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Background: We hypothesized that there is an influence of socioeconomic status (SES) on association between pregnancy complications and premature coronary artery disease (PCAD) risk. Materials and Methods: This project involved a data linkage approach merging three databases of South Australian cohorts using retrospective, age-matched case?control study design. Cases (n?=?721), that is, women aged

Abstract Background Secreted Frizzled‐Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) Methods Plasma cSFRP5 concentrations were measured using enzyme‐linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64). Results Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p

IntroductionCarcinoid heart disease (CHD), a complication of carcinoid syndrome (CS), is a rare condition that can lead to right sided valvular heart disease and has been traditionally associated with a poor prognosis. We conducted a systematic review and meta-analysis to explore the accuracy of biomarkers and echocardiography in diagnosing CHD amongst patients who are already known to have neuroendocrine tumours and to assess whether surgical management of CHD leads to a reduction in mortality.MethodsA systematic literature search of MEDLINE, EMBASE, EBM Reviews, Google Scholar, ClinicalTrials.gov was conducted. All studies on patients with carcinoid heart disease (CHD) reporting on biomarkers, echocardiographic and surgical outcomes were included. The National Heart, Lung, and Blood Institute quality assessment tool was used to assess the methodological study quality. Data analysis was performed using Stata Statistical Software and R Studio, and individual meta-analyses were performed for biomarkers, echocardiographic findings, and surgical outcomes.ResultsA total of 36 articles were included in the systematic review analysis. N terminal pro-brain natriuretic peptide (NTproBNP) and 5-hydroxyindole acetate (5-HIAA) levels were higher in patients with CHD compared with those without CHD. 32% of CS patients had echocardiographic evidence of cardiac involvement, of which 79% involved tricuspid valve abnormalities. Moderate-severe tricuspid regurgitation was the most common echocardiographic abnormality (70% of patients). However, these analyses had substantial heterogeneity due to the high variability of cardiac involvement across studies. Pooled surgical mortality for CHD was 11% at 1 month, 31% at 12 months and 56% at 24 months. When assessing surgical outcomes longitudinally, the one-month surgical results showed a trend towards more recent surgeries having lower mortality rates than those reported in earlier years, however this was not statistically significant.DiscussionThere is not enough data in current literature to determine a clear cut-off value of NTproBNP and 5-HIAA to help diagnose or determine CHD severity. Surgical management of CHD is yet to show significant mortality benefit, and there are no consistent comparisons to medical treatment in current literature.

Abstract Background Depression is the leading cause of global disability and can develop following the change in body image and functional capacity associated with stoma surgery. However, reported prevalence across the literature is unknown. Accordingly, we performed a systematic review and meta-analysis aiming to characterise depressive symptoms after stoma surgery and potential predictive factors. Methods PubMed/MEDLINE, Embase, CINAHL and Cochrane Library were searched from respective database inception to 6 March 2023 for studies reporting rates of depressive symptoms after stoma surgery. Risk of bias was assessed using the Downs and Black checklist for non-randomised studies of interventions (NRSIs), and Cochrane RoB2 tool for randomised controlled trials (RCTs). Meta-analysis incorporated meta-regressions and a random-effects model. Registration: PROSPERO, CRD42021262345. Results From 5,742 records, 68 studies were included. According to Downs and Black checklist, the 65 NRSIs were of low to moderate methodological quality. According to Cochrane RoB2, the three RCTs ranged from low risk of bias to some concerns of bias. Thirty-eight studies reported rates of depressive symptoms after stoma surgery as a proportion of the respective study populations, and from these, the median rate across all timepoints was 42.9% 42.9% (IQR: 24.2–58.9%). Pooled scores for respective validated depression measures (Hospital Anxiety and Depression Score (HADS), Beck Depression Inventory (BDI), and Patient Health Questionnaire-9 (PHQ-9)) across studies reporting those scores were below clinical thresholds for major depressive disorder according to severity criteria of the respective scores. In the three studies that used the HADS to compare non-stoma versus stoma surgical populations, depressive symptoms were 58% less frequent in non-stoma populations. Region (Asia–Pacific; Europe; Middle East/Africa; North America) was significantly associated with postoperative depressive symptoms (p = 0.002), whereas age (p = 0.592) and sex (p = 0.069) were not. Conclusions Depressive symptoms occur in almost half of stoma surgery patients, which is higher than the general population, and many inflammatory bowel disease and colorectal cancer populations outlined in the literature. However, validated measures suggest this is mostly at a level of clinical severity below major depressive disorder. Stoma patient outcomes and postoperative psychosocial adjustment may be enhanced by increased psychological evaluation and care in the perioperative period.

