Development and application of Adverse drug reactions reports QUality Algorithm (AQUA-12) score: a single-centre quality improvement initiative.

PURPOSE: To develop a reliable assessment tool to monitor the quality of adverse drug reaction (ADR) reports and evaluate its performance within a quaternary hospital setting. METHODS: Adverse drug reactions report QUality Algorithm (AQUA-12) was developed by a multidisciplinary team with the expertise in the management of ADRs. The design was based on data elements required to establish medication causality. Inter-rater reliability of AQUA-12 was evaluated over three rounds in two phases: development and prospective evaluation phases, by independent assessors both internal and external to the institutional ADR review processes. The characteristics and quality of ADR reports were subsequently assessed, and potential factors contributing to low-quality reports were identified. RESULTS: A total of 70 ADR reports were assessed, 20 in development and 50 in evaluation phases. The inter-rater reliability of AQUA-12 was found to be excellent in all three rounds (Cronbach's alpha of  ≥ 0.9, p < 0.001 for all). Approximately one in five reports concerned immediate hypersensitivity reactions while delayed hypersensitivity reactions constituted 60% of all reactions. AQUA-12 identified 18 (25.7%) reports as 'low-quality' with a score of  < 10. Identification of suspected medications (37.1%), description of index ADR (27.1%), and key events (ADR narrative, 35.7%) were the top data elements incomplete or missing from all reports. Univariable analyses identified the severity of the reaction as a factor associated with low quality of reports (p = 0.008). CONCLUSIONS: AQUA-12 is a practical and highly reliable assessment tool that can be utilised in hospital settings to regularly monitor the completeness of ADR reports to guide quality improvement initiatives.

Bullous pemphigoid associated with anti-programmed cell death protein 1 and anti-programmed cell death ligand 1 therapy: A case series of 13 patients.

We present a case series of 13 patients, the first Australian single-centre study of bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICI): cytotoxic T-lymphocyte antigen (CTLA4) and programmed cell death receptor (PD1) inhibitors. All our patients achieved adequate control of BP with a combination of treatments including oral prednisolone, intravenous immunoglobulin, rituximab and omalizumab. The majority of patients ceased or interrupted immunotherapy treatment upon diagnosis of BP and greater tumour progression was seen in the cohort who ceased immunotherapy.

Management of atopic dermatitis: a narrative review.

Atopic dermatitis (atopic eczema) is the most common inflammatory skin disease and has a significant burden on the quality of life of patients, families and caregivers. Its pathogenesis is a complex interplay between genetics and environment, involving impaired skin barrier function, immune dysregulation primarily involving the Th2 inflammatory pathway, itch, and skin microbiome. Restoration of skin barrier integrity with regular emollients and prompt topical anti-inflammatory therapies are mainstays of treatment. Systemic therapy is considered for moderate to severe disease. New understanding of inflammatory pathways and developments in targeted systemic immunotherapies have significantly advanced atopic dermatitis management. Dupilumab is a safe and effective treatment that is now available in Australia. Other promising agents for atopic dermatitis include Janus kinase, interleukin (IL)-13 and IL-31 inhibitors.

A long-term cohort study of acitretin for prevention of keratinocyte carcinoma in solid organ transplant recipients.

BACKGROUND: Solid organ transplant recipients (SOTR) are at high risk of keratinocyte carcinoma (KC). Long-term evidence for acitretin as chemoprophylaxis in this population is lacking. OBJECTIVE: To determine the benefit of long-term acitretin for KC chemoprevention in SOTR. METHODS: A retrospective cohort study of SOTR treated with acitretin at an Australian transplant dermatology clinic was performed. General estimating equations were used to evaluate change in rates of histologically confirmed KC in the 6-12 months prior to acitretin and following a minimum 6 months of treatment. A control group of patients within the same service was included, comprising SOTR who were not treated with acitretin. RESULTS: Twenty-two patients received acitretin treatment for at least 6 months, eighteen for at least 5 years and four for at least 9 years. The median KC rate pretreatment was 3.31 per year (IQR 1.93, 5.40). There was a significant reduction in the rate of KC in the first year of acitretin treatment (IRR 0.41, 95% CI 0.22, 0.76, P = 0.005), and this effect was observed for 5 years (IRR at 5 years 0.34, 95% CI 0.17, 0.67, P = 0.002). The control group had no statistically significant change in KC rate over time in the study. CONCLUSIONS: Acitretin appears to be well-tolerated and effective in reducing KC in SOTR for at least 5 years. Study limitations include its retrospective nature, small sample size and lack of blinding.

VEXAS syndrome: A dermatological perspective.

VEXAS (Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic mutation) syndrome is a genetically defined disorder identified in 2020, describing patients with inflammatory syndromes associated with haematological dysfunction. It is a severe, treatment-resistant condition, with estimated mortality between 40% and 63%. A wide range of cutaneous manifestations have been described. Here, we report on two patients with treatment-resistant neutrophilic dermatosis and myelodysplastic syndrome, who were subsequently diagnosed with VEXAS syndrome. Our cases highlight the need for dermatologists' awareness of this novel condition and to initiate early referral to haematologists for appropriate multidisciplinary care.

Prolonged survival with the early use of a novel extracorporeal photopheresis regimen in patients with Sézary syndrome.

Extracorporeal photopheresis (ECP) has demonstrated therapeutic benefit in patients with Sézary syndrome (SS) and erythrodermic mycosis fungoides (e-MF). To examine the efficacy of ECP in the modern era of novel therapies, we conducted a retrospective analysis of 65 patients with a diagnosis of SS or e-MF with blood involvement who were treated with ECP at our institute. Overall survival (OS), time to next treatment (TTNT), and skin response rate (RR) were used as the study end points to determine patient outcome. The median follow-up from diagnosis was 48 months (range 1-225 months), with a median predicted OS of 120 months. The majority (88%) of patients commenced ECP at treatment lines 1 to 3, either as a monotherapy or in conjunction with other systemic agents. The use of ECP monotherapy resulted in a significantly longer median TTNT when compared with interferon-α (P = .0067), histone deacetylase inhibitors (P = .0003), novel immunotherapy agents (P = .028), low-dose methotrexate (P < .0001), and chemotherapy (P < .0001). In particular, early commencement of ECP at treatment lines 1 to 3 yielded a TTNT of 47 months. The results of our study support the utilization of ECP for SS/e-MF, and we recommend that ECP should be considered as early as possible in the treatment paradigm for these patients.

Melanoma in a cohort of organ transplant recipients: Experience from a dedicated transplant dermatology clinic in Victoria, Australia.

BACKGROUND: There is limited information on the profile of melanomas diagnosed in a specialist transplant dermatology clinic. OBJECTIVE: To describe the incidence and characteristics of incident primary melanomas in a cohort of organ transplant recipients (OTRs) attending a specialized transplant dermatology clinic and determine the number of pigmented lesions needed to excise for every melanoma diagnosed. METHODS: A retrospective study of 327 OTRs monitored by an Australian clinic during a 10-year period. RESULTS: There were 11 incident melanomas diagnosed during a total follow-up of 1280 patient-years. The mean interval between the first transplant and diagnosis was 5.5 years. Only 2 melanomas were >1 mm in Breslow thickness. Seven melanomas (64%) arose de novo. A contiguous nevus was present in 4 cases. Metastatic disease did not develop in the melanoma patients during the follow-up period, and all remain alive. The needed to excise for every melanoma diagnosed ratio was 16:1. LIMITATIONS: The crude incidence rates were age standardized, unlike the comparison rates of melanoma in the general population, and the cohort was small. CONCLUSION: Most melanomas diagnosed in OTR patients attending a specialized transplant dermatology service were detected early. Our data suggest early detection may reduce the proportion of OTRs presenting with thick melanomas, thus improving prognosis and patient outcomes. A needed to excise for every melanoma diagnosed ratio of 16:1 is not unreasonable for this cohort of high-risk patients. To our knowledge, this is the first time this ratio has been calculated for a cohort of OTRs.

Psoriasis and cancer. An Australian/New Zealand narrative.

