Isn't it time for health professionals to shift their focus from preaching politics to promoting peace?

The magnitude of suffering on both the Israeli and Palestinian sides of the current war is beyond comprehension. Political agendas, misinformation and bias related to the conflict are being seen far too frequently in healthcare and medical academia. We believe it is time for healthcare professionals to redirect our attention away from politics and use our medical training to advocate for peace, care, and the welfare of all people, regardless of which side of the conflict they fall into. Politics in the workplace, particularly when disseminated information is divisive and, at times, based on opinion rather than fact, risks significant harm to patients, their families, and healthcare staff, as well as to institutional reputation. If we genuinely care for the well-being of patients and staff, we must lead by example and prevent healthcare systems and medical journals from being hijacked by politics.

The role of surveillance imaging for resected high-risk melanoma.

BACKGROUND: Recommendations for surveillance imaging for resected melanoma vary considerably. This study examined the utility of imaging in patients with a high-risk primary melanoma undergoing a protocolized imaging schedule. METHODS: This retrospective study involved data collection regarding imaging, recurrence, and outcome characteristics for patients referred to the Victorian Melanoma Service from January 2016-April 2020 and managed for resected stage IIC or III melanoma. Patients with a T4b tumor who did not undergo a sentinel lymph node biopsy were included (T4bNX). Recurrences were "clinically detected" if they were primarily detected by patient symptoms or physical examination, or 'imaging-detected' if the patient was asymptomatic. Cox regression models including time-varying co-variates were used to assess the impact of imaging-detected versus clinically-detected recurrence on overall survival. RESULTS: Over a median follow-up time of 2.7 years, 199 patients underwent surveillance imaging (T4bNX:22, IIC:33, IIIA:22, IIIB:60, IIIC:61, IIID:1), and 44% (n = 88) experienced disease recurrence. Imaging detected over half (53%) of all recurrences. In adjusted analyses, mortality risk was reduced after an imaging-detected compared to clinically-detected recurrence at any given time from the start of surveillance (hazard ratio 0.25, 95% confidence interval 0.10-0.66, p = .005). CONCLUSION: Our study indicates that routine imaging in the early follow-up period of resected T4bNX, stage IIC and III melanoma plays an important role in the detection of asymptomatic recurrences. Imaging-detected recurrence may be associated with a survival benefit and studies with more prolonged follow-up are required to confirm these findings.

Association between hypertension and cutaneous melanoma, and the effect of aspirin: extended follow-up of a large randomised controlled trial.

BACKGROUND: The association between hypertension and melanoma is unclear, and previous analyses of data from the ASPirin in Reducing Events in the Elderly (ASPREE) study demonstrated a reduced number of invasive melanoma events amongst aspirin-exposed hypertensive individuals. METHODS: Data from the ASPREE study which included (1) the intervention period with a median follow-up of 4.7 years, and (2) the observational period with an additional 2 years follow-up, were combined for this analysis. Logistic regression analyses examined the association between baseline hypertension and treatment status and past melanoma history. Survival analyses examined the association between hypertension and melanoma risk, and the effect of aspirin across hypertension groups. Cox proportional hazards models were used to compare incidence across groups. RESULTS: 19,114 participants (median age of 74 years) were randomised to daily 100 mg aspirin or placebo. At baseline, hypertension and past melanoma history were recorded in 14,195 and 685 individuals, respectively. After adjustment for confounders, hypertension was significantly associated with past melanoma history (OR=1.34, 95%CI: 1.11-1.62). In a prospective analysis, baseline hypertension was not associated with melanoma risk. However, aspirin was associated with a reduced risk of incident melanoma amongst individuals with uncontrolled hypertension (blood pressure ≥140/90 mmHg; HR=0.63, 95%CI 0.44-0.89), but not in those with controlled hypertension (HR=1.04, 95%CI 0.74-1.46). CONCLUSION: Our results support a reduced melanoma incidence amongst individuals with uncontrolled hypertension exposed to aspirin. Additional studies are required to confirm these findings.

Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial.