Abstract Currently available anti-erosive agents only provide partial protection, emphasizing the need to enhance their performance. By characterizing erosive enamel wear at the nanoscale, the aim of this in vitro study was to assess the anti-erosive effects of SnF2 and CPP-ACP both individually and synergistically. Erosion depths were assessed longitudinally on 40 polished human enamel specimens after 1, 5, and 10 erosion cycles. Each cycle comprised one-min erosion in citric acid (pH 3.0) and one-min treatment in whole saliva (control group) or a slurry of one of the three anti-erosive pastes (10% CPP-ACP; 0.45% SnF2 (1100 ppm F); or SnF2/CPP-ACP (10% CPP-ACP + 0.45% SnF2)) (n = 10 per group). Scratch depths were assessed longitudinally in separate experiments using a similar protocol after 1, 5, and 10 cycles. Compared with the control groups, all slurries reduced erosion depths after 1 cycle (p ≤ 0.004) and scratch depths after 5 cycles (p ≤ 0.012). The order of anti-erosive potential was SnF2/CPP-ACP > SnF2 > CPP-ACP > control for erosion depth analysis, and SnF2/CPP-ACP > (SnF2 = CPP-ACP) > control for scratch depth analysis. These data provide ‘proof of concept’ evidence that SnF2/CPP-ACP has superior anti-erosive potential compared to SnF2 or CPP-ACP alone.

Introduction: Current guidelines suggest preoperative direct oral anticoagulant levels of

Abstract Background Stereotactic radiosurgery (SRS) is the preferred treatment for vestibular schwannoma (VS) in patients with preserved hearing and tumour diameter

Background: There is growing awareness of breast density in women attending breast cancer screening; however, it is unclear whether this awareness is associated with increased knowledge. This study aims to evaluate breast density knowledge among Australian women attending breast cancer screening. Method: This cross-sectional study was conducted on women undergoing breast cancer screening at The Queen Elizabeth Hospital Breast/Endocrine outpatient department. Participants were provided with a questionnaire to assess knowledge, awareness, and desire to know their own breast density. Result: Of the 350 women who participated, 61% were familiar with ‘breast density’ and 57% had ‘some knowledge’. Prior breast density notification (OR = 4.99, 95% CI = 2.76, 9.03; p = 0.004), awareness (OR = 4.05, 95% CI = 2.57, 6.39; p = 0.004), younger age (OR = 0.97, 95% CI = 0.96, 0.99; p = 0.02), and English as the language spoken at home (OR = 3.29, 95% CI = 1.23, 8.77; p = 0.02) were independent predictors of ‘some knowledge’ of breast density. A significant proportion of participants (82%) expressed desire to ascertain their individual breast density. Conclusions: While knowledge of breast density in this Australian cohort is generally quite low, we have identified factors associated with increased knowledge. Further research is required to determine optimal interventions to increase breast density knowledge.

Background: Patients with coronary microvascular disorders often experience recurrent angina for which there are limited evidence-based therapies. These patients have been found to exhibit increased plasma levels of endothelin; thus, selective endothelin–A (Et-A) receptor blockers such as zibotentan may be an effective anti-anginal therapy in these patients. The study evaluated the impact of a 10 mg daily dose of zibotentan on spontaneous angina episodes in patients with the coronary slow-flow phenomenon who had refractory angina (i.e., experiencing angina at least three times/week despite current anti-anginal therapy). Methods: Using a randomized, double-blind, placebo-controlled, crossover trial design with 4-week treatment periods, 18 patients (63.2 ± 9.9 years, 33% females) were recruited. The primary endpoint was angina frequency as measured by an angina diary, with secondary endpoints including nitrate consumption, angina duration/severity and the Seattle Angina Questionnaire (SAQ) domains. Results: During the 4 weeks of therapy, angina frequency significantly improved with zibotentan therapy (placebo 41.4 (58.5) vs. zibotentan 29.2 (31.6), p < 0.05), and sublingual nitrate consumption significantly reduced (placebo 11.8 (15.2) vs. zibotentan 8.8 (12.9), p < 0.05. Conclusions: Zibotentan improved the frequency of spontaneous angina episodes and reduced sublingual nitrate consumption in patients unresponsive to standard anti-anginal therapy.

Summary: Background: Communication is the foundation of a strong doctor–patient relationship. Holistic care of the patient involves good communication and empathy. There are various tools and interventions aimed at increasing the Surgeon's performance, but these have the drawback of heavy cost and time commitments. In contrast, patient focused interventions are often simple and cheap. In surgery this is an evolving field, and little is known about the impact these interventions have on clinical encounters. The aim of this review is to determine how patient focussed interventions impact communication in the Surgical Outpatient Consultation. Methods: In this systematic review and meta-analysis, two reviewers independently searched MEDLINE (incl. PubMed), EMBASE, EMCARE, CINAHL, and the Cochrane Library for the period starting 01 February 1990 to 01 February 2022. Filtration and screening was performed in accordance with PRISMA guidelines. Conflicts were resolved by discussion. Risk of Bias was assessed using the RoB 2 tool. Meta-analyses were conducted by an independent statistician using Stata Statistical Software. This systematic review was prospectively registered with PROSPERO (ID CRD42022311112). Findings: After screening, 38 papers were included in the final analysis. These involved 6392 patients consisting of 32 randomised controlled trials (RCT), one crossover RCT, three non-randomised experimental studies, and three cohort studies. All articles were published between 1999 and 2022. Four types of intervention were identified: Patient Decision Aids, Educational Materials, Question Prompt Lists and Patient Reported Outcome Measures. There was much heterogeneity in the reported results but ultimately four recurring domains for assessing quality of communication were identified: Patient knowledge; decisional conflict; satisfaction; and anxiety. Meta-analyses showed that patient focussed interventions increased patient knowledge and reduced decisional conflict. Meta-regression demonstrated significant knowledge increases in females compared with males. Results regarding satisfaction and anxiety were not statistically significant. Interpretation: Our study suggested that patient focused interventions demonstrate promising results for increasing patient engagement and improving communication. Further multicentre randomised controlled trials with consistent validated endpoints should be conducted to evaluate this evolving field. Funding: There was no funding source for this study.

