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In Australia and New Zealand, in parallel with other developed countries, the number of patients prescribed opioids on a long-term basis has grown rapidly over the last decade. The burden of chronic pain is more widely recognised and there has been an increase in the use of opioids for both cancer and non-cancer indications. While the prevalence of illicit opioid use has remained relatively stable, the diversion and abuse of prescription opioids has escalated, as has the number of individuals receiving methadone or buprenorphine pharmacotherapy for opioid addiction. As a result, the proportion of opioid-tolerant patients requiring acute pain management has increased, often presenting clinicians with greater challenges than those faced when treating the opioid-naïve. Treatment aims include effective relief of acute pain, prevention of drug withdrawal, assistance with any related social, psychiatric and behavioural issues, and ensuring continuity of long-term care. Pharmacological approaches incorporate the continuation of usual medications (or equivalent), short-term use of sometimes much higher than average doses of additional opioid, and prescription of non-opioid and adjuvant drugs, aiming to improve pain relief and attenuate opioid tolerance and/or opioid-induced hyperalgesia. Discharge planning should commence at an early stage and may involve the use of a 'Reverse Pain Ladder' aiming to limit duration of additional opioid use. Legislative requirements may restrict which drugs can be prescribed at the time of hospital discharge. At all stages, there should be appropriate and regular consultation and liaison with the patient, other treating teams and specialist services. [ABSTRACT FROM AUTHOR]

Background: The aging process occurs at variable rates both among and within species and may be related to the variability in oxygen consumption and free radical production impacting oxidative stress. The current study was designed to test whether nonagenarians have a relatively low metabolic rate and whether it is associated with low levels of oxidative stress relative to age.Methods: Resting metabolic rate (RMR) and markers of oxidative stress to lipids, proteins, and DNA were measured in three groups of individuals aged 20-34 (n=47), 60-74 (n=49), and>or=90 years (n=74).Results: RMR, adjusted for fat-free mass, fat mass, and sex, was lower in both older groups when compared to the young group (pConclusions: This study confirms an age-related decline in RMR independent of changes in body composition but surprisingly did not show an accumulation of oxidative damage with increasing age. Our data challenge the theory that RMR is a significant determinant of oxidative stress and therefore contributes to the aging process. [ABSTRACT FROM AUTHOR]

There is accumulating evidence that high levels of dietary iron may play a role in colon carcinogenesis. We used a mouse model to investigate the impact of elevated dietary iron on incidence of aberrant crypt foci (ACF : a preneoplastic lesion) on tumor formation and on induction of oxidative stress. A/J mice were injected intraperitoneally, once a week for 6 weeks, with the colontropic carcinogen, azoxymethane (AOM) or saline (vehicle controls). Following AOM or saline treatments, mice were placed on diets of high (3,000 ppm) and low (30 ppm) iron. Mice in each treatment group were sacrificed at 6 and 10 weeks following the final injection with AOM or saline. Colons were removed for subsequent histopathological analysis, which revealed average increases of 4.6 ± 1.3 vs. 10.4 ± 2.5 total tumors at 6 weeks and 30.75 ± 2.7 vs. 41.5 ± 4.4 total tumors at 10 weeks per AOM-treated mouse on low- and high-iron diets, respectively. There were no significant differences in incidence of ACF attributable to iron, although there was a trend toward greater crypt multiplicity per focus in mice on high-iron diets. Notably, no tumors were observed in mice receiving vehicle control injections in place of carcinogen, regardless of the level of dietary iron. These data suggest that iron exerts its effect at the stage of tumor promotion, but is not sufficient to initiate tumor formation. To learn more about mechanisms by which iron promotes tumor growth, colons were assayed for several biomarkers of oxidative stress [BOS : total F2-isoprostanes (F2-IsoPs), 15-F2t-isoprostanes (8-IsoPGF2[alpha]s), Isofurans (IsoFs), and 8-hydroxyguanosines (8-OH[d]Gs)], as well as iron absorption, programmed cell death, and cellular proliferation. Elevated PCNA and TUNEL staining of the colon epithelium revealed hyperproliferative and apoptotic responses to iron, while no significant differences between iron groups were observed in each of the BOS that were assayed. Our results suggest that, following carcinogen exposure, elevated dietary iron promotes the growth of tumors with altered cellular homeostasis through a mechanism that is independent of oxidative stress. [ABSTRACT FROM AUTHOR]

