Increased nitrate intake from beetroot juice over 4 weeks affects nitrate metabolism, but not vascular function or blood pressure in older adults with hypertension.

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate via nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × âˆ¼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST). Measurements included nitrate and nitrite in plasma and saliva; endothelial-dependent and -independent forearm blood flow (FBF) responses to acetylcholine (FBFACh) and glyceryltrinitrate (FBFGTN); and clinic-, home- and 24-hour ambulatory blood pressure. Compared to placebo, plasma and salivary nitrate and nitrite increased at 3H and 4WK POST following nitrate treatment (P < 0.01), suggesting a functioning nitrate-nitrite-NO pathway in the participants of this study. There were no differences between treatments in FBFACh and FBFGTN-area under the curve (AUC) ratios [AUC ratios after (3H POST, 4WK POST) compared with before (PRE) the intervention], or 24-hour ambulatory blood pressure or home blood pressure measures (P > 0.05). These findings do not support the hypothesis that an increased intake of dietary nitrate exerts sustained beneficial effects on FBF or blood pressure in hypertensive older adults, providing important information on the efficacy of nitrate-based interventions for healthy vascular aging. This study was registered under ClinicialTrials.gov (NCT04584372).

Comparative Risk of Gout Flares When Initiating or Escalating Various Urate-Lowering Therapy: A Systematic Review With Network Meta-Analysis.

OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.

Sleep apnea multi-level surgery trial: long-term observational outcomes.

STUDY OBJECTIVES: The sleep apnea multi-level surgery (SAMS) randomized clinical trial showed surgery improved outcomes at 6 months compared to ongoing medical management in patients with moderate or severe obstructive sleep apnea (OSA) who failed continuous positive airway pressure therapy. This study reports the long-term outcomes of the multi-level surgery as a case series. METHODS: Surgical participants were reassessed >2 years postoperatively with the same outcomes reported in the main SAMS trial. Primary outcomes were apnea-hypopnea index (AHI) and Epworth sleepiness scale (ESS), with secondary outcomes including other polysomnography measures, symptoms, quality of life, and adverse events. Long-term effectiveness (baseline to long-term follow-up [LTFU]) and interval changes (6 month to LTFU) were assessed using mixed effects regression models. Control participants were also reassessed for rate of subsequent surgery and outcomes. RESULTS: 36/48 (75%) of surgical participants were reevaluated (mean (standard deviation)) 3.5 (1.0) years following surgery, with 29 undergoing polysomnography. AHI was 41/h (23) at preoperative baseline and 21/h (18) at follow-up, representing persistent improvement of -24/h (95% CI -32, -17; p < 0.001). ESS was 12.3 (3.5) at baseline and 5.5 (3.9) at follow-up, representing persistent improvement of -6.8 (95% CI -8.3, -5.4; p < 0.001). Secondary outcomes were improved long term, and adverse events were minor. Interval change analysis suggests stability of outcomes. 36/43 (84%) of the control participants were reevaluated, with 25 (69%) reporting subsequent surgery, with symptom and quality of life improvements. CONCLUSION: Multi-level upper airway surgery improves OSA burden with long-term maintenance of treatment effect in adults with moderate or severe OSA in whom conventional therapy failed. CLINICAL TRIAL: Multi-level airway surgery in patients with moderate-severe obstructive sleep apnea (OSA) who have failed medical management to assess change in OSA events and daytime sleepiness; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366019&isReview=true; ACTRN12614000338662.

Extent of Abdominal Aortic Calcification Is Associated With Incident Rapid Weight Loss Over 5 Years: The Perth Longitudinal Study of Ageing Women.

