 2017. The searches were conducted on PUBMED, AgeLine, Academic Search, Academic Search Premier, and CINAHL. We identified the most common medications/classes described as PIM. We also identified the drug-disease interactions and drug-drug interactions reported among criteria. RESULTS: From 2933 articles screened, 36 met our inclusion criteria. The majority used the Delphi method to validate their criteria. We identified 907 different medications/classes, 536 different drug disease interactions involving 84 diseases/conditions, and 159 drug-drug interactions. Benzodiazepines and nonsteroidal anti-inflammatory drugs were the medications most commonly reported as potentially inappropriate for older people. CONCLUSION: Although approaches aimed at detecting inappropriate prescribing have intensified in recent years, we observed limited overlap between different PIM lists. Additionally, some PIM lists did not provide special considerations of use and alternative therapies to avoid PIMs. These facts may compromise the use of PIM lists in clinical practice. Future PIM lists should integrate information about alternative therapies and special considerations of use in order to help clinicians in the drug prescription.

The impact of frailty on coagulation and responses to warfarin in acute older hospitalised patients with atrial fibrillation: a pilot study.

BACKGROUND: The evidence on coagulation changes with frailty is not consistent and clinical studies suggest that frail older people may be at an increased risk of bleeding complications with anticoagulant therapy. AIMS: This study aims to assess the impact of frailty on coagulation function and on response to warfarin. METHODS: Inpatients aged over 65 years with atrial fibrillation (AF) were recruited. Frailty was determined using the Reported Edmonton Frail Scale. The Overall Haemostatic Potential (OHP) and Calibrated Automated Thrombogram (CAT) were used to globally assess coagulation function. RESULTS: Data of 95 participants were analysed, mean age 85.5 ± 6.2, 40% female, and 50.5% frail. Among participants not on anticoagulants (N = 36), there was an increased fibrin generation and decreased thrombin generation compared to the local established normal ranges in young healthy volunteers; the frail had significantly reduced fibrin generation compared to the non-frail. In the warfarin-treated group (N = 59), there was no difference on coagulation profiles between the frail and the non-frail from any of the coagulation tests. CONCLUSION: In this cohort of acute hospitalised patients with AF, the observed decreased fibrin generation in the frail may reflect decreased acute phase response as suggested with the lower plasma fibrinogen in that group. There was no difference in coagulation profiles between the frail and the non-frail amongst those taking warfarin. Compared to young healthy volunteers, older inpatients had increased fibrin generation and decreased thrombin generation. The findings reflect the complex interaction between age, frailty, acute illness, and coagulation.

Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.

While age-related insulin resistance and hyperinsulinemia are usually considered to be secondary to changes in muscle, the liver also plays a key role in whole-body insulin handling and its role in age-related changes in insulin homeostasis is largely unknown. Here, we show that patent pores called 'fenestrations' are essential for insulin transfer across the liver sinusoidal endothelium and that age-related loss of fenestrations causes an impaired insulin clearance and hyperinsulinemia, induces hepatic insulin resistance, impairs hepatic insulin signaling, and deranges glucose homeostasis. To further define the role of fenestrations in hepatic insulin signaling without any of the long-term adaptive responses that occur with aging, we induced acute defenestration using poloxamer 407 (P407), and this replicated many of the age-related changes in hepatic glucose and insulin handling. Loss of fenestrations in the liver sinusoidal endothelium is a hallmark of aging that has previously been shown to cause deficits in hepatic drug and lipoprotein metabolism and now insulin. Liver defenestration thus provides a new mechanism that potentially contributes to age-related insulin resistance.

N-Acetyl cysteine does not prevent liver toxicity from chronic low-dose plus subacute high-dose paracetamol exposure in young or old mice.

Paracetamol is an analgesic commonly used by people of all ages, which is well documented to cause severe hepatotoxicity with acute overexposures. The risk of hepatotoxicity from nonacute paracetamol exposures is less extensively studied, and this is the exposure most common in older adults. Evidence on the effectiveness of N-acetyl cysteine (NAC) for nonacute paracetamol exposures, in any age group, is lacking. This study aimed to examine the effect of long-term exposure to therapeutic doses of paracetamol and subacute paracetamol overexposure, in young and old mice, and to investigate whether NAC was effective at preventing paracetamol hepatotoxicity induced by these exposures. Young and old male C57BL/6 mice were fed a paracetamol-containing (1.33 g/kg food) or control diet for 6 weeks. Mice were then dosed orally eight times over 3 days with additional paracetamol (250 mg/kg) or saline, followed by either one or two doses of oral NAC (1200 mg/kg) or saline. Chronic low-dose paracetamol exposure did not cause hepatotoxicity in young or old mice, measured by serum alanine aminotransferase (ALT) elevation, and confirmed by histology and a DNA fragmentation assay. Subacute paracetamol exposure caused significant hepatotoxicity in young and old mice, measured by biochemistry (ALT) and histology. Neither a single nor double dose of NAC protected against this toxicity from subacute paracetamol in young or old mice. This finding has important clinical implications for treating toxicity due to different paracetamol exposure types in patients of all ages, and implies a need to develop new treatments for subacute paracetamol toxicity.