One Health Determinants of Escherichia coli Antimicrobial Resistance in Humans in the Community: An Umbrella Review.

To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment. The aim of this umbrella review is to conduct a systematic synthesis of existing evidence on Escherichia coli AMR in humans in the community from a One Health perspective. PubMed, EMBASE, and CINAHL were searched on "antibiotic resistance" and "systematic review" from inception until 25 March 2022 (PROSPERO: CRD42022316431). The methodological quality was assessed, and the importance of identified variables was tabulated across all included reviews. Twenty-three reviews were included in this study, covering 860 primary studies. All reviews were of (critically) low quality. Most reviews focused on humans (20), 3 on animals, and 1 on both human and environmental variables. Antibiotic use, urinary tract infections, diabetes, and international travel were identified as the most important human variables. Poultry farms and swimming in freshwater were identified as potential sources for AMR transmission from the animal and environmental perspectives. This umbrella review highlights a gap in high-quality literature investigating the time between variable exposure, AMR testing, and animal and environmental AMR variables.

Preparing for an aging Australia: The development of multidisciplinary core competencies for the Australian health and aged care workforce.

Appropriately skilled staff are required to meet the health and care needs of aging populations yet, shared competencies for the workforce are lacking. This study aimed to develop multidisciplinary core competencies for health and aged care workers in Australia through a scoping review and Delphi survey. The scoping review identified 28 records which were synthesized through thematic analysis into draft domains and measurable competencies. Consensus was sought from experts over two Delphi rounds (n = 111 invited; n = 59 round one; n = 42 round two). Ten domains with 66 core competencies, to be interpreted and applied according to the worker's scope of practice were finalized. Consensus on multidisciplinary core competencies which are inclusive of a broad range of registered health professionals and unregistered aged care workers was achieved. Shared knowledge, attitudes, and skills across the workforce may improve the standard and coordination of person-centered, integrated care for older Australians from diverse backgrounds.

Use of over-the-counter laxatives by community-dwelling adults to treat and prevent constipation: a national cross-sectional study.

PURPOSE: Constipation is commonly self-managed with over-the-counter laxatives. The study aim was to explore laxative choice, healthcare professional recommendations in laxative selection, and laxative effectiveness when laxatives are used for treatment and for prevention of constipation by community-dwelling adults. METHODS: A nationally representative sample of community-dwelling adults in Australia was surveyed. Participants completed an online questionnaire. Z tests for differences in proportions were used to compare the proportion of laxatives by class when used either for treatment or for prevention of constipation by choice of laxative, healthcare professional recommendation, and perceived effectiveness. RESULTS: The questionnaire was completed by 2024 participants. Laxatives were used by 37% (n = 747) of participants with 31.3% using laxatives for treatment, 19.3% for prevention, and 49.7% using laxatives for both purposes. The most common laxatives used for treatment and prevention were contact laxatives (39.8% and 31.1% respectively) and bulk-forming laxatives (34.3% and 44.6% respectively). Of all laxatives used, 56.4% of laxatives were chosen with healthcare professional recommendation, and 53.5% of laxatives were found effective. CONCLUSION: Laxatives were used both for treatment and for prevention of constipation. However, laxatives are often perceived to be ineffective and healthcare professionals are not always involved in laxative choice. Modified guidelines which address the use of laxatives for both treatment and prevention, and increased healthcare professional involvement in appropriate choice and use of laxatives, may be required to improve constipation management in the community.

Letter to the Editor: Integrating the Roles of Pharmacy Practice and Drug Delivery in Mitigating COVID-19.

No Abstract Available.

Chronic Constipation in the Community: A National Survey of Australian Adults.

PURPOSE: The aim of this study was to determine the prevalence of chronic constipation and identify factors associated with chronic constipation in community-dwelling adults. DESIGN: Cross-sectional study. METHODS: The target population was community-dwelling Australian adults; 1978 participants completed an online questionnaire exploring symptoms, management, and factors potentially associated with constipation. Chronic constipation was identified using Rome III criteria. Multivariate logistic regression model was used to identify factors associated with chronic constipation. RESULTS: The prevalence of chronic constipation was 23.9%. Factors significantly associated with chronic constipation in the multivariate model were female gender (odds ratio [OR] = 1.42, 95% confidence interval [CI], 1.12-1.81), current employment (OR = 1.45, 95% CI, 1.11-1.88), regular smoking (OR = 1.60, 95% CI, 1.19-2.14), poor self-rated health (OR = 2.57, 95% CI, 1.28-5.19), thyroid disease (OR = 1.77, 95% CI, 1.21-2.79), depression (OR = 1.49, 95% CI, 1.08-2.06), hemorrhoids (OR = 2.98, 95% CI, 1.84-4.83), irritable bowel syndrome (OR = 2.45, 95% CI, 1.73-3.46), and use of anti-inflammatory/antirheumatic medications (OR = 2.06, 95% CI, 1.15-3.68). In contrast to these factors, use of medications acting on the renin-angiotensin system was associated with a reduced likelihood of chronic constipation (OR = 0.47, 95% CI, 0.24-0.91). CONCLUSIONS: Chronic constipation is prevalent among community-dwelling adults. Various factors associated with chronic constipation have been identified, and knowledge of these factors may help health care professionals recognize individuals who are at high risk of chronic constipation.