BACKGROUND: Abdominal aortic calcification (AAC), a marker of vascular disease, is associated with disease in other vascular beds including gastrointestinal arteries. We investigated whether AAC is related to rapid weight loss over 5 years and whether rapid weight loss is associated with 9.5-year all-cause mortality in community-dwelling older women. METHODS: Lateral spine images from dual-energy x-ray absorptiometry (1998/1999) were used to assess AAC (24-point AAC scoring method) in 929 older women. Over 5 years, body weight was assessed at 12-month intervals. Rapid weight loss was defined as >5% decrease in body weight within any 12-month interval. Multivariable-adjusted logistic regression was used to assess AAC and rapid weight loss and Cox regression to assess the relationship between rapid weight loss and 9.5-year all-cause mortality. RESULTS: Mean±SD age of women was 75.0±2.6 years. During the initial 5 years, 366 (39%) women presented with rapid weight loss. Compared with women with low AAC (24-point AAC score 0-1), those with moderate (24-point AAC score 2-5: odds ratio, 1.36 [95% CI, 1.00-1.85]) and extensive (24-point AAC score 6+: odds ratio, 1.59 [95% CI, 1.10-2.31]) AAC had higher odds for presenting with rapid weight loss. Results remained similar after further adjustment for dietary factors (alcohol, protein, fat, and carbohydrates), diet quality, blood pressure, and cholesterol measures. The estimates were similar in subgroups of women who met protein intake (n=599) and physical activity (n=735) recommendations (extensive AAC: odds ratios, 1.81 [95% CI, 1.12-2.92] and 1.58 [95% CI, 1.02-2.44], respectively). Rapid weight loss was associated with all-cause mortality over the next 9.5 years (hazard ratio, 1.49 [95% CI, 1.17-1.89]; P=0.001). CONCLUSIONS: AAC extent was associated with greater risk for rapid weight loss over 5 years in older women, a risk for all-cause mortality. Since the association was unchanged after taking nutritional intakes into account, these data support the possibility that vascular disease may play a role in the maintenance of body weight.

A Multi-Season Randomised Controlled Trial of Advax-Adjuvanted Seasonal Influenza Vaccine in Participants with Chronic Disease or Older Age.

BACKGROUND: The aim of this study was to determine the safety and immunogenicity of trivalent inactivated influenza vaccine (TIV) alone or formulated with Advax™ delta inulin adjuvant in those of older age (> 60 years) or with chronic disease. METHODS: Over four consecutive years from 2008-2011, adult participants with chronic disease or over 60 years were recruited into a randomised controlled study to assess the safety, tolerability and immunogenicity of Advax-adjuvanted versus standard TIV. The per protocol (PP) population with at least one post-baseline measurement of influenza antibodies comprised 1297 participants: 447 in the TIV, and 850 in the Advax-adjuvanted TIV, groups. RESULTS: No safety issues were identified. Variables negatively affecting vaccine responses included obesity and diabetes mellitus. Advax adjuvant had a positive impact on anti-influenza IgM responses and on H3N2 and B strain seropositivity as assessed by hemagglutination inhibition. CONCLUSIONS: Advax-adjuvanted TIV was safe and well tolerated in individuals with chronic disease. There is an ongoing need for research into improved influenza vaccines for high-risk populations. Australia New Zealand Clinical Trial Registry: ACTRN 12608000364370.

Acute on chronic liver failure: A South Australian experience.

