Darolutamide does not interfere with OATP-mediated uptake of docetaxel.

The addition of darolutamide, an androgen receptor signalling inhibitor, to therapy with docetaxel has recently been approved as a strategy to treat metastatic prostate cancer. OATP1B3 is an SLC transporter that is highly expressed in prostate cancer and is responsible for the accumulation of substrates, including docetaxel, into tumours. Given that darolutamide inhibits OATP1B3 in vitro, we sought to characterise the impact of darolutamide on docetaxel pharmacokinetics. We investigated the influence of darolutamide on OATP1B3 transport using in vitro and in vivo models. We assessed the impact of darolutamide on the tumour accumulation of docetaxel in a patient-derived xenograft (PDX) model and on an OATP1B biomarker in patients. Darolutamide inhibited OATP1B3 in vitro at concentrations higher than the reported Cmax. Consistent with these findings, in vivo studies revealed that darolutamide does not influence the pharmacokinetics of Oatp1b substrates, including docetaxel. Docetaxel accumulation in PDX tumours was not decreased in the presence of darolutamide. Metastatic prostate cancer patients had similar levels of OATP1B biomarkers, regardless of treatment with darolutamide. Consistent with a low potential to inhibit OATP1B3-mediated transport in vitro, darolutamide does not significantly impede the transport of Oatp1b substrates in vivo or in patients. Our findings support combined treatment with docetaxel and darolutamide, as no OATP1B3 transporter based drug-drug interaction was identified.

Benchmarking online food delivery applications against menu labelling laws: a cross-sectional observational analysis.

OBJECTIVE: It is unknown how well menu labelling schemes that enforce the display of kilojoule (kJ) labelling at point-of-sale have been implemented on online food delivery (OFD) services in Australia. This study aimed to examine the prevalence of kJ labelling on the online menus of large food outlets with more than twenty locations in the state or fifty locations nationally. A secondary aim was to evaluate the nutritional quality of menu items on OFD from mid-sized outlets that have fewer locations than what is specified in the current scheme. DESIGN: Cross-sectional analysis. Prevalence of kJ labelling by large food outlets on OFD from August to September 2022 was examined. Proportion of discretionary ('junk food') items on menus from mid-sized outlets was assessed. SETTING: Forty-three unique large food outlets on company (e.g. MyMacca's) and third party OFD (Uber Eats, Menulog, Deliveroo) within Sydney, Australia. Ninety-two mid-sized food outlets were analysed. PARTICIPANTS: N/A. RESULTS: On company OFD apps, 35 % (7/23) had complete kJ labelling for each menu item. In comparison, only 4·8 % (2/42), 5·3 % (2/38) and 3·6 % (1/28) of large outlets on Uber Eats, Menulog and Deliveroo had complete kJ labelling at all locations, respectively. Over three-quarters, 76·3 % (345/452) of menu items from mid-sized outlets were classified as discretionary. CONCLUSIONS: Kilojoule labelling was absent or incomplete on a high proportion of online menus. Mid-sized outlets have abundant discretionary choices and yet escape criteria for mandatory menu labelling laws. Our findings show the need to further monitor the implementation of nutrition policies on OFD.

Targeting OCT3 attenuates doxorubicin-induced cardiac injury.

Doxorubicin is a commonly used anticancer agent that can cause debilitating and irreversible cardiac injury. The initiating mechanisms contributing to this side effect remain unknown, and current preventative strategies offer only modest protection. Using stem-cell-derived cardiomyocytes from patients receiving doxorubicin, we probed the transcriptomic landscape of solute carriers and identified organic cation transporter 3 (OCT3) (SLC22A3) as a critical transporter regulating the cardiac accumulation of doxorubicin. Functional validation studies in heterologous overexpression models confirmed that doxorubicin is transported into cardiomyocytes by OCT3 and that deficiency of OCT3 protected mice from acute and chronic doxorubicin-related changes in cardiovascular function and genetic pathways associated with cardiac damage. To provide proof-of-principle and demonstrate translational relevance of this transport mechanism, we identified several pharmacological inhibitors of OCT3, including nilotinib, and found that pharmacological targeting of OCT3 can also preserve cardiovascular function following treatment with doxorubicin without affecting its plasma levels or antitumor effects in multiple models of leukemia and breast cancer. Finally, we identified a previously unrecognized, OCT3-dependent pathway of doxorubicin-induced cardiotoxicity that results in a downstream signaling cascade involving the calcium-binding proteins S100A8 and S100A9. These collective findings not only shed light on the etiology of doxorubicin-induced cardiotoxicity, but also are of potential translational relevance and provide a rationale for the implementation of a targeted intervention strategy to prevent this debilitating side effect.

Retrospective analysis of regional and metropolitan school food environments using Google Street View: A case study in New South Wales, Australia with youth consultation.

ISSUE ADDRESSED: Food environments surrounding schools have a strong influence on the adolescent's food choices. Moreover, the prevalence of diet-related chronic diseases is higher in regional than metropolitan areas in Australia. Understanding school food environments in these different settings is crucial for informing future strategies to improve adolescent health. METHODS: Google Street View was used to identify food outlets within 1.6 km around all secondary schools in Wagga Wagga and Blacktown in New South Wales which were selected as regional and metropolitan case study areas. Based on food outlet type, healthfulness categories were assigned, and Chi-squared tests were performed. The Health Advisory Panel for Youth at the University of Sydney (HAPYUS) were engaged to obtain their perspectives on findings. RESULTS: Unhealthful food outlets were consistently most prevalent around schools in Wagga Wagga and Blacktown over 17 years. In 2023, these were predominantly restaurants (19.4% vs. 21.1%), cafés (16.8% vs. 11.1%), fast-food franchise outlets (15.1% vs. 17.4%) and independent takeaway stores (14.1% vs. 9.6%). No significant difference in healthfulness between regional and metropolitan areas was found. Youth advisors recognised price and social reasons as major contributors to food choices. CONCLUSIONS: Google Street View was used as a novel resource to examine school food environments in regional and metropolitan areas which have remained consistently unhealthful for nearly two decades. SO WHAT?: Unhealthful school food environments may encourage poor diets and exacerbate rates of adolescent overweight and obesity. Critical government action is needed to improve school food environments.

Influence of Tyrosine Kinase Inhibition on Organic Anion Transporting Polypeptide 1B3-Mediated Uptake.

The organic anion transporting polypeptide family member (OATP) 1B3 is a hepatic uptake transporter that has a broad substrate recognition and plays a significant role in regulating elimination of endogenous biomolecules or xenobiotics. OATP1B3 works in tandem with OATP1B1, with which it shares approximately 80% sequence homology and a high degree of substrate overlap. Despite some substrates being recognized solely by OATP1B3, its ability to compensate for loss of OATP1B1-mediated elimination and recognition by regulatory agencies, little is known about OATP1B3 regulatory factors and how they are involved with drug-drug interaction. It was recently discovered that OATP1B1 function is mediated by the activity of a particular tyrosine kinase that is sensitive to a variety of tyrosine kinase inhibitors (TKIs). This study reports that OATP1B3 is similarly regulated, as at least 50% of its activity is reduced by 20 US Food and Drug Administration -approved TKIs. Nilotinib was assessed as the most potent OATP1B3 inhibitor among the investigated TKIs, which can occur at clinically relevant concentrations and acted predominantly through noncompetitive inhibition without impacting membrane expression. Finally, OATP1B3 function was determined to be sensitive to the knockdown of the Lck/Yes novel tyrosine kinase that is sensitive to nilotinib and has been previously implicated in mediating OATP1B1 activity. Collectively, our findings identify tyrosine kinase activity as a major regulator of OATP1B3 function which is sensitive to kinase inhibition. Given that OATP1B1 is similarly regulated, simultaneous disruption of these transporters can have drastic effects on systemic drug concentrations, which would promote adverse events. SIGNIFICANCE STATEMENT: The organic anion transporting polypeptide family member (OATP) 1B3 is a facilitator of hepatic drug elimination, although much is unknown of how OATP1B3 activity is mediated, or how such regulators contribute to drug-drug interactions. This study reports that OATP1B3 activity is dependent on the Lck/Yes novel tyrosine kinase, which is sensitive to numerous tyrosine kinase inhibitors. These findings provide insight into the occurrence of many clinical drug-drug interactions, and a rationale for future study of tyrosine kinases regulating drug disposition.

