122 results on '"Prasad S, Nishtala"'
Search Results
2. Analysis of the adverse events following the mRNA-1273 COVID-19 vaccine
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Angel Shabu and Prasad S. Nishtala
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adverse events (aes) ,covid-19 ,mrna-1273 ,moderna ,sars-cov-2 ,Internal medicine ,RC31-1245 - Abstract
Objective This study aims to characterize the adverse events (AEs) following the administration of the mRNA-1273 COVID-19 vaccine from the Vaccine Adverse Event Reporting System (VAERS) data. Methods In this case/non-case analysis, reports between 1 January 2021, and 27 October 2022, were extracted from VAERS. AEs were defined as preferred terms (PTs) by Medical Dictionary for Regulatory Activities (MedDRA) terminology. Disproportionality analyses were conducted to calculate the reporting odds and proportional reporting ratios. The Bayesian approach was used to calculate information component (IC) values and Empirical Bayesian Geometric Mean scores for all the AEs detected. Results 186 MedDRA PTs compromising 702,495 AEs associated with the mRNA-1273 vaccine were identified. Three statistically significant signals were identified for general and systemic AEs, administration site conditions, and product issues. Cardiac disorders were rarely reported, the most common being; 489 reports for ‘myocarditis’ (19.44%), 475 for ‘acute myocardial infarction’ (18.88%), 457 for ‘myocardial infarction’ (18.16%), 290 for ‘bradycardia’ (11.53%) and 281 for ‘pericarditis’ (11.17%). Conclusions The most frequently identified AEs following mRNA-1273 vaccination agree with those listed within the Summary of Product Characteristics. In addition, disproportionality analysis did not find any statistically significant signals for myocarditis or pericarditis.
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- 2023
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3. Safety outcomes associated with the moderna COVID-19 vaccine (mRNA-1273): a literature review
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Angel Shabu and Prasad S. Nishtala
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covid-19 ,mrna-1273 ,moderna ,safety ,sars-cov-2 ,Internal medicine ,RC31-1245 - Abstract
Introduction Current safety data from Phase 3 clinical trials have concluded that apart from transient local and systemic reactions, no safety concerns were identified for the Moderna COVID-19 vaccine (mRNA-1273). However, Phase 3 studies are insufficient to detect rare adverse events (AEs). A literature search of the two major electronic databases, Embase and PubMed, was performed to enable the identification and characterization of all relevant articles from December 2020 to November 2022. Areas Covered This narrative review summarizes the key safety outcomes associated with the mRNA-1273 vaccine to inform healthcare decisions and increase public awareness of mRNA-1273 vaccine safety. The primary adverse events (AEs) reported within a diverse population, receiving the mRNA-1273 vaccine, were; localized injection site pain, fatigue, headache, myalgia, and chills. In addition, the mRNA-1273 vaccine was also associated with; less than a 1-day change in the menstrual cycle, a 10-fold higher risk of myocarditis and pericarditis within young males aged 18–29 years and increased levels of anti-polyethylene glycol (PEG) antibodies. Expert Opinion The transient nature of commonly observed AEs and the rare occurrence of severe events within mRNA-1273 recipients show no significant safety concerns which should prevent vaccination. However, large-scale epidemiological studies with longer follow-up periods are required to surveillance rare safety outcomes.
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- 2023
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4. Application of machine learning approaches in predicting clinical outcomes in older adults – a systematic review and meta-analysis
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Robert T. Olender, Sandipan Roy, and Prasad S. Nishtala
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Older adults ,Machine learning ,Predictive modelling ,Model performance evaluation ,Health informatics ,Risk management ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background Machine learning-based prediction models have the potential to have a considerable positive impact on geriatric care. Design Systematic review and meta-analyses. Participants Older adults (≥ 65 years) in any setting. Intervention Machine learning models for predicting clinical outcomes in older adults were evaluated. A random-effects meta-analysis was conducted in two grouped cohorts, where the predictive models were compared based on their performance in predicting mortality i) under and including 6 months ii) over 6 months. Outcome measures Studies were grouped into two groups by the clinical outcome, and the models were compared based on the area under the receiver operating characteristic curve metric. Results Thirty-seven studies that satisfied the systematic review criteria were appraised, and eight studies predicting a mortality outcome were included in the meta-analyses. We could only pool studies by mortality as there were inconsistent definitions and sparse data to pool studies for other clinical outcomes. The area under the receiver operating characteristic curve from the meta-analysis yielded a summary estimate of 0.80 (95% CI: 0.76 – 0.84) for mortality within 6 months and 0.81 (95% CI: 0.76 – 0.86) for mortality over 6 months, signifying good discriminatory power. Conclusion The meta-analysis indicates that machine learning models display good discriminatory power in predicting mortality. However, more large-scale validation studies are necessary. As electronic healthcare databases grow larger and more comprehensive, the available computational power increases and machine learning models become more sophisticated; there should be an effort to integrate these models into a larger research setting to predict various clinical outcomes.
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- 2023
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5. The association between anticholinergic burden and mobility: a systematic review and meta-analyses
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Geofrey O. Phutietsile, Nikoletta Fotaki, Hamish A. Jamieson, and Prasad S. Nishtala
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Anticholinergic burden ,Antimuscarinic ,Physical function ,Gait ,Polypharmacy ,Elderly ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background As people age, they accumulate several health conditions, requiring the use of multiple medications (polypharmacy) to treat them. One of the challenges with polypharmacy is the associated increase in anticholinergic exposure to older adults. In addition, several studies suggest an association between anticholinergic burden and declining physical function in older adults. Objective/Purpose This systematic review aimed to synthesise data from published studies regarding the association between anticholinergic burden and mobility. The studies were critically appraised for the strength of their evidence. Methods A systematic literature search was conducted across five electronic databases, EMBASE, CINAHL, PSYCHINFO, Cochrane CENTRAL and MEDLINE, from inception to December 2021, to identify studies on the association of anticholinergic burden with mobility. The search was performed following a strategy that converted concepts in the PECO elements into search terms, focusing on terms most likely to be found in the title and abstracts of the studies. For observational studies, the risk of bias was assessed using the Newcastle Ottawa Scale, and the Cochrane risk of bias tool was used for randomised trials. The GRADE criteria was used to rate confidence in evidence and conclusions. For the meta-analyses, we explored the heterogeneity using the Q test and I2 test and the publication bias using the funnel plot and Egger’s regression test. The meta-analyses were performed using Jeffreys’s Amazing Statistics Program (JASP). Results Sixteen studies satisfied the inclusion criteria from an initial 496 studies. Fifteen studies identified a significant negative association of anticholinergic burden with mobility measures. One study did not find an association between anticholinergic intervention and mobility measures. Five studies included in the meta-analyses showed that anticholinergic burden significantly decreased walking speed (0.079 m/s ± 0.035 MD ± SE,95% CI: 0.010 to 0.149, p = 0.026), whilst a meta-analysis of four studies showed that anticholinergic burden significantly decreased physical function as measured by three variations of the Instrumental Activities of Daily Living (IADL) instrument 0.27 ± 0.12 (SMD ± SE,95% CI: 0.03 to 0.52), p = 0.027. The results of both meta-analyses had an I2 statistic of 99% for study heterogeneity. Egger’s test did not reveal publication bias. Conclusion There is consensus in published literature suggesting a clear association between anticholinergic burden and mobility. Consideration of cognitive anticholinergic effects may be important in interpreting results regarding the association of anticholinergic burden and mobility as anticholinergic drugs may affect mobility through cognitive effects.
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- 2023
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6. Risk of antimicrobial-associated organ injury among the older adults: a systematic review and meta-analysis
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Tichawona Chinzowu, Sandipan Roy, and Prasad S. Nishtala
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Systematic review ,meta-analysis ,Older adults ,Antimicrobial ,Organ injury ,Geriatrics ,RC952-954.6 - Abstract
Abstract Background Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for organ injury risk among older adults following antimicrobial exposure. This systematic review and meta-analysis examined the relationship between antimicrobial exposure and organ injury in older adults. Methodology We searched for original research articles in PubMed, Embase.com , Web of Science core collection, Web of Science BIOSIS citation index, Scopus, Cochrane Central Register of Controlled Trials, ProQuest, and PsycINFO databases, using key words in titles and abstracts, and using MeSH terms. We searched for all available articles up to 31 May 2021. After removing duplicates, articles were screened for inclusion into or exclusion from the study by two reviewers. The Newcastle-Ottawa scale was used to assess the risk of bias for cohort and case-control studies. We explored the heterogeneity of the included studies using the Q test and I2 test and the publication bias using the funnel plot and Egger’s test. The meta-analyses were performed using the OpenMetaAnalyst software. Results The overall absolute risks of acute kidney injury among older adults prescribed aminoglycosides, glycopeptides, and macrolides were 15.1% (95% CI: 12.8–17.3), 19.1% (95% CI: 15.4–22.7), and 0.3% (95% CI: 0.3–0.3), respectively. Only 3 studies reported antimicrobial associated drug-induced liver injury. Studies reporting on the association of organ injury and antimicrobial exposure by age or duration of treatment were too few to meta-analyse. The funnel plot and Egger’s tests did not indicate evidence of publication bias. Conclusion Older adults have a significantly higher risk of sustaining acute kidney injury when compared to the general adult population. Older adults prescribed aminoglycosides have a similar risk of acute kidney injury to the general adult population.
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- 2021
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7. Deprescribing to reduce polypharmacy: study protocol for a randomised controlled trial assessing deprescribing of anticholinergic and sedative drugs in a cohort of frail older people living in the community
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Ulrich Bergler, Nagham J. Ailabouni, John W. Pickering, Sarah N. Hilmer, Dee Mangin, Prasad S. Nishtala, Hamish Jamieson, and Sponsor-investigator
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Deprescribing ,Elderly ,Polypharmacy ,Anticholinergic ,Sedatives ,Drug burden index ,Medicine (General) ,R5-920 - Abstract
Abstract Background Targeted deprescribing of anticholinergic and sedative medications in older people may improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community. Methods and analysis The standard protocol items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomized controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients. Study population Community-dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly. Intervention New Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend anticholinergic and sedative medications that could be deprescribed to the participant’s general practitioner. The total use of anticholinergic and sedative medications will be quantified using the Drug Burden Index (DBI). Outcomes The primary outcome will be the change in total DBI between baseline and 6-month follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalization, and death. Data collection points Data will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3). Ethics and dissemination Ethical approval has been obtained from the Human, Disability and Ethics Committee: ethical number (17CEN265). Trial registration ClinicalTrials.gov ACTRN12618000729224 . Registered on May 2, 2018, with the Australian New Zealand Clinical Trials Registry
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- 2021
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8. Antimicrobial-associated organ injury among the elderly: a systematic review and meta-analysis protocol
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Prasad S Nishtala, Tichawona Chinzowu, and Sandipan Roy
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Medicine - Published
- 2022
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9. Acute renal failure and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections: Analysis using the US FDA adverse event reporting system
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Lisajo Orogun, Te-yuan Chyou, and Prasad S. Nishtala
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Health Policy ,Public Health, Environmental and Occupational Health ,General Medicine - Abstract
BACKGROUND: Recently, antivirals, including remdesivir, have been repurposed to treat COVID-19 infections. Initial concerns have been raised about the adverse renal and cardiac events associated with remdesivir. OBJECTIVE: This study aimed to analyse the adverse renal and cardiac events associated with remdesivir in patients with COVID-19 infections using the US FDA adverse event reporting system. METHOD: A case/non-case method was used to determine adverse drug events associated with remdesivir as the primary suspect drug between January 1, 2020, and November 11, 2021, for patients with COVID-19 infections. Cases were reports for remdesivir with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes ‘Renal and urinary disorders’ or ‘cardiac’ disorders. To measure disproportionality in reporting of ADEs, frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, and EBGM > 1 for ADEs with ≥4 reports. Sensitivity analyses were undertaken by excluding reports for non-Covid indications and medications strongly associated with AKI and cardiac arrhythmias. RESULTS: In the main analysis for remdesivir use in patients with COVID-19 infections, we identified 315 adverse cardiac events comprising 31 different MeDRA PTs and 844 adverse renal events comprising 13 different MeDRA PTs. Regarding adverse renal events, disproportionality signals were noted for “renal failure” (ROR = 2.8 (2.03–3.86); EBGM = 1.92 (1.58–2.31), “acute kidney injury” (ROR = 16.11 (12.52–20.73); EBGM = 2.81 (2.57–3.07), “renal impairment” (ROR = 3.45 (2.68–4.45); EBGM = 2.02 (1.74–2.33). Regarding adverse cardiac events, strong disproportionality signals were noted for “electrocardiogram QT prolonged” (ROR = 6.45 (2.54–16.36); EBGM = 2.04 (1.65–2.51), “pulseless electrical activity” (ROR = 43.57 (13.64–139.20); EBGM = 2.44 (1.74–3.33), “sinus bradycardia” (ROR = 35.86 (11.16–115.26); EBGM = 2.82 (2.23–3.53), “ventricular tachycardia” (ROR = 8.73 (3.55–21.45); EBGM = 2.52 (1.89–3.31). The risk of AKI and cardiac arrythmias were confirmed by sensitivity analyses. CONCLUSION: This hypothesis-generating study identified AKI and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections. The relationship between AKI and cardiac arrhythmias should be further investigated using registries or large clinical data to assess the impact of age, genetics, comorbidity, and the severity of Covid infections as potential confounders.