The effects of aspirin on melanoma are unclear, with studies reporting conflicting results. Data from two periods of the ASPirin in Reducing Events in the Elderly (ASPREE) study; the randomized placebo-controlled trial period examining daily 100 mg aspirin in older adults with a median follow-up of 4.7 years, and the second period, an additional 2 years of observational follow-up, were utilized in this secondary analysis to examine whether aspirin exposure is associated with a reduced cutaneous melanoma incidence. All melanoma cases were adjudicated and Cox proportional hazards models were used to compare incidence between randomized treatment groups. ASPREE recruited 19,114 participants with a median age of 74 years. During the trial period, 170 individuals (76 aspirin, 94 placebo) developed an invasive melanoma, and no significant effect of aspirin was observed on incident melanoma [HR = 0.81; 95% confidence interval (CI), 0.60-1.10]. Including the additional 2 years of observational follow-up (median follow-up of 6.3 years), 268 individuals (119 aspirin, 149 placebo) developed an invasive melanoma, and similar results were observed (HR = 0.81; 95% CI, 0.63-1.03). A reduced number of events was observed with aspirin among females in a subgroup analysis (HR = 0.65; 95% CI, 0.44-0.92); however, the interaction effect with males (HR = 0.92; 95% CI, 0.68-1.25) was nonsignificant (P = 0.17). Our findings from this randomized trial do not provide strong support that aspirin is associated with a reduced risk of invasive melanoma in older individuals. Additional studies are required to further explore this relationship. PREVENTION RELEVANCE: Melanoma prevention is an important strategy to improve outcomes and while preventive efforts have largely focused on sun protection, the role of potential chemopreventive agents such as aspirin warrants investigation.

Yield of baseline imaging for distant metastases in high-risk primary melanoma.

BACKGROUND: The yield of baseline imaging in patients presenting with higher risk primary tumours, at least American Joint Committee on Cancer 8th edition stage IIC or III melanoma, is unclear. METHODS: This retrospective study included patients referred to the Victorian Melanoma Service from January 2017 to April 2020, diagnosed with at least stage IIC or stage III melanoma. Patients with a T4b tumour and no sentinel lymph node biopsy were included as 'T4bNX'. RESULTS: One hundred and sixty-four patients (median age 65 years) with baseline imaging (T4bNX: 19, IIC: 30, IIIA: 21, IIIB: 43, IIIC: 50, IIID: 1) were included. The majority were male (73%), and those with T4bNX melanoma tended to be older (median age 79 years). Distant metastases were detected in 21% (4/19) of T4bNX, 3% (1/30) of stage IIC, 0% (0/21) of stage IIIA, and 6% (6/94) of stages IIIB-D melanoma patients. All stage III patients with distant metastases had palpable lymphadenopathy a presentation. Two patients had brain metastases, both of whom had T4bNX melanoma and synchronous extra-cranial metastases. CONCLUSIONS: Compared to stage IIC, baseline imaging detects higher rates of extra-cranial distant disease in stages IIIB-D and T4bNX melanoma. Intracranial imaging has greater yield in patients with distant extra-cranial disease.

Improving Skin cancer Management with ARTificial Intelligence (SMARTI): protocol for a preintervention/postintervention trial of an artificial intelligence system used as a diagnostic aid for skin cancer management in a specialist dermatology setting.

INTRODUCTION: Convolutional neural networks (CNNs) can diagnose skin cancers with impressive accuracy in experimental settings, however, their performance in the real-world clinical setting, including comparison to teledermatology services, has not been validated in prospective clinical studies. METHODS AND ANALYSIS: Participants will be recruited from dermatology clinics at the Alfred Hospital and Skin Health Institute, Melbourne. Skin lesions will be imaged using a proprietary dermoscopic camera. The artificial intelligence (AI) algorithm, a CNN developed by MoleMap Ltd and Monash eResearch, classifies lesions as benign, malignant or uncertain. This is a preintervention/postintervention study. In the preintervention period, treating doctors are blinded to AI lesion assessment. In the postintervention period, treating doctors review the AI lesion assessment in real time, and have the opportunity to then change their diagnosis and management. Any skin lesions of concern and at least two benign lesions will be selected for imaging. Each participant's lesions will be examined by a registrar, the treating consultant dermatologist and later by a teledermatologist. At the conclusion of the preintervention period, the safety of the AI algorithm will be evaluated in a primary analysis by measuring its sensitivity, specificity and agreement with histopathology where available, or the treating consultant dermatologists' classification. At trial completion, AI classifications will be compared with those of the teledermatologist, registrar, treating dermatologist and histopathology. The impact of the AI algorithm on diagnostic and management decisions will be evaluated by: (1) comparing the initial management decision of the registrar with their AI-assisted decision and (2) comparing the benign to malignant ratio (for lesions biopsied) between the preintervention and postintervention periods. ETHICS AND DISSEMINATION: Human Research Ethics Committee (HREC) approval received from the Alfred Hospital Ethics Committee on 14 February 2019 (HREC/48865/Alfred-2018). Findings from this study will be disseminated through peer-reviewed publications, non-peer reviewed media and conferences. TRIAL REGISTRATION NUMBER: NCT04040114.