MATE1 Deficiency Exacerbates Dofetilide-Induced Proarrhythmia.

Dofetilide is a rapid delayed rectifier potassium current inhibitor widely used to prevent the recurrence of atrial fibrillation and flutter. The clinical use of this drug is associated with increases in QTc interval, which predispose patients to ventricular cardiac arrhythmias. The mechanisms involved in the disposition of dofetilide, including its movement in and out of cardiomyocytes, remain unknown. Using a xenobiotic transporter screen, we identified MATE1 (SLC47A1) as a transporter of dofetilide and found that genetic knockout or pharmacological inhibition of MATE1 in mice was associated with enhanced retention of dofetilide in cardiomyocytes and increased QTc prolongation. The urinary excretion of dofetilide was also dependent on the MATE1 genotype, and we found that this transport mechanism provides a mechanistic basis for previously recorded drug-drug interactions of dofetilide with various contraindicated drugs, including bictegravir, cimetidine, ketoconazole, and verapamil. The translational significance of these observations was examined with a physiologically-based pharmacokinetic model that adequately predicted the drug-drug interaction liabilities in humans. These findings support the thesis that MATE1 serves a conserved cardioprotective role by restricting excessive cellular accumulation and warrant caution against the concurrent administration of potent MATE1 inhibitors and cardiotoxic substrates with a narrow therapeutic window.

Does weight loss reduce the incidence of total knee and hip replacement for osteoarthritis?-A prospective cohort study among middle-aged and older adults with overweight or obesity.

OBJECTIVE: This study aims to investigate the association between weight change and total knee or hip replacement (TKR or THR) for OA among middle-aged and older adults with overweight or obesity. METHOD: Weight data were collected in 2006-2009 and in 2010 from the 45 and Up Study-a population-based cohort aged ≥45 years in New South Wales, Australia. Participants were included if they had a baseline body mass index (BMI) ≥ 25 kg/m2 and no history of TKR or THR. Weight change was categorised into four groups: >7.5% loss; >5-7.5% loss; stable (≤5% change) and >5% gain. Hospital admission data were linked to identify TKR and THR for OA, and multivariable Cox regression was used to assess risk of TKR and THR. RESULTS: Of 23,916 participants, 2139 lost >7.5% weight, 1655 lost 5-7.5% weight, and 4430 gained >5% weight. Over 5.2 years, 1009 (4.2%) underwent TKR and 483 (2.0%) THR. Compared to weight-stable, weight loss of >7.5% was associated with reduced risk of TKR after adjusting for age, sex, BMI, socioeconomic and lifestyle factors (hazard ratio 0.69, 95%CI 0.54-0.87), but had no association with THR. Weight loss of 5-7.5% was not associated with altered risk of either TKR or THR. Weight gain was associated with increased risk of THR after adjusting for confounders, but not TKR. CONCLUSION: This study suggests that a weight loss target >7.5% is required to reduce the risk of TKR in adults with overweight or obesity. Weight gain should be avoided as it increases the risk of THR.

Diet Quality following Total Meal Replacement Compared with Food-Based Weight-Loss Diets in Postmenopausal Women with Obesity: A Secondary Analysis of the TEMPO Diet Trial.

BACKGROUND: Severely energy-restricted diets that utilize meal-replacement products are the most effective dietary treatment for obesity. However, there are concerns they may fail to educate individuals on how to adopt a healthy food-based diet after weight loss. OBJECTIVES: The aim of this research was to compare changes in diet quality following total meal replacement compared with food-based weight-loss diets. METHODS: In this secondary analysis of a randomized controlled trial, 79 postmenopausal women aged 45-65 y, with a BMI (in kg/m2) of 30-40, were randomly assigned to either a total meal-replacement diet (energy intake restricted by 65-75% relative to requirements) for 16 wks, followed by a food-based diet (energy intake restricted by 25-35% relative to requirements) until 52 wks, or the food-based diet for the entire 52-wk period. Diet quality was scored at baseline and 52 wks using the Healthy Eating Index for Australian Adults, with score changes compared between groups using an independent t test. RESULTS: Diet quality improved from baseline in both groups, but less so in the total meal-replacement group, with a mean (SD) increase of 3.6 (10.8) points compared with 11.8 (13.9) points in the food-based group, resulting in a mean between-group difference of -8.2 (P = 0.004; 95% CI: -13.8, -2.7) points. This improvement in diet quality within both groups was mostly driven by a reduction in the intake of discretionary foods. Intake remained below the recommendations at 52 wks for 4 of the 5 food groups in both dietary interventions. CONCLUSIONS: In postmenopausal women with obesity, weight-loss interventions that involve either a total meal-replacement diet or a food-based diet both improve diet quality, however, not sufficiently to meet recommendations. This highlights the importance of addressing diet quality as a part of all dietary weight-loss interventions. This trial is registered with the Australia and New Zealand Clinical Trials Registry as 12612000651886.

#SupportLocal: how online food delivery services leveraged the COVID-19 pandemic to promote food and beverages on Instagram.

OBJECTIVE: To explore the promotion of discretionary foods/beverages and marketing strategies employed by the top three online food delivery services' (OFDS) Instagram accounts in three countries before and during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: Publicly available data were extracted for the top three OFDS Instagram accounts for Australia, United Kingdom (UK) and the United States of America (USA) from March to May 2019 and 2020. Food/beverage items from posts were classified as 'discretionary' or from the five food groups (FFG) according to the Australian Dietary Guidelines. Marketing strategies were coded using an existing framework. Posts referring to COVID-19 were coded under four marketing strategies: (i) appropriating frontline workers; (ii) combatting the pandemic; (iii) selling social distancing; and (iv) accelerating digitalisation. RESULTS: From 581 posts, 618 food/beverage items were shown, of which 69 % (427/618) were classified as discretionary. In 2019, the most used marketing strategies were product imagery (unbranded) (137/195, 70 %), links (111/195, 57 %) and sponsorships/partnerships (58/195, 30 %). In 2020, the most used were links (252/386, 68 %), product imagery (unbranded) (179/386, 49 %) and branding elements (175/386, 45 %). The most common COVID-19 marketing strategy was combatting the pandemic (76/123, 62 %) followed by selling social distancing (53/123, 43 %), appropriating frontline workers (34/123, 28 %) and accelerating digitalisation (32/123, 26 %). CONCLUSIONS: Following the COVID-19 pandemic, OFDS adapted their marketing, creating content with the theme of 'combatting the pandemic'. Due to the growing number of discretionary foods/beverages promoted on Instagram, this highlights the need for policy action to counter the potential influence social media platforms have on dietary behaviours.

Androgen receptor signalling impairs docetaxel efficacy in castration-resistant prostate cancer.

Androgen receptor (AR) signalling drives neoplastic growth and therapy resistance in prostate cancer. Recent clinical data show that docetaxel combined with androgen deprivation therapy improves outcome in hormone-sensitive disease. We studied whether testosterone and AR signalling interferes with docetaxel treatment efficacy in castration-resistant prostate cancer (CRPC). We found that testosterone supplementation significantly impaired docetaxel tumour accumulation in a CRPC model, resulting in decreased tubulin stabilisation and antitumour activity. Furthermore, testosterone competed with docetaxel for uptake by the drug transporter OATP1B3. Irrespective of docetaxel-induced tubulin stabilisation, AR signalling by testosterone counteracted docetaxel efficacy. AR-pathway activation could also reverse long-term tumour regression by docetaxel treatment in vivo. These results indicate that to optimise docetaxel efficacy, androgen levels and AR signalling need to be suppressed. This study lends evidence for continued maximum suppression of AR signalling by combining targeted therapeutics with docetaxel in CRPC.

Role of Oatp2b1 in Drug Absorption and Drug-Drug Interactions.

The organic anion transporting polypeptide (OATP)2B1 is localized on the basolateral membrane of hepatocytes and is expressed in enterocytes. Based on its distribution pattern and functional similarity to OATP1B-type transporters, OATP2B1 might have a role in the absorption and disposition of a range of xenobiotics. Although several prescription drugs, including hydroxymethylglutaryl-coenzyme A-CoA reductase inhibitors (statins) such as fluvastatin, are OATP2B1 substrates in vitro, evidence supporting the in vivo relevance of this transporter remains limited, and most has relied on substrate-inhibitor interactions resulting in altered pharmacokinetic properties of the victim drugs. To address this knowledge deficit, we developed and characterized an Oatp2b1-deficient mouse model and evaluated the impact of this transporter on the absorption and disposition of fluvastatin. Consistent with the intestinal localization of Oatp2b1, we found that the genetic deletion or pharmacological inhibition of Oatp2b1 was associated with decreased absorption of fluvastatin by 2- to 3-fold. The availability of a viable Oatp2b1-deficient mouse model provides an opportunity to unequivocally determine the contribution of this transporter to the absorption and drug-drug interaction potential of drugs. SIGNIFICANCE STATEMENT: The current investigation suggests that mice deficient in Oatp2b1 provide a valuable tool to study the in vivo importance of this transporter. In addition, our studies have identified novel potent inhibitors of OATP2B1 among the class of tyrosine kinase inhibitors, a rapidly expanding class of drugs used in various therapeutic areas that may cause drug-drug interactions with OATP2B1 substrates.

Adherence to eye examination guidelines among individuals with diabetes: An analysis of linked health data.

IMPORTANCE: Screening for diabetic retinopathy for early detection and treatment can prevent vision loss. BACKGROUND: We aimed to assess rates of eye examination of people with diabetes, adherence with national guidelines and investigate characteristics of those who do not adhere. DESIGN: We used data from the 45 and Up Study, a cohort study of 267 153 randomly selected residents aged ≥45 years from New South Wales, Australia. Individual survey data collected in 2006 to 2009 were linked to corresponding national Medicare Benefits Schedule claims data for 2006 to 2016. PARTICIPANTS: The study sample included 24 832 participants who reported having diabetes and at least 5 years of observation. METHODS: Claims for visits to optometrists or ophthalmologists were assessed to estimate rates of eye examination. Poisson regression models were used to investigate factors associated with non-adherence. MAIN OUTCOME MEASURE: Participants were classified as adherent if the average time between eye care claims was consistent with national guideline of having an eye exam every 2 years. RESULTS: Of 50% to 75% people with diabetes met the biennial eye examination guidelines and only 21% to 28% with diabetes duration ≥10 years were adherent to the annual eye examination guideline. Characteristics associated with greatest (~1.3-fold) risk of non-adherence were smoking, age <60 years and higher income. CONCLUSIONS AND RELEVANCE: There is a clear need to improve rates of adherence to eye examination guidelines among people with diabetes to reduce the personal and societal burden of diabetic retinopathy.

Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions.

Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a rapid decline in kidney function caused by ischemic or toxic injury to renal tubular cells. The widely used chemotherapy drug cisplatin accumulates preferentially in the renal tubular cells and is a frequent cause of drug-induced AKI. During the development of AKI the quiescent tubular cells reenter the cell cycle. Strategies that block cell-cycle progression ameliorate kidney injury, possibly by averting cell division in the presence of extensive DNA damage. However, the early signaling events that lead to cell-cycle activation during AKI are not known. In the current study, using mouse models of cisplatin nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6 (CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in inhibition of cell-cycle progression, amelioration of kidney injury, and improved overall survival. Of additional significance, these compounds were found to be potent inhibitors of organic cation transporter 2 (OCT2), which contributes to the cellular accumulation of cisplatin and subsequent kidney injury. The unique cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with their potential for clinical translation, support their further exploration as therapeutic candidates for prevention of AKI.

Examining Internet and eHealth Practices and Preferences: Survey Study of Australian Older Adults With Subjective Memory Complaints, Mild Cognitive Impairment, or Dementia.