Background and Aim: Acute on chronic liver failure (ACLF) is a clinical syndrome described in patients with acute decompensation (AD) of cirrhosis, characterized by organ failures and high mortality. Intensive management, including liver transplantation (LT), has been shown to improve survival. To address the limited Australian data on ACLF, we describe the prevalence, clinical profile, and outcome of ACLF in an Australian cohort of hospitalized patients. Methods: A retrospective review of hepatology admissions in a tertiary hospital from 1 January 2017 to 31 December 2019 identified AD and ACLF cohorts, as defined by the European Association for Study of the Liver definition. Patient characteristics, clinical course, survival at 28- and 90-day survival, and feasibility of LT were analyzed. Results: Among the 192 admissions with AD, 74 admissions (39%) met ACLF criteria. A prior diagnosis of alcohol-related cirrhosis was highly prevalent in both cohorts. Grade-1 ACLF was the most frequent (60%), with renal failure being the commonest organ failure; 28-day (23% vs 2%, P = <0.001) and 90-day mortality (36% vs 16%, P = 0.002) were higher in ACLF than AD. Due to ongoing alcohol use disorder (AUD), only six patients underwent LT assessment during ACLF admission. Conclusion: ACLF was common in our cohort of cirrhosis with AD and was associated with high mortality. AUD despite prior cirrhosis diagnosis was a barrier to LT. Prioritization of ACLF patients for LT after addressing AUD and relaxation of the 6-month abstinence rule may improve ACLF survival and should be addressed in prospective studies.

Systolic blood pressure levels and mortality in Australian medical inpatients.

The epidemiology of elevations in blood pressure is incompletely characterized, particularly in Australia. Given the lack of evidence regarding the frequency and the optimal management of in-hospital hypertension, the authors performed a multicenter retrospective cohort study of consecutive medical admissions in South Australia over a 2-year period to investigate systolic blood pressure levels and their association with in-hospital mortality. Among 16 896 inpatients, 76% had at least one systolic blood pressure reading of ≥140 mmHg and 11.7% of ≥180 mmHg during hospitalization. A statistically significant negative relationship was observed between having at least one reading ≥140 mmHg and a likelihood of in-hospital mortality (odds ratio 0.41, 95% CI: 0.35 to 0.49, P < .001). Our results suggest that elevations in systolic blood pressure are common in Australian medical inpatients. However, the inverse association observed between systolic blood pressure values ≥140 mmHg and in-hospital mortality warrants further research to determine the clinical significance and optimal management of blood pressure elevations in this group.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

A comprehensive review of machine learning algorithms and their application in geriatric medicine: present and future.

The increasing access to health data worldwide is driving a resurgence in machine learning research, including data-hungry deep learning algorithms. More computationally efficient algorithms now offer unique opportunities to enhance diagnosis, risk stratification, and individualised approaches to patient management. Such opportunities are particularly relevant for the management of older patients, a group that is characterised by complex multimorbidity patterns and significant interindividual variability in homeostatic capacity, organ function, and response to treatment. Clinical tools that utilise machine learning algorithms to determine the optimal choice of treatment are slowly gaining the necessary approval from governing bodies and being implemented into healthcare, with significant implications for virtually all medical disciplines during the next phase of digital medicine. Beyond obtaining regulatory approval, a crucial element in implementing these tools is the trust and support of the people that use them. In this context, an increased understanding by clinicians of artificial intelligence and machine learning algorithms provides an appreciation of the possible benefits, risks, and uncertainties, and improves the chances for successful adoption. This review provides a broad taxonomy of machine learning algorithms, followed by a more detailed description of each algorithm class, their purpose and capabilities, and examples of their applications, particularly in geriatric medicine. Additional focus is given on the clinical implications and challenges involved in relying on devices with reduced interpretability and the progress made in counteracting the latter via the development of explainable machine learning.

Interactions between Mediterranean Diet Supplemented with Dairy Foods and the Gut Microbiota Influence Cardiovascular Health in an Australian Population.

The impact of a Mediterranean diet on the intestinal microbiome has been linked to its health benefits. We aim to evaluate the effects of a Mediterranean diet supplemented with dairy foods on the gut microbiome in Australians at risk of cardiovascular disease. In a randomised controlled cross-over study, 34 adults with a systolic blood pressure ≥120 mmHg and with risk factors for cardiovascular disease were randomly allocated to a Mediterranean diet with 3-4 daily serves of dairy foods (Australian recommended daily intake (RDI) of 1000-1300 mg per day (MedDairy)) or a low-fat (LFD) control diet. Between each 8-week diet, participants underwent an 8-week washout period. Microbiota characteristics of stool samples collected at the start and end of each diet period were determined by 16S rRNA amplicon sequencing. MedDairy-associated effects on bacterial relative abundance were correlated with clinical, anthropometric, and cognitive outcomes. No change in the overall faecal microbial structure or composition was observed with either diet (p > 0.05). The MedDairy diet was associated with changes in the relative abundance of several bacterial taxa, including an increase in Butyricicoccus and a decrease in Colinsella and Veillonella (p < 0.05). Increases in Butyricicoccus relative abundance over 8 weeks were inversely correlated with lower systolic blood pressure (r = -0.38, p = 0.026) and positively correlated with changes in fasting glucose levels (r = 0.39, p = 0.019), specifically for the MedDairy group. No significant associations were observed between the altered taxa and anthropometric or cognitive measures (p > 0.05). Compared to a low-fat control diet, the MedDairy diet resulted in changes in the abundance of specific gut bacteria, which were associated with clinical outcomes in adults at risk of CVD.

FIT for purpose: study protocol for a randomized controlled trial to personalize surveillance colonoscopy for individuals at elevated risk of colorectal cancer.

PURPOSE: There is increasing demand for colorectal cancer (CRC) surveillance, but healthcare capacity is limited. The burden on colonoscopy resources could be reduced by personalizing surveillance frequency using the fecal immunochemical test (FIT). This study will determine the safety, cost-effectiveness, and patient acceptance of using FIT to extend surveillance colonoscopy intervals for individuals at elevated risk of CRC. METHODS: This multicenter, prospective, randomized controlled trial will invite participants who are scheduled for surveillance colonoscopy (due to a personal history of adenomas or a family history of CRC) and who have returned a low fecal hemoglobin (< 2 µg Hb/g feces; F-Hb) using a two-sample FIT (OC Sensor, Eiken Chemical Company) in the prior 3 years. A total of 1344 individuals will be randomized to either surveillance colonoscopy as scheduled or delayed by 1 or 2 years for individuals originally recommended a 3- or 5-year surveillance interval, respectively. The primary endpoint is incidence of advanced neoplasia (advanced adenoma and/or CRC). Secondary endpoints include cost-effectiveness and consumer acceptability of extending surveillance intervals, determined using surveys and discrete choice experiments. CONCLUSION: This study will establish the safety, cost-effectiveness, and acceptability of utilizing a low FIT Hb result to extend colonoscopy surveillance intervals in a cohort at elevated risk for CRC. This personalized approach to CRC surveillance will lead to a reduction in unnecessary colonoscopies, increases in healthcare savings, and a better patient experience.  TRIAL REGISTRATION: Registration was approved on December 9, 2019 with the Australian New Zealand Clinical Trials Registry ANZCTR 12619001743156.

Health status and mental distress in people with cancer and comorbid conditions: The Australian National Health Survey analysis.

INTRODUCTION: Data on the impact of specific comorbidities on health outcomes is limited. We compared health status and mental distress between individuals with and without cancer according to comorbidity type. METHODS: A cross-sectional analysis using data from the Australian National Health Survey 2017-18 including all respondents aged ≥25 years with and without a history of cancer. The odds of poor health and mental distress were reported according to cancer status, and specific individual and cluster of comorbidities. RESULTS: There were 1982 individuals (52% female) with cancer and 12,635 (51% female) without cancer. Individuals with cancer were older, and more likely to have a comorbidity compared with those without cancer. They were more likely to report poor health than those without cancer for each specific comorbidity; except for skin conditions and infectious diseases; with the adjusted odds ratio (aOR) ranging from 1.34 (95% CI = 1.01-1.79) for digestive disorders to 2.93 (95% CI = 1.62-5.29) for blood conditions. The strongest association with poor health (aOR 2.79, 95% CI = 2.27-3.43) and mental distress (aOR 9.01, 95% CI = 7.25-11.20) was observed for those with a comorbid mental illness. Exploratory cluster analysis identified four distinct comorbidity clusters: low comorbidity, musculoskeletal, respiratory and cardiometabolic; cancer survivors in the cardiometabolic cluster had a higher odds of reporting poor health (aOR 3.50, 95% CI = 2.48-4.92) and mental distress (aOR 2.33, 95% CI = 1.53-3.55) than those with a low comorbidity. CONCLUSIONS: Comorbidities in cancer survivors were common and associated with inferior health status, although the magnitude of the effect varied by comorbidity type. Risk assessment and management of comorbidities should be an important priority for cancer care and research.