Abstract Background The prevalence of anaemia in patients planned for total hip and knee arthroplasty is about 20%. Optimising pre-operative haemoglobin levels by iron supplementation has been shown to decrease transfusion rates, complications and associated morbidity. The need for universal screening with iron studies of all elective arthroplasty patients is not clearly defined at present. Methods Retrospective review of 2 sequential cohorts of patients undergoing primary hip or knee arthroplasty by a single surgeon at a single centre between January 2013 and December 2017. The first group of patients underwent pre-operative iron studies only if found to be anaemic, with a haemoglobin below 12g/dl. From January 2015, all patients irrespective of the presence of anaemia were screened with a complete iron profile before surgery. Patients with a confirmed iron deficiency were administered with intravenous iron prior to surgery. The 2 cohorts were compared with regard to blood transfusion rate post-operatively and cost efficiency for universal screening with iron studies. Results There was a net decrease in the allogenic blood transfusion rate from 4.76 to 2.92% when universal iron studies were introduced but the difference was not statistically significant. Obtaining universal pre-operative iron studies is cost neutral with the price of allogenic blood transfusion in a similar cohort. We also diagnosed 5 patients with occult malignancies. Conclusions Universal screening with pre-operative iron studies and iron infusion in elective arthroplasty patients may reduce allogenic blood requirements and is cost neutral. An additional benefit is the potential to diagnose asymptomatic malignancies. Further studies are required to show the true benefit of universal pre-operative iron screening.

Introduction Transient ischaemic attack (TIA) may be a warning sign of stroke and difficult to differentiate from minor stroke and TIA-mimics. Urgent evaluation and diagnosis is important as treating TIA early can prevent subsequent strokes. Recent improvements in mass spectrometer technology allow quantification of hundreds of plasma proteins and lipids, yielding large datasets that would benefit from different approaches including machine learning. Using plasma protein, lipid and radiological biomarkers, our study will develop predictive algorithms to distinguish TIA from minor stroke (positive control) and TIA-mimics (negative control). Analysis including machine learning employs more sophisticated modelling, allowing non-linear interactions, adapting to datasets and enabling development of multiple specialised test-panels for identification and differentiation.Methods and analysis Patients attending the Emergency Department, Stroke Ward or TIA Clinic at the Royal Adelaide Hospital with TIA, minor stroke or TIA-like symptoms will be recruited consecutively by staff-alert for this prospective cohort study. Advanced neuroimaging will be performed for each participant, with images assessed independently by up to three expert neurologists. Venous blood samples will be collected within 48 hours of symptom onset. Plasma proteomic and lipid analysis will use advanced mass spectrometry (MS) techniques. Principal component analysis and hierarchical cluster analysis will be performed using MS software. Output files will be analysed for relative biomarker quantitative differences between the three groups. Differences will be assessed by linear regression, one-way analysis of variance, Kruskal-Wallis H-test, χ2 test or Fisher’s exact test. Machine learning methods will also be applied including deep learning using neural networks.Ethics and dissemination Patients will provide written informed consent to participate in this grant-funded study. The Central Adelaide Local Health Network Human Research Ethics Committee approved this study (HREC/18/CALHN/384; R20180618). Findings will be disseminated through peer-reviewed publication and conferences; data will be managed according to our Data Management Plan (DMP2020-00062).

Abstract Background and Aim Commonly used classifications for colorectal lesions (CLs) include the Narrow Band Imaging (NBI) International Colorectal Endoscopic (NICE) and Japan NBI Expert Team (JNET) classifications. However, both lack a sessile serrated adenoma/polyp (SSA/P) category. This has been addressed by the modified Sano's (MS) and Workgroup serrAted polypS and Polyposis (WASP) classifications. This study aims to compare the accuracy of wNICE and wJNET (WASP added to both) with the stand‐alone MS classification. Methods Patients undergoing colonoscopy at an Australian tertiary hospital who had at least one CL detected were prospectively enrolled. In the exploratory phase, CLs were characterized in real time with NBI and magnification using all classifications. In the validation phase, CLs were assessed with both NBI and Blue Laser Imaging (BLI) by four external endoscopists in Japan. The primary outcome was the comparison of wJNET and MS. Secondary outcomes included comparisons among all classifications and the calculation of interrater reliability. Results A total of 483 CLs were evaluated in real time in the exploratory phase, and four sets of 30 CL images (80 on NBI and 40 on BLI) were scored in the validation phase. For high‐confidence diagnoses, MS accuracy was superior to wJNET in both the exploratory (86% vs 79%, P

Abstract Background The Oncotype DX 21-gene Recurrence Score is a genomic-based algorithm that guides adjuvant chemotherapy treatment decisions for women with early-stage, oestrogen receptor (ER)-positive breast cancer. However, there are age-related differences in chemotherapy benefit for women with intermediate Oncotype DX Recurrence Scores that are not well understood. Menstrual cycling in younger women is associated with hormonal fluctuations that might affect the expression of genomic predictive biomarkers and alter Recurrence Scores. Here, we use paired human breast cancer samples to demonstrate that the clinically employed Oncotype DX algorithm is critically affected by patient age. Methods RNA was extracted from 25 pairs of formalin-fixed paraffin-embedded, invasive ER-positive breast cancer samples that had been collected approximately 2 weeks apart. A 21-gene signature analogous to the Oncotype DX platform was assessed through quantitative real-time PCR, and experimental recurrence scores were calculated using the Oncotype DX algorithm. Results There was a significant inverse association between patient age and discordance in the recurrence score. For every 1-year decrease in age, discordance in recurrence scores between paired samples increased by 0.08 units (95% CI − 0.14, − 0.01; p = 0.017). Discordance in recurrence scores for women under the age of 50 was driven primarily by proliferation- and HER2-associated genes. Conclusion The Oncotype DX 21-gene Recurrence Score algorithm is critically affected by patient age. These findings emphasise the need for the consideration of patient age, particularly for women younger than 50, in the development and application of genomic-based algorithms for breast cancer care.

Background and Aim Endoscopic submucosal dissection (ESD) is a challenging procedure. A dissection speed of ≥9 cm2/h has been acknowledged as a mark for expertise, alongside a complication rate of ≤5% and en bloc resection rate of ≥90%. However, there is lack of objective information on whether the three measures correlate with each other. This study aims to evaluate the dissection speed, safety, and efficacy of colorectal ESDs performed by experts and trainees. Methods Consecutive patients undergoing colorectal ESD at a Japanese hospital (2006–2017) were included in a prospectively collected database. Information on patient demographics, proceduralist, and intra‐/postprocedure data was retrieved. The primary outcome was the comparison in dissection speed. The secondary outcomes included differences in safety and efficacy. Log‐linear regression models adjusted for confounders (e.g. R0 resection) were used to assess the differences in dissection speed. Results Five hundred ninety procedures (514 patients) performed by 26 endoscopists were analyzed. Experts performed a higher number of difficult lesions (e.g. F2 fibrosis) but achieved higher dissection speed (10.3 vs 6.7 cm2/h). The difference was statistically significant for both unadjusted and adjusted models (P

Aim or Purpose: The increasing prevalence of erosive tooth wear among children and young adults is an issue of growing concern, emphasising the need for improvement in the currently used preventive strategies. Our aim was to evaluate individual and synergistic effects of SnF2 and CPP-ACP pastes in inhibiting erosion at a nano-scale. Materials and Methods: Forty flat, polished enamel specimens were subjected to 10 erosion cycles, with each cycle comprising one-min erosion in citric acid (pH 3.0) and one-min exposure to human saliva. In each of the 3 experimental groups (n = 10 per group), a remineralising paste (10% CPP-ACP or 0.45% SnF2 (1,100 ppm F) or SnF2/CPP-ACP (combined 10% CPP-ACP and 0.45% SnF2)) was applied as a slurry in saliva between erosion cycles. No remineralising agent was used in control specimens (n = 10). Erosion was assessed by calculating erosion depth using a novel photolithographic technique combined with high-resolution 3D laser scanning microscopy from baseline to 1 min, 5 min and 10 min. Results: A significant increase in erosion depth was detected in the control group as early as 1 min (69.4 nm) (P < 0.001), with the erosion depths being smaller for all three remineralising agents after 1 min (P ≤ 0.004). The overall trend of erosion depth reduction was SnF2/CPP-ACP > SnF2 > CPP-ACP > control. Conclusions: Application of SnF2-enriched CPP-ACP agent reduces dental erosion more than either SnF2 or CPP-ACP alone, offering a potentially more-effective preventive strategy to manage this condition.

Background Microscopic evaluation of urine is inconsistently performed in veterinary clinics. The IDEXX SediVue Dx® Urine Sediment Analyzer (SediVue) recently was introduced for automated analysis of canine and feline urine and may facilitate performance of urinalyses in practice. Objective Compare the performance of the SediVue with manual microscopy for detecting clinically relevant numbers of cells and 2 crystal types. Samples Five‐hundred thirty urine samples (82% canine, 18% feline). Methods For SediVue analysis (software versions [SW] 1.0.0.0 and 1.0.1.3), uncentrifuged urine was pipetted into a cartridge. Images were captured and processed using a convolutional neural network algorithm. For manual microscopy, urine was centrifuged to obtain sediment. To determine sensitivity and specificity of the SediVue compared with manual microscopy, thresholds were set at ≥5/high power field (hpf) for red blood cells (RBC) and white blood cells (WBC) and ≥1/hpf for squamous epithelial cells (sqEPI), non‐squamous epithelial cells (nsEPI), struvite crystals (STR), and calcium oxalate dihydrate crystals (CaOx Di). Results The sensitivity of the SediVue (SW1.0.1.3) was 85%‐90% for the detection of RBC, WBC, and STR; 75% for CaOx Di; 71% for nsEPI; and 33% for sqEPI. Specificity was 99% for sqEPI and CaOx Di; 87%‐90% for RBC, WBC, and nsEPI; and 84% for STR. Compared to SW1.0.0.0, SW1.0.1.3 had increased sensitivity but decreased specificity. Performance was similar for canine versus feline and fresh versus stored urine samples. Conclusions and Clinical Importance The SediVue exhibits good agreement with manual microscopy for the detection of most formed elements evaluated, but improvement is needed for epithelial cells.

Background/aimsMaternal and infant morbidities associated with pregnant women with cardiac conditions are a global issue contingent upon appropriate care. This study aimed to describe the clinical variables and their association with the adherence scores to perinatal guidelines for pregnant women with cardiac conditions. The clinical variables included cardiac, perinatal, and neonatal outcomes and complications.MethodsUsing a retrospective cross-sectional medical record audit, data were abstracted and categorised as cardiac, obstetric, and neonatal predictors. Linear regression modelling was used to find the mean difference (MD) in adherence scores for each predictor, including a 95% confidence interval (CI) and a significance value for all the three categories' clinical outcomes.ResultsThis maternal cohort's (n = 261) cardiac complications were primarily arrhythmias requiring treatment (29.9%), particularly SVT (28%), a new diagnosis of valvular heart disease and congenital heart disease (24%) and decompensated heart failure (HF) (16%). Women with HF had associated increased adherence scores (MD = 3.546, 95% CI: 1.689, 5.403) compared to those without HF. Elective LSCS mode of delivery was associated with a higher adherence score (MD = 5.197, 95% CI: 3.584, 6.811) than non-elective LSCS subgroups. Babies admitted to intensive /special care had greater adherence to the guidelines (MD = 3.581, 95% CI: 1.822, 5.340) than those not requiring the same care.ConclusionsSome pregnancy associated complications and morbidities were associated with higher adherence scores, reflecting that a diagnosis, identification of morbidities or risk factors, initiation of appropriate multidisciplinary involvement and adherence to guidelines were associated. Conversely, potentially avoidable major complications such as sepsis were associated with a low adherence score.Trial registrationACTRN12617000417381.

We performed a systematic review and meta-analysis of randomised controlled trials (RCTs) conducted from January 2005 to June 2021 to update the evidence of Botulinum toxin A (BoNT-A) in neuropathic pain (NP) in addition to quality of life (QOL), mental health, and sleep outcomes. We conducted a Cochrane Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria analysis of RCTs from the following data sources: EMBASE, CINAHL, WHO International Clinical Trial Registry Platform, ClinicalTrials.gov, Cochrane database, Cochrane Clinical Trial Register, Australia New Zealand Clinical Trials Registry, and EU Clinical Trials Register. Meta-analysis of 17 studies showed a mean final VAS reduction in pain in the intervention group of 2.59 units (95% confidence interval: 1.79, 3.38) greater than the mean for the placebo group. The overall mean difference for sleep, Hospital Anxiety and Depression Scale (HADS) anxiety, HADS depression, and QOL mental and physical sub-scales were, respectively, 1.10 (95% CI: −1.71, 3.90), 1.41 (95% CI: −0.61, 3.43), −0.16 (95% CI: −1.95, 1.63), 0.85 (95% CI: −1.85, 3.56), and −0.71 (95% CI: −3.39, 1.97), indicating no significance. BoNT-A is effective for NP; however, small-scale RCTs to date have been limited in evidence. The reasons for this are discussed, and methods for future RCTs are developed to establish BoNT-A as the first-line agent.

IntroductionIntertrochanteric fractures are common fragility injuries in the elderly. Surgical fixation using intramedullary devices are one of the widely used management options. To date, evidence demonstrating the effects of lag screw configuration and the mode of lag screw locking in these devices is lacking. The purpose of this study is to investigate whether the lag screw configuration (single vs integrated dual interlocking screw) and the mode of lag screw locking (static vs dynamic) of a femoral nail device result in differences in clinical and functional outcomes.Methods and analysisA multicentre, pragmatic, single-blinded randomised controlled trial (RCT) with a three-arm parallel group design is proposed. Nine-hundred patients with intertrochanteric fractures (A1 and A2 AO/OTA) will be randomised to fracture treatment using a Gamma3 nail (Stryker; proximally dynamic) or a Trigen Intertan nail (Smith & Nephew) in a dynamic or static lag screw configuration. The primary outcome measure consists of radiological evidence of construct failure within 6 months following surgery, with failure being defined as breakage of the femoral nail or distal locking screw, a change in tip-apex distance of more than 10 mm or lag screw cut-out through the femoral head. Secondary outcomes include surgical data (operation time, fluoroscopy time), complications (surgical site infection, reoperation, patient death), return to mobility and home circumstances, functional independence, function and pain. Patients who are able to walk independently with or without a mobility aid and are able to answer simple questions and follow instructions will be asked to participate in three dimensional gait analysis at 6 weeks and 6 months to assess hip biomechanics from this cohort. Additional secondary measures of gait speed, hip range of motion, joint contact and muscle forces and gross activity monitoring patterns will be obtained in this subgroup.Ethics and disseminationThe Central Adelaide Local Health Network Human Research Ethics Committee has approved the protocol for this RCT (HREC/17/RAH/433). The results will be disseminated via peer-reviewed publications and presentations at relevant conferences.Trial registration numberACTRN12618001431213.

Abstract Background Distal radial fractures are one of the most common orthopaedic cases that present to the A&E department. Surgical intervention is warranted in displaced intraarticular fractures and fractures with more than the recommended angulation or shortening, and is most commonly treated with volarly placed fixed angle locking plates. The aim of this study is to determine and compare the efficacy of two different plates for surgical treatment of distal radius fractures. The VRP 2.0 is a new plate produced by the Austofix company and this system will be compared against the VA-LP (Variable angle-locking plate) produced by Depuy-Synthes which has been used as the standard treatment device. Methods and Design Patients between the ages of 18 and 80 presenting to the Royal Adelaide Hospital with isolated closed distal radial fractures will be invited to participate in this study. A total of 200 patients are required to provide 90% statistical power at a 5% alpha level to detect a difference of 11.5 points on the PRWE (Patient rated Wrist evaluation) score. The primary outcome measure will be the PRWE score while the secondary outcome measures will include the DASH score, EQ5D score, clinical range of movements, grip strength as well as patient perceived return of function at the wrist and time to resumption to work. These will be measured at 6 weeks, 3 months and 12 months. Radiographic indices including the radial tilt, length, volar inclination and plate prominence will also be measured. Complications will be recorded up to 12 months. Post hoc comparisons will be done using paired t tests. An intention to treat and a per protocol analysis will be done to compare the 2 groups. Discussion Distal radial fractures are increasingly being treated by internal fixation using volar locking plates. However, there is no prospective study to date comparing one plate against another in terms of outcome and complications. This study could provide more information about the best way to treat these injuries surgically. Trial registration The trial is registered with the Australia New Zealand Clinical Trials Registry (ANZCTR). Trial registration date-17/11/2016. Trial registration number-ACTRN12616001590459.

There is increasing recognition of the importance of nutrition for reproductive health, but little is known regarding the diet quality of younger vs. older reproductive aged women, and how their intakes relate to dietary recommendations. The purpose of the study was to examine the diets of younger (19–35 years old) compared to older (35–50 years old) reproductive aged women, and how they align with dietary recommendations. Women aged 19–50 years from the 2011–13 Australian National Nutrition and Physical Activity Survey were included (n = 2323). Dietary intakes were assessed by a single 24-h dietary recall and were compared to (i) Australian Dietary Guidelines; (ii) Acceptable Macronutrient Distribution for protein, carbohydrates, and fat; and (iii) Dietary Guideline Index (DGI). Regression analyses comparing younger and older women against recommendations were undertaken, with confounders determined a priori. There was no difference between older and younger women in meeting food group recommendations, with 26% of all women meeting recommendations for fruit, and meat and alternatives, and p > 0.05), older women had higher component scores in limiting saturated fat, consuming low-fat milk, and limiting adding salt during cooking. Continued health promotion for women of reproductive age should be a key priority to improve their own health and that of future generations.

Prominent reports have assessed the challenges to antibiotic innovation and recommended implementing “pull” incentives, i.e., mechanisms that give increased and predictable revenues for important, marketed antibiotics. We set out to understand countries’ perceptions of these recommendations, through frank and anonymous dialogue. In 2019 and 2020, we performed in-depth interviews with national policymakers and antibiotic resistance experts in 13 countries (ten European countries and three non-European) for a total of 73 individuals in 27 separate interviews. Interviewees expressed high-level support for antibiotic incentives in 11 of 13 countries. There is recognition that new economic incentives are needed to maintain a reliable supply to essential antibiotics. However, most countries are uncertain which incentives may be appropriate for their country, which antibiotics should be included, how to implement incentives, and how much it will cost. There is a preference for a multinational incentive, so long as it is independent of national pricing, procurement, and reimbursement processes. Nine countries indicated a preference for a model that ensures access to both existing and new antibiotics, with the highest priority for existing antibiotics. Twelve of thirteen countries indicated that shortages of existing antibiotics is a serious problem. Since countries are skeptical about the public health value of many recently approved antibiotics, there is a mismatch regarding revenue expectations between policymakers and antibiotic innovators. This paper presents important considerations for the design and implementation of antibiotic pull mechanisms. We also propose a multinational model that appears to match the needs of both countries and innovators.

BACKGROUND:We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). METHODS:We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990-Jan 2016). Two authors extracted data. FINDINGS:71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80-2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06-2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59-90%). The effects of alcohol reduction interventions were inconclusive. CONCLUSIONS:Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.

The 2014/2015 West African Ebola Virus Disease (EVD) outbreak attracted global attention. Numerous opinions claimed that the global response was impaired, in part because, the EVD research was neglected, although quantitative or qualitative studies did not exist. Our objective was to analyse how the EVD research landscape evolved by exploring the existing research network and its communities before and during the outbreak in West Africa.Social network analysis (SNA) was used to analyse collaborations between institutions named by co-authors as affiliations in publications on EVD. Bibliometric data of publications on EVD between 1976 and 2015 was collected from Thomson Reuters' Web of Science Core Collection (WoS). Freely available software was used for network analysis at a global-level and for 10-year periods. The networks are presented as undirected-weighted graphs. Rankings by degree and betweenness were calculated to identify central and powerful network positions; modularity function was used to identify research communities. Overall 4,587 publications were identified, of which 2,528 were original research articles. Those yielded 1,644 authors' affiliated institutions and 9,907 connections for co-authorship network construction. The majority of institutions were from the USA, Canada and Europe. Collaborations with research partners on the African continent did exist, but less frequently. Around six highly connected organisations in the network were identified with powerful and broker positions. Network characteristics varied widely among the 10-year periods and evolved from 30 to 1,489 institutions and 60 to 9,176 connections respectively. Most influential actors are from public or governmental institutions whereas private sector actors, in particular the pharmaceutical industry, are largely absent.Research output on EVD has increased over time and surged during the 2014/2015 outbreak. The overall EVD research network is organised around a few key actors, signalling a concentration of expertise but leaving room for increased cooperation with other institutions especially from affected countries. Finding innovative ways to maintain support for these pivotal actors while steering the global EVD research network towards an agenda driven by agreed, prioritized needs and finding ways to better integrate currently peripheral and newer expertise may accelerate the translation of research into the development of necessary live saving products for EVD ahead of the next outbreak.

Studies assessing dietary intake and its relationship to metabolic phenotype are emerging, but limited. The aims of the study are to identify dietary patterns in Australian adults, and to determine whether these dietary patterns are associated with metabolic phenotype and obesity. Cross-sectional data from the Australian Bureau of Statistics 2011 Australian Health Survey was analysed. Subjects included adults aged 45 years and over (n = 2415). Metabolic phenotype was determined according to criteria used to define metabolic syndrome (0–2 abnormalities vs. 3–7 abnormalities), and additionally categorized for obesity (body mass index (BMI) ≥30 kg/m2 vs. BMI

Background: Depression and debt are common in the UK. Debt Counselling for Depression in Primary Care: an adaptive randomised controlled pilot trial (DeCoDer) aimed to assess the clinical effectiveness and cost-effectiveness of the addition of a primary care debt counselling advice service to usual care for patients with depression and debt. However, the study was terminated early during the internal pilot trial phase because of recruitment delays. This report describes the rationale, methods and findings of the pilot study, and implications for future research. Objectives: The overarching aim of the internal pilot was to identify and resolve problems, thereby assessing the feasibility of the main trial. The specific objectives were to confirm methods for practice recruitment and the ability to recruit patients via the proposed approaches; to determine the acceptability of the study interventions and outcome measures; to assess contamination; to confirm the randomisation method for main trial and the level of participant attrition; and to check the robustness of data collection systems. Design: An adaptive, parallel, two-group multicentre randomised controlled pilot trial with a nested mixed-methods process and economic evaluation. Both individual- and cluster (general practice)-level were was used in the pilot phase to assign participants to intervention or control groups. Setting: General practices in England and Wales. Participants: Individuals were included who were aged ≥ 18 years, scored ≥ 14 on the Beck Depression Inventory II and self-identified as having debt worries. The main exclusion criteria were being actively suicidal or psychotic and/or severely depressed and unresponsive to treatment; having a severe addiction to alcohol/illicit drugs; being unable/unwilling to give written informed consent; currently participating in other research including follow-up phases; having received Citizens Advice Bureau (CAB) debt advice in the past year; and not wanting debt advice via a general practice. Interventions: The participants in the intervention group were given debt advice provided by the CAB and shared biopsychosocial assessment, in addition to treatment as usual (TAU) and two debt advice leaflets. The participants in the control group were given advice leaflets provided by the general practitioner and TAU only. Main outcome measures: (1) Outcomes of the pilot trial – the proportion of eligible patients who consented, the number of participants recruited compared with target, assessment of contamination, and assessment of patient satisfaction with intervention and outcome measures. (2) Participant outcomes – primary – Beck Depression Inventory II; secondary – psychological well-being, health and social care utilisation, service satisfaction, substance misuse, record of priority/non-priority debts, life events and difficulties, and explanatory measures. Outcomes were assessed at baseline (pre-randomisation) and at 4 months post randomisation. Other data sources – qualitative interviews were conducted with participants, clinicians and CAB advisors. Results: Of the 238 expressions of interest screened, 61 participants (26%) were recruited and randomised (32 in the intervention group and 29 in the control group). All participants provided baseline outcomes and 52 provided the primary outcome at 4 months’ follow-up (14.7% dropout). Seventeen participants allocated to the intervention saw a CAB advisor. Descriptive statistics are reported for participants with complete outcomes at baseline and 4 months’ follow-up. Our qualitative findings suggest that the relationship between debt and depression is complex, and the impact of each on the other is compounded by other psychological, social and contextual influences. Conclusions: As a result of low recruitment, this trial was terminated at the internal pilot phase and was too small for inferential statistical analysis. We recommend ways to reduce this risk when conducting complex trials among vulnerable populations recruited in community settings. These cover trial design, the design and delivery of interventions, recruitment strategies and support for sites. Trial registration: Current Controlled Trials ISRCTN79705874. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 35. See the NIHR Journals Library website for further project information. Mark Gabbay and Adele Ring are part-funded by NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) North West Coast and Richard Byng and Rod S Taylor, Vashti Berry and Elizabeth Shaw part-funded by NIHR CLAHRC South West Peninsula.

Enterococcus faecalis is the most frequent species present in post-treatment disease and plays a significant role in persistent periapical infections following root canal treatment. Its ability to persist in stressful environments is inter alia, due to its ability to form biofilms. The presence of certain D-amino acids (DAAs) has previously been shown to reduce formation of Bacillus subtilis biofilms. The aims of this investigation were to determine if DAAs disrupt biofilms in early and late growth stages for clinical E. faecalis strains and to test their efficacy in disrupting E. faecalis biofilms grown in sub-minimum inhibitory concentrations of commonly used endodontic biocides. From thirty-seven E. faecalis strains, the ten "best" biofilm producers were used to test the ability of a mixture containing D-leucine, D-methionine, D-tyrosine and D-tryptophan to reduce biofilm growth over a period of 24, 72 and 144 hours and when compared to their cognate L-Amino Acids (LAAs). We have previously shown that sub-MIC levels of tetracycline and sodium hypochlorite promotes biofilm growth in clinical strains of E. faecalis. DAAs were therefore tested for their effectiveness to reduce biofilm growth in the presence of sub-minimal concentrations of sodium hypochlorite (NaOCl-0.031%) and Odontocide™ (0.25% w/v), and in the presence of Odontopaste™ (0.25% w/v). DAAs significantly reduced biofilm formation for all strains tested in vitro, while DAAs significantly reduced biofilm formation compared to LAAs. The inhibitory effect of DAAs on biofilm formation was concentration dependent. DAAs were also shown to be effective in reducing E. faecalis biofilms in the presence of Odontopaste™ and sub-MIC levels of NaOCl and Odontocide™. The results suggest that the inclusion of DAAs into current endodontic procedures may reduce E. faecalis biofilms.

BACKGROUND:Research on Neglected Tropical Diseases (NTDs) has increased in recent decades, and significant need-gaps in diagnostic and treatment tools remain. Analysing bibliometric data from published research is a powerful method for revealing research efforts, partnerships and expertise. We aim to identify and map NTD research networks in Germany and their partners abroad to enable an informed and transparent evaluation of German contributions to NTD research. METHODOLOGY/PRINCIPAL FINDINGS:A SCOPUS database search for articles with German author affiliations that were published between 2002 and 2012 was conducted for kinetoplastid and helminth diseases. Open-access tools were used for data cleaning and scientometrics (OpenRefine), geocoding (OpenStreetMaps) and to create (Table2Net), visualise and analyse co-authorship networks (Gephi). From 26,833 publications from around the world that addressed 11 diseases, we identified 1,187 (4.4%) with at least one German author affiliation, and we processed 972 publications for the five most published-about diseases. Of those, we extracted 4,007 individual authors and 863 research institutions to construct co-author networks. The majority of co-authors outside Germany were from high-income countries and Brazil. Collaborations with partners on the African continent remain scattered. NTD research within Germany was distributed among 220 research institutions. We identified strong performers on an individual level by using classic parameters (number of publications, h-index) and social network analysis parameters (betweenness centrality). The research network characteristics varied strongly between diseases. CONCLUSIONS/SIGNIFICANCE:The share of NTD publications with German affiliations is approximately half of its share in other fields of medical research. This finding underlines the need to identify barriers and expand Germany's otherwise strong research activities towards NTDs. A geospatial analysis of research collaborations with partners abroad can support decisions to strengthen research capacity, particularly in low- and middle-income countries, which were less involved in collaborations than high-income countries. Identifying knowledge hubs within individual researcher networks complements traditional scientometric indicators that are used to identify opportunities for collaboration. Using free tools to analyse research processes and output could facilitate data-driven health policies. Our findings contribute to the prioritisation of efforts in German NTD research at a time of impending local and global policy decisions.