Opportunities and barriers for the use of Australian cancer registries as platforms for randomized clinical trials.

It is well recognized that randomized controlled trials (RCTs) are a powerful tool to investigate causal relationships, and are considered the gold standard level of research evidence. However, RCTs can be expensive and time-consuming, and when they employ strict eligibility criteria, it results in an unrepresentative population and limited external validity. Recently, the registry-based randomized clinical trial (RRCT) has emerged as an alternative trial design. Utilizing registries to underpin such studies, RRCTs can have advantages including rapid recruitment, and enhanced generalizability. In Australia, legislated mandatory reporting of cancer diagnoses means that jurisdictional cancer registries are a rich source of systematically collected patient details, representing sound platforms for comprehensive data capture that can serve as a key tool for further research. We review the roles of cancer registries in Australia, discuss important considerations relevant to the design of RRCTs, and outline the opportunities provided by cancer registries to strengthen cancer research.

The Importance of Incorporating Human Factors in the Design and Implementation of Artificial Intelligence for Skin Cancer Diagnosis in the Real World.

Artificial intelligence (AI) algorithms have been shown to diagnose skin lesions with impressive accuracy in experimental settings. The majority of the literature to date has compared AI and dermatologists as opponents in skin cancer diagnosis. However, in the real-world clinical setting, the clinician will work in collaboration with AI. Existing evidence regarding the integration of such AI diagnostic tools into clinical practice is limited. Human factors, such as cognitive style, personality, experience, preferences, and attitudes may influence clinicians' use of AI. In this review, we consider these human factors and the potential cognitive errors, biases, and unintended consequences that could arise when using an AI skin cancer diagnostic tool in the real world. Integrating this knowledge in the design and implementation of AI technology will assist in ensuring that the end product can be used effectively. Dermatologist leadership in the development of these tools will further improve their clinical relevance and safety.

Methods of melanoma detection and of skin monitoring for individuals at high risk of melanoma: new Australian clinical practice.

INTRODUCTION: The evidence-based national clinical practice guidelines for the management of cutaneous melanoma published in 2008 are currently being updated. This article summarises the findings from multiple chapters of the guidelines on different methods of melanoma detection and of monitoring the skin for patients at high risk of melanoma. Early detection of melanoma is critical, as thinner tumours are associated with enhanced survival; therefore, strategies to improve early detection are important to reduce melanoma-related mortality. MAIN RECOMMENDATIONS: Clinicians who perform skin examinations for the purpose of detecting skin cancer should be trained in and use dermoscopy. The use of short term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual melanocytic lesions of concern. The use of long term sequential digital dermoscopy imaging to detect melanomas that lack dermoscopic features of melanoma is recommended to assess individual or multiple melanocytic lesions for routine surveillance of high risk patients. The use of total body photography should be considered in managing patients at increased risk for melanoma, particularly those with high naevus counts and dysplastic naevi. There is insufficient evidence to recommend the routine use of automated instruments for the clinical diagnosis of primary melanoma. MANAGEMENT OVERVIEW: Determining the relative indications for each diagnostic method and how each method should be introduced into the surveillance of a patient requires careful consideration and an individualised approach.

Tumour mutation status and melanoma recurrence following a negative sentinel lymph node biopsy.