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- 2023
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10. Analysis of the nervous system and gastrointestinal adverse events associated with solifenacin in older adults using the US FDA adverse event reporting system
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Connie Nicholls, Te-yuan Chyou, and Prasad S Nishtala
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reporting odds ratio ,Antimuscarinics ,pharmacoepidemiology ,SDG 3 - Good Health and Well-being ,pharmacovigilance ,Health Policy ,patient safety ,Public Health, Environmental and Occupational Health ,General Medicine ,elderly - Abstract
BACKGROUND: Antimuscarinics are the backbone of the pharmacological management of overactive bladder. Still, concerns have been raised over the nervous system (NS) adverse drug events (AEs) due to their dissimilarities to muscarinic receptor-subtype affinities. OBJECTIVE: This study aimed to identify the nervous system and gastrointestinal adverse drug events (ADEs) associated with solifenacin use in older adults (≥65 years). METHODS: A case/non-case analysis was performed on the reports submitted to the FDA Adverse Event Reporting System (FAERS) between 01/01/2004 and 30/06/2020. Cases were reports for solifenacin with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes ‘nervous system’ or ‘gastrointestinal’ disorders. Non-cases were all other remaining reports for solifenacin. The case/non-cases was compared between solifenacin and other bladder antimuscarinics. Frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used to measure disproportionality. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1, for ADEs with ≥4 reports. RESULTS: 107 MedDRA preferred terms (PTs) comprising 970 ADE reports were retrieved for nervous system disorders associated with solifenacin. For gastrointestinal disorders, 129 MedDRA PTs comprising 1817 ADE reports were retrieved. Statistically significant results were found for ‘altered state of consciousness’: ROR = 9.71 (2.13–44.35), PRR = 9.69 (2.12–44.2) and IC = 1.29 (0.93–1.66). CONCLUSIONS: The disproportionality reporting of ‘altered state of consciousness’, a previously unidentified ADE, was unexpected. Further monitoring of this ADE is needed to ensure patient safety, as this could be linked to poor balance and falls in older adults.
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- 2023
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11. An overview of pharmacodynamic
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Mohammed Saji Salahudeen and Prasad S. Nishtala
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Pharmacodynamics ,Pharmacodynamic model ,Ligand binding ,Emax model ,Competitive binding ,Receptor ,Fractional occupancy ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect (E) of a drug as a function of the drug concentration (C) and estimate an unknown PD parameter (θpd). The PD models have been described as fixed, linear, log-linear, Emax, sigmoid Emax, and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site. The pharmacological effect is produced by the drug binding to the receptor to either activate or antagonise the receptor. Ligand binding models describe a system of interacting components, i.e. the interaction of one or more ligands with one or more binding sites. The Emax model is the central method that provides an empirical justification for the concentration/dose-effect relationship. However, for ligand binding models justification is provided by theory of receptor occupancy. In essence, for ligand binding models, the term fractionaloccupancy is best used to describe the fraction of receptors occupied at a particular ligand concentration. It is stated that the fractionaloccupancy=occupiedbindingsites/totalbindingsites, which means the effect of a drug should depend on the fraction of receptors that are occupied. In the future, network-based systems pharmacology models using ligand binding principles could be an effective way of understanding drug-related adverse effects. This will facilitate and strengthen the development of rational drug therapy in clinical practice.
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- 2017
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12. Antibacterial‐associated acute kidney injury among older adults: A post‐marketing surveillance study using the <scp>FDA</scp> adverse events reporting system
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Tichawona Chinzowu, Te‐Yuan Chyou, and Prasad S. Nishtala
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Sulfamethoxazole ,data signal ,United States Food and Drug Administration ,Epidemiology ,adverse event ,Bayes Theorem ,Acute Kidney Injury ,elderly ,antibiotics ,Trimethoprim ,United States ,Anti-Bacterial Agents ,reporting odds ratio ,Vancomycin ,Adverse Drug Reaction Reporting Systems ,Humans ,Pharmacology (medical) ,Gentamicins ,Aged - Abstract
Purpose: Antibacterials induce a differential risk of acute kidney injury (AKI) in older adults. This study investigated the reporting risk of AKI associated with antibacterials using the individual case safety reports (ICSRs) submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: A case/non-case method was used to assess AKI risk associated with antibacterials between 1 January 2000 and 30 September 2021. Cases were ICSRs for antibacterials with AKI as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes ‘Renal and urinary disorders’ disorders. The analyses were completed on a de-duplicated data set containing only the recent version of the ICSR. Signals were defined by a lower 95% confidence interval (CI) of reporting odds ratio (ROR) ≥ 2, proportional reporting ratio (PRR) ≥ 2, information component (IC) > 0, Empirical Bayes Geometric Mean (EBGM) > 1 and reports ≥4. Sensitivity analyses were conducted a priori to assess the robustness of signals. Results: A total of 3 680 621 reports on ADEs were retrieved from FAERS over the study period, of which 92 194 were antibacterial reports. Gentamicin, sulfamethoxazole, trimethoprim and vancomycin consistently gave strong signals of disproportionality on all four disproportionality measures and across the different sensitivity analyses: gentamicin (ROR = 2.95[2.51–3.46]), sulfamethoxazole (ROR = 2.97[2.68–3.29]), trimethoprim (ROR = 2.81[2.29–3.46]) and vancomycin (ROR = 3.35[3.08–3.64]). Conclusion: Signals for gentamicin, sulfamethoxazole, trimethoprim and vancomycin were confirmed by using antibacterials as a comparator, adjusting for drug-related competition bias and event-related competition bias.
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- 2022
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13. The Influence of Patient Characteristics on Anticholinergic Events in Older People
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Mohammed Saji Salahudeen, Prasad S. Nishtala, and Stephen B. Duffull
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Anticholinergic events ,Risk factors ,Adverse events ,Elderly ,Older people ,Antimuscarinic response ,Anticholinergic burden ,Neurology. Diseases of the nervous system ,RC346-429 ,Geriatrics ,RC952-954.6 - Abstract
Aims: To examine patient characteristics that predict adverse anticholinergic-type events in older people. Methods: This retrospective population-level study included 2,248 hospitalised patients. Individual data on medicines that are commonly associated with anticholinergic events (delirium, constipation and urinary retention) were identified. Patient characteristics examined were medicines with anticholinergic effects (ACh burden), age, sex, non-anticholinergic medicines (non-ACM), Charlson comorbidity index scores and ethnicity. The Akaike information criterion was used for model selection. The data were analysed using logistic regression models for anticholinergic events using the software NONMEM. Results: ACh burden was found to be a significant independent predictor for developing an anticholinergic event [adjusted odds ratio (aOR): 3.21, 95% CI: 1.23-5.81] for those taking an average of 5 anticholinergic medicines compared to those taking 1. Both non-ACM and age were also independent risk factors (aOR: 1.41, 95% CI: 1.31-1.51 and aOR: 1.08, 95% CI: 1.05-1.10, respectively). Conclusion: To our knowledge, this is the first study that has examined population-level data in a nonlinear model framework to predict anticholinergic-type adverse events. This study evaluated the relationship between important patient characteristics and the occurrence of anticholinergic-type events. These findings reinforce the clinical significance of reviewing anticholinergic medicines in older people.
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- 2016
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14. Antibiotic utilisation and the impact of antimicrobial resistance action plan on prescribing among older adults in New Zealand between 2005 and 2019
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Tichawona Chinzowu, Te-yuan Chyou, Sandipan Roy, Hamish Jamieson, and Prasad S Nishtala
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PurposeThe objectives of this study were to examine the overall utilisation of systematic antibiotics and the impact of the launch of the antimicrobial resistance action plan in older adults (65 years or more) living in New Zealand between 2005 and 2019, using data from a national database (Pharmaceutical collections), stratified by antibiotic class, patient age, and sex.MethodsPopulation-level systemic antibiotic dispensing data for older adults in New Zealand was analysed using repeated cross-sectional analysis between 01/01/2005 and 31/12/2019. Data were extracted on the prescribed systemic antibiotics using a unique identifier for each case. Antibiotic utilisation was measured in DDD/TOPD values. In addition, an interrupted time series (ITS) analysis using the autoregressive integrated moving average (ARIMA) models was performed to determine the impact of the antimicrobial resistance action plan.ResultsMost of the antibiotic classes included in this study showed a significant overall decrease in utilisation ranging from 38.64% for sulphonamides to 80.64% for fluoroquinolones compared to 2005. Systemic antibiotic utilisation decreased by 49.6% from the predicted usage between January 2018 and December 2019 following the launch of the antimicrobial resistance action plan. ARIMA model supported the reduction in utilisation with a step change of -0.2206 and slope change of -0.0029.ConclusionsThe ITS analysis has demonstrated that the intervention may have hugely impacted the antibiotic utilisation rate among older adults. Further studies are required to determine whether the reduced consumption rates of antibiotics are associated with reduced rates of antibiotic-associated adverse drug events such as acute kidney injury and haematological abnormalities.
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- 2023
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15. Deprescribing Anticholinergic and Sedative Drugs to Reduce Polypharmacy in Frail Older Adults Living in the Community: A Randomized Controlled Trial
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Hamish Jamieson, Prasad S Nishtala, Hans Ulrich Bergler, Susan K Weaver, John W Pickering, Nagham J Ailabouni, Rebecca Abey-Nesbit, Carolyn Gullery, Joanne Deely, Susan B Gee, Sarah N Hilmer, Dee Mangin, Jamieson, Hamish, Nishtala, Prasad S, Bergler, Hans Ulrich, Weaver, Susan K, Pickering, John W, Ailabouni, Nagham J, Abey-Nesbit, Rebecca, Gullery, Carolyn, Deely, Joanne, Gee, Susan B, Hilmer, Sarah N, and Mangin, Dee
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Aging ,Drug Burden Index ,interRAI ,frailty ,Geriatrics and Gerontology - Abstract
Background Polypharmacy is associated with poor outcomes in older adults. Targeted deprescribing of anticholinergic and sedative medications may improve health outcomes for frail older adults. Our pharmacist-led deprescribing intervention was a pragmatic 2-arm randomized controlled trial stratified by frailty. We compared usual care (control) with the intervention of pharmacists providing deprescribing recommendations to general practitioners. Methods Community-based older adults (≥65 years) from 2 New Zealand district health boards were recruited following a standardized interRAI needs assessment. The Drug Burden Index (DBI) was used to quantify the use of sedative and anticholinergic medications for each participant. The trial was stratified into low, medium, and high-frailty. We hypothesized that the intervention would increase the proportion of participants with a reduction in DBI ≥ 0.5 within 6 months. Results Of 363 participants, 21 (12.7%) in the control group and 21 (12.2%) in the intervention group had a reduction in DBI ≥ 0.5. The difference in the proportion of −0.4% (95% confidence interval [CI]: −7.9% to 7.0%) provided no evidence of efficacy for the intervention. Similarly, there was no evidence to suggest the effectiveness of this intervention for participants of any frailty level. Conclusion Our pharmacist-led medication review of frail older participants did not reduce the anticholinergic/sedative load within 6 months. Coronavirus disease 2019 (COVID-19) lockdown measures required modification of the intervention. Subgroup analyses pre- and post-lockdown showed no impact on outcomes. Reviewing this and other deprescribing trials through the lens of implementation science may aid an understanding of the contextual determinants preventing or enabling successful deprescribing implementation strategies.
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- 2023
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16. Donepezil Adherence, Persistence and Time to First Discontinuation in a Three-Year Follow-Up of Older People
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Henry C. Ndukwe and Prasad S. Nishtala
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Donepezil ,Persistence ,Discontinuation ,Geriatric epidemiology ,Population-based study ,Adherence ,Older people ,Neurology. Diseases of the nervous system ,RC346-429 ,Geriatrics ,RC952-954.6 - Abstract
Background: Donepezil is indicated for the management of mild to moderate dementia, particularly in Alzheimer's disease. Several studies have described low adherence rates with donepezil. Aim: To examine and measure donepezil adherence, persistence and time to first discontinuation in older New Zealanders. Methods: An inception cohort of 1,999 new users of donepezil, aged 65 years or older, were identified from the Pharmaceutical Collections and National Minimum Dataset from 1 November 2010 to 31 December 2013. Kaplan-Meier curves and Cox regression analysis were used to estimate the cumulative probability and risk of time to first discontinuation of donepezil therapy. Results: The mean age of the cohort was 79.5 ± 6.4 years and included 42.7% females. Adherence was high (89.0%), while the proportion of donepezil dispensings (81.0-32.5%) declined between 6 and 36 months. Persistence between the 1st and 6th dispensing visit decreased by 19.0%, and 11.0% of the total cohort had a gap of 31 days or more. The adjusted risk of time to first discontinuation in the non-adherent group was 2.2 times (95% CI 1.9-2.6) that of the adherent group. Conclusions: The non-adherent new donepezil users, on average, discontinued faster than the adherent group. Time to first discontinuation in this study was higher compared to discontinuation rates observed in clinical trials.
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- 2015
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17. Application of machine learning approaches in predicting clinical outcomes in older adults – a systematic review and meta-analysis
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Robert T Olender, Sandipan Roy, and Prasad S Nishtala
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Background Machine learning-based prediction models have the potential to have a considerable positive impact on geriatric care. Design: Systematic review and meta-analyses. Participants: Older adults (≥ 65 years) in any setting. Intervention: Machine learning models for predicting clinical outcomes in older adults were evaluated. A meta-analysis was conducted where the predictive models were compared based on their performance in predicting mortality. Outcome measures: Studies were grouped by the clinical outcome, and the models were compared based on the area under the receiver operating characteristic curve metric. Results 29 studies that satisfied the systematic review criteria were appraised and six studies predicting a mortality outcome were included in the meta-analyses. We could only pool studies by mortality as there were inconsistent definitions and sparse data to pool studies for other clinical outcomes. The area under the receiver operating characteristic curve from six studies included in the meta-analysis yielded a summary estimate of 0.82 (95%CI: 0.76–0.87), signifying good discriminatory power in predicting mortality. Conclusion The meta-analysis indicates that machine learning models can predict mortality. As electronic healthcare databases grow larger and more comprehensive, the available computational power increases and machine learning models become more sophisticated; they should be integrated into a larger research setting to predict various clinical outcomes.
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- 2022
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18. An Updated Analysis of Psychotropic Medicine Utilisation in Older People in New Zealand from 2005 to 2019
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Prasad S. Nishtala and Te-yuan Chyou
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Pharmacology (medical) ,Geriatrics and Gerontology - Abstract
Background: Psychotropic medicine utilisation in older adults continues to be of interest because of overuse and concerns surrounding its safety and efficacy. Objective: This study aimed to characterise the utilisation of psychotropic medicines in older people in New Zealand. Methods: We conducted a repeated cross-sectional analysis of national dispensing data from 1 January, 2005 to 31 December, 2019. We defined utilisation using the Anatomical Therapeutic Chemical classification defined daily dose system. Utilisation was measured in terms of the defined daily dose (DDD) per 1000 older people per day (TOPD). Results: Overall, the utilisation of psychotropic medicines increased marginally by 0.42% between 2005 and 2019. The utilisation increased for antidepressants (72.42 to 75.21 DDD/TOPD) and antipsychotics (6.06–19.04 DDD/TOPD). In contrast, the utilisation of hypnotics and sedatives (53.74–38.90 DDD/TOPD) and anxiolytics decreased (10.20–9.87 DDD/TOPD). The utilisation of atypical antipsychotics increased (4.06–18.72 DDD/TOPD), with the highest percentage change in DDD/TOPD contributed by olanzapine (520.6 %). In comparison, utilisation of typical antipsychotics was relatively stable (2.00–2.06 DDD/TOPD). The utilisation of venlafaxine increased remarkably by 5.7 times between 2005 and 2019. The utilisation of zopiclone was far greater than that of other hypnotics in 2019. Conclusions: There was only a marginal increase in psychotropic medicines utilisation from 2005 to 2019 in older adults in New Zealand. There was a five-fold increase in the utilisation of antipsychotic medicines. Continued monitoring of psychotropic medicine utilisation will be of interest to understand the utilisation of antidepressants and antipsychotic medicines during the coronavirus disease 2019 pandemic year.
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- 2022
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19. Risk of delirium associated with antimuscarinics in older adults: a case‐time‐control study
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Prasad S. Nishtala and Te‐Yuan Chyou
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Aged, 80 and over ,Urinary Bladder, Overactive ,Epidemiology ,mental disorders ,Delirium ,Humans ,Pharmacology (medical) ,Muscarinic Antagonists ,Solifenacin Succinate ,Cholinergic Antagonists ,Aged - Abstract
Background: Older adults are at an increased risk of delirium because of age, polypharmacy, multiple comorbidities and acute illness. Antimuscarinics are the backbone of the pharmacological management of overactive bladder. However, the safety profiles of antimuscarinics vary because of their dissimilarities to muscarinic receptor-subtype affinities and are associated with differential central anticholinergic adverse effects. Objective: This study aimed to examine delirium risk in new users of oxybutynin and solifenacin in older adults (≥ 65 years). In the secondary analyses, we examined the risk of delirium by type and dose of antimuscarinic. Method: We applied a case-time-control design to investigate delirium risk in older adults who started taking oxybutynin and solifenacin. We used a nationwide inpatient hospital data (2005–2016), National Minimum Data Set, maintained by the Ministry of Health, New Zealand (NZ), to identify older adults with a new-onset diagnosis of delirium. Eligible patients were older adults aged 65 at entry into the cohort on 1/1/2006. We used dispensing claims data to determine antimuscarinic treatment exposure. The antimuscarinic included in the study were new users of oxybutynin and solifenacin. These two antimuscarinics are subsidised by the Pharmaceutical Management Agency and are the most frequently used antimuscarinic in NZ. A conditional logistic regression model was used to compute matched odds ratios (MORs) and 95% confidence intervals (CIs). In the case-time-control design, we made separate analyses to evaluate the dose–response risk of delirium. Results: We identified 4818 individuals (mean age 82.14) from 2005 to 2015 with incident delirium and were exposed to at least one of the antimuscarinic of interest. The case-time-control matched odds ratio (MOR) for delirium with oxybutynin was (2.06, 95% confidence interval [CI] 1.07–3.96). Solifenacin was not associated with delirium (0.89 95%CI 0.64–1.23). In the sensitivity analyses, the case-time-control MOR for delirium using a shorter risk period (0–3 days) did not change the results. The dose–response risk of delirium was significant for oxybutynin (0.05, 95%CI 0.02–0.08) but not for solifenacin (−0.01, 95%CI −0.03 to 0.00). In addition, in the subgroup analyses, a statistically significant association of delirium was found for oxybutynin but not for solifenacin in the non-dementia cohort (2.11,95% CI 1.08–4.13) and the dementia cohort (1.25, 95%CI 0.05–26.9). Conclusion: The study found that oxybutynin but not solifenacin is associated with a risk of new-onset delirium in older adults. The higher blockade of M1 and M2 receptors by oxybutynin is likely to contribute to delirium than solifenacin, which is highly selective for the M3 receptor subtype. Therefore, the treatment choice with an M3 selective agent must be given due consideration, particularly in those with pre-existing cognitive impairment.
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- 2022
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20. Development and validation of a frailty index compatible with three interRAI assessment instruments
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Rebecca Abey-Nesbit, Ulrich Bergler, John W Pickering, Prasad S Nishtala, and Hamish Jamieson
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Aging ,Frailty ,Frail Elderly ,Humans ,General Medicine ,Geriatrics and Gerontology ,Geriatric Assessment ,Home Care Services ,Aged - Abstract
Background a Frailty Index (FI) calculated by the accumulation of deficits is often used to quantify the extent of frailty in individuals in specific settings. This study aimed to derive a FI that can be applied across three standardised international Residential Assessment Instrument assessments (interRAI), used at different stages of ageing and the corresponding increase in support needs. Methods deficit items common to the interRAI Contact Assessment (CA), Home Care (HC) or Long-Term Care Facilities assessment (LTCF) were identified and recoded to form a cumulative deficit FI. The index was validated using a large dataset of needs assessments of older people in New Zealand against mortality prediction using Kaplan Meier curves and logistic regression models. The index was further validated by comparing its performance with a previously validated index in the HC cohort. Results the index comprised 15 questions across seven domains. The assessment cohort and their mean frailty (SD) were: 89,506 CA with 0.26 (0.15), 151,270 HC with 0.36 (0.15) and 83,473 LTCF with 0.41 (0.17). The index predicted 1-year mortality for each of the CA, HC and LTCF, cohorts with area under the receiver operating characteristic curves (AUCs) of 0.741 (95% confidence interval, CI: 0.718–0.762), 0.687 (95%CI: 0.684–0.690) and 0.674 (95%CI: 0.670–0.678), respectively. Conclusions the results for this multi-instrument FI are congruent with the differences in frailty expected for people in the target settings for these instruments and appropriately associated with mortality at each stage of the journey of progressive ageing.
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- 2022
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21. Rates of psychotropic medicine prescribing in paediatric populations in Australian general practice from 2000-2016
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Laila Tanana, Christopher Harrison, Prasad S. Nishtala, and Timothy F. Chen
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Pharmacology ,Psychotropic Drugs ,Adolescent ,General Practice ,Australia ,Psychiatry and Mental health ,Neurology ,Humans ,Pharmacology (medical) ,Female ,Central Nervous System Stimulants ,Neurology (clinical) ,Child ,Biological Psychiatry ,Antipsychotic Agents - Abstract
General practitioner (GP) prescribing of psychotropic medicines to paediatric patients is increasing across countries, sparking the need for additional research into this field. We examined prescribing rates, GP and patient characteristics and indications associated with prescribing psychotropic medicines to paediatric patients in Australian general practice, using data from the Bettering the Evaluation and Care of Health (BEACH) program. We extracted all encounters with children aged 3 to 17 from 2000 to 2016. Psychotropic medicines were defined as those in the ATC codes N05 (Psycholeptics) and N06 (Psychoanaleptics). Of the 144,397 encounters, GPs prescribed 1829 psychotropic medicines to paediatric patients at an average rate of 1.16 prescriptions per 100 encounters (95% confidence interval 1.09-1.23). We found that the rate of psychotropic medicines prescribed to paediatric patients in Australian general practice increased. Patients who were adolescent, female, socio-economically disadvantaged or from an English-speaking background were significantly more likely to be prescribed a psychotropic medicine. GP practices in remote or regional areas and Australian graduate GPs were more likely to prescribe psychotropic medicines to paediatric patients. Depression, attention deficit hyperactivity disorder, anxiety and autism were the most common psychiatric indications managed with psychotropic medicines. Antidepressants, psychostimulants, benzodiazepines, antipsychotics and other psychotropic medicines were prescribed, signifying a high rate of off-label use. Sertraline was the most common psychotropic medicine prescribed, followed by fluoxetine and methylphenidate. Future studies involving data from other prescribers, e.g. paediatricians and psychiatrists, and studies linking prescribed medicines to their indications may widen our understanding of psychotropic medicine prescribing in Australian paediatric patients.
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- 2022
22. An Updated Analysis of Psychotropic Medicine Utilisation in Older People in New Zealand from 2005 to 2019
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Prasad S, Nishtala and Te-Yuan, Chyou
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Psychotropic Drugs ,Cross-Sectional Studies ,COVID-19 ,Humans ,Hypnotics and Sedatives ,Antidepressive Agents ,Aged ,Antipsychotic Agents ,New Zealand - Abstract
Psychotropic medicine utilisation in older adults continues to be of interest because of overuse and concerns surrounding its safety and efficacy.This study aimed to characterise the utilisation of psychotropic medicines in older people in New Zealand.We conducted a repeated cross-sectional analysis of national dispensing data from 1 January, 2005 to 31 December, 2019. We defined utilisation using the Anatomical Therapeutic Chemical classification defined daily dose system. Utilisation was measured in terms of the defined daily dose (DDD) per 1000 older people per day (TOPD).Overall, the utilisation of psychotropic medicines increased marginally by 0.42% between 2005 and 2019. The utilisation increased for antidepressants (72.42 to 75.21 DDD/TOPD) and antipsychotics (6.06-19.04 DDD/TOPD). In contrast, the utilisation of hypnotics and sedatives (53.74-38.90 DDD/TOPD) and anxiolytics decreased (10.20-9.87 DDD/TOPD). The utilisation of atypical antipsychotics increased (4.06-18.72 DDD/TOPD), with the highest percentage change in DDD/TOPD contributed by olanzapine (520.6 %). In comparison, utilisation of typical antipsychotics was relatively stable (2.00-2.06 DDD/TOPD). The utilisation of venlafaxine increased remarkably by 5.7 times between 2005 and 2019. The utilisation of zopiclone was far greater than that of other hypnotics in 2019.There was only a marginal increase in psychotropic medicines utilisation from 2005 to 2019 in older adults in New Zealand. There was a five-fold increase in the utilisation of antipsychotic medicines. Continued monitoring of psychotropic medicine utilisation will be of interest to understand the utilisation of antidepressants and antipsychotic medicines during the coronavirus disease 2019 pandemic year.
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- 2022
23. Analysis of the adverse nervous system and gastrointestinal events associated with solifenacin in older adults using the US FDA adverse event reporting system
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Connie, Nicholls, Te-Yuan, Chyou, and Prasad S, Nishtala
- Abstract
Antimuscarinics are the backbone of the pharmacological management of overactive bladder. Still, concerns have been raised over the nervous system (NS) adverse drug events (AEs) due to their dissimilarities to muscarinic receptor-subtype affinities.This study aimed to identify the nervous system and gastrointestinal adverse drug events (ADEs) associated with solifenacin use in older adults (≥65 years).A case/non-case analysis was performed on the reports submitted to the FDA Adverse Event Reporting System (FAERS) between 01/01/2004 and 30/06/2020. Cases were reports for solifenacin with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'nervous system' or 'gastrointestinal' disorders. Non-cases were all other remaining reports for solifenacin. The case/non-cases was compared between solifenacin and other bladder antimuscarinics. Frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used to measure disproportionality. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC 0, EBGM 1, for ADEs with ≥4 reports.107 MedDRA preferred terms (PTs) comprising 970 ADE reports were retrieved for nervous system disorders associated with solifenacin. For gastrointestinal disorders, 129 MedDRA PTs comprising 1817 ADE reports were retrieved. Statistically significant results were found for 'altered state of consciousness': ROR = 9.71 (2.13-44.35), PRR = 9.69 (2.12-44.2) and IC = 1.29 (0.93-1.66).The disproportionality reporting of 'altered state of consciousness', a previously unidentified ADE, was unexpected. Further monitoring of this ADE is needed to ensure patient safety, as this could be linked to poor balance and falls in older adults.
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- 2022
24. Challenges and Enablers of Deprescribing: A General Practitioner Perspective.
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Nagham J Ailabouni, Prasad S Nishtala, Dee Mangin, and June M Tordoff
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Medicine ,Science - Abstract
AIMS:Deprescribing is the process of reducing or discontinuing medicines that are unnecessary or deemed to be harmful. We aimed to investigate general practitioner (GP) perceived challenges to deprescribing in residential care and the possible enablers that support GPs to implement deprescribing. METHODS:A qualitative study was undertaken using semi-structured, face-to-face interviews from two cities in New Zealand and a purpose-developed pilot-tested interview schedule. Interviews were recorded with permission and transcribed verbatim. Transcripts were read and re-read and themes were identified with iterative building of a coding list until all data was accounted for. Interviews continued until saturation of ideas occurred. Analysis was carried out with the assistance of a Theoretical Domains Framework (TDF) and constant comparison techniques. Several themes were identified. Challenges and enablers of deprescribing were determined based on participants' answers. RESULTS:Ten GPs agreed to participate. Four themes were identified to define the issues around prescribing for older people, from the GPs' perspectives. Theme 1, the 'recognition of the problem', discusses the difficulties involved with prescribing for older people. Theme 2 outlines the identified behaviour change factors relevant to the problem. Deprescribing challenges were drawn from these factors and summarised in Theme 3 under three major headings; 'prescribing factors', 'social influences' and 'policy and processes'. Deprescribing enablers, based on the opinions and professional experience of GPs, were retrieved and summarised in Theme 4. CONCLUSION:The process of deprescribing is laced with many challenges for GPs. The uncertainty of research evidence in older people and social factors such as specialists' and nurses' influences were among the major challenges identified. Deprescribing enablers encompassed support for GPs' awareness and knowledge, improvement of communication between multiple prescribers, adequate reimbursement and pharmacists being involved in the multidisciplinary team.
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- 2016
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25. Serum Anticholinergic Activity and Cognitive and Functional Adverse Outcomes in Older People: A Systematic Review and Meta-Analysis of the Literature.
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Mohammed Saji Salahudeen, Te-Yuan Chyou, and Prasad S Nishtala
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Medicine ,Science - Abstract
INTRODUCTION:Studies have reported associations between serum anticholinergic activity (SAA) and decline in cognitive performance, delirium, and functional impairment. The aim of this meta-analysis was to explore and quantify associations between SAA and adverse cognitive and functional outcomes in older people. MATERIALS AND METHODS:A literature search in Ovid MEDLINE, EMBASE, PsycINFO and IPA from 1946-2014 was completed. The primary outcomes of interest were cognitive and functional adverse outcomes associated with SAA in older people aged 55 years and above. The Cochrane Risk-Bias assessment tool was used to assess bias in randomised controlled trials (RCTs). The Newcastle-Ottawa Scale was used to assess the quality of non-RCTs. Meta-analyses were conducted for RCTs and cohort studies separately. Heterogeneity was assessed using I2 tests. RESULTS:The primary electronic literature search identified a total of 1559 records in the 4 different databases. On the basis of full-text analysis, 33 studies that met the inclusion criteria. The review included 4 RCTs, 5 prospective cohort studies, 3 longitudinal cohort studies, 17 cross-sectional studies, and 4 case-control studies. Twenty-four of the retrieved studies examined an association between SAA and cognitive outcomes, 2 studies examined an association with SAA and functional outcomes and 8 studies examined associations between SAA and both cognitive, and functional outcomes. The meta-analysis on 4 RCTs showed no association with higher SAA and cognitive performance (I2 = 89.38%, H2 = 25.53 and p-value =
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- 2016
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26. Predictors of Residential Care Admission in Community-Dwelling Older People With Dementia
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Rebecca Abey-Nesbit, Ling Han, Joanne M. Deely, John W. Pickering, Heather G. Allore, Prasad S. Nishtala, and Hamish A. Jamieson
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Gerontology ,Activities of daily living ,Ethnic group ,Article ,03 medical and health sciences ,0302 clinical medicine ,Activities of Daily Living ,Humans ,Medicine ,Dementia ,030212 general & internal medicine ,Effects of sleep deprivation on cognitive performance ,Social isolation ,General Nursing ,Depression (differential diagnoses) ,Aged ,business.industry ,Health Policy ,General Medicine ,medicine.disease ,Home Care Services ,Confidence interval ,Hospitalization ,Observational study ,Independent Living ,Geriatrics and Gerontology ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Objectives The objectives of this study were to identify variables associated with dementia and entry into aged residential care (ARC) and derive and validate a risk prediction model for dementia and entry into ARC. Design This was an observational study of prospectively collected Home Care International Residential Assessment Instrument (interRAI-HC) assessment data. Setting and Participants Participants included all people age ≥65 years who had completed an interRAI-HC assessment between July 1, 2012 and June 30, 2018. Exclusion criteria included death or entry into ARC within 30 days of assessment and not living at home at the time of the assessment. Measures InterRAI data from 94,202 older New Zealanders were evaluated for presence or absence of dementia. A multivariable competing-risks model for entry into ARC with death as the competing event was used to estimate subdistribution hazard ratios (SHR). Results In total, there were 18,672 (19.8%) persons with dementia (PWD). PWD were almost twice as likely to enter ARC as persons without dementia [42.8% vs 25.3%; difference 17.5% (95% confidence interval 16.7%‒18.2%)]. PWD at highest risk of entering ARC were those where there was a desire to live elsewhere (SHR 1.44), depression (indicated, SHR 1.15), poor cognitive performance (Cognitive Performance Scale minimal SHR 1.32 and severe plus SHR 1.91), and wandering (SHR 1.19). Factors associated with reduced risks of PWD entering ARC were living with a child or relative, alcohol consumption, and comorbidities. Conclusions and Implications A desire to live elsewhere, social isolation, independent activities of daily living, and depression were independently associated with entry into ARC. Supporting caregivers may improve outcomes for PWD that delay entry into ARC. Future revisions of the interRAI questionnaire could provide more insight on this matter.
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- 2020
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27. Comparative risk of Parkinsonism associated with olanzapine, risperidone and quetiapine in older adults‐a propensity score matched cohort study
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Revathi Nishtala, Te-yuan Chyou, and Prasad S. Nishtala
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Male ,Olanzapine ,medicine.medical_specialty ,pharmacoepidemiology ,Time Factors ,Databases, Factual ,Epidemiology ,Population ,elderly ,Risk Assessment ,030226 pharmacology & pharmacy ,Quetiapine Fumarate ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Parkinson Disease, Secondary ,Propensity Score ,education ,Aged ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Risperidone ,business.industry ,atypical antipsychotics ,Incidence ,Parkinsonism ,Hazard ratio ,extrapyramidal side effects ,Age Factors ,medicine.disease ,Confidence interval ,Propensity score matching ,adverse effects ,Quetiapine ,Female ,business ,Antipsychotic Agents ,New Zealand ,medicine.drug - Abstract
Purpose: The purpose of this study was to examine the incidence of Parkinsonism in new users of second-generation antipsychotics (SGAs) in older adults (≥65 years). In the secondary analyses, we examined the risk of Parkinsonism by type and dose of SGA and conducted age-sex interactions. Method: This population-based study included older adults who had a new-onset diagnosis of Parkinsonism and who started taking olanzapine, risperidone or quetiapine between 1 January 2005, and 30 December 2016. The Cox proportional hazard (COXPH) model with inverse probability treatment weighted (IPTW) covariates was used to evaluate the risk of new-onset Parkinsonism associated with SGAs, using quetiapine as the reference. We used the Generalized Propensity Score method to evaluate the dose-response risk of Parkinsonism associated with SGAs. Results: After IPTW adjustment for covariates, the COXPH model showed that compared to quetiapine, the use of olanzapine and risperidone were associated with an increased risk of Parkinsonism. The IPTW-hazard ratios are 1.76 (95% confidence interval 1.57-1.97) and 1.31 (95%CI 1.16-1.49), respectively. The dose-response risk of Parkinsonism was highest for olanzapine with a hazard ratio of 1.69 (95%CI 1.40-2.05) and the least for quetiapine with a hazard ratio of 1.22 (95%CI 1.14-1.31). The risk of Parkinsonism in the 65 to 74-year age group was higher for both sexes with risperidone compared to olanzapine, but the risk increased with olanzapine for both sexes in the 85+ age group. Conclusion: The study found that the risk of new-onset Parkinsonism in older adults is 31% and 76% higher with risperidone and olanzapine respectively compared to quetiapine.
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- 2020
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28. Credentials for a PharmD graduate: The voyage never ends
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Mohammed Saji Salahudeen and Prasad S Nishtala
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Medicine (General) ,R5-920 - Abstract
Doctor of Pharmacy (PharmD) is a professional pharmacy degree qualification offered by universities world-wide. While the graduates from the West are familiar with scope and job opportunities that present on completion of a PharmD degree, graduates from Asia and the Middle-East are coming to grips with the future of PharmD program and the role that it could play in career advancement. Through this review, we would like to highlight that numerous credential programs are available which can be added to the armory of PharmD graduates for advancement of their professional careers. The credentials detailed in this review are designed for PharmD graduates to optimize pharmaceutical care in specialized clinical settings such as geriatrics and ambulatory medicine. We have assembled an extensive list of post-PharmD educational opportunities to enhance professional practice for pharmacy graduates.
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- 2015
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29. Examining the Risks of Major Bleeding Events in Older People Using Antithrombotics
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Sarah N. Hilmer, Prasad S. Nishtala, Hamish A. Jamieson, Te-yuan Chyou, and H. Carl Hanger
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0301 basic medicine ,Male ,medicine.medical_specialty ,Gastrointestinal bleeding ,Databases, Factual ,medicine.drug_class ,030204 cardiovascular system & hematology ,Risk Assessment ,03 medical and health sciences ,0302 clinical medicine ,Fibrinolytic Agents ,Risk Factors ,Internal medicine ,Antithrombotic ,medicine ,Humans ,Pharmacology (medical) ,Aged ,Pharmacology ,Aspirin ,business.industry ,Anticoagulant ,Bleeding ,Warfarin ,Age Factors ,Anticoagulants ,Atrial fibrillation ,General Medicine ,medicine.disease ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,Relative risk ,Antithrombotics ,Polypharmacy ,Original Article ,Female ,Cardiology and Cardiovascular Medicine ,business ,Gastrointestinal Hemorrhage ,Intracranial Hemorrhages ,Platelet Aggregation Inhibitors ,medicine.drug ,New Zealand - Abstract
Background Real-world evidence for the safety of using antithrombotics in older people with multimorbidity is limited. We investigated the risks of gastrointestinal bleeding (GI-bleeding) and intracranial (IC-bleeding) associated with antithrombotics either as monotherapy, dual antiplatelet therapy (DAPT) or as triple therapy (TT) [DAPT plus anticoagulant] in older individuals aged 65 years and above. Methods We identified all individuals, 65 years and above, who had a first-time event of either IC- or GI-bleeding event from the hospital discharge data. We employed a case-crossover design and conditional logistic regression analyses to estimate the adjusted relative risks (ARR) of bleeding. Results We found 66,500 individuals with at least one event of IC- or GI-bleeding between 01/01/2005 and 31/12/2014. DAPT use was associated with an increased risk relative to non-use of any antithrombotics in IC-bleeding (ARR = 3.13, 95% CI = [2.64, 3.72]) and GI-bleeding (ARR = 1.34, 95% CI = [1.14, 1.57]). The increased bleeding risk relative to non-use of any antithrombotics was highest with TT use (IC-bleeding, ARR = 17.28, 95% CI = [6.69, 44.61]; GI-bleeding, ARR = 4.85, 95% CI = [1.51, 15.57]). Conclusions Using population-level data, we were able to obtain estimates on the bleeding risks associated with antithrombotic agents in older people often excluded from clinical trials because of either age or comorbidities. Electronic supplementary material The online version of this article (10.1007/s10557-019-06867-z) contains supplementary material, which is available to authorized users.
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- 2019
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30. Frailty of Māori, Pasifika, and non-Māori/non-Pasifika older people in New Zealand: a national population study of older people referred for home care services
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Philip J. Schluter, Rebecca Abey-Nesbit, Joanne M. Deely, Hamish A. Jamieson, Nancye M. Peel, Ulrich Bergler, John W. Pickering, Hector Matthews, Prasad S. Nishtala, and Ruth E. Hubbard
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Male ,Aging ,Native Hawaiian or Other Pacific Islander ,Ethnic group ,Frailty Index ,Māori ,Pasifika ,Age and sex ,InterRAI ,White People ,Indigenous ,03 medical and health sciences ,Sex Factors ,0302 clinical medicine ,Prevalence ,Ethnicity ,Humans ,Medicine ,New Zealand European ,030212 general & internal medicine ,Geriatric Assessment ,Referral and Consultation ,Aged ,Aged, 80 and over ,030505 public health ,Marital Status ,Frailty ,business.industry ,Proportional hazards model ,Age Factors ,Home Care Services ,Ageing ,Older persons ,Cohort ,Population study ,Female ,Geriatrics and Gerontology ,0305 other medical science ,business ,Older people ,Demography ,New Zealand - Abstract
Background Little is known about the prevalence of frailty in indigenous populations. We developed a frailty index (FI) for older New Zealand Māori and Pasifika who require publicly funded support services. Methods An FI was developed for New Zealand adults aged 65 and older who had an interRAI Home Care assessment between June 1, 2012 and October 30, 2015. A frailty score for each participant was calculated by summing the number of deficits recorded and dividing by the total number of possible deficits. This created a FI with a potential range from 0 to 1. Linear regression models for FIs with ethnicity were adjusted for age and sex. Cox proportional hazards models were used to assess the association between the FI and mortality for Māori, Pasifika, and non-Māori/non-Pasifika. Results Of 54 345 participants, 3096 (5.7%) identified as Māori, 1846 (3.4%) were Pasifika, and 49 415 (86.7%) identified as neither Māori nor Pasifika. New Zealand Europeans (48 178, 97.5%) constituted most of the latter group. Within each sex, the mean FIs for Māori and Pasifika were greater than the mean FIs for non-Māori and non-Pasifika, with the difference being more pronounced in women. The FI was associated with mortality (Māori subhazard ratio [SHR] 2.53, 95% CI 1.63–3.95; Pasifika SHR 6.03, 95% CI 3.06–11.90; non-Māori and non-Pasifika SHR 2.86, 95% CI 2.53–3.25). Conclusions This study demonstrated differences in FI between the ethnicities in this select cohort. After adjustment for age and sex, increases in FI were associated with increased mortality. This suggests that FI is predictive of poor outcomes in these ethnic groups.
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- 2021
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31. Antimicrobial-associated Organ Injury among the Older Adults: A Systematic Review and Meta-Analysis
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Prasad S. Nishtala, Sandipan Roy, and Tichawona Chinzowu
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medicine.medical_specialty ,business.industry ,Internal medicine ,Meta-analysis ,medicine ,Antimicrobial ,business - Abstract
Background: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for organ injury risk among older adults following antimicrobial exposure. This systematic review and meta-analysis examined the relationship between antimicrobial exposure and organ injury in older adults. Methodology: We searched for Psych INFO, PubMed, and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles were screened for inclusion into or exclusion from the study by two reviewers. The Newcastle-Ottawa scale was used to assess the risk of bias for cohort and case-control studies. The Cochrane collaboration's tool for risk of bias (version 2) was used to assess the risk of bias for randomised control trials. We explored the heterogeneity of the included studies using the Q test and I2 test and the publication bias using the funnel plot and Egger's test. Results: The overall absolute risks of acute kidney injury among older adults prescribed aminoglycosides, glycopeptides, and macrolides were 15.1%, 19.1%, and 0.3%, respectively. Only 3 studies reported antimicrobial associated drug-induced liver injury. Studies reporting on the association of organ injury and antimicrobial exposure by age or duration of treatment were too few to meta-analyse. The funnel plot and Egger's tests did not indicate evidence of publication bias.Conclusion: Older adults have a significantly higher risk of sustaining acute kidney injury when compared to the general adult population. Older adults prescribed aminoglycosides have a similar risk of acute kidney injury to the general adult population.
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- 2021
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32. An International Comparison of the Information in the Regulatory-Approved Drug Labeling and Prescribing Guidelines for Pediatric Depression
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David Taylor, Laila Tanana, Timothy F. Chen, Asam Latif, and Prasad S. Nishtala
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medicine.medical_specialty ,Internationality ,Guidelines as Topic ,Off-label use ,Approved drug ,SmPC ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,off-label use ,Pharmacology (medical) ,Pediatrics, Perinatology, and Child Health ,Practice Patterns, Physicians' ,Child ,Drug Approval ,Depression (differential diagnoses) ,Drug Labeling ,Psychotropic Drugs ,Drug labeling ,Depression ,drug labeling ,business.industry ,Age Factors ,Australia ,Off-Label Use ,United Kingdom ,030227 psychiatry ,Psychiatry and Mental health ,pediatric ,antidepressants ,Family medicine ,North America ,depression ,Pediatrics, Perinatology and Child Health ,business ,030217 neurology & neurosurgery - Abstract
Objectives: To determine the differences in information between prescribing guidelines and drug labeling, as well as to compare the approval of psychotropic medicines for major depression in pediatric patients ("pediatric depression") across countries. Methods: The recommendations of The Maudsley Prescribing Guidelines in Psychiatry (MPGP) for the treatment of pediatric depression (
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- 2021
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33. Deprescribing to reduce polypharmacy: study protocol for a randomised controlled trial assessing deprescribing of anticholinergic and sedative drugs in a cohort of frail older people living in the community
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Sarah N. Hilmer, Ulrich Bergler, Nagham J. Ailabouni, Dee Mangin, Hamish A. Jamieson, Prasad S. Nishtala, John W. Pickering, Bergler, Ulrich, Ailabouni, Nagham J, Pickering, John W, Hilmer, Sarah N, Mangin, Dee, Nishtala, Prasad S, and Jamieson, Hamish
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Medicine (General) ,medicine.medical_specialty ,drug burden index ,medicine.drug_class ,Frail Elderly ,Pharmacist ,Medicine (miscellaneous) ,Anticholinergic ,elderly ,Cholinergic Antagonists ,law.invention ,Study Protocol ,R5-920 ,Elderly ,Deprescriptions ,Randomized controlled trial ,Deprescribing ,SDG 3 - Good Health and Well-being ,deprescribing ,law ,Sedatives ,anticholinergic ,medicine ,interRAI ,Humans ,Hypnotics and Sedatives ,Pharmacology (medical) ,polypharmacy ,Aged ,Randomized Controlled Trials as Topic ,Polypharmacy ,business.industry ,sedatives ,Australia ,Checklist ,Drug burden index ,Clinical trial ,Pharmaceutical Preparations ,Family medicine ,Cohort ,business - Abstract
Background Targeted deprescribing of anticholinergic and sedative medications in older people may improve their health outcomes. This trial will determine if pharmacist-led reviews lead to general practitioners deprescribing anticholinergic and sedative medications in older people living in the community. Methods and analysis The standard protocol items: Recommendations for Interventional Trials (SPIRIT) checklist was used to develop and report the protocol. The trial will involve older adults stratified by frailty (low, medium, and high). This will be a pragmatic two-arm randomized controlled trial to test general practitioner uptake of pharmacist recommendations to deprescribe anticholinergic and sedative medications that are causing adverse side effects in patients. Study population Community-dwelling frail adults, 65 years or older, living in the Canterbury region of New Zealand, seeking publicly funded home support services or admission to aged residential care and taking at least one anticholinergic or sedative medication regularly. Intervention New Zealand registered pharmacists using peer-reviewed deprescribing guidelines will visit participants at home in the community, review their medications, and recommend anticholinergic and sedative medications that could be deprescribed to the participant’s general practitioner. The total use of anticholinergic and sedative medications will be quantified using the Drug Burden Index (DBI). Outcomes The primary outcome will be the change in total DBI between baseline and 6-month follow-up. Secondary outcomes will include entry into aged residential care, prolonged hospitalization, and death. Data collection points Data will be collected at the time of interRAI assessments (T0), at the time of the baseline review (T1), at 6 months following the baseline review (T2), and at the end of the study period, or end of study participation for participants admitted into aged residential care, or who died (T3). Ethics and dissemination Ethical approval has been obtained from the Human, Disability and Ethics Committee: ethical number (17CEN265). Trial registration ClinicalTrials.gov ACTRN12618000729224. Registered on May 2, 2018, with the Australian New Zealand Clinical Trials Registry
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- 2021
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34. Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults
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Prasad S. Nishtala, Sakirat Gill, and Te-yuan Chyou
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medicine.medical_specialty ,Epidemiology ,MedDRA ,Cardiomyopathy ,030226 pharmacology & pharmacy ,law.invention ,03 medical and health sciences ,Adverse Event Reporting System ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Odds Ratio ,Adverse Drug Reaction Reporting Systems ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Adverse effect ,Aged ,business.industry ,United States Food and Drug Administration ,Hydroxychloroquine ,Bayes Theorem ,Odds ratio ,medicine.disease ,Confidence interval ,United States ,business ,medicine.drug - Abstract
Purpose The purpose of this study is to analyze the US FDA Adverse Event Reporting System (FAERS) to identify adverse cardiac events of hydroxychloroquine in older adults. Method A case/non‐case method was used to determine adverse events associated with hydroxychloroquine as the primary suspect drug between January 1, 2004, and December 31, 2019, for older adults (≥65 years). Adverse events are preferred terms (PTs) defined in MedDRA. We used frequentist approaches, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) to measure disproportionality. We used Bayesian approaches to derive information component (IC) value and Empirical Bayesian Geometric Mean (EBGM) score. Signals were defined as the number of reports > 3 and the lower limit of 95% confidence intervals (CI) of ROR ≥ 2, PRR ≥ 2, IC > 0, EBGM > 1. Results We identified 334 adverse cardiac events comprising 71 different MedDRA PTs from 2004 to 2019 for hydroxychloroquine in older adults. Strong disproportionality signals were noted for “Restrictive cardiomyopathy” (ROR = 272.43 (138.09–537.47); EBGM = 149.78 (77.34–264.67), “Right ventricular hypertrophy” (219.49 (85.32–564.70); 102.74 (39.67–222.81), “Cardiac septal hypertrophy” (226.77 (78.65–653.80); 93.82 (32.19–219.81), “Myocardial fibrosis” (57.29 (21.06–155.85); 42.99 (14.74–100.75), and “Cardiotoxicity” (43.90 (26.66–72.27); 40.28 (24.02–63.72). Conclusions The risk of cardiomyopathy and myocardial disorders is high following exposure to hydroxychloroquine in older adults. Due to the current lack of safety data from randomized controlled trials as well as large observational studies to confirm the risk of adverse cardiac events associated with hydroxychloroquine, findings from analyses of post‐marketing data may serve as interim guidance.
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- 2020
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35. Antimicrobial-associated Organ Injury Among Older Adults: A Systematic Review and Meta-analyses Protocol
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Tichawona Chinzowu, Prasad S. Nishtala, and Sandipan Roy
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Protocol (science) ,medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Antimicrobial ,business - Abstract
Background: Older adults (aged 65 years and above) constitute the fastest growing population cohort in the western world. There is increasing evidence that the burden of infections disproportionately affects older adults, and hence this vulnerable population is frequently exposed to antimicrobials. There is currently no systematic review summarising the evidence for risk of organ injury following antimicrobial exposure among older adults. This protocol will outline how we will conduct a systematic review and meta-analyses to examine the relationship between antimicrobial exposure and organ injury in older adults. Methodology: We will search for Psych INFO, PubMed, and EMBASE databases for relevant articles using MeSH terms where applicable. After removing duplicates, articles will be screened for inclusion into or exclusion from the study by two reviewers. Title and abstract screening will be done first, followed by full-text screening. The Newcastle-Ottawa scale will be used to assess the risk of bias for cohort and case-control studies, and the Cochrane collaboration's tool will be used to assess the risk of bias for randomised control trials. We will explore the potential sources of heterogeneity and bias using funnel and forest plots of the included studies. Discussion and registration: In this protocol, systematic review methods to identify relevant literature on antimicrobial exposure and associated organ injury have been described. The findings from the review are intended to increase our understanding of the different types of antimicrobials associated with organ injury among older adults, therefore has the potential for improving the prescribing practice for this vulnerable population. This protocol is registered in the PROSPERO database (registration number CRD42020152621).
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- 2020
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36. A Disproportionality Analysis of the Adverse Drug Events Associated with Lurasidone in Paediatric Patients Using the US FDA Adverse Event Reporting System (FAERS)
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Kate E, Rees, Te-Yuan, Chyou, and Prasad S, Nishtala
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Male ,Lurasidone Hydrochloride ,Adolescent ,United States Food and Drug Administration ,Adverse Drug Reaction Reporting Systems ,Humans ,Female ,Child ,United States ,Antipsychotic Agents - Published
- 2020
37. A Disproportionality Analysis of the Adverse Drug Events Associated with Lurasidone in Paediatric Patients Using the US FDA Adverse Event Reporting System (FAERS)
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Prasad S. Nishtala, Kate E Rees, and Te-yuan Chyou
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Drug ,Pharmacology ,medicine.medical_specialty ,business.industry ,media_common.quotation_subject ,Pharmacology toxicology ,MEDLINE ,Toxicology ,Adverse Event Reporting System ,medicine ,Pharmacology (medical) ,Intensive care medicine ,business ,media_common ,Paediatric patients ,Lurasidone ,medicine.drug - Published
- 2020
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38. Safety of fluoxetine use in children and adolescents: a disproportionality analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database
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Te-yuan Chyou, Prasad S. Nishtala, and Iole N Christodoulos
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Male ,medicine.medical_specialty ,Serotonin Syndrome ,Adolescent ,Vomiting ,Pharmacology toxicology ,MEDLINE ,Anxiety ,Heart Septal Defects, Atrial ,Suicidal Ideation ,Food and drug administration ,Adverse Event Reporting System ,Pregnancy ,Seizures ,Fluoxetine ,Medicine ,Adverse Drug Reaction Reporting Systems ,Humans ,Pharmacology (medical) ,Child ,Pharmacology ,business.industry ,Depression ,United States Food and Drug Administration ,Infant, Newborn ,Infant ,General Medicine ,United States ,Case-Control Studies ,Child, Preschool ,Prenatal Exposure Delayed Effects ,Emergency medicine ,Antidepressive Agents, Second-Generation ,Female ,business ,medicine.drug - Published
- 2020
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39. Impact of Anticholinergic Burden on Cognitive Performance: A Cohort Study of Community-Dwelling Older Adults
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Hamish A. Jamieson, Prasad S. Nishtala, Ling Han, Te-yuan Chyou, Heather G. Allore, and Sarah N. Hilmer
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Gerontology ,medicine.drug_class ,Nursing(all) ,MEDLINE ,Cholinergic Antagonists ,Article ,Cohort Studies ,Cognition ,SDG 3 - Good Health and Well-being ,Anticholinergic ,Medicine ,Humans ,Cognitive Dysfunction ,Effects of sleep deprivation on cognitive performance ,General Nursing ,Aged ,business.industry ,Health Policy ,General Medicine ,Independent Living ,Geriatrics and Gerontology ,business ,Cohort study - Abstract
Older people are susceptible to the adverse effects of anticholinergic medications, including cognitive impairment. A systematic review of observational studies reported mixed associations between high anticholinergic burden, a cumulative measure of anticholinergic medications, and cognitive performance in older people. Observational studies may have biased estimates of the impact of exposures, as the exposed and unexposed may systematically differ in covariates associated with the outcomes.
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- 2020
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40. Association rules method and big data: Evaluating frequent medication combinations associated with fractures in older adults
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Prasad S. Nishtala, Te yuan Chyou, Danijela Gnjidic, David G. Le Couteur, and Fabian Held
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Big Data ,Male ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Epidemiology ,Poison control ,030226 pharmacology & pharmacy ,Occupational safety and health ,Fractures, Bone ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pharmacovigilance ,Injury prevention ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Aged ,Aged, 80 and over ,Zopiclone ,Cross-Over Studies ,business.industry ,Codeine ,Pharmacoepidemiology ,Quetiapine ,Drug Therapy, Combination ,Female ,business ,New Zealand ,medicine.drug - Abstract
Background The association rules method is a novel methodology to ascertain patterns of medication use and combinations associated with adverse drug events. Objectives The aim of this case-crossover study was to apply the association rules method to ascertain medication combinations contributing to the risk of fractures in older adults. Methods A nationwide representative sample of New Zealanders aged ≥65 years was sourced from the pharmaceutical collection. The first-time coded diagnosis of fracture was extracted from the National Minimum Dataset. Association rule method is a data mining technique that can be used to quickly traverse big datasets to identify a combination of items that co-occur. The association rules method were applied to identify frequent 11 medication combinations in the case and the control periods (1-14 days as hazard period, with 35-day washout period), and the association of fractures with each frequent medication combination were tested by computing a matched odd ratio (OR) and its 95% CI. Results We identified a total of 72 184 individuals (mean age 81.5 years) from 2005 to 2014 with incident fracture and exposed to at least 1 medication of interest. The association rules method revealed codeine phosphate (aOR = 11.50, 95% CI, 7.09-15.20, concomitantly with ibuprofen), zopiclone (aOR = 2.34, 95% CI, 1.49-3.67, concomitantly with morphine) and quetiapine (OR = 1.95, 95% CI, 1.28-2.98, concomitantly with zopiclone) were associated with fractures. Conclusion The association rules method identified medication exposure combinations containing psychotropic medications and codeine are frequently associated with fractures. This novel methodology applied to big data can be an important tool to ascertain medication combinations associated with adverse drug events.
