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.

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.

High rates of treatment stage migration for early hepatocellular carcinoma and association with adverse outcomes: An Australian multicenter study.

Background and Aim: The rate of contraindications to percutaneous ablation (PA) for inoperable early hepatocellular carcinoma (HCC) and subsequent outcomes is not well described. We investigated the prevalence and outcomes of inoperable early HCC patients with contraindications to PA, resulting in treatment stage migration (TSM). Methods: Barcelona Clinic Liver Cancer (BCLC) 0/A patients diagnosed between September 2013 and September 2019 across five hospitals were identified. Primary endpoint was proportion of BCLC 0/A HCCs with contraindications to PA. Secondary endpoints included overall survival (OS), local tumor control (LTC), and recurrence-free survival (RFS). The causal effects of PA versus TSM were assessed using a potential outcome means (POM) framework in which the average treatment effects (ATEs) of PA were estimated after accounting for potential selection bias and confounding. Results: Two hundred twenty patients with inoperable BCLC 0/A HCC were identified. One hundred twenty-two patients (55.5%) had contraindications to PA and received TSM therapy, 98 patients (44.5%) received PA. The main contraindication to PA was difficult tumor location (51%). Patients who received TSM therapy had lower median OS (2.4 vs 5.3 years), LTC (1.0 vs 4.8 years), and RFS (0.8 vs 2.9 years); P < 0.001, respectively, compared with PA. The ATE for PA versus TSM yielded an additional 1.11 years (P = 0.019), 2.45 years (P < 0.001), and 1.64 years (P < 0.001) for OS, LTC, and RFS, respectively. Three-year LTC after PA was suboptimal (65%). Conclusion: Our study highlights high rates of contraindication to PA in early HCCs, resulting in TSM and poorer outcomes. The LTC rate for PA appears suboptimal despite being considered as curative therapy. Both findings support the exploration of improved treatment options for early HCCs.

Institutional variation in early mortality following isolated coronary artery bypass graft surgery.

BACKGROUND: Thirty-day mortality following coronary artery bypass grafting (CABG) is a widely accepted marker for quality of care. Although surgical mortality has declined, the utility of this measure to profile quality has not been questioned. We assessed the institutional variation in risk-standardised mortality rates (RSMR) following isolated CABG within Australia and New Zealand (ANZ). METHODS: We used an administrative dataset from all public and most private hospitals across ANZ to capture all isolated CABG procedures recorded between 2010 and 2015. The primary outcome was all-cause death occurring in-hospital or within 30-days of discharge. Hospital-specific RSMRs and 95% CI were estimated using a hierarchical generalised linear model accounting for differences in patient characteristics. RESULTS: Overall, 60,953 patients (mean age 66.1 ± 10.1y, 18.7% female) underwent an isolated CABG across 47 hospitals. The observed early mortality rate was 1.69% (n = 1029) with 81.8% of deaths recorded in-hospital. The risk-adjustment model was developed with good discrimination (C-statistic = 0.81). Following risk-adjustment, a 3.9-fold variation was observed in RSMRs among hospitals (median:1.72%, range:0.84-3.29%). Four hospitals had RSMRs significantly higher than average, and one hospital had RSMR lower than average. When in-hospital mortality alone was considered, the median in-hospital RSMR was 1.40% with a 5.6-fold variation across institutions (range:0.57-3.19%). CONCLUSIONS: Average mortality following isolated CABG is low across ANZ. Nevertheless, in-hospital and 30-day mortality vary among hospitals, highlighting potential disparities in care quality and the enduring usefulness of 30-day mortality as an outcome measure. Clinical and policy interventions, including participating in clinical quality registries, are needed to standardise CABG care.

Identifying rates and risk factors for medication errors during hospitalization in the Australian Parkinson's disease population: A 3-year, multi-center study.