Marriage, a marker event for the transition from adolescence to young adulthood, brings with it many changes, including shifts in values, new roles, and adjustments in a couple's relationship. Marriage also appears to generate shifts in alcohol use and alcohol consumption, changes that can occur even before the marriage ceremony takes place. Alcohol plays a role in marital violence, marital quality, and marital disruptions. However, high levels of individual alcohol consumption in a marriage do not uniformly lead to lower marital quality. Rather, it may be the nature of a couple's drinking partnership (ie, the interplay of each spouse's drinking context and drinking patterns) that has the most effect on the health of a marriage. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study determined the sources and frequency of diagnostic uncertainty for patients with chronic psychosis and active cocaine abuse or dependence and assessed the usefulness of prospective follow-up in clarifying diagnosis. METHODS: A total of 165 male patients with chronic psychoses and cocaine abuse or dependence on inpatient units of a Veterans Affairs medical center were evaluated using the Structured Clinical Interview for DSM-III-R (SCID-R), urine tests, hospital records, and interviews with collateral sources. An algorithm allowing key SCID-R items and diagnostic criteria to be designated as provisionally met or uncertain was applied, resulting in a provisional diagnosis and a list of alternate diagnoses. The assessment was repeated 18 months later in an attempt to resolve diagnostic uncertainty. RESULTS: In 30 cases (18 percent), initial assessment produced a definitive diagnosis, including 21 cases of schizophrenia, six of schizoaffective disorder, and three of psychostimulant-induced psychotic disorder. In the other 135 cases, a definitive diagnosis could not be reached because of one or more sources of diagnostic uncertainty, including insufficient periods of abstinence (78 percent), poor memory (24 percent), and inconsistent reporting (20 percent). Reassessment at 18 months led to definitive diagnoses in 12 additional cases. CONCLUSIONS: It was frequently difficult to distinguish schizophrenia from chronic substance-induced psychoses. Rather than concluding prematurely that psychotic symptoms are, or are not, substance induced, clinicians should initiate treatment of both psychosis and the substance use disorder in uncertain cases. The persistence or resolution of psychosis during abstinence and additional history from the stabilized patient or collateral sources may clarify the diagnosis. [ABSTRACT FROM AUTHOR]

Fatty acid oxidation leads to formation of highly reactive γ-ketoaldehydes termed isoketals that adduct to protein lysines. We have shown that hypertension causes isoketals to accumulate in dendritic cells (DCs) and activate T cells. Human monocytes traversing the endothelium differentiate into DCs expressing CD83, MHC-II, and CD11c. We hypothesized that oxidative stress catalyzes the formation of isoketals which alters monocyte and DC function to promote monocyte transformation to DCs and T cell activation. Thus, we co-cultured human monocytes with aortic endothelial cells exposed to either a hypertensive 10% stretch or a normotensive 5% stretch for 48 hours using the Uniflex® culture system. We used flow cytometry to detect human DC markers (CD14-/CD83+) in monocytes exposed to stretch. We detected conversion of CD14-/CD83+ from CD14+ human monocytes and found they contained increased levels of isoketal-ligated proteins in the 10% compared to 5% stretch (77.47 ± 7.3 vs. 12.14 ± 3.5). We also found a 1.8 fold increase of the CD86 activation marker compared to controls. Exposure of murine monocyte-derived DCs to tert-butyl hydroperoxide (t-BHP) led to a 3-fold increase in isoketals and a 2-fold increase in CD86 in the CD11b+/CD11c+ population compared to controls. Isoketal formation in DCs exposed to t-BHP was scavenged with pre-treatment of 2-hydroxybenzylamine (2-HOBA) in vitro. DCs treated with t-BHP were co-cultured with T cells for 7 days. This promoted T cell survival and proliferation of CD8+ and CD4+ T cells compared to untreated controls; this effect was attenuated with pre-treatment of 2-HOBA. Moreover, adoptive transfer of t-BHP treated DCs to normal mice elevated the hypertensive response to a generally subpressor dose of angiotensin-II (128 ± 0.80 vs. 114 ± 0.48 in controls). We conclude that oxidant stress and isoketal formation in murine DCs promote T cell activation and hypertension. We hypothesize that exposure to hypertensive stretch in human endothelial cells transfers an oxidant signal to monocytes and promotes their transformation to DCs, which mature and promote an immune response. These findings provide a mechanism as to how T cells are activated in hypertension and provide insight into the inflammatory nature of this disease. [ABSTRACT FROM AUTHOR]