Defining constipation to estimate its prevalence in the community: results from a national survey.

BACKGROUND: Different definitions of constipation have been used to estimate its prevalence in the community but this creates difficulties when comparing results from various studies. This study explores the impact of different definitions on prevalence estimates in the same population and compares the performance of simple definitions with the Rome III criteria. METHODS: The prevalence of constipation in a large nationally representative sample of community-dwelling adults was estimated using five simple definitions of constipation and compared with definitions based on the Rome III criteria. The sensitivity, specificity, and positive and negative predictive values, were calculated for each definition using the Rome III criteria as the gold standards for chronic and sub-chronic constipation. RESULTS: Prevalence estimates for the five simple definitions ranged from 9.4 to 58.9%, while the prevalence estimates using the Rome III criteria were 24.0% (95%CI: 22.1, 25.9) for chronic constipation and 39.6% (95%CI: 37.5, 41.7) for sub-chronic constipation. None of the simple definitions were adequate compared to the Rome III criteria. Self-reported constipation over the past 12 months had the highest sensitivity (91.1%, 95%CI: 88.8, 93.4) and negative predictive value (94.5%, 95%CI: 93.1, 96.1) compared to the Rome III criteria for chronic constipation but an unacceptably low specificity (51.3%, 95%CI: 48.8, 53.8) and positive predictive value (37.1%, 95%CI: 34.4, 39.9). CONCLUSIONS: The definition used to identify constipation within a population has a considerable impact on the prevalence estimate obtained. Simple definitions, commonly used in research, performed poorly compared with the Rome III criteria. Studies estimating population prevalence of constipation should use definitions based on the Rome criteria where possible.

Anticholinergic and sedative medication use in older community-dwelling people: A national population study in the Netherlands.

PURPOSE: To identify the proportion of older adults with a high anticholinergic/sedative load and to identify patient subgroups based on type of central nervous system (CNS)-active medication used. METHODS: A cross-sectional study of a nationwide sample of patients with anticholinergic/sedative medications dispensed by 1779 community pharmacies in the Netherlands (90% of all community pharmacies) in November 2016 was conducted. Patients aged older than 65 years with a high anticholinergic/sedative load defined as having a drug burden index (DBI) greater than 1 were included. Proportion of patients with a high anticholinergic/sedative load was calculated by dividing the number of individuals in our study population by the 2.4 million older patients using medications dispensed from study pharmacies. Patient subgroups based on type of CNS-active medications used were identified with latent class analysis. RESULTS: Overall, 8.7% (209 472 individuals) of older adults using medications had a DBI greater than 1. Latent class analysis identified four patient subgroups (classes) based on the following types of CNS-active medications used: "combined psycholeptic/psychoanaleptic medication" (class 1, 57.9%), "analgesics" (class 2, 17.9%), "antiepileptic medication" (class 3, 17.8%), and "anti-Parkinson medication" (class 4, 6.3%). CONCLUSIONS: A large proportion of older adults in the Netherlands had a high anticholinergic/sedative load. Four distinct subgroups using specific CNS-active medication were identified. Interventions aiming at reducing the overall anticholinergic/sedative load should be tailored to these subgroups.

Antidepressant switching patterns in the elderly.