BACKGROUND: Admission to hospital introduces risks for people with Parkinson's disease in maintaining continuity of their highly individualized medication regimens, which increases their risk of medication errors. This is of particular concern as omitted medications and irregular dosing can cause an immediate increase in an individual's symptoms as well as other adverse outcomes such as swallowing difficulties, aspiration pneumonia, frozen gait and even potentially fatal neuroleptic malignant type syndrome. OBJECTIVE: To determine the occurrence and identify factors that contribute to Parkinson's medication errors in Australian hospitals. METHODS: A retrospective discharge diagnosis code search identified all admissions for people with Parkinson's disease to three tertiary metropolitan hospitals in South Australia, Australia over a 3-year period. Of the 405 case notes reviewed 351 admissions met our inclusion criteria. RESULTS: Medication prescribing (30.5%) and administration (85%) errors during admission were extremely common, with the most frequent errors related to administration of levodopa preparations (83%). A higher levodopa equivalent dosage, patients with a modified swallowing status or nil by mouth order during admission, and patients who did not have a pharmacist led medication history within 24 hours of admission had significantly higher rates of medication errors. CONCLUSIONS: This study identified 3 major independent factors that increased the risk of errors during medication management for people with Parkinson's disease during hospitalization. Thus, targeting these areas for preventative interventions have the greatest chance of producing a clinically meaningful impact on the number of hospital medication errors occurring in the Parkinson's population.

Geospatial analysis of Helicobacter pylori infection in South Australia: Should location influence eradication therapy?

BACKGROUND AND AIM: Rates of antimicrobial-resistant Helicobacter pylori infection are rising globally; however, geospatial location and its interaction with risk factors for infection have not been closely examined. METHODS: Gastric biopsy specimens were collected to detect H. pylori infection at multiple centers in Adelaide, South Australia, between 1998 and 2017. The geospatial distribution of antibiotic-resistant H. pylori in the Greater Adelaide region was plotted using choropleth maps. Moran's I was used to assess geospatial correlation, and multivariate linear regression (MLR) was used to examine associations between migration status, socioeconomic status, age, gender, and rates of H. pylori positivity and antibiotic resistance. Geographically weighted regression (GWR) was used to determine the extent to which the associations varied according to geospatial location. RESULTS: Of 20 108 biopsies across 136 postcodes within the Greater Adelaide region, 1901 (9.45%) were H. pylori positive. Of these, 797 (41.9%) displayed clarithromycin, tetracycline, metronidazole, or amoxicillin resistance. In MLR, migration status was associated with the rate of H. pylori positivity (ß = 3.85% per 10% increase in a postcode's migrant population; P < 0.001). H. pylori positivity and resistance to any antibiotic were geospatially clustered (Moran's I = 0.571 and 0.280, respectively; P < 0.001 for both). In GWR, there was significant geospatial variation in the strength of the migrant association for both H. pylori positivity and antibiotic resistance. CONCLUSION: Our study demonstrates the heterogeneous geospatial distribution of H. pylori positivity and antibiotic resistance, as well as its interaction with migrant status. Geographic location and migrant status are important factors to consider for H. pylori eradication therapy.

Prevalence, characteristics and risk factors of frequently readmitted patients to an internal medicine service.