Aims: To investigate tear neuropeptide Y (NPY) and substance P concentrations in individuals with type 1 diabetes, comparing those with and without both diabetic retinopathy (DR) and peripheral neuropathy., Methods: This cross-sectional study involved 41 participants with type 1 diabetes and none to moderate DR, and 22 healthy controls. Assessments included clinical ocular surface parameters, quantification of corneal nerve attributes (based on in vivo confocal microscopy imaging), DR grading, and evaluation for small and large fibre neuropathy. Concentrations of NPY and substance P in tear samples were measured using enzyme-linked immunosorbent assay., Results: Mean (±standard deviation) tear NPY concentrations in participants with type 1 diabetes and length-dependent small fibre neuropathy (SFN) was lower than in controls (10.84±4.10 ng/mL vs 14.72±3.12 ng/mL; p=0.004), but not significantly different from type 1 diabetes participants without SFN (13.39±4.66 ng/mL; p=0.11). Tear NPY levels were lower in individuals with type 1 diabetes and mild/moderate non-proliferative DR (10.44±3.46 ng/mL) compared to none/minimal DR (13.79±4.76 ng/mL; p=0.0005) and controls. In separate linear regression models, both the presence of SFN ((β=-0.75, p=0.02) and the presence of mild/moderate DR (β=-0.84, p=0.009) were significantly associated with tear NPY levels relative to controls, after adjusting for participant age, sex, and dry eye disease. There were no inter-group differences for tear substance P concentrations., Conclusions: Tear NPY has potential utility as an indicator of peripheral microvascular complications associated with type 1 diabetes., (Copyright © 2024. Published by Elsevier Inc.)

In 2023, a Diploma of Rural Generalist Anaesthesia (DipRGA) was implemented across Australia. Developed collaboratively by the Australian and New Zealand College of Anaesthetists (ANZCA), the Australian College of Rural and Remote Medicine (ACRRM) and the Royal Australian College of General Practitioners (RACGP), the 12-month qualification is completed during or following ACRRM or RACGP Rural Generalist Fellowship training. Focused on the needs of rural and remote communities for elective and emergency surgery, maternity care, resuscitative care for medical illness or injury, and stabilisation for retrieval, the DipRGA supports rural generalist anaesthetists working within collaborative teams in geographically isolated settings. The goal is a graduate who can anaesthetise American Society of Anesthesiologists physical status class 1, 2 and stable 3 patients for elective surgery, provide obstetric anaesthesia and analgesia, anaesthetise paediatric patients and undertake advanced crisis care within their scope of practice. Crucially, they also recognise both limitations of their skills and local resources available when considering whether to provide care, defer, refer or transfer patients. DipRGA curriculum design commenced by adapting the ANZCA specialist training curriculum with consideration of the training approach of both the ACRRM and the RACGP, particularly the rural and remote context. Curriculum content is addressed in seven entrustable professional activities supported by workplace-based assessments and multisource feedback. Trainees are supervised by rural generalist anaesthetists and specialist anaesthetists, and complete flexible learning activities to accommodate geographical dispersion. Standardised summative assessments include an early test of knowledge and an examination, adapted from the ACRRM structured assessment using multiple patient scenarios., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LR is an ANZCA staff member and JA was contracted by ANZCA to lead the curriculum design work. Each contributed to the development of this manuscript in her own time.

Purpose of Review: An increasing number of peripheral neuro(no)pathies are identified as involving other components of the neurological system, particularly those that further impair balance. Here we aim to outline an evidence-based approach to the diagnosis of patients who present with a somatosensory disorder which also involves at least one other area of neurological impairment such as the vestibular, auditory, or cerebellar systems., Recent Findings: Detailed objective investigation of patients who present with sensory impairment, particularly where the degree of imbalance is greater than would be expected, aids the accurate diagnosis of genetic, autoimmune, metabolic, and toxic neurological disease., Summary: Diagnosis and management of complex somatosensory disorders benefit from investigation which extends beyond the presenting sensory impairment., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Previous studies have established that bullying is a pervasive problem in healthcare. However, most investigations of bullying in anaesthesia use self-labelled survey questions in which respondents' subjective perceptions of bullying are central in defining prevalence. This study applied the validated revised Negative Acts Questionnaire (NAQ-r) for a more objective assessment of bullying prevalence and types of negative behaviours experienced by anaesthesia trainees in Australia and New Zealand.An online questionnaire was distributed by the Australian and New Zealand College of Anaesthetists (ANZCA) Clinical Trials Network to 990 randomly selected ANZCA trainees. Bullying prevalence was assessed using both a self-labelled survey tool and the NAQ-r, which requires respondents to select from a list of negative acts, with validated cut-offs that define bullying. Sources of bullying, impact on recipients and barriers to reporting were also examined. This design allowed comparison of the two methods for evaluating bullying prevalence.Twenty-six percent of trainees surveyed completed both bullying survey instruments. Thirty percent of these respondents self-labelled as having experienced bullying in the previous six months, with 8% reporting bullying at least monthly. With the NAQ-r, most respondents (96%) reported experiencing at least one negative act in the prior six months, with 54% reporting these on a monthly basis. The most frequent behaviours described were humiliation and intimidation. Using NAQ-r cut-offs, 36% of respondents experienced occasional bullying and 10% were victims of severe workplace bullying.The NAQ-r provides a more nuanced and objective insight into bullying faced by ANZCA trainees than do self-labelled surveys. The results of the present study provide a valuable baseline for ongoing assessment.

The pet food market is constantly changing and adapting to meet the needs and desires of pets and their owners. One trend that has been growing in popularity lately is the feeding of fresh, human-grade foods. Human-grade pet foods contain ingredients that have all been stored, handled, processed, and transported in a manner that complies with regulations set for human food production. While most human-grade pet foods are based on animal-derived ingredients, vegan options also exist. To our knowledge, no in vivo studies have been conducted to analyze the performance of human-grade vegan diets. Therefore, the objective of this study was to investigate the amino acid (AA) digestibility and nitrogen-corrected true metabolizable energy (TME n ) of mildly cooked human-grade vegan dog foods using precision-fed cecectomized rooster and conventional rooster assays. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets (Bramble Cowbell diet (BC); Bramble roost diet (BR)), while the third was a chicken-based extruded dog diet (chicken and brown rice recipe diet (CT)). Prior to the rooster assays, both mildly cooked diets were lyophilized, and then all three diets were ground. Diets were fed to cecectomized roosters to determine AA digestibility, while conventional roosters were used to determine TME n . All data were analyzed using the mixed models procedure of SAS (version 9.4). The majority of indispensable and dispensable AA across all diets had digestibilities higher than 80%, with a few exceptions (BC: histidine, lysine, threonine, and valine; BR: histidine). The only difference in indispensable AA digestibility among diets was observed with tryptophan, with its digestibility being higher ( P = 0.0163) in CT than in BC. TME n values were higher ( P = 0.006) in BC and BR (4.55 and 4.66 kcal/g dry matter, respectively) than that in CT (3.99 kcal/g dry matter). The TME n /GE was also higher ( P = 0.0193) in BR than in CT. Metabolizable energy (ME) estimates using Atwater factors accurately estimated the energy content of CT, but modified Atwater factors and the predictive equations for ME recommended by the National Research Council underestimated energy content. All calculations underestimated the measured TME n values of BC and BR, with Atwater factors being the closest. Although testing in dogs is required, these data suggest that mildly cooked human-grade vegan dog diets are well-digested. Moreover, TME n data suggest that existing methods and equations underestimate the ME of the mildly cooked human-grade vegan foods tested., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Vegan, mildly cooked, and human-grade dog foods are becoming more popular, as beliefs and views of pet owners change. To our knowledge, however, dog studies have not examined the digestibility of commercial vegan diets. Therefore, the objective of this study was to determine the apparent total tract digestibility (ATTD) of mildly cooked human-grade vegan dog foods and their effects on blood metabolites and fecal microbiota, characteristics, and metabolites of adult dogs consuming them. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets, while the third was a chicken-based extruded dog diet. Twelve healthy adult female beagles (7.81 ± 0.65 kg; 7.73 ± 1.65 yr) were used in a replicated 3 × 3 Latin Square design. The study consisted of three experimental periods, with each composed of a 7 d diet adaptation phase, 15 d of consuming 100% of the diet, a 5 d phase for fecal collection for ATTD measurement, and 1 d for blood collection for serum chemistry and hematology. During the fecal collection period, a fresh sample was collected for fecal scoring and dry matter, pH, metabolite, and microbiota measurements. All data were analyzed using the Mixed Models procedure of SAS (version 9.4). All three diets were shown to be highly digestible, with all macronutrients having digestibility values above 80%. The vegan diets had higher (P < 0.001) ATTD of fat, but lower (P < 0.05) ATTD of organic matter than the extruded diet. Dogs consuming the vegan diets had lower circulating cholesterol (P < 0.001), triglyceride (P < 0.001), and platelet (P < 0.009) concentrations and lower (P < 0.010) blood neutrophil percentages than dogs consuming the extruded diet. Dogs consuming vegan diets had lower (P < 0.001) fecal dry matter percentages, lower (P < 0.001) fecal phenol and indole concentrations, and higher (P = 0.05) fecal short-chain fatty acid concentrations than those consuming the extruded diet. Fecal bacterial alpha and beta diversities were not different (P > 0.05) among diets, but dogs consuming vegan diets had altered (P < 0.05) relative abundances of nearly 20 bacterial genera when compared with those consuming the extruded diet. In conclusion, the mildly cooked human-grade vegan dog foods tested in this study performed well, resulting in desirable fecal characteristics, ATTD, and serum chemistries. The vegan diets tested also led to positive changes to serum lipids and fecal metabolites, and interesting changes to the fecal microbial community., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Peripheral neuropathy has been reported commonly in several spinocerebellar ataxia (SCA) types. To date, there is a lack of robust evidence for neuropathy or neuronopathy in SCA type 6 (SCA6). Here, we aim to evaluate the presence of neuropathy or neuronopathy in a cohort of SCA6 patients., Methods: Twenty-four individuals with genetically confirmed SCA6 underwent detailed neurophysiological assessment. This included nerve conduction studies, and in some, cutaneous silent periods, blink reflexes, tilt table tests, quantitative sudomotor axon reflex tests, and somatosensory (median and tibial) evoked potentials., Results: Mean age was 56.1 years (range, 22-94 years) at the time of testing. Four patients were presymptomatic of SCA6 at recruitment. The mean disease duration of symptomatic patients was 11.9 years (range, 1-40 years). Most patients (79.2%, 19/24) had no neurophysiological evidence of a peripheral neuropathy. One with impaired glucose tolerance had mild, large, and small fiber sensorimotor polyneuropathy. One elderly patient had length-dependent axonal sensorimotor polyneuropathy. Two had minor sensory abnormalities (one had type II diabetes and previous chemotherapy). One other had minor small fiber abnormalities. Ten patients (41.7%) had median neuropathies at the wrist. All somatosensory evoked potential (15/15), and most autonomic function tests (13/14) were normal., Conclusions: A large proportion of subjects (79.2%) in our cohort had no evidence of large or small fiber neuropathy. This study does not support the presence of neuropathy or neuronopathy as a common finding in SCA6 and confirms the importance of considering comorbidities as the cause of neurophysiological abnormalities., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 by the American Clinical Neurophysiology Society.)

Increasingly, cerebellar syndromes are recognized as affecting multiple systems. Extracerebellar features include peripheral neuropathies affecting proprioception; cranial neuropathies such as auditory and vestibular; and neuronopathies, for example, dorsal root and vestibular. The presence of such features, which in and of themselves may cause ataxia, likely contribute to key disabilities such as gait instability and falls. Based on the evolving available literature and experience, we outline a clinical approach to the diagnosis of adult-onset ataxia where a combination of cerebellar and peripheral or cranial nerve pathology exists. Objective diagnostic modalities including electrophysiology, oculomotor, and vestibular function testing are invaluable in accurately defining an individual's phenotype. Advances in MRI techniques have led to an increased recognition of disease-specific patterns of cerebellar pathology, including those conditions where neuronopathies may be involved. Depending on availability, a stepwise approach to genetic testing is suggested. This is guided by factors such as pattern of inheritance and age at disease onset, and genetic testing may range from specific genetic panels through to whole-exome and whole-genome sequencing. Management is best performed with the involvement of a multidisciplinary team, aiming at minimization of complications such as falls and aspiration pneumonia and maximizing functional status., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

This randomized, double-masked, placebo-controlled trial evaluated the effects of oral omega-3 (n-3) fatty acid supplementation on peripheral nerves in type 1 diabetes. Participants with type 1 diabetes were assigned (1:1) to n-3 (1,800 mg/day fish oil) or placebo (600 mg/day olive oil) supplements for 180 days. The primary outcome was change from baseline in central corneal nerve fiber length (CNFL) at day 180. Secondary outcomes included change in other corneal nerve parameters, corneal sensitivity, peripheral small and large nerve fiber function, and ocular surface measures. Efficacy was analyzed according to the intention-to-treat principle. Safety assessments included diabetic retinopathy grade and adverse events. Between July 2017 and September 2019, 43 participants received n-3 ( n = 21) or placebo ( n = 22) supplements. All participants, except for two assigned to placebo, completed the trial. At day 180, the estimated increase in CNFL in the n-3 group, compared with placebo, was 2.70 mm/mm 2 (95% CI 1.64, 3.75). The Omega-3 Index increased relative to placebo (3.3% [95% CI 2.4, 4.2]). There were no differences in most small or large nerve fiber functional parameters. Adverse events were similar between groups. In conclusion, we found in this randomized controlled trial that long-chain n-3 supplements impart corneal neuroregenerative effects in type 1 diabetes, indicating a role in modulating peripheral nerve health., (© 2021 by the American Diabetes Association.)

Long-Acting Reversible Contraception (LARCs) has the potential to decrease unintended pregnancies but only if women can easily access a requested method. Retrospective electronic chart review identified women desiring LARC placement over a one-year period ending 31 December 2016. Most of the 311 insertions were for family planning, with 220 new insertions and 60 replacements. Delays occurred in 38% ( n = 118) of patients, averaged 5 ± 5 weeks, and 47% received interval contraception. Reasons included absence of qualified provider ( n = 44, 37%), pending cultures ( n = 31, 26%), and Mirena availability. Teenage LARC use favored Nexplanon whereas older women preferred Mirena ( p < 0.01). Of the 11% choosing early LARC removal, a significant number were African Americans ( p = 0.040) or teenagers ( p = 0.048). Retention time varied by device type; most patients switched to other contraceptives. No patients experienced IUD expulsion. Understanding barriers, attempting to remedy them, and addressing the side effects associated with LARC use is of importance in this inner-city patient population in the United States.

Background: COVID-19 has resulted in a massive increase in telehealth utilisation., Aims: To determine the user and clinician satisfaction during this period and compare to a pre-COVID-19 cohort., Methods: A prospectively collected voluntary questionnaire following the telehealth appointment at a tertiary-level hospital with all adult and paediatric-based specialities was conducted over two time periods: COVID-19 (16 March 2020 to 15 April 2020) and pre-COVID-19 (1 January 2019 to 31 December 2019). There were four groups of participants: patients; parents; adult-based clinicians; and paediatric-based clinicians. The outcomes assessed included perceived standard of care, willingness for repeat telehealth consultations, and patient and parental perceptions of safety., Results: Five thousand and thirty-three telehealth consultations occurred in the COVID-19 period with 1757 questionnaires completed, compared to 1917 consultations with 271 questionnaires completed in the pre-COVID-19 period. Clinicians were more likely to have previously used telehealth in both time periods than end-users. In COVID-19, 1240 actual onsite hospital outpatients' visits were prevented. All groups reported a good overall impression of the telehealth quality; patients/parents scored higher compared to clinicians: 3.6/4 versus 3.3/4, P = 0.02 (pre-COVID-19) and 3.3/4 versus 2.8/4, P = 0.001 (COVID-19). The majority of patients and parents (90%, 1379/1528) felt safer by having a telehealth appointment compared to a face-to-face appointment in the COVID-19 pandemic. All participant groups reported an overall good standard of care, good levels of engagement and were strongly willing to use telehealth again in both of the study time periods. Patients and parents consistently rated higher than clinicians., Conclusions: During a rapid increase in its utilisation and scope due to the COVID-19 pandemic, telehealth was generally well accepted by patients, parents and clinicians, which was consistent with pre-COVID-19 experiences., (© 2021 Royal Australasian College of Physicians.)

Hypertension remains a major health problem in Western Societies, and blood pressure is poorly controlled in a third of patients despite use of multiple drugs. Mitochondrial dysfunction contributes to hypertension, and mitochondria-targeted agents can potentially improve treatment of hypertension. We have proposed that mitochondrial oxidative stress produces reactive dicarbonyl lipid peroxidation products, isolevuglandins, and that scavenging of mitochondrial isolevuglandins improves vascular function and reduces hypertension. To test this hypothesis, we have studied the accumulation of mitochondrial isolevuglandins-protein adducts in patients with essential hypertension and Ang II (angiotensin II) model of hypertension using mass spectrometry and Western blot analysis. The therapeutic potential of targeting mitochondrial isolevuglandins was tested by the novel mitochondria-targeted isolevuglandin scavenger, mito2HOBA. Mitochondrial isolevuglandins in arterioles from hypertensive patients were 250% greater than in arterioles from normotensive subjects, and ex vivo mito2HOBA treatment of arterioles from hypertensive subjects increased deacetylation of a key mitochondrial antioxidant, SOD2 (superoxide dismutase 2). In human aortic endothelial cells stimulated with Ang II plus TNF (tumor necrosis factor)-α, mito2HOBA reduced mitochondrial superoxide and cardiolipin oxidation, a specific marker of mitochondrial oxidative stress. In Ang II-infused mice, mito2HOBA diminished mitochondrial isolevuglandins-protein adducts, raised Sirt3 (sirtuin 3) mitochondrial deacetylase activity, reduced vascular superoxide, increased endothelial nitric oxide, improved endothelium-dependent relaxation, and attenuated hypertension. Mito2HOBA preserved mitochondrial respiration, protected ATP production, and reduced mitochondrial permeability pore opening in Ang II-infused mice. These data support the role of mitochondrial isolevuglandins in endothelial dysfunction and hypertension. We conclude that scavenging of mitochondrial isolevuglandins may have therapeutic potential in treatment of vascular dysfunction and hypertension.

Children undergoing computed tomography (CT) scans have an increased risk of cancer in subsequent years, but it is unclear how much of the excess risk is due to reverse causation bias or confounding, rather than to causal effects of ionising radiation. An examination of the relationship between excess cancer risk and organ dose can help to resolve these uncertainties. Accordingly, we have estimated doses to 33 different organs arising from over 900 000 CT scans between 1985 and 2005 in our previously described cohort of almost 12 million Australians aged 0-19 years. We used a multi-tiered approach, starting with Medicare billing details for government-funded scans. We reconstructed technical parameters from national surveys, clinical protocols, regulator databases and peer-reviewed literature to estimate almost 28 000 000 individual organ doses. Doses were age-dependent and tended to decrease over time due to technological improvements and optimisation., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Lipid peroxidation generates reactive dicarbonyls including isolevuglandins (IsoLGs) and malondialdehyde (MDA) that covalently modify proteins. Humans with familial hypercholesterolemia (FH) have increased lipoprotein dicarbonyl adducts and dysfunctional HDL. We investigate the impact of the dicarbonyl scavenger, 2-hydroxybenzylamine (2-HOBA) on HDL function and atherosclerosis in Ldlr -/- mice, a model of FH. Compared to hypercholesterolemic Ldlr -/- mice treated with vehicle or 4-HOBA, a nonreactive analogue, 2-HOBA decreases atherosclerosis by 60% in en face aortas, without changing plasma cholesterol. Ldlr -/- mice treated with 2-HOBA have reduced MDA-LDL and MDA-HDL levels, and their HDL display increased capacity to reduce macrophage cholesterol. Importantly, 2-HOBA reduces the MDA- and IsoLG-lysyl content in atherosclerotic aortas versus 4-HOBA. Furthermore, 2-HOBA reduces inflammation and plaque apoptotic cells and promotes efferocytosis and features of stable plaques. Dicarbonyl scavenging with 2-HOBA has multiple atheroprotective effects in a murine FH model, supporting its potential as a therapeutic approach for atherosclerotic cardiovascular disease.