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- 2018
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41. A Systematic Review Evaluating the Use of the interRAI Home Care Instrument in Research for Older People
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Prasad S. Nishtala and Mohammed Saji Salahudeen
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Male ,Gerontology ,Health (social science) ,Social Psychology ,Psychological intervention ,Risk Assessment ,03 medical and health sciences ,Cognition ,0302 clinical medicine ,Quality of life (healthcare) ,Outcome Assessment, Health Care ,Humans ,Medicine ,Longitudinal Studies ,Prospective Studies ,Mortality ,Geriatric Assessment ,Aged ,Retrospective Studies ,Aged, 80 and over ,Minimum Data Set ,030214 geriatrics ,business.industry ,Retrospective cohort study ,Caregiver burden ,Home Care Services ,Integrated care ,Hospitalization ,Clinical Psychology ,Cross-Sectional Studies ,Caregivers ,Scale (social sciences) ,Quality of Life ,Female ,Geriatrics and Gerontology ,Risk assessment ,business ,030217 neurology & neurosurgery - Abstract
Objective: To summarize studies that used the international Resident Assessment home care instrument (interRAI HC) to examine study outcomes for older people. Methods: A comprehensive systematic search was performed to identify relevant studies, using five databases from 1990 until October 2016. The Cochrane Risk-Bias assessment tool and Newcastle-Ottawa Scale was used to assess the quality of RCTs and non-RCTs, respectively. Results: Based on the full-text analysis, 40 studies met the inclusion criteria out of 506 total records. The review included 6 RCTs, 2 quasi-experimental, 17 prospective and retrospective studies, 13 cross-sectional and 2 longitudinal studies. A series of interventions and/or applications were identified from this review that employed the use of interRAI HC instrument: (a) in health services, (b) as a new integrated care model and for implementing machine learning algorithm, (c) as a comprehensive geriatric assessment tool, (d) in case management, (e) for care planning and screening, (f) in drug therapy assessment, (g) to assess caregiver burden, and (h) for various risk assessments. Studies that employed the interRAI HC instrument reported an array of health-outcome measures mostly related to functional, cognition, hospitalization and mortality. Conclusions: Application of the interRAI HC tool varied markedly across all studies, and the outcomes measures were heterogeneous. Future research directions are discussed. Clinical Implications: The results from this study facilitate the use of interRAI HC as a tool to measure an intervention's effect that leads to improvements in specific geriatric-related health outcome measures emphasizes on functional status and quality of life and ascertain its utility as a quality indicator for the care of older individuals.
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- 2018
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42. Population-based study examining the utilization of preventive medicines by older people in the last year of life
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Sujita W. Narayan and Prasad S. Nishtala
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Aspirin ,medicine.medical_specialty ,business.industry ,030503 health policy & services ,Warfarin ,General Medicine ,Clopidogrel ,Logistic regression ,Odds ,Dabigatran ,Dipyridamole ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cohort ,Medicine ,030212 general & internal medicine ,0305 other medical science ,business ,medicine.drug - Abstract
AIM To examine the patterns of preventive medicines (PM) use in the last year of life of older adults. METHODS This study cohort included individuals (n = 99 809) aged ≥75 years who were in their last year of life. PM examined in this study included low-dose aspirin (≤325 mg/day), clopidogrel, dipyridamole, warfarin, dabigatran, statins and bisphosphonates. Logistic regression models examined the influence of age, sex, multimorbidity, socioeconomic status, and a diagnosis of cancer on the number and type of PM prescribed from 2007 to 2012. RESULTS The number of PM prescribed was higher for men compared with women (OR 1.11, 95% CI 1.08-1.14). Increasing age did not have an effect on the number of PM prescribed. The use of clopidogrel increased almost threefold from 2007 to 2012 (OR 5.53, 95% CI 4.61-6.65). In contrast, bisphosphonates use decreased significantly during the same period (OR 0.35, 95% CI 0.32-0.39). Individuals with a diagnosis of cancer had increased odds of PM utilization for antiplatelets, aspirin monotherapy and statins, which had remarkably high odds (OR 4.11, 95% CI 3.88-4.34, P < 0.001). CONCLUSIONS The present explorative study highlighted that some PM, such as statins, continue to be prescribed until death, particularly those that might have been beneficial earlier in life, but have an uncertain or unfavorable risk-benefit ratio towards the end-of-life. Geriatr Gerontol Int 2018; 18: 892-898.
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- 2018
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43. International trends in antipsychotic use
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Corinne Zara Yahni, Koji Kawakami, Yu-Chiau Shyu, Svetlana Skurtveit, Takuya Kinoshita, Lise Aagaard, Jorge Enrique Machado-Alba, Izumi Sato, Helga Zoega, Sallie-Anne Pearson, Kari Furu, Catharina C. M. Schuiling-Veninga, Christian Bachmann, Falk Hoffmann, Johan Reutfors, Melisa Litchfield, Miquel Bernardo, Soffy C. López, Manuel Enrique Machado-Duque, Luuk J. Kalverdijk, Helle Kieler, Anna Coma Fusté, Prasad S. Nishtala, Lena Brandt, Mufaddal Mahesri, Krista F. Huybrechts, Liang-Jen Wang, Kristina Garuoliene, Hélène Verdoux, Oskar Halfdanarson, Leena K. Saastamoinen, and PharmacoTherapy, -Epidemiology and -Economics
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Olanzapine ,Internationality ,Cross-sectional study ,Antipsychotic agents ,medicine.medical_treatment ,CHILDREN ,NATIONAL TRENDS ,0302 clinical medicine ,ADOLESCENTS ,Pharmacology (medical) ,Child ,education.field_of_study ,Age Factors ,BIPOLAR DISORDER ,Pharmacoepidemiology ,Middle Aged ,SAFETY WARNINGS ,PREVALENCE ,Psychiatry and Mental health ,Neurology ,DRUG USE ,Child, Preschool ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Population ,Atypical antipsychotic ,03 medical and health sciences ,Young Adult ,Sex Factors ,Drug Therapy ,DISEASE PATTERNS ,medicine ,Humans ,ANTIDEPRESSANT USE ,education ,Antipsychotic ,Psychiatry ,Biological Psychiatry ,Aged ,Pharmacology ,Risperidone ,business.industry ,Infant, Newborn ,Infant ,030227 psychiatry ,Minors ,Cross-Sectional Studies ,Quetiapine ,MENTAL-HEALTH-CARE ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Demography - Abstract
The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.
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- 2017
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44. Development and validation of a Medicines Comorbidity Index for older people
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Prasad S. Nishtala and Sujita W. Narayan
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Adult ,Male ,medicine.medical_specialty ,Comorbidity ,Drug Prescriptions ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Medical prescription ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pharmacology ,Receiver operating characteristic ,business.industry ,030503 health policy & services ,Hazard ratio ,Regression analysis ,Retrospective cohort study ,General Medicine ,Middle Aged ,Pharmacoepidemiology ,medicine.disease ,Cohort ,Physical therapy ,Female ,0305 other medical science ,business - Abstract
An index for estimating multimorbidity based on prescription claims data is important for predicting health outcomes for older people in pharmacoepidemiological studies. We aimed to develop a Medicines Comorbidity Index (MCI) based on nationwide prescription claims data and evaluate its performance in predicting adverse outcomes in older individuals. The index was developed on a retrospective cohort comprising of all individuals aged ≥ 65 years old, captured in the claims dataset from 1st January to 31st December 2012. The cohort was followed for 1 year to identify an event of hospitalisation or mortality. A list of medications for 20 comorbidities based on the Chronic Disease Score framework was collated. Predictive performance of the MCI was evaluated against the Charlson Comorbidity Index (CCI) using measures of discrimination (Receiver Operating Characteristic curves), sensitivity and specificity (c-statistic) and calibration (Brier scores) for regression models. The MCI was validated for an outcome of mortality (n = 161,461) and hospitalisation (n = 149,729). For mortality, MCI had a marginally lower c-statistic in comparison to CCI (0.70, 95% CI 0.70–0.71 vs 0.72, 95% CI 0.71–0.72 at p
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- 2017
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45. An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice
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Prasad S. Nishtala and Mohammed Saji Salahudeen
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Fractional occupancy ,0301 basic medicine ,Drug ,Stereochemistry ,media_common.quotation_subject ,Pharmaceutical Science ,Review ,03 medical and health sciences ,0302 clinical medicine ,Binding site ,Receptor ,Ligand binding ,Pharmacodynamic model ,media_common ,Pharmacology ,Chemistry ,Emax model ,Competitive binding ,Ligand (biochemistry) ,Clinical Practice ,030104 developmental biology ,Drug concentration ,Pharmacodynamics ,030217 neurology & neurosurgery ,Systems pharmacology - Abstract
The study of the magnitude and variation of drug response is defined as pharmacodynamics (PDs). PD models examine plasma concentration and effect relationship. It can predict the archetypal effect ([Formula: see text]) of a drug as a function of the drug concentration ([Formula: see text]) and estimate an unknown PD parameter ([Formula: see text]). The PD models have been described as fixed, linear, log-linear, [Formula: see text], sigmoid [Formula: see text], and indirect PD response. Ligand binding model is an example of a PD model that works on the underpinning PD principle of a drug, eliciting its pharmacological effect at the receptor site. The pharmacological effect is produced by the drug binding to the receptor to either activate or antagonise the receptor. Ligand binding models describe a system of interacting components, i.e. the interaction of one or more ligands with one or more binding sites. The [Formula: see text] model is the central method that provides an empirical justification for the concentration/dose-effect relationship. However, for ligand binding models justification is provided by theory of receptor occupancy. In essence, for ligand binding models, the term [Formula: see text] is best used to describe the fraction of receptors occupied at a particular ligand concentration. It is stated that the [Formula: see text], which means the effect of a drug should depend on the fraction of receptors that are occupied. In the future, network-based systems pharmacology models using ligand binding principles could be an effective way of understanding drug-related adverse effects. This will facilitate and strengthen the development of rational drug therapy in clinical practice.
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- 2017
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46. Drug burden index and its association with hip fracture among older adults:a national population-based study
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Prasad S. Nishtala, Darrell R. Abernethy, Rebecca Abey-Nesbit, Philip J. Schluter, Sarah D. Berry, Joanne M. Deely, Cameron Lacey, Sarah N. Hilmer, Vincent Mor, Hamish A. Jamieson, and Richard Scrase
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Male ,Aging ,Pediatrics ,medicine.medical_specialty ,Activities of daily living ,Medication Therapy Management ,Medications ,Anticholinergic agents ,Risk Assessment ,030226 pharmacology & pharmacy ,Cholinergic Antagonists ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Activities of Daily Living ,medicine ,Humans ,Hypnotics and Sedatives ,030212 general & internal medicine ,Aged ,Polypharmacy ,Hip fracture ,Hip Fractures ,business.industry ,Incidence ,Incidence (epidemiology) ,Confounding ,Regression analysis ,medicine.disease ,Comorbidity ,Ageing ,RAI ,Accidental Falls ,Female ,Falls ,Independent Living ,Geriatrics and Gerontology ,business ,New Zealand - Abstract
Background: The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study was to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors. Methods: A competing-risks regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (International Resident Assessment Instrument) assessment between September 1, 2012, and October 31, 2015, the study's end date. Outcome measures were survival status and hip fracture, with time-varying DBI exposure derived from 90-day time intervals. The multivariable competing-risks regression model was adjusted for a large number of medical comorbidities and activities of daily living. Results: Among 70,553 adults assessed, 2,249 (3.2%) experienced at least one hip fracture, 20,194 (28.6%) died without experiencing a fracture, and 48,110 (68.2%) survived without a fracture. The mean follow-up time was 14.9 months (range: 1 day, 37.9 months). The overall DBI distribution was highly skewed, with median time-varying DBI exposure ranging from 0.93 (Q 1 = 0.0, Q 3 = 1.84) to 0.96 (Q 1 = 0.0, Q 3 = 1.90). DBI was significantly related to fracture incidence in unadjusted (p 3 compared with those with DBI = 0 in the adjusted analysis. Conclusions: In this study, increasing DBI was associated with a higher likelihood of fractures after accounting for the competing risk of mortality and adjusting for confounders. The results of this unique study are important in validating the DBI as a guide for medication management and it could help reduce the risk of hip fractures in older adults.