BACKGROUND: Unplanned hospital readmissions (HRA), which have been used as key performance index of healthcare quality, are becoming more prevalent. They are associated with substantial financial burden to hospital systems and considerable impacts on patients' physical and mental health. Patients with frequent readmissions are not well studied. AIMS: To determine the prevalence, characteristics and risk factors associated with frequent readmissions (FRA) to an internal medicine service at a tertiary public hospital. METHOD: A retrospective observational study was conducted at an internal medicine service in a tertiary teaching hospital between 1 January 2010 and 30 June 2016. FRA was defined as four or more readmissions within 12 months of discharge from the index admission (IA). Demographic and clinical characteristics and potential risk factors were evaluated. RESULTS: A total of 50 515 patients was included; 1657 (3.3%) had FRA and were associated with nearly 2.5 times higher in 12-month mortality rates. They were older, had higher rates of indigenous Australians (3.2%), more disadvantaged status (index of relative socio-economic disadvantage decile of 5.3) and more comorbidities (mean Charlson comorbidity index 1.4) in comparison, to infrequent readmission group. The mean length of hospital stay during the IA was 6 days for FRA group (21.4% staying more than 7 days) with higher incidence of discharge against medical advice (2.0% higher). Intensive care unit admission rate was 6.6% for FRA group compared with 3.9% for infrequent readmission group. Multivariate analysis showed mental disease and disorders, neoplastic, alcohol/drug use and alcohol/drug-induced organic mental disorders are associated with FRA. CONCLUSION: The risk factors associated with FRA were older age, indigenous status, being socially disadvantaged, having higher comorbidities and discharging against medical advice. Conditions that lead to FRA were mental disorders, alcohol/drug use and alcohol/drug-induced organic mental disorders and neoplastic disorders.

Development of a Food Composition Database for Assessing Nitrate and Nitrite Intake from Animal-based Foods.

SCOPE: Nitrate and nitrite are approved food additives in some animal-based food products. However, nitrate and nitrite in foods are strictly regulated due to health concerns over methaemoglobinaemia and the potential formation of carcinogenic nitrosamines. In contrast, plants (like leafy vegetables) naturally accumulate nitrate ions; a growing body of research reveals beneficial metabolic effects of nitrate via its endogenous conversion to nitric oxide. To refine the association of dietary nitrate and nitrite intake with health outcomes, reliable measures of nitrate and nitrite intake from dietary food records are required. While a vegetable nitrate content database has been developed, there is a need for a comprehensive up-to-date nitrate and nitrite content database of animal-based foods. METHODS AND RESULTS: A systematic literature search (1980-September 2020) on the nitrate and nitrite content of animal-based foods is carried out. Nitrate and nitrite concentration data and other relevant information are extracted and compiled into a database. The database contains 1921 entries for nitrate and 2077 for nitrite, extracted from 193 publications. The highest median nitrate content is observed in chorizo (median [IQR]; 101.61 [60.05-105.93] mg kg-1 ). Canned fish products have the highest median nitrite level (median [IQR]; 20.32 [6.16-30.16] mg kg-1 ). By subgroup, the median nitrate value in industrial processed meat products (e.g., uncured burger, patties and sausages), whole milk powder and in particular red meat are higher than cured meat products. Processed meat products from high-income regions have lower median nitrate and nitrite content than those of middle-income regions. CONCLUSION: This database can now be used to investigate the associations between nitrate and nitrite dietary intake and health outcomes in clinical trials and observational studies.

Utilisation and safety of catheter ablation of atrial fibrillation in public and private sector hospitals.

BACKGROUND: Little is known about the utilisation and safety of catheter ablation of atrial fibrillation (AF) among public and private sector hospitals. AIMS: To examine the uptake of AF ablations and compare procedural safety between the sectors. METHOD: Hospitalisation data from all public and private hospitals in four large Australian states (NSW, QLD, VIC and WA) were used to identify patients undergoing AF ablation from 2012 to 17. The primary endpoint was any procedure-related complications up to 30-days post-discharge. Logistic regression was used to evaluate the association between treatment at a public hospital and risk of complications adjusting for covariates. RESULTS: Private hospitals performed most of the 21,654 AF ablations identified (n = 16,992, 78.5 %), on patients who were older (63.5 vs. 59.9y) but had lower rates of heart failure (7.9 % vs. 10.4 %), diabetes (10.2 % vs. 14.1 %), and chronic kidney diseases (2.4 % vs. 5.2 %) (all p < 0.001) than those treated in public hospitals. When compared with private hospitals, public hospitals had a higher crude rate of complications (7.25 % vs. 4.70 %, p < 0.001). This difference remained significant after adjustment (OR 1.74 [95 % CI 1.54-2.04]) and it occurred with both in-hospital (OR 1.83 [1.57-2.14]) and post-discharge (OR 1.39 [1.06-1.83]) complications, with certain complications including acute kidney injury (OR 5.31 [3.02-9.36]), cardiac surgery (OR 5.18 [2.19-12.27]), and pericardial effusion (OR 2.18 [1.50-3.16]). CONCLUSIONS: Private hospitals performed most of AF ablations in Australia with a lower rate of complications when compared with public hospitals. Further investigations are needed to identify the precise mechanisms of this observed difference.

Patterns of Anti-Inflammatory and Immunomodulating Drug Usage and Microvascular Endothelial Function in Rheumatoid Arthritis.

Objectives: Specific anti-inflammatory and/or immunomodulating drugs (AIDs) can influence endothelial function which is often impaired in patients with rheumatoid arthritis (RA). We sought to determine whether overall patterns of AID usage are similarly associated with endothelial function. Methods: The reactive hyperaemia index (RHI), a marker of microvascular endothelial function, was measured in 868 RA patients reporting their intake of seven AIDs known to affect endothelial function. Latent class analysis (LCA) was performed to characterise patterns of AID usage. Models for 2-6 classes were compared using the AIC and BIC statistics and Lo-Mendell-Rubin likelihood ratio tests. Associations between the classes and RHI were adjusted for age, gender, body mass index, diabetes, HDL-cholesterol, LDL-cholesterol, family history of ischaemic heart disease, smoking status, RA duration, DAS28 score, steroid dose, existing hypertension, and C-reactive protein. Results: LCA identified five distinct AID usage classes: Class 1, generally low medication usage; Class 2, using either sulfasalazine or non-tumour necrosis factor (TNF) inhibitors; Class 3, methotrexate users; Class 4, TNF-inhibitor users; and Class 5, hydroxychloroquine users. The geometric mean for the RHI for subjects in classes 1 to 5 was 1.92, 1.81, 1.94, 2.10, and 2.07, respectively, with subjects in classes 4 and 5 having better endothelial function than subjects in class 2 (p = 0.003 for each). The glucocorticoid dosage did not influence the classes formed or the association between the classes and the RHI in sensitivity analyses. Conclusion: There were five broad patterns (classes) of AID usage in RA patients. The RHI was relatively lower in users of either sulfasalazine or non-TNF inhibitors. TNF inhibitors or hydroxychloroquine may counteract the negative effects of RA on endothelial function.

Volumetric magnetic resonance imaging analysis of multilevel upper airway surgery effects on pharyngeal structure.

STUDY OBJECTIVES: The Sleep Apnea Multilevel Surgery (SAMS) trial found that modified uvulopalatopharyngoplasty with tonsillectomy (if tonsils present) combined with radiofrequency tongue ablation reduced obstructive sleep apnea (OSA) severity and daytime sleepiness in moderate-severe OSA. This study aimed to investigate mechanisms of effect on apnea-hypopnea index (AHI) reduction by assessing changes in upper airway volumes (airway space, soft palate, tongue, and intra-tongue fat). METHODS: This is a case series analysis of 43 participants of 51 randomized to the surgical arm of the SAMS trial who underwent repeat magnetic resonance imaging (MRI). Upper airway volume, length, and cross-sectional area, soft palate and tongue volumes, and tongue fat were measured. Relationships between changes in anatomical structures and AHI were assessed. RESULTS: The participant sample was predominantly male (79%); mean ± SD age 42.7 ± 13.3 years, body mass index 30.8 ± 4.1 kg/m2, and AHI 47.0 ± 22.3 events/hour. There were no, or minor, overall volumetric changes in the airway, soft palate, total tongue, or tongue fat volume. Post-surgery there was an increase in the minimum cross-sectional area by 0.1 cm2 (95% confidence interval 0.04-0.2 cm2) in the pharyngeal airway, but not statistically significant on corrected analysis. There was no association between anatomical changes and AHI improvement. CONCLUSIONS: This contemporary multilevel upper airway surgery has been shown to be an effective OSA treatment. The current anatomical investigation suggests there are not significant post-operative volumetric changes associated with OSA improvement 6-month post-surgery. This suggests that effect on OSA improvement is achieved without notable deformation of airway volume. Reduced need for neuromuscular compensation during wake following anatomical improvement via surgery could explain the lack of measurable volume change. Further research to understand the mechanisms of action of multilevel surgery is required. CLINICAL TRIAL: This manuscript presents a planned image analysis of participants randomized to the surgical arm or the clinical trial multilevel 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=266019&isReview=true%20Australian%20New%20Zealand%20Clinical%20Trials%20Registry%20ACTRN12514000338662, prospectively registered on March 31, 2014.

Delayed Treatment with Human Dental Pulp Stem Cells Accelerates Functional Recovery and Modifies Responses of Peri-Infarct Astrocytes Following Photothrombotic Stroke in Rats.

Dental pulp contains multipotent mesenchymal stem cells that improve outcomes when administered early after temporary middle cerebral artery occlusion in rats. To further assess the therapeutic potential of these cells, we tested whether functional recovery following stroke induced by photothrombosis could be modified by a delayed treatment that was initiated after the infarct attained maximal volume. Photothrombosis induces permanent focal ischemia resulting in tissue changes that better reflect key aspects of the many human strokes in which early restoration of blood flow does not occur. Human dental pulp stem cells (approximately 400 × 103 viable cells) or vehicle were injected into the infarct and adjacent brain tissue of Sprague-Dawley rats at 3 days after the induction of unilateral photothrombotic stroke in the sensorimotor cortex. Forepaw function was tested up to 28 days after stroke. Cellular changes in peri-infarct tissue at 28 days were assessed using immunohistochemistry. Rats treated with the stem cells showed faster recovery compared with vehicle-treated animals in a test of forelimb placing in response to vibrissae stimulation and in first attempt success in a skilled forelimb reaching test. Total success in the skilled reaching test and forepaw use during exploration in a Perspex cylinder were not significantly different between the 2 groups. At 28 days after stroke, rats treated with the stem cells showed decreased immunolabeling for glial fibrillary acidic protein in tissue up to 1 mm from the infarct, suggesting decreased reactive astrogliosis. Synaptophysin, a marker of synapses, and collagen IV, a marker of capillaries, were not significantly altered at this time by the stem-cell treatment. These results indicate that dental pulp stem cells can accelerate recovery without modifying initial infarct formation. Decreases in reactive astrogliosis in peri-infarct tissue could have contributed to the change by promoting adaptive responses in neighboring neurons.

Left ventricular ischemia in pre-capillary pulmonary hypertension: a cardiovascular magnetic resonance study.

BACKGROUND: Prognosis in pulmonary arterial hypertension (PAH) is largely dependent on right ventricular (RV) function. However, recent studies have suggested the presence of left ventricular (LV) dysfunction in PAH patients. The potential role of LV ischemia, as a contributor to progressive LV dysfunction, has not been systematically studied in PAH. We aim to assess the presence and extent of LV myocardial ischemia in patients with known PH and without obstructive coronary artery disease (CAD), using oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) and stress/rest CMR T1 mapping. METHODS: We prospectively recruited 28 patients with right heart catheter-proven PH and no significant CAD, 8 patients with known CAD and 11 normal age-matched controls (NC). OS-CMR images were acquired using a T2* sequence and T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at rest and adenosine-induced stress vasodilatation; ΔOS-CMR signal intensity (SI) index (stress/rest SI) and ΔT1 reactivity (stress-rest/rest T1 mapping) were calculated. RESULTS: Global LV ΔOS SI index was significantly lower in PH patients compared with controls (11.1%±6.7% vs. 20.5%±10.5%, P=0.016), as was ΔT1 reactivity (5.2%±4.5% vs. 8.0%±2.9%, P=0.047). The ischemic segments of CAD patients had comparable ΔOS SI (10.3%±6.4% vs. 11.1%±6.7%, P=0.773) to PH patients, but lower ΔT1 reactivity (1.1%±4.2% vs. 5.2%±4.5%, P=0.036). CONCLUSIONS: Decreased OS-CMR SI and T1 reactivity signify the presence of impaired myocardial oxygenation and vasodilatory response in PH patients. Given their unobstructed epicardial coronary arteries, this is likely secondary to coronary microvascular dysfunction (CMD).

