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- Bennett, Alexander, et al.
(författare)
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Prevalence and Impact of Fall-Risk-Increasing Drugs, Polypharmacy, and Drug-Drug Interactions in Robust Versus Frail Hospitalised Falls Patients : A Prospective Cohort Study
- 2014
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Ingår i: Drugs & Aging. - : Springer Science and Business Media LLC. - 1170-229X .- 1179-1969. ; 31:3, s. 225-232
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Tidskriftsartikel (refereegranskat)abstract
- Background Several measures of medication exposure are associated with adverse outcomes in older people. Exposure to and the clinical outcomes of these measures in robust versus frail older inpatients are not known. Objective In older robust and frail patients admitted to hospital after a fall, we investigated the prevalence and clinical impact of fall-risk-increasing drugs (FRIDs), total number of medications, and drug-drug interactions (DDIs). Methods Patients >= 60 years of age admitted with a fall to a tertiary referral teaching hospital in Sydney were recruited and frailty was assessed. Data were collected at admission, discharge, and 2 months after admission. Results A total of 204 patients were recruited (mean age 80.5 +/- 8.3 years), with 101 robust and 103 frail. On admission, compared with the robust, frail participants had significantly higher mean +/- SD number of FRIDs (frail 3.4 +/- 2.2 vs. robust 1.6 +/- 1.5, P < 0.0001), total number of medications (9.8 +/- 4.3 vs. 4.4 +/- 3.3, P < 0.0001), and DDI exposure (35 vs. 5 %, P = 0.001). Number of FRIDs on discharge was significantly associated with recurrent falls [odds ratio (OR) 1.7 (95 % confidence interval [CI] 1.3-2.1)], which were most likely to occur with 1.5 FRIDs in the frail and 2.5 FRIDs in the robust. Number of medications on discharge was also associated with recurrent falls [OR 1.2 (1.0-1.3)], but DDIs were not. Conclusion Exposure to FRIDs and other measures of high-risk medication exposures is common in older people admitted with falls, especially the frail. Number of FRIDs and to a lesser extent total number of medicines at discharge were associated with recurrent falls.
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| 2. |
- Chen, Lynna, et al.
(författare)
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The association between benzodiazepine use and sleep quality in residential aged care facilities : a cross-sectional study
- 2016
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Ingår i: BMC Geriatrics. - : Springer Science and Business Media LLC. - 1471-2318. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Benzodiazepines are commonly prescribed in residential aged care facilities (RACFs) for their sedative and anxiolytic effects. The objective of this study was to investigate the association between benzodiazepine use and sleep quality in residents of RACFs. Methods: A cross-sectional study involving 383 participants was conducted in six Australian RACFs. Night-time sleep quality, day-time drowsiness and day-time napping behavior were assessed using a validated questionnaire. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for the association between benzodiazepine use and sleep quality. Covariates included pain, dementia severity, depression, insomnia and other sedative use. Results: Of the 383 residents (mean age 87.5 years, 77.5% female), 96(25.1%) used a benzodiazepine on a regular basis. Residents who used long-acting benzodiazepines on a regular basis had higher night-time sleep quality than non-users (AOR = 4.00, 95%CI 1.06 - 15.15). Residents who used short-acting benzodiazepines on a PRN only basis had longer daytime napping times than non-users (AOR = 1.77, 95% CI 1.01 - 3.08). No benzodiazepine category was associated with day-time drowsiness. Conclusions: The association between benzodiazepine use and sleep quality is dependent on the half-life and prescribing pattern of the benzodiazepine. Short-acting PRN benzodiazepines were associated with lower night time sleep quality and longer day-time napping compared to long-acting regular benzodiazepines. Longitudinal studies are needed to determine whether these findings reflect channeling of short-acting agents to residents at higher risk of sleep disorders.
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| 3. |
- Eroli, Francesca, et al.
(författare)
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Chronic polypharmacy impairs explorative behavior and reduces synaptic functions in young adult mice
- 2020
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 12:11, s. 10147-10161
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in the health care system is the lack of knowledge about the possible harmful effects of multiple drug treatments in old age. The present study aims to characterize a mouse model of polypharmacy, in order to investigate whether long-term exposure to multiple drugs could lead to adverse outcomes. To this purpose we selected five drugs from the ten most commonly used by older adults in Sweden (metoprolol, paracetamol, aspirin, simvastatin and citalopram). Five-month-old wild type male mice were fed for eight weeks with control or polypharmacy diet. We report for the first time that young adult polypharmacy-treated mice showed a significant decrease in exploration and spatial working memory compared to the control group. This memory impairment was further supported by a significant reduction of synaptic proteins in the hippocampus of treated mice. These novel results suggest that already at young adult age, use of polypharmacy affects explorative behavior and synaptic functions. This study underlines the importance of investigating the potentially negative outcomes from concomitant administration of different drugs, which have been poorly explored until now. The mouse model proposed here has translatable findings and can be applied as a useful tool for future studies on polypharmacy.
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| 4. |
- Francesca, Eroli, et al.
(författare)
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Long-term exposure to polypharmacy impairs cognitive functions in young adult female mice
- 2021
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Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 13:11, s. 14729-14744
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Tidskriftsartikel (refereegranskat)abstract
- The potential harmful effects of polypharmacy (concurrent use of 5 or more drugs) are difficult to investigate in an experimental design in humans. Moreover, there is a lack of knowledge on sex-specific differences on the outcomes of multiple-drug use. The present study aims to investigate the effects of an eight-week exposure to a regimen of five different medications (metoprolol, paracetamol, aspirin, simvastatin and citalopram) in young adult female mice. Polypharmacy-treated animals showed significant impairment in object recognition and fear associated contextual memory, together with a significant reduction of certain hippocampal proteins involved in pathways necessary for the consolidation of these types of memories, compared to animals with standard diet. The impairments in explorative behavior and spatial memory that we reported previously in young adult male mice administered the same polypharmacy regimen were not observed in females in the current study. Therefore, the same combination of medications induced different negative outcomes in young adult male and female mice, causing a significant deficit in non-spatial memory in female animals. Overall, this study strongly supports the importance of considering sex-specific differences in designing safer and targeted multiple-drug therapies.
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| 5. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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