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- 2019
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47. Factors associated with inappropriate prescribing among older adults with complex care needs who have undergone the interRAI assessment
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Sharmin S. Bala, Prasad S. Nishtala, and Hamish A. Jamieson
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Male ,medicine.medical_specialty ,Potentially Inappropriate Medication List ,Inappropriate Prescribing ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,hemic and lymphatic diseases ,Activities of Daily Living ,Prevalence ,Humans ,Medicine ,030212 general & internal medicine ,Intensive care medicine ,Geriatric Assessment ,Aged ,Retrospective Studies ,Aged, 80 and over ,Complex care needs ,business.industry ,Potentially Inappropriate Medications ,Geriatric assessment ,General Medicine ,Cross-Sectional Studies ,Logistic Models ,Female ,business ,Risk assessment - Abstract
Aim To identify factors associated with prescribing potentially inappropriate medications (PIMs) in older adults (≥ 65 years) with complex care needs, who have undertaken a comprehensive geriatric risk assessment.METHODS: A nationwide cross-sectional (retrospective, observational) study was performed. The national interRAI Home Care assessments conducted in New Zealand in 2015 for older adults were linked to the national pharmaceutical prescribing data (PHARMS). The 2015 Beers criteria were applied to the cross-matched data to identify the prevalence of PIMs. The factors influencing PIMs were analysed using a multinomial logistic regression model.RESULTS: 16,568 older adults were included in this study. Individuals diagnosed with cancer, dementia, insomnia, depression, anxiety, and who were hospitalized in the last 90 days, were more likely to be prescribed PIMs than those who were not diagnosed with the above disorders, and who were not hospitalized in the last 90 days. Individuals over 75 years of age, the Māori ethnic group among other ethnicities, individuals who were diagnosed with certain clinical conditions (diabetes, chronic obstructive pulmonary disease, stroke, or congestive cardiac failure), individuals requiring assistance with activities of daily living and better self-reported health, were associated with a lesser likelihood of being prescribed PIMs.CONCLUSION: The study emphasizes the identification of factors associated with the prescription of PIMs during the first completed comprehensive geriatric assessment. Targeted strategies to reduce modifiable factors associated with the prescription of PIMs in subsequent assessments has the potential to improve medication management in older adults.
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- 2019
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48. Reducing Potentially Inappropriate Medications in Older Adults: A Way Forward
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Prasad S. Nishtala, Sharmin S. Bala, and Timothy F. Chen
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medicine.medical_specialty ,Health (social science) ,Population ,Beers Criteria ,Inappropriate Prescribing ,030226 pharmacology & pharmacy ,Medication prescription ,03 medical and health sciences ,0302 clinical medicine ,Deprescriptions ,Medication Reconciliation ,medicine ,Humans ,030212 general & internal medicine ,Medical prescription ,education ,Potentially Inappropriate Medication List ,Aged ,Community and Home Care ,Gynecology ,Aged, 80 and over ,education.field_of_study ,business.industry ,Mesh term ,Potentially Inappropriate Medications ,Inappropriate Prescriptions ,Narrative review ,Geriatrics and Gerontology ,business ,Gerontology - Abstract
La reduction des medicaments potentiellement inappropries (MPI) chez les personnes âgees est un enjeu important selon de nombreux cliniciens et chercheurs a travers le monde, car ces medicaments accroissent significativement la morbidite et la mortalite dans la population plus âgee. La prevalence des MPI est un probleme repandu malgre l'existence de plusieurs criteres explicites et implicites de reduction des MPI chez les personnes âgees, les plus courants etant les criteres de Beers, les criteres STOPP/START et plusieurs criteres nationaux specifiques. Cette revue non systematique visait a examiner les criteres de reference pour la reduction des MPI et a clarifier le role de certaines mesures, dont la deprescription, pour optimiser la prescription des medicaments chez les personnes âgees. Des recherches par mots-cles et termes MeSH ont ete menees dans des bases de donnees electroniques. Les nombreux criteres disponibles ont chacun leurs avantages et inconvenients. La deprescription, qui vise a reduire l'utilisation des MPI, a considerablement gagne en importance dans les initiatives associees a l'amelioration des pratiques de prescription. La deprescription est une approche methodique qui implique l'arret graduel, eclaire et individualise des medicaments inappropries, avec un suivi rigoureux des patients pour assurer la detection d'evenements indesirables ou de symptomes de rebond. Une approche combinee centree sur le patient et le soignant favorise la collaboration entre les prescripteurs et les pharmaciens afin de reduire le nombre de MPI chez les personnes âgees. Reducing potentially inappropriate medications (PIMs) in older adults is an area of sustained interest for many clinicians and researchers across the globe, as PIMs contribute to a significant burden of morbidity and mortality in the aging population. The prevalence of PIMs is a pervasive problem despite the presence of several explicit and implicit criteria for reducing PIMs in older adults, the most common being the Beers criteria, the Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment (STOPP/START) criteria, and several country-specific criteria. This narrative review aims to discuss the frequently used published criteria for reducing PIMs, and elucidates the role of certain measures, especially de-prescribing, to optimise medication prescription in older adults. Electronic databases were searched using keywords and MeSH terms. The numerous available criteria have their specific advantages and drawbacks. De-prescribing, an initiative to reduce the use of PIMs, has gained significant importance in improving appropriate prescribing practices. De-prescribing is a methodical approach to gradually stopping inappropriate medications judiciously for each patient and simultaneously monitoring the patient carefully for the onset of adverse events or rebound symptoms. A combined caregiver–patient-centred approach encourages the collaboration between prescribers and pharmacists to reduce PIMs in older adults.
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- 2019
49. Identifying drug combinations associated with acute kidney injury using association rules method
- Author
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Prasad S. Nishtala and Te-yuan Chyou
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Drug ,Male ,medicine.medical_specialty ,pharmacoepidemiology ,Drug-Related Side Effects and Adverse Reactions ,Epidemiology ,media_common.quotation_subject ,030226 pharmacology & pharmacy ,association rules ,older people ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Anti-Infective Agents ,Internal medicine ,Pharmacovigilance ,medicine ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Medical prescription ,Diuretics ,media_common ,Aged ,Polypharmacy ,Aged, 80 and over ,case-crossover design ,Cross-Over Studies ,business.industry ,Odds ratio ,Pharmacoepidemiology ,Acute Kidney Injury ,Confidence interval ,Analgesics, Opioid ,acute kidney injury ,pharmacovigilance ,Cohort ,Drug Therapy, Combination ,Female ,business ,New Zealand - Abstract
Background: Older adults are at an increased risk of acute kidney injury (AKI) because of aging, multiple comorbidities, and polypharmacy. Objectives: The aim of this case-crossover study was to apply association rule (AR) analysis to ascertain drug combinations contributing to the risk of AKI in adults aged 65 years and older. Methods: We sourced a nationwide representative sample of New Zealanders aged ≥65 years from the pharmaceutical collections and hospital discharge information. Prescription records (2005-2015) of drugs of interest were sourced from New Zealand pharmaceutical collections (Pharms). We classified medication exposure, as a binary variable, at individual drug level belonging to medication classes including antimicrobials, antihistamines, diuretics, opioids, nonsteroidal anti-inflammatory medications. Several studies have associated the drugs of interest from these medication classes with AKI in older adults. We extracted the first-time coded diagnosis of AKI from the National Minimal Data Set. A unique patient identifier linked the prescription data set to the event data set, to set up a case-crossover cohort, indexed at the first AKI event. ARs were then applied to identify frequent drug combinations in the case and the control periods (l-day observation with a 35-day washout period), and the association of AKI with each frequent drug combination was tested by computing a matched odds ratio (MOR) and its 95% confidence interval (CI). Results: We identified 55 747 individuals (mean age 82.14) from 2005 to 2014 with incident AKI and exposed to at least one of the drugs of interest. ARs identified several medication classes including antimicrobials, nonsteroidal anti-inflammatory drugs, and opioids are associated with AKI. The frequently used medicines associated with AKI are trimethoprim (MOR = 1.68; 95% CI = [1.54-1.80]), ondansetron (MOR = 1.43; 95% CI = [1.25-1.64]), codeine phosphate plus metoclopramide (MOR = 1.37; 95% CI = [1.11-1.63]), and norfloxacin (MOR = 1.24; 95% CI [1.05-1.42]). Conclusions: We applied ARs, a novel methodology, to big data to ascertain drug combinations associated with AKI. ARs uncovered previously implicated medication classes that increase the risk of AKI in older adults. The finding that ondansetron increases the risk of AKI requires further investigation.
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- 2019
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50. Determinants of prescribing potentially inappropriate medications in a nationwide cohort of community dwellers with dementia receiving a comprehensive geriatric assessment
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Sharmin S. Bala, Prasad S. Nishtala, and Hamish A. Jamieson
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Male ,Gerontology ,Activities of daily living ,medicine.drug_class ,Ethnic group ,Beers Criteria ,Inappropriate Prescribing ,Logistic regression ,Cholinergic Antagonists ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,SDG 3 - Good Health and Well-being ,Risk Factors ,hemic and lymphatic diseases ,Activities of Daily Living ,Prevalence ,Anticholinergic ,interRAI ,Humans ,Medicine ,Dementia ,prescribing in older adults ,potentially inappropriate medications ,Potentially Inappropriate Medication List ,Aged ,Aged, 80 and over ,030214 geriatrics ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Logistic Models ,Cohort ,Population study ,Female ,Self Report ,Geriatrics and Gerontology ,business ,dementia - Abstract
Objective: To identify the prevalence and predictors of prescribing potentially inappropriate medications (PIMs) in a nationwide cohort of community dwellers with dementia requiring complex care needs. Methods: A cross-matched data of the International Resident Assessment Instrument-Home Care (9.1) (interRAI-HC) and prescribing data obtained from the Pharmaceutical Claims Data Mart (Pharms) extract files for older adults (≥65 y) requiring complex care needs were utilized for this study. The 2015 Beers criteria were applied to identify the prevalence of PIMs in older adults with dementia. Sociodemographic and clinical predictors of PIMs were analysed using a logistic regression model. Results: The study population consisted of 16 568 individuals who had their first interRAI assessment from 1 January 2015 to 31 December 2015. The estimated prevalence of dementia was 13.2% (2190/16 568). 66.9% (1465/2190) of the older adults diagnosed with dementia were prescribed PIMs, of which anticholinergic medications constituted 59.6% (873/1465). Males and individuals who were prescribed a greater number of medications were more likely to be prescribed PIMs. Individuals over 85 years of age, Māori ethnic group of individuals, older adults who were being supervised with respect to their activities of daily living, and individuals who reported good or excellent self-reported health had a lesser likelihood of being prescribed PIMs. Conclusion: We found that PIMs are prescribed frequently in older adults with dementia. Comprehensive geriatric assessments can serve as a potential tool to decrease the occurrence of PIMs in vulnerable groups with poor functional and cognitive status.
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- 2019
- Full Text
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