Modification of diet, exercise and lifestyle (MODEL) study: a randomised controlled trial protocol.

INTRODUCTION: Most cardiovascular disease (CVD)-related events could be prevented or substantially delayed with improved diet and lifestyle. Providing information on structural vascular disease may improve CVD risk factor management, but its impact on lifestyle change remains unclear. This study aims to determine whether providing visualisation and pictorial representation of structural vascular disease (abdominal aortic calcification (AAC)) can result in healthful diet and lifestyle change. METHODS AND ANALYSIS: This study, including men and women aged 60-80 years, is a 12-week, two-arm, multisite randomised controlled trial. At baseline, all participants will have AAC assessed from a lateral spine image captured using a bone densitometer. Participants will then be randomised to receive their AAC results at baseline (intervention group) or a usual care control group that will receive their results at 12 weeks. All participants will receive information about routinely assessed CVD risk factors and standardised (video) diet and lifestyle advice with three simple goals: (1) increase fruit and vegetable (FV) intake by at least one serve per day, (2) improve other aspects of the diet and (3) reduce sitting time and increase physical activity. Clinical assessments will be performed at baseline and 12 weeks. OUTCOMES: The primary outcome is a change in serum carotenoid concentrations as an objective measure of FV intake. The study design, procedures and treatment of data will adhere to Standard Protocol Items for Randomized Trials guidelines. ETHICS AND DISSEMINATION: Ethics approval for this study has been granted by the Edith Cowan University and the Deakin University Human Research Ethics Committees (Project Numbers: 20513 HODGSON and 2019-220, respectively). Results of this study will be published in peer-reviewed academic journals and presented in scientific meetings and conferences. Information regarding consent, confidentiality, access to data, ancillary and post-trial care and dissemination policy has been disclosed in the participant information form. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (ACTRN12618001087246).

Detection of advanced colorectal neoplasia and relative colonoscopy workloads using quantitative faecal immunochemical tests: an observational study exploring the effects of simultaneous adjustment of both sample number and test positivity threshold.

OBJECTIVE: When screening for colorectal cancer (CRC) using quantitative faecal immunochemical tests (FIT), test parameters requiring consideration are the faecal haemoglobin concentration (f-Hb) positivity cut-off and the number of stools sampled. This observational study explored variation in f-Hb between samples and the relationship between sensitivity for advanced neoplasia (AN, cancer or advanced adenoma) and colonoscopy workload across a range of independently-adjusted parameter combinations. DESIGN: Quantitative FIT data (OC-Sensor) were accessed from individuals undergoing personalised colonoscopic screening with an offer of 2-sample FIT in the intervening years. We estimated variation in f-Hb between samples in 12 710 completing 2-sample FIT, plus test positivity rates (colonoscopy workload) and sensitivity for AN according to parameter combinations in 4037 instances where FIT was done in the year preceding colonoscopy. RESULTS: There was large within-subject variability between samples, with the ratio for the second to the first sample f-Hb ranging up to 18-fold for all cases, and up to 56-fold for AN cases. Sensitivity for AN was greatest at lower f-Hb cut-offs and/or using 2-sample FIT. Colonoscopy workload varied according to how parameters were combined. Using different cut-offs for 1-sample FIT and 2-sample FIT to return similar sensitivity, workload was less with 2-sample FIT when the sensitivity goal exceeded 35%. CONCLUSION: Variation in f-Hb between samples is such that both parameters are crucial determinants of sensitivity and workload; independent adjustment of each should be considered. The 2-sample FIT approach is best for detecting advanced adenomas as well as CRC provided that the colonoscopy workload is feasible.

Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial.

Importance: Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated. Objective: To determine whether combined palatal and tongue surgery to enlarge or stabilize the upper airway is an effective treatment for patients with OSA when conventional device treatment failed. Design, Setting, and Participants: Multicenter, parallel-group, open-label randomized clinical trial of upper airway surgery vs ongoing medical management. Adults with symptomatic moderate or severe OSA in whom conventional treatments had failed were enrolled between November 2014 and October 2017, with follow-up until August 2018. Interventions: Multilevel surgery (modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on sleep positioning, weight loss; n = 51). Main Outcomes and Measures: Primary outcome measures were the apnea-hypopnea index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and >30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates pathological sleepiness). Baseline-adjusted differences between groups at 6 months were assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units for ESS. Results: Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18 [18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at 6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical management group (mean baseline-adjusted between-group difference at 6 mo, -17.6 events/h [95% CI, -26.8 to -8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 mo, -6.7 [95% CI, -8.2 to -5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for observation following hematemesis of old blood). Conclusions and Relevance: In this preliminary study of adults with moderate or severe OSA in whom conventional therapy had failed, combined palatal and tongue surgery, compared with medical management, reduced the number of apnea and hypopnea events and patient-reported sleepiness at 6 months. Further research is needed to confirm these findings in additional populations and to understand clinical utility, long-term efficacy, and safety of multilevel upper airway surgery for treatment of patients with OSA. Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12614000338662.

Phenolic composition of 91 Australian apple varieties: towards understanding their health attributes.

INTRODUCTION: Apples, an important contributor to total dietary phenolic intake, are associated with cardiovascular health benefits. Determining the phenolic composition of apples, their individual variation across varieties, and the phenolic compounds present in plasma after apple consumption is integral to understanding the effects of apple phenolics on cardiovascular health. METHODS: Using liquid chromatography we quantified five important polyphenols and one phenolic acid with potential health benefits: quercetin glycosides, (-)-epicatechin, procyanidin B2, phloridzin, anthocyanins, and chlorogenic acid, in the skin and flesh of 19 apple varieties and 72 breeding selections from the Australian National Apple Breeding program. Furthermore, we measured the phenolic compounds in the plasma of 30 individuals post-consumption of an identified phenolic-rich apple, Cripp's Pink. RESULTS: Considerable variation in concentration of phenolic compounds was found between genotypes: quercetin (mean ± SD: 16.1 ± 5.9, range: 5.8-30.1 mg per 100 g); (-)-epicatechin (mean ± SD: 8.6 ± 5.8, range: 0.2-19.8 mg per 100 g); procyanidin B2 (mean ± SD: 11.5 ± 6.6, range: 0.5-26.5 mg per 100 g); phloridzin (mean ± SD: 1.1 ± 0.6, range: 0.3-4.3 mg per 100 g); anthocyanins (mean ± SD: 1.8 ± 4.4, range: 0-40.8 mg per 100 g); and chlorogenic acid (mean ± SD: 11.3 ± 9.9, range: 0.4-56.0 mg per 100 g). All phenolic compounds except chlorogenic acid were more concentrated in the skin compared with flesh. We observed a significant increase, with wide variation, in 14 phenolic compounds in plasma post-consumption of a phenolic-rich apple. CONCLUSION: This information makes an important contribution to understanding the potential health benefits of apples.

Effect of antenatal depression on adverse birth outcomes in Gondar town, Ethiopia: A community-based cohort study.