BACKGROUND: Interest in electronic health (eHealth) technologies to screen for and treat a variety of medical and mental health problems is growing exponentially. However, no studies to date have investigated the feasibility of using such e-tools for older adults with mild cognitive impairment (MCI) or dementia. OBJECTIVE: The objective of this study was to describe patterns of Internet use, as well as interest in and preferences for eHealth technologies among older adults with varying degrees of cognitive impairment. METHODS: A total of 221 participants (mean age=67.6 years) attending the Healthy Brain Ageing Clinic at the University of Sydney, a specialist mood and memory clinic for adults ≥50 years of age, underwent comprehensive clinical and neuropsychological assessment and completed a 20-item self-report survey investigating current technology use and interest in eHealth technologies. Descriptive statistics and Fisher exact tests were used to characterize the findings, including variability in the results based on demographic and diagnostic factors, with diagnoses including subjective cognitive impairment (SCI), MCI, and dementia. RESULTS: The sample comprised 27.6% (61/221) SCI, 62.0% (137/221) MCI, and 10.4% (23/221) dementia (mean Mini-Mental State Examination=28.2). The majority of participants reported using mobile phones (201/220, 91.4%) and computers (167/194, 86.1%) routinely, with most respondents having access to the Internet at home (204/220, 92.6%). Variability was evident in the use of computers, mobile phones, and health-related websites in relation to sociodemographic factors, with younger, employed respondents with higher levels of education being more likely to utilize these technologies. Whereas most respondents used email (196/217, 90.3%), the use of social media websites was relatively uncommon. The eHealth intervention of most interest to the broader sample was memory strategy training, with 82.7% (172/208) of participants reporting they would utilize this form of intervention. Preferences for other eHealth interventions varied in relation to educational level, with university-educated participants expressing greater interest in interventions related to mood (P=.01), socialization (P=.02), memory (P=.01), and computer-based exercises (P=.046). eHealth preferences also varied in association, with diagnosis for interventions targeting sleep (P=.01), nutrition (P=.004), vascular risk factors (P=.03), and memory (P=.02). CONCLUSIONS: Technology use is pervasive among older adults with cognitive impairment, though variability was noted in relation to age, education, vocational status, and diagnosis. There is also significant interest in Web-based interventions targeting cognition and memory, as well as other risk factors for cognitive decline, highlighting the urgent need for the development, implementation, and study of eHealth technologies tailored specifically to older adults, including those with MCI and early dementia. Strategies to promote eHealth use among older adults who are retired or have lower levels of education will also need to be considered.

Loss of SLCO1B3 drives taxane resistance in prostate cancer.

BACKGROUND: Both taxanes, docetaxel and cabazitaxel, are effective treatments for metastatic castration-resistant prostate cancer (mCRPC). However, resistance to taxanes is common. Our objective was to investigate mechanisms of taxane resistance in prostate cancer. METHODS: Two docetaxel-resistant patient-derived xenografts (PDXs) of CRPC were established (PC339-DOC and PC346C-DOC) in male athymic nude mice by frequent intraperitoneal administrations of docetaxel. Next-generation sequencing was performed on PDX tissue pre- and post-docetaxel resistance and gene expression profiles were compared. [(14)C]-docetaxel and [(14)C]-cabazitaxel uptake assays in vitro and cytotoxicity assays were performed to validate direct involvement of transporter genes in taxane sensitivity. RESULTS: Organic anion-transporting polypeptide (SLCO1B3), an influx transporter of docetaxel, was significantly downregulated in PC346C-DOC tumours. In accordance with this finding, intratumoural concentrations of docetaxel and cabazitaxel were significantly decreased in PC346C-DOC as compared with levels in chemotherapy-naive PC346C tumours. In addition, silencing of SLCO1B3 in chemo-naive PC346C resulted in a two-fold decrease in intracellular concentrations of both taxanes. Overexpression of SLCO1B3 showed higher sensitivity to docetaxel and cabazitaxel. CONCLUSIONS: The SLCO1B3 determines intracellular concentrations of docetaxel and cabazitaxel and consequently influences taxane efficacy. Loss of the drug transporter SLCO1B3 may drive taxane resistance in prostate cancer.

Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2.

Oxaliplatin is an integral component of colorectal cancer therapy, but its clinical use is associated with a dose-limiting peripheral neurotoxicity. We found that the organic cation transporter 2 (OCT2) is expressed on dorsal root ganglia cells within the nervous system where oxaliplatin is known to accumulate. Cellular uptake of oxaliplatin was increased by 16- to 35-fold in cells overexpressing mouse Oct2 or human OCT2, and this process was associated with increased DNA platination and oxaliplatin-induced cytotoxicity. Furthermore, genetic or pharmacologic knockout of Oct2 protected mice from hypersensitivity to cold or mechanical-induced allodynia, which are established tests to assess acute oxaliplatin-induced neurotoxicity. These findings provide a rationale for the development of targeted approaches to mitigate this debilitating toxicity.

Developing the DIGIFOOD Dashboard to Monitor the Digitalization of Local Food Environments: Interdisciplinary Approach.

BACKGROUND: Online food delivery services (OFDS) enable individuals to conveniently access foods from any deliverable location. The increased accessibility to foods may have implications on the consumption of healthful or unhealthful foods. Concerningly, previous research suggests that OFDS offer an abundance of energy-dense and nutrient-poor foods, which are heavily promoted through deals or discounts. OBJECTIVE: In this paper, we describe the development of the DIGIFOOD dashboard to monitor the digitalization of local food environments in New South Wales, Australia, resulting from the proliferation of OFDS. METHODS: Together with a team of data scientists, we designed a purpose-built dashboard using Microsoft Power BI. The development process involved three main stages: (1) data acquisition of food outlets via web scraping, (2) data cleaning and processing, and (3) visualization of food outlets on the dashboard. We also describe the categorization process of food outlets to characterize the healthfulness of local, online, and hybrid food environments. These categories included takeaway franchises, independent takeaways, independent restaurants and cafes, supermarkets or groceries, bakeries, alcohol retailers, convenience stores, and sandwich or salad shops. RESULTS: To date, the DIGIFOOD dashboard has mapped 36,967 unique local food outlets (locally accessible and scraped from Google Maps) and 16,158 unique online food outlets (accessible online and scraped from Uber Eats) across New South Wales, Australia. In 2023, the market-leading OFDS operated in 1061 unique suburbs or localities in New South Wales. The Sydney-Parramatta region, a major urban area in New South Wales accounting for 28 postcodes, recorded the highest number of online food outlets (n=4221). In contrast, the Far West and Orana region, a rural area in New South Wales with only 2 postcodes, recorded the lowest number of food outlets accessible online (n=7). Urban areas appeared to have the greatest increase in total food outlets accessible via online food delivery. In both local and online food environments, it was evident that independent restaurants and cafes comprised the largest proportion of food outlets at 47.2% (17,437/36,967) and 51.8% (8369/16,158), respectively. However, compared to local food environments, the online food environment has relatively more takeaway franchises (2734/16,158, 16.9% compared to 3273/36,967, 8.9%) and independent takeaway outlets (2416/16,158, 14.9% compared to 4026/36,967, 10.9%). CONCLUSIONS: The DIGIFOOD dashboard leverages the current rich data landscape to display and contrast the availability and healthfulness of food outlets that are locally accessible versus accessible online. The DIGIFOOD dashboard can be a useful monitoring tool for the evolving digital food environment at a regional scale and has the potential to be scaled up at a national level. Future iterations of the dashboard, including data from additional prominent OFDS, can be used by policy makers to identify high-priority areas with limited access to healthful foods both online and locally.

Use of online food retail platforms throughout the COVID-19 pandemic and associated diet-related chronic disease risk factors: A systematic review of emerging evidence.

Food accessibility was considerably impacted by restrictions during the coronavirus disease 2019 (COVID-19) pandemic, leading to growth in the online food retail sector, which offered contact-free delivery. This systematic review aimed to assess the change in use of online food retail platforms during COVID-19. The secondary aim was to identify diet-related chronic disease risk factors including dietary intake, eating behaviors, and/or weight status associated with the use of online food retail platforms during the pandemic. The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022320498) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Nine electronic databases were searched between January 2020 and October 2023. Studies that reported the frequency or change in use of online groceries, meal delivery applications, and/or meal-kit delivery services before and during the pandemic were included. A total of 53 studies were identified, including 46 cross-sectional studies, 4 qualitative studies, 2 longitudinal cohort studies, and 1 mixed-methods study. Overall, 96% (43/45) of outcomes showed an increase in the use of online groceries during COVID-19, while 55% (22/40) of outcomes showed a decrease in meal delivery applications. Eight of nine outcomes associated the use of online food retail with weight gain and emotional eating. Further research is needed to investigate the links between online food retail and obesity.

Sex differences in risk of incident microvascular and macrovascular complications: a population-based data-linkage study among 25 713 people with diabetes.

BACKGROUND: The global prevalence of diabetes is similar in men and women; however, there is conflicting evidence regarding sex differences in diabetes-related complications. The aim of this study was to investigate sex differences in incident microvascular and macrovascular complications among adults with diabetes. METHODS: This prospective cohort study linked data from the 45 and Up Study, Australia, to administrative health records. The study sample included 25 713 individuals (57% men), aged ≥45 years, with diabetes at baseline. Incident cardiovascular disease (CVD), eye, lower limb, and kidney complications were determined using hospitalisation data and claims for medical services. Multivariable Cox proportional hazards models were used to assess the association between sex and incident complications. RESULTS: Age-adjusted incidence rates per 1000 person years for CVD, eye, lower limb, and kidney complications were 37, 52, 21, and 32, respectively. Men had a greater risk of CVD (adjusted hazard ratio (aHR) 1.51, 95% CI 1.43 to 1.59), lower limb (aHR 1.47, 95% CI 1.38 to 1.57), and kidney complications (aHR 1.55, 95% CI 1.47 to 1.64) than women, and a greater risk of diabetic retinopathy (aHR 1.14, 95% CI 1.03 to 1.26). Over 10 years, 44%, 57%, 25%, and 35% of men experienced a CVD, eye, lower limb, or kidney complication, respectively, compared with 31%, 61%, 18%, and 25% of women. Diabetes duration (<10 years vs ≥10 years) had no substantial effect on sex differences in complications. CONCLUSIONS: Men with diabetes are at greater risk of complications, irrespective of diabetes duration. High rates of complications in both sexes highlight the importance of targeted complication screening and prevention strategies from diagnosis.

Sex and age differences in the use of medications for diabetes and cardiovascular risk factors among 25,733 people with diabetes.

AIM: To determine sex and age differences in the use of medications for diabetes and cardiovascular risk factors in people with diabetes in Australia. METHODS: Pharmaceutical claims data of participants in the 45 and Up Study who self-reported having diabetes before 2013, were alive on 1st January 2013 and had at least one medication dispensing record between 1st January 2013 and 31st December 2019 were analysed. Annual sex and age-specific percentages of participants supplied specific medications were estimated for years 2013 to 2019. Percentages were reported for any glucose lowering medications and by drug class, any lipid modifying agents, and any blood pressure lowering medications. RESULTS: Altogether 25,733 participants (45.2% women) with diabetes were included. The percentage of participants who were supplied with glucose lowering medications was consistently lower in women compared to men. In both sexes, the percentage of participants who were supplied with glucose lowering medications was lowest among those aged ≥75 years and this decreased over time. Similar findings were observed for lipid modifying agents and blood pressure lowering medications. The use of sodium glucose co-transporter 2 inhibitors increased substantially in participants aged <75 years since it became available in 2013. However, no sex differences were observed in its use among people with hospital-recorded history of cardiovascular disease. CONCLUSIONS: Practitioners should be aware of possible sex disparities in the pharmacological treatment of diabetes and cardiovascular risk factors in people with diabetes in Australia. There is a possible time lag between reporting of research findings and uptake of sodium glucose co-transporter 2 inhibitors prescribing in individuals with diabetes and high cardiovascular risk in clinical practice, nevertheless, the result observed was consistent with the management guidelines at the time of the study.