ABSTRACTBackground:Switching between antidepressants is complex due to potential adverse outcomes such as serotonin syndrome and antidepressant discontinuation syndrome, yet switching is often required due to non-response to initial treatment. This study aimed to examine the patterns and extent of antidepressant switching in a cohort of older adults in long-term residential care. METHODS: A cohort study of medication supply data from 6011 aged care residents in 60 long-term care facilities was conducted. Incident antidepressant users were followed for 12 months and their patterns of antidepressant use determined. The type of switching from and to different antidepressant classes was determined according to National and International recommendations for antidepressant switching. RESULTS: In total, 11% (n = 44) of the residents were initiated on an antidepressant medication (n = 402) switched to a different antidepressant agent within 12 months. Residents commenced on a SNRI or TCA were most likely to switch antidepressants (17% in each group). Almost half of the switches (n = 21, 48% of all switches) were not implemented according to guideline recommendations. Direct switch and taper followed by wash out and switch, accounted for all of the inappropriate switching (29% and 71%, respectfully), with half occurring to mirtazapine (N = 7) or from mirtazapine (N = 3). CONCLUSIONS: Over one in 10 long-term aged care residents who commence an antidepressant will switch to a different antidepressant within 12 months. Current antidepressant switching practices in long-term residential aged care may be increasing the risk of harm associated with antidepressant switching, with around half of all switches not following current guideline recommendations.

Leveraging new information technology to monitor medicine use in 71 residential aged care facilities: variation in polypharmacy and antipsychotic use.

OBJECTIVE: The aim of this study was to use routinely collected electronic medicines administration (eMAR) data in residential aged care (RAC) to investigate the quality use of medicines. DESIGN: A cross-sectional analysis of eMAR data. SETTING: 71 RAC facilities in New South Wales and the Australian Capital Territory, Australia. PARTICIPANTS: Permanent residents living in a participating facility on 1 October 2015. INTERVENTION: None. MAIN OUTCOME MEASURES: Variation in polypharmacy (≥5 medications), hyper-polypharmacy (≥10 medications) and antipsychotic use across facilities was examined using funnel plot analysis. RESULTS: The study dataset included 4775 long-term residents. The mean resident age was 85.3 years and 70.6% of residents were female. The median facility size was 60 residents and 74.3% were in metropolitan locations. 84.3% of residents had polypharmacy, 41.2% hyper-polypharmacy and 21.0% were using an antipsychotic. The extent of polypharmacy (69.75-100% of residents), hyper-polypharmacy (38.81-76.19%) and use of antipsychotic medicines (0-75.6%) varied considerably across the 71 facilities. CONCLUSIONS: Using eMAR data we found substantial variation in polypharmacy, hyper-polypharmacy and antipsychotic medicine use across 71 RAC facilities. Further investigation into the policies and practices of facilities performing above or below expected levels is warranted to understand variation and drive quality improvement.

A systematic review of the outcomes reported in trials of medication review in older patients: the need for a core outcome set.

AIM: Medication review has been advocated as one of the measures to tackle the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. This study aimed to assess outcome reporting in trials of medication review in older patients. METHODS: Randomized controlled trials (RCTs), prospective studies and RCT protocols involving medication review performed in patients aged 65 years or older in any setting of care were identified from: (1) a recent systematic review; (2) RCT registries of ongoing studies; (3) the Cochrane library. The type, definition, and frequency of all outcomes reported were extracted independently by two researchers. RESULTS: Forty-seven RCTs or prospective published studies and 32 RCT protocols were identified. A total of 327 distinct outcomes were identified in the 47 published studies. Only one fifth (21%) of the studies evaluated the impact of medication reviews on adverse events such as drug reactions or drug-related hospital admissions. Most of the outcomes were related to medication use (n = 114, 35%) and healthcare use (n = 74, 23%). Very few outcomes were patient-related (n = 24, 7%). A total of 248 distinct outcomes were identified in the 32 RCT protocols. Overall, the number of outcomes and the number and type of health domains covered by the outcomes varied largely. CONCLUSION: Outcome reporting from RCTs concerning medication review in older patients is heterogeneous. This review highlights the need for a standardized core outcome set for medication review in older patients, to improve outcome reporting and evidence synthesis.

Cross-national comparison of medication use in Australian and Dutch nursing homes.

Background: cross-national comparisons can be used to explore therapeutic areas and identify potential medication issues. Methods: we used cross-sectional pharmacy supply data to explore medication use for nursing home residents in Australia (AU n = 26 homes, 1,560 residents) and the Netherlands (NL n = 6 homes, 2,037 residents). Binary logistic regression analysis was used to calculate the sex and aged adjusted odds ratios (OR) and associated 95% confidence intervals with a flexible Bonferroni-Holm procedure used to adjust for multiple hypothesis testing. Results: total use of antipsychotics (AU: 37.7%, NL: 40.3%; OR 0.91 (0.79-1.04, P = 0.16) and antibacterials (66.8% AU, 62.4% NL, OR 1.08 (0.93-1.24, P = 0.31) was similar, but choice of individual agents differed between the two countries. Differences were observed in the use of antithrombotics (46.7% AU, 64.7% NL, OR 0.48 (0.42-0.56, P > 0.01), ophthalmologicals (44.3% AU, 22.1% NL, OR 2.80 (2.42-3.24, P < 0.001), laxatives (77.1% AU, 65.8% NL, OR 1.65 (1.41-1.92, P < 0.001). Conclusion: while the general prevalence of medication use in nursing home residents was similar across the two countries, distinct differences existed in the choice of agent among therapeutic groups. Comparing use between countries identified a number of potential medication related problem areas that need further exploration.

Laxative Use and Self-Reported Constipation in a Community-Dwelling Elderly Population: A Community-Based Survey From Australia.

The objectives of this study were to (1) determine the prevalence of laxative use and self-reported constipation and (2) identify risk factors associated with constipation in a community-dwelling elderly population. A retrospective cross-sectional survey using data from the Australian Longitudinal Study of Ageing was used to explore laxative use and constipation in a cohort of community-dwelling older persons. The prevalence of laxative use was 15% and the prevalence of self-reported constipation was 21%. Females were more likely to report constipation and use laxatives. Of those using laxatives, men were more likely to have their laxatives prescribed by a doctor whereas women were more likely to self-medicate. Poor self-rated health and a higher need for assistance with activities of daily living were identified as risk factors for constipation. Constipation is a common condition affecting the community-dwelling elderly. There is a need to optimize the management of constipation and use of laxatives in such populations.

The use of antipsychotics among people treated with medications for dementia in residential aged care facilities.

BACKGROUND: Antipsychotic agents have limited efficacy for Behavioral and Psychological Symptoms of Dementia (BPSD) and there are concerns about their safety. Despite this, they are frequently used for the management of BPSD. This study aimed to assess the use of antipsychotics among people on anti-dementia medicines in Australian residential aged care facilities. METHODS: Data were obtained from an individual patient unit dose packaging database covering 40 residential aged care facilities in New South Wales, Australia. Residents supplied an anti-dementia medicine between July 2008 and June 2013 were included. Prevalence of concurrent antipsychotic use was established. Incident antipsychotic users between January 2009 and December 2011 were identified. We examined initial antipsychotic dose, maximum titrated doses, type and duration of antipsychotic use, and compared use with Australian guidelines. RESULTS: There were 291 residents treated with anti-dementia medicines, 129 (44%) of whom received antipsychotics concomitantly with an anti-dementia medicine. Among the 59 incident antipsychotic users, risperidone (73%) was the most commonly used antipsychotic agent. Amongst the risperidone initiators, 43% of patients had initial doses greater than 0.5 mg/day and 6% of patients exceeded 2.0 mg/day for their maximum dose. 53% of concomitant users received daily treatment for greater than six months. CONCLUSIONS: Our study using records of individual patient unit dose supply, which represents the intended medication consumption schedule, shows high rates of concurrent use of antipsychotics and anti-dementia medicines and long durations of use. The use of antipsychotics in patients with dementia needs to be carefully monitored to improve patient outcomes.

Does a Mobile Phone Depression-Screening App Motivate Mobile Phone Users With High Depressive Symptoms to Seek a Health Care Professional's Help?

BACKGROUND: The objective of disease screening is to encourage high-risk subjects to seek health care diagnosis and treatment. Mobile phone apps can effectively screen mental health conditions, including depression. However, it is not known how effective such screening methods are in motivating users to discuss the obtained results of such apps with health care professionals. Does a mobile phone depression-screening app motivate users with high depressive symptoms to seek health care professional advice? This study aimed to address this question. METHOD: This was a single-cohort, prospective, observational study of a free mobile phone depression app developed in English and released on Apple's App Store. Apple App Store users (aged 18 or above) in 5 countries, that is, Australia, Canada, New Zealand (NZ), the United Kingdom (UK), and the United States (US), were recruited directly via the app's download page. The participants then completed the Patient Health Questionnaire (PHQ-9), and their depression screening score was displayed to them. If their score was 11 or above and they had never been diagnosed with depression before, they were advised to take their results to their health care professional. They were to follow up after 1 month. RESULTS: A group of 2538 participants from the 5 countries completed PHQ-9 depression screening with the app. Of them, 322 participants were found to have high depressive symptoms and had never been diagnosed with depression, and received advice to discuss their results with health care professionals. About 74% of those completed the follow-up; approximately 38% of these self-reported consulting their health care professionals about their depression score. Only positive attitude toward depression as a real disease was associated with increased follow-up response rate (odds ratio (OR) 3.2, CI 1.38-8.29). CONCLUSIONS: A mobile phone depression-screening app motivated some users to seek a depression diagnosis. However, further study should investigate how other app users use the screening results provided by such apps.

Measuring anticholinergic drug exposure in older community-dwelling Australian men: a comparison of four different measures.

AIMS: Anticholinergic drug exposure is associated with adverse outcomes in older people. While a number of tools have been developed to measure anticholinergic drug exposure, there is limited information about the agreement and overlap between the various scales. The aim of this study was to investigate the agreement and overlap between different measures of anticholinergic drug exposure in a cohort of community-dwelling older men. METHODS: A cross-sectional study was used to compare anticholinergic drug exposure calculated using the Anticholinergic Risk Scale (ARS), the Anticholinergic Drug Scale (ADS), the Anticholinergic Cognitive Burden (ACB) and the Drug Burden Index anticholinergic subscale (DBI-ACH) in a cohort of community-dwelling men aged 70 years and older (n = 1696). Statistical agreement, expressed as Cohen's kappa (κ), between these measurements was calculated. RESULTS: Differences were found between the tools regarding the classification of anticholinergic drug exposure for individual participants. Thirteen percent of the population used a drug listed as anticholinergic on the ARS, 39% used a drug listed on the ADS and the ACB, and 18% of the population used one or more anticholinergic drugs listed on the DBI-ACH. While agreement was good between the ACB and ADS (κ = 0.628, 95% CI 0.593, 0.664), little agreement was found between remaining tools (κ = 0.091-0.264). CONCLUSIONS: With the exception of the ACB and ADS, there was poor agreement regarding anticholinergic drug exposure among the four tools compared in this study. Great care should be taken when interpreting anticholinergic drug exposure using existing scales due to the wide variability between the different scales.

Safety of opioid patch initiation in Australian residential aged care.

OBJECTIVE: To explore opioid use by aged care facility residents before and after initiation of transdermal opioid patches. DESIGN: A cross-sectional cohort study, analysing pharmacy data on individual patient supply between 1 July 2008 and 30 September 2013. SETTING: Sixty residential aged care facilities in New South Wales. PARTICIPANTS: Residents receiving an initial opioid patch during the study period. MAIN OUTCOME MEASURE: The proportion of residents who were opioid-naive in the 4 weeks prior to patch initiation was determined. In addition, the patch strength at initiation and the daily dose of transdermal patches and of additional opioids 1 month after initiation were determined. RESULTS: An opioid patch was initiated in 596 of 5297 residents (11.3%: 2.6% fentanyl, 8.7% buprenorphine) in the 60 residential aged care facilities. The mean age at initiation was 87 years, and 74% of the recipients were women. The proportion of recipients who were opioid-naive before patch initiation was 34% for fentanyl and 49% for buprenorphine. Most were initiated at the lowest available patch strength, and the dose was up-titrated after initiation. Around 15% of fentanyl users and 10% of buprenorphine users needed additional regular opioids after patch initiation. CONCLUSIONS: The results suggest some inappropriate initiation of opioid patches in Australian residential aged care facilities. Contrary to best practice, a third of residents initiated on fentanyl patches were opioid-naive in the 4 weeks before initiation.

Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

Relationship between medication safety-related processes and medication use in residential aged care facilities.

OBJECTIVE: To explore the association between the implementation of medication safety-related processes measured with the Medication Safety Self-Assessment for Long-Term Care (MSSA-LTC) tool and medication use in residential aged care facilities (RACFs). METHODS: A descriptive cross-sectional study was conducted in Australian RACFs. Data on facility characteristics, aggregated medication use at the facility level for selected medications commonly associated with a high risk of harm and the MSSA-LTC were completed by clinical pharmacists providing clinical pharmacy services. The Spearman's correlation test was used to evaluate the association between the MSSA-LTC score and medication use. A scatter plot between the MSSA-LTC score and medication use data was generated, and a linear trend line was plotted using the least squares method. RESULTS: Data were collected from 31 RACFs servicing 2986 residents. Most medication safety-related processes were implemented in Australian RACFs. A higher facility MSSA-LTC score was associated with a lower proportion of residents with polypharmacy (r = -.48, p = .01) and one or more benzodiazepines (r = -.41, p = .03). In addition, a negative linear trend was observed between the MSSA-LTC score and the average number of medications per resident, the proportion of residents with one or more anticonvulsants and the proportion of residents using one or more opioid analgesics. CONCLUSIONS: This study indicates that implementing medication safety-related processes may improve medication use in RACFs.

Zerumbone liquid crystalline nanoparticles protect against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro.

The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1ß and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.