BACKGROUND: The impact of antenatal depression on pregnancy outcomes has been well investigated in developed countries, but few studies have been conducted in low-income countries. As depression is significantly affected by socio-economic and cultural factors, it would be difficult to generalize evidence from high-income countries to low-income countries. We conducted a community-based cohort study to estimate the incidence of adverse birth outcomes and the direct and indirect pathways via which depression and other psychosocial risk factors may impact such birth outcomes within Gondar town, Ethiopia. METHODS: The study followed 916 pregnant women who were screened for antenatal depression using the Edinburgh Postnatal Depression Scale (EPDS). We also assessed the incidence of preterm births, Low Birth Weight (LBW) and stillbirths. Modified Poisson regression was used to estimate the relative risk of predictors on adverse birth outcomes and a Generalized Structural Equation Model (GSEM) was used to estimate the direct and indirect effect of antenatal depression and other psychological risk factors on adverse birth outcomes. RESULTS: The cumulative incidence of stillbirth, LBW and preterm was 1.90%, 5.25%, and 16.42%, respectively. The risk of preterm birth was 1.61, 1.46, 1.49, and 1.77 times higher among participants who identified as Muslim, reported being fearful of delivery, were government employee's, and who had no antenatal care services, respectively. Partner support moderated the association between depression, preterm birth, and LBW. Depression had no direct effect on birth outcomes but indirectly affected preterm birth via partner support. Religion had both direct and indirect effects on preterm birth, while occupation and fear of delivery had direct effects. The risk of LBW was 9.44 and 2.19 times higher among preterm births and those who had exposure to tobacco, respectively. Stress coping was indirectly associated, and preterm birth and tobacco exposure were directly associated with LBW. The risk of stillbirth was 3.22 times higher in women with antenatal depression and 73% lower in women with higher coping abilities. CONCLUSIONS: There was a high incidence of all adverse birth outcomes in Gondar Town. Depression and psychosocial risk factors had important indirect negative effects on risk, while partner support provided a positive indirect effect on the incidence of adverse birth outcomes. Interventions that focus on increasing partner engagement and participation in antenatal support may help reduce adverse birth outcomes by enhancing maternal resilience.

Association of flavonoids and flavonoid-rich foods with all-cause mortality: The Blue Mountains Eye Study.

BACKGROUND: Higher intakes of flavonoids provide health benefits, however, the importance of each flavonoid class and which population groups may receive the greatest protection from higher flavonoid intake warrants further investigation. OBJECTIVE: To explore the associations of flavonoid and flavonoid-rich wholefood intakes with all-cause mortality and the moderating effects of early mortality risk factors. DESIGN: The study included 2349 participants of The Blue Mountains Eye Study, with a mean ± SD age at baseline of 64.7 ± 9.2 years. Flavonoid intake was calculated from baseline food frequency questionnaires using US Department of Agriculture food composition databases. Associations were examined using adjusted Cox proportional hazards models. RESULTS: After 14 years of follow-up, 677 participants died. There was a flavonoid threshold effect with the greatest risk reduction seen between low and moderate intakes of total flavonoids, flavonoid classes and flavonoid-rich foods. Amongst the whole cohort, participants in the highest tertile of anthocyanidin intake had a significantly lower risk of all-cause mortality [multivariable adjusted HR (95%CI): 0.76 (0.61, 0.94)] when compared to those in the lowest tertile. Amongst participants with at least one early mortality risk factor (smoking, high alcohol consumption, no regular exercise or obesity), risk of all-cause mortality was lower in those in the highest intake tertile for total flavonoids [adjusted HR: 0.77 (0.59, 1.00)], flavan-3-ols [0.75 (0.58, 0.98)], anthocyanidins [0.70 (0.54, 0.92)], and proanthocyanidins [0.69 (0.52, 0.92)], compared to those in the lowest tertile. No similar associations were observed among those without any risk factors. Similarly, consumption of apples, tea and the individual flavonoid compounds, quercetin and epicatechin, were associated with a lower risk of all-cause mortality among participants with at least one risk factor, but not amongst other participants. CONCLUSION: Moderate to high intakes of flavonoids and certain flavonoid subclasses may provide health benefits, particularly for individuals with at least one early mortality risk factor.