BACKGROUND: A proportion of patients develop recurrence following a tumour-negative sentinel lymph node biopsy (SLNB). This study aimed to explore whether melanoma patients with BRAF or NRAS mutant tumours have an increased risk of developing disease recurrence following a negative SLNB compared to patients with wild-type tumours. METHODS: Prospective cohort study of melanoma patients at three tertiary referral centres in Melbourne, who underwent SLNB. Clinical, pathological and molecular characteristics and recurrence data were prospectively recorded. Multivariate Cox proportional hazards regression models estimated the adjusted hazard ratio (aHR) and corresponding 95% confidence interval (CI) for the association between mutation status and development of recurrence following a negative-SLNB. RESULTS: Overall, 344/477 (72.1%) patients had a negative SLNB. Of these, 54 (15.7%) developed subsequent recurrence. The risk of disease recurrence following a negative SLNB was increased for patients with either a BRAF or NRAS mutant tumour compared to wild-type tumours (aHR 1.92, 95% CI: 1.02-3.60, p = 0.04). CONCLUSION: Melanoma patients with BRAF or NRAS mutant tumours had an increased risk compared to patients with BRAF/NRAS wild-type tumours of developing disease recurrence following a tumour-negative SLNB. The findings also confirm the importance of continued surveillance to monitor for disease recurrence among SLNB-negative patients.

Concordance of somatic mutational profile in multiple primary melanomas.

This study aimed to determine the frequency and concordance of BRAF and NRAS mutation in tumours arising in patients with multiple primary melanoma (MPM). Patients with MPM managed at one of three tertiary referral centres in Melbourne, Australia, from 2010 to 2015 were included. Incident and subsequent melanomas underwent mutation testing. Cohen's kappa (κ) coefficient assessed agreement between incident and subsequent primary melanomas for both BRAF and NRAS mutation status (mutant versus wild-type). Mutation testing of at least two primary tumours from 64 patients was conducted. There was poor agreement for both BRAF and NRAS mutation status between incident and subsequent melanomas (κ = 0.10, 95% CI -0.10 to 0.42; κ = 0.06, 95% CI -0.10 to 0.57, respectively). In view of the low concordance in BRAF mutation status between incident and subsequent melanomas, mutational analysis of metastatic tissue, rather than of a primary melanoma, in patients with MPM should be used to guide targeted therapy.

Renal safety of short-term empiric gentamicin therapy in aged patients.

OBJECTIVE: To determine the incidence of acute kidney injury (AKI) in aged patients receiving empiric gentamicin therapy. METHODS: Patients aged ≥65 years receiving gentamicin upon admission between 2013 and 2015 at two Australian hospitals were retrospectively studied. AKI was defined as a rise in creatinine by ≥50% and/or ≥26.5 µmol/L. RESULTS: Most patients (95%) received a single dose of gentamicin. The incidence of AKI was 15% (36/242 patients). A composite outcome of persistent kidney injury, requirement for renal replacement therapy or inpatient death in a patient with AKI occurred in 10 (4%) patients. Patients who developed AKI were older (median 80.5 vs 78 years, P = 0.03), had higher Charlson Co-morbidity Index (median 7 vs 5, P = 0.0004) and had more advanced chronic kidney disease at baseline (Stages IV and V) (OR 4.38, 95% confidence interval 1.45-13.2, P = 0.01). CONCLUSION: Empiric gentamicin use in patients with advancing age is associated with low rates of predominantly transient renal impairment.

Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions: experience from two Australian tertiary hospitals.

BACKGROUND: Drug-induced liver injury (DILI) can be associated with certain cutaneous adverse drug reaction (cADR). AIMS: To demonstrate the prevalence of DILI in patients with cADRs. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. METHODS: A retrospective cohort study of patients with cADRs was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. RESULTS: One hundred and four patients with cADRs were identified. Of these, 33 (31.7%) had liver injury, representing 50% of patients with drug reaction with eosinophilia and systemic symptoms, and 30.2% of patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Most cases of liver injury (69.7%) were of a cholestatic/mixed pattern with severe disease in 18.2%. No significant risk factors for development of liver injury were noted, but peripheral lymphocytosis may represent a risk in patients with SJS (odds ratio, OR = 6.0, 95% confidence interval, CI: 1.8-19.7, P = 0.003). Antimicrobials were the most common class to be implicated in DILI. The median length of inpatient stay was longer in patients with liver injury compared to those without (19 vs 11 days, P = 0.002). The mortality rate in those with liver injury was 15.2% and 9.9% in those without. No patients required liver transplantation. CONCLUSIONS: DILI commonly occurs in patients with cADRs and is associated with longer inpatient stay. Patients with SJS/TEN and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury.