Surgery triage during the COVID-19 pandemic.

BACKGROUND: The novel coronavirus, SARS-CoV-2, caused the COVID-19 global pandemic. In response, the Australian and New Zealand governments activated their respective emergency plans and hospital frameworks to deal with the potential increased demand on scarce resources. Surgical triage formed an important part of this response to protect the healthcare system's capacity to respond to COVID-19. METHOD: A rapid review methodology was adapted to search for all levels of evidence on triaging surgery during the current COVID-19 outbreak. Searches were limited to PubMed (inception to 10 April 2020) and supplemented with grey literature searches using the Google search engine. Further, relevant articles were also sourced through the Royal Australasian College of Surgeons COVID-19 Working Group. Recent government advice (May 2020) is also included. RESULTS: This rapid review is a summary of advice from Australian, New Zealand and international speciality groups regarding triaging of surgical cases, as well as the peer-reviewed literature. The key theme across all jurisdictions was to not compromise clinical judgement and to enable individualized, ethical and patient-centred care. The topics reported on include implications of COVID-19 on surgical triage, competing demands on healthcare resources (surgery versus COVID-19 cases), and the low incidence of COVID-19 resulting in a possibility to increase surgical caseloads over time. CONCLUSION: During the COVID-19 pandemic, urgent and emergency surgery must continue. A carefully staged return of elective surgery should align with a decrease in COVID-19 caseload. Combining evidence and expert opinion, schemas and recommendations have been proposed to guide this process in Australia and New Zealand.

Multicentre randomised trial comparing contact force with electrical coupling index in atrial flutter ablation (VERISMART trial).

INTRODUCTION: Electrical coupling index (ECI) and contact force (CF) have been developed to aid lesion formation during catheter ablation. ECI measures tissue impedance and capacitance whilst CF measures direct contact. The aim was to determine whether the presence of catheter / tissue interaction information, such as ECI and CF, reduce time to achieve bidirectional cavotricuspid isthmus block during atrial flutter (AFL) ablation. METHODS: Patients with paroxysmal or persistent AFL were randomised to CF visible (range 5-40g), CF not visible, ECI visible (change of 12%) or ECI not visible. Follow-up occurred at 3 and 6 months and included a 7 day ECG recording. The primary endpoint was time to bidirectional cavotricuspid isthmus block. RESULTS: 114 patients were randomised, 16 were excluded. Time to bidirectional block was significantly shorter when ECI was visible (median 30.0 mins (IQR 31) to median 10.5mins (IQR 12) p 0.023) versus ECI not visible. There was a trend towards a shorter time to bidirectional block when CF was visible. Higher force was applied when CF was visible (median 9.03g (IQR 7.4) vs. 11.3g (5.5) p 0.017). There was no difference in the acute recurrence of conduction between groups. The complication rate was 2%, AFL recurrence was 1.1% and at 6 month follow-up, 12% had atrial fibrillation. CONCLUSION: The use of tissue contact information during AFL ablation was associated with reduced time taken to achieve bidirectional block when ECI was visible. Contact force data improved contact when visible with a trend towards a reduction in the procedural endpoint. ClinicalTrials.gov trial identifier: NCT02490033.

A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas.

INTRODUCTION: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation. METHODS AND RESULTS: High frequency stimulation was delivered through a Smart-Touch catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. Three dimensional locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia, or no effect. CARTO maps were exported, registered, and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated (AVD-GP) effects. There were 10 AVD-GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD-GPs (>20%) was identified in: inferoseptal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). CONCLUSION: It is feasible to map the entire left atrium for AVD-GPs before AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterize the autonomic network.

Why do surgeons receive more complaints than their physician peers?

BACKGROUND: Compared with other doctors, surgeons are at an increased risk of medicolegal events, including patient complaints and negligence claims. This retrospective study aimed to describe the frequency and nature of complaints involving surgeons compared with physicians. METHODS: We assembled a national data set of complaints about surgeons and physicians lodged with medical regulators in Australia from 2011 to 2016. We classified the complaints into 19 issues across four domains: treatment and procedures, other performance, professional conduct and health. We assessed differences in complaint risk using incidence rate ratios (IRRs). Finally, we used a multivariate model to identify predictors of complaints among surgeons. RESULTS: The rate of complaints was 2.3 times higher for surgeons than physicians (112 compared with 48 complaints per 1000 practice years, P < 0.001). Two-fifths (41%) of the higher rate of complaints among surgeons was attributable to issues other than treatments and procedures, including fees (IRR = 2.68), substance use (IRR = 2.10), communication (IRR = 1.98) and interpersonal behaviour (IRR = 1.92). Male surgeons were at a higher risk of complaints, as were specialists in orthopaedics, plastic surgery and neurosurgery. DISCUSSION: Surgeons are more than twice as likely to attract complaints as their physician peers. This elevated risk arises partly from involvement in surgical procedures and treatments, but also reflects wider concerns about interpersonal skills, professional ethics and substance use. Improved understanding of these patterns may assist efforts to reduce harm and support safe practise.

Hyperglycemia causes renal cell damage via CCN2-induced activation of the TrkA receptor: implications for diabetic nephropathy.

CCN2, a secreted profibrotic protein, is highly expressed in diabetic nephropathy (DN) and implicated in its pathogenesis; however, the actions of CCN2 in DN remain elusive. We previously demonstrated that CCN2 triggers signaling via tropomyosin receptor kinase A (TrkA). Trace expression of TrkA is found in normal kidneys, but its expression is elevated in several nephropathies; yet its role in DN is unexplored. In this study we show de novo expression of TrkA in human and murine DN. We go on to study the molecular mechanisms leading to TrkA activation and show that it involves hypoxia, as demonstrated by ischemia-reperfusion injury and in vitro experiments mimicking hypoxia, implicating hypoxia as a common pathway leading to disease. We also expose renal cells to hyperglycemia, which led to TrkA phosphorylation in mesangial cells, tubular epithelial cells, and podocytes but not in glomerular endothelial cells and renal fibroblasts. In addition, we report that hyperglycemia caused an induction of phosphorylated extracellular signal-related kinase 1/2 and Snail1 that was abrogated by silencing of TrkA or CCN2 using small interfering RNA. In conclusion, we provide novel evidence that TrkA is activated in diabetic kidneys and suggest that anti-TrkA therapy may prove beneficial in DN.

A population pharmacokinetic/pharmacodynamic model of methotrexate and mucositis scores in osteosarcoma.

Methotrexate, when used in high doses (12 g/m²) in the treatment of osteosarcoma, shows wide between-subject variability (BSV) in its pharmacokinetics. High-dose methotrexate is associated with severe toxicity; therefore, therapeutic drug monitoring (TDM) is carried out to guide rescue therapy and monitor for nephrotoxicity. Mucositis is a commonly encountered dose-limiting toxicity that often leads to delays in subsequent courses of chemotherapy. This, in turn, results in a reduction in the dosing intensity, which is essential in the treatment of osteosarcoma. The aims of this study were to develop a population pharmacokinetic (PK) model from TDM using physiologically relevant covariates and to investigate the correlation between mucositis scores and methotrexate pharmacokinetics. In total, 46 osteosarcoma patients (30 men and 16 women; age, 4-51 years) were recruited, and blood samples were collected for routine TDM once every 24 hours. Mucositis scores, graded according to the National Cancer Institute Common Toxicity Criteria, were recorded for 28 of the patients (18 men and 10 women; age, 8-51 years) predose and postdose. A population PK model was developed in NONMEM VI. A 2-compartment PK model was chosen, and clearance (CL) was divided into filtration and secretion/metabolism components. All parameters were scaled with body weight, and, in addition, total CL was scaled with age- and sex-adjusted serum creatinine. Between-subject variability was modeled for all parameters, and between-occasion variability was included in CL. For a typical 70 kg man of 18 years or older, the parameter estimates for the final model were CL(filt) = 2.69 L/h/70 kg, CL(sec) = 10.9 L/h/70 kg, V1 = 74.3 L/70 kg, Q = 0.110 L/h/70 kg, and V2 = 4.10 L/70 kg. Sequential pharmacodynamic modeling consisted of mucositis scores as 5-point ordered categorical data. A significant linear relationship between individual area under the curve (AUC) and mucositis score probability was found, and the probability of having mucositis score ≥ 1 increased with increasing AUC and was almost 50% at the average cumulative AUC after 2 consecutive methotrexate doses.

A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain.

OBJECTIVES: To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain. METHODS: A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg). RESULTS: There were 892 participants (mean age 60.6, range 40-84 years); 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (p<0.01) for pain relief (determined by mean change from baseline in WOMAC pain; n=786). At 13 weeks, significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with paracetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (p<0.001; paracetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively). CONCLUSIONS: Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefits for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive. Study no ISRCTN77199439.