General practitioners' perspectives on discharge summaries from a health network of three hospitals in South Australia.

Objectives To explore general practitioners' perspectives on the discharge summaries they receive about their patients who have been discharged from hospital. Methods A survey of general practitioners in the catchment of a major metropolitan South Australian health service consisting of three teaching hospitals was undertaken. Surveys were disseminated electronically and via hardcopy mailout to general practitioners. The 36-question survey focused on five constructs of discharge summaries: accessibility, length and clarity, format, transparency, and medicines content. Results A total of 150 general practitioners responded (response rate, 27.6%). Respondents were vocationally registered (96%), predominately from metropolitan practices (90.2%), and 65.8% were female. Overwhelmingly, 86.7% of general practitioners stated that the optimal time for receipt of discharge summaries was <48 h post-discharge, and 96.6% considered that late arrival of discharge summaries adversely impacts patient care. The ideal length of discharge summaries was reported as <4 pages by 64% of respondents. A large proportion of respondents (84.6%) would like to be notified when their patients are admitted and discharged from hospital, and 82.7% were supportive of patients receiving their own copy of the discharge summary. A total of 76.7% general practitioners reported that they had detected omissions or discrepancies in the discharge summaries. Provision of rationale for medication changes was viewed as important by 86.7%, however, only 29.3% reported that it is always or often communicated. Conclusions General practitioners supported timely receipt, concise length of discharge summary and format refinement to improve the utility and communication of this important clinical handover from hospital to community care.

Individualized Hospital to Home, Exercise-Nutrition Self-Managed Intervention for Pre-Frail and Frail Hospitalized Older Adults: The INDEPENDENCE Randomized Controlled Pilot Trial.

Purpose: Pre-frailty and frailty in older adults are associated with poor health outcomes and increase health-care costs, and further worsening during hospitalization. This study aimed to examine the effect of an individualized hospital to home, exercise-nutrition self-managed intervention for pre-frail and frail hospitalized older adults. Patients and Methods: Older adults admitted to an acute medical unit of a tertiary hospital in South Australia who were pre-frail or frail were recruited from September 2020 to June 2021, randomized to either control or intervention group and followed up at 3 and 6 months. The outcome variables were program adherence, frailty status by the Edmonton Frail Scale (EFS) score, lower extremity physical function, handgrip strength, nutritional status, cognition, mood, health-related quality of life, risk of functional decline, unplanned readmissions. Results: Participants were 79.2 ±6.6 years old, 63% female, mostly frail (67%), with EFS of 8.6±1.9. Adherence to the inpatient and home visits/telehealth intervention were high (91±13% and 92±21%, respectively). Intention-to-treat analysis using linear regression models showed that participants in the intervention group had significantly greater reduction in EFS at 3 (-3.0; 95% CI: -4.8 to -3.0) and 6 months (-2.5; 95% CI: -3.8 to -1.0, P<0.001 for both) compared to the control group; particularly the functional performance component. There were also improvements in overall Short Physical Performance Battery score at 3 (4.0; 95% CI: 1.3 to 6.6) and 6 months (3.9; 95% CI: 1.0 to 6.9, P<0.05 for both), mini-mental state examination (2.6; 95% 0.3-4.8, P=0.029) at 3 months and handgrip strength (3.7; 95% CI: 0.2-7.1, P=0.039) and Geriatric Depression Scale, at 6 months (-2.2; 95% CI: -4.1 to -0.30, P=0.026) in the intervention group as compared to control. Conclusion: This study provided evidence of acceptability to a patient self-managed exercise-nutrition program that may benefit and alleviate pre-frailty and frailty in hospitalised older adults.

A Method for Increasing the Robustness of Stable Feature Selection for Biomarker Discovery in Molecular Medicine Developed Using Serum Small Extracellular Vesicle Associated miRNAs and the Barrett's Oesophagus Disease Spectrum.

The biomarker development field within molecular medicine remains limited by the methods that are available for building predictive models. We developed an efficient method for conservatively estimating confidence intervals for the cross validation-derived prediction errors of biomarker models. This new method was investigated for its ability to improve the capacity of our previously developed method, StaVarSel, for selecting stable biomarkers. Compared with the standard cross validation method, StaVarSel markedly improved the estimated generalisable predictive capacity of serum miRNA biomarkers for the detection of disease states that are at increased risk of progressing to oesophageal adenocarcinoma. The incorporation of our new method for conservatively estimating confidence intervals into StaVarSel resulted in the selection of less complex models with increased stability and improved or similar predictive capacities. The methods developed in this study have the potential to improve progress from biomarker discovery to biomarker driven translational research.

Opioid prescribing among aged care residents during the first year of the COVID-19 pandemic: an analysis using general practice health records in Australia.

BACKGROUND: Opioid use is common among adults 65 years and older, while long-term use of opioids remains controversial and poses risks of drug dependence and other adverse events. The acute disease caused by the SARS-CoV-2 (COVID-19) pandemic has created new challenges and barriers to healthcare access, particularly for long-term care residents. Australia had a relatively low incidence and deaths due to COVID-19 during the first year of the pandemic compared to most OECD countries. In this context, we examined opioid prescribing rates and their dosage in residential aged care facilities (RACFs) before (2019) and during the COVID-19 pandemic (2020) from March to December in Australia. METHODS: We conducted a retrospective cohort using general practice electronic health records. This includes 17,304 RACF residents aged 65 years and over from 361 general practices in New South Wales and Victoria. Number of opioid prescriptions and percentage of opioids over 50 mg/day of oral morphine equivalent (OME) were described. Multivariate generalized estimating equations were applied to estimate odds ratios [aORs (95% confidence intervals)] for 1) opioids prescribed per consultation and 2) prescription opioids over 50 mg/day OME. RESULTS: In 2020 among 11,154 residents, 22.8% of 90,897 total prescriptions were opioids, and of the opioids, 11.3% were over 50 mg/day OME. In 2019 among 10,506 residents, 18.8% of 71,829 total prescriptions were opioids, of which 10.3% were over 50 mg/day OME. Year [2020 vs. 2019: aOR (95% CI):1.50 (1.44, 1.56); 1.29 (1.15, 1.46)] and regionality [rural/regional vs. metropolitan: 1.37 (1.26, 1.49); 1.40 (1.14, 1.71)] were associated with higher odds of prescription opioids and OME > 50 mg/day, respectively. Similar results were found when limited to the same residents (n = 7,340) recorded in both years. CONCLUSIONS: Higher prescription rates of opioids were observed during the COVID-19 pandemic in 2020 than in 2019 in Australian RACFs. The higher odds of prescription opioids and higher dosing in rural/regional than metropolitan areas indicate a widening of the gap in the quality of pain management during the pandemic. Our findings contribute to the limited data that indicate increased opioid prescriptions in long-term care facilities, likely to continue while COVID-19 pandemic restrictions remain.

Efficacy of mindfulness and goal setting interventions for increasing resilience and reducing smoking in lower socio-economic groups: randomised controlled trial protocol.

BACKGROUND: Smoking and resulting health problems disproportionately impact low socioeconomic status (SES) individuals. Building resilience presents an approach to 'closing the gap'. Mindfulness-based interventions and setting realistic goals are preferred in low socioeconomic communities. We aim to test if these interventions, delivered online and consolidated with peer support offered via ex-smokers, are successful in promoting smoking cessation and resilience. Our conceptualisation of resilience encompasses the inner capacity/skills and external resources (e.g., social support) which smokers utilise to bounce back from adversity. We include a process evaluation of barriers/facilitators to interventions and cost-effectiveness analysis (from health system perspective). METHODS: We plan a four-arm parallel 12-month RCT with a 6-month follow-up to test the efficacy of three group-based interventions each followed by peer support. Arm 1: mindfulness-integrated cognitive behavioural therapy; Arm 2: mindfulness training; Arm 3: setting realistic goals; Arm 4: active control group directed to quit services. All interventions will be administered online. Participants are adult smokers in Australia (N = 812) who have an average weekly household income less than $457AUD or receive welfare benefits. Group-based interventions will occur over 6 months, followed by 6 months of forum-based peer support. PRIMARY OUTCOME: self-reported 14-day period prevalence of smoking abstinence at 6 months, with remote biochemical verification of saliva cotinine (< 30 ng/mL). Secondary outcomes include: internal resilience (Connor-Davidson Resilience Scale-25); external resilience (ENRICHD social support tool); quality adjusted life years (EQ-5D-5L); self-efficacy for smoking abstinence (Smoking-Abstinence Self-Efficacy Questionnaire); motivation to quit smoking (Biener and Abrams Contemplation Ladder); nicotine dependence (Fagerstrom Test for Nicotine Dependency); equanimity (Equanimity Scale-16); stress (Perceived Stress Scale-10); goal assessment/attainment (Problems and Goals Assessment Scale). DISCUSSION: This study is the first to compare resilience interventions for low SES smokers which have been identified by them as acceptable. Our various repeated measures and process evaluation will facilitate exploration of mechanisms of impact. We intervene within the novel framework of the Psychosocial Model of Resilience, applying a promising paradigm to address a critical and inequitable public health problem. Trial registration Australian New Zealand Clinical Trials Registry ID: ACTRN12621000445875, registered 19 April 2021 ( https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381007&isReview=true ). The Universal Trial Number is U1111-1261-8951.

Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study.

Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p < 0.001 and −1.47 ± 0.20 p < 0.001, respectively), which was significantly different from the HabDiet group over time (p < 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.

Risk factors for intra-articular involvement in proximal humeral fractures.

INTRODUCTION: Identification of intra-articular involvement in proximal humeral fractures is important for operative decision making. The aim of this study was to identify the risk factors associated with intra-articular involvement in proximal humeral fractures. MATERIALS AND METHODS: One hundred consecutive three-dimensional computed tomography reconstructions of proximal humeral fractures were identified. The fracture lines were then accurately transcribed onto a two-dimensional superior view of the humeral head and each fracture was assessed for intra-articular involvement. Statistical analyses were undertaken to identify risk factors for intra-articular involvement and extent of involvement. Furthermore, for each risk factor, common fracture patterns were identified and compared to anatomical landmarks. RESULTS: Overall, 58% of the fractures involved the articular surface. High-energy mechanism, female gender, age ≥ 65, and posterior dislocation were risk factors for intra-articular involvement. Low-energy mechanism, female gender, age ≥ 65, varus angulation, and posterior dislocation were risk factors for increased extension of the fracture onto the articular surface. CONCLUSION: Intra-articular involvement in proximal humeral fractures is influenced by demographics and fracture characteristics (mechanism of injury, angulation, and dislocation). Patients with identified risk factors should be appropriately evaluated for intra-articular fractures during preoperative planning to assist in operative decision making. LEVEL OF EVIDENCE: Basic science; anatomy study.