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co-risk factors such as obesity. The increase in treatment-independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T-cell lymphoma is substantially higher in patients with moderate-to-severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co-risk factors. The risk of cancer from low-dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients' specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug-drug interaction with cancer-directed therapies, including radiotherapy.

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.

Retrospective audit of patients referred for further treatment following Mohs surgery for non-melanoma skin cancer.

BACKGROUND/OBJECTIVES: To describe the characteristics, subsequent management and outcomes of patients referred for further management following Mohs micrographic surgery (MMS) for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). METHODS: Retrospective analysis of patients referred to a quaternary cancer centre from 2000 to 2015. RESULTS: In total, 83 lesions in 82 patients were referred for further management; 52 (62%) were SCC and 80 (96%) were located in the head and neck. Reasons for referral included high-risk disease for consideration for adjuvant radiotherapy (37/83, 45%), inadequate resection (28/83, 34%) or recurrence following previous MMS (15/83, 17%). Fewer than 40% of the 69 referrals received from MMS surgeons included photos or an operative report and diagram. There was discordance in pathology opinion in 11 (13%) of cases. Histopathology from MMS was reviewed in eight cases and there was discordance with the in-hospital pathology opinion in six of these. In-hospital re-excision was performed in 19 cases and in five of these the pathology report on the paraffin-sectioned re-excised tissue was discordant with prior MMS assessment. Significantly, two cases were associated with a misinterpretation of lymphocytic infiltrate as residual disease in patients with chronic lymphocytic leukaemia (CLL). CONCLUSION: This study highlights some of the challenges and limitations of MMS. Early referral for multidisciplinary management is recommended when MMS resection margins are inadequate or uncertain, especially for high-risk SCC. We recommend that referrals be accompanied by histological material, as well as a detailed report with operative photos and diagrams. CLL can pose an intraoperative diagnostic challenge. Discrepancies in the interpretation of MMS slides present an opportunity for improvement, and our findings support the role of ongoing quality assurance programs.

Two cases of amoxycillin-induced follicular acute localised exanthematous pustulosis.

We report two cases of Caucasian women who developed folliculocentric pustulosis after exposure to amoxycillin. A literature review found that most amoxycillin-related pustular eruptions were reported as acute generalised exanthematous pustulosis (AGEP) or acute localised exanthematous pustulosis (ALEP). Histopathology from both our cases showed sterile suppurative folliculitis, which resolved on the cessation of amoxycillin.

Localised pityriasis rosea-like eruption during radiotherapy. Report of 2 cases.

Pityriasis rosea is a common skin condition that presents acutely with asymptomatic, scaly and oval plaques, usually in a well-recognised distribution over the trunk. Two men developed ovoid, scaly and annular lesions limited to the radiotherapy field during treatment for pelvic malignancies and without a preceding herald patch. Other causes of the eruption were excluded on clinical and pathological grounds and the histopathological features were consistent with a pityriasis rosea-like eruption. In both cases the lesions resolved spontaneously by 8 weeks. These are the first reported cases of a localised pityriasis rosea-like eruption arising during radiotherapy.

Deep breathing in your hands: designing and assessing a DTx mobile app.

Digital Therapeutics (DTx) are experiencing rapid advancements within mobile and mental healthcare sectors, with their ubiquity and enhanced accessibility setting them apart as uniquely effective solutions. In this evolving context, our research focuses on deep breathing, a vital technique in mental health management, aiming to optimize its application in DTx mobile platforms. Based on well-founded theories, we introduced a gamified and affordance-driven design, facilitating intuitive breath control. To enhance user engagement, we deployed the Mel Frequency Cepstral Coefficient (MFCC)-driven personalized machine learning method for accurate biofeedback visualization. To assess our design, we enlisted 70 participants, segregating them into a control and an intervention group. We evaluated Heart Rate Variability (HRV) metrics and collated user experience feedback. A key finding of our research is the stabilization of the Standard Deviation of the NN Interval (SDNN) within Heart Rate Variability (HRV), which is critical for stress reduction and overall health improvement. Our intervention group observed a pronounced stabilization in SDNN, indicating significant stress alleviation compared to the control group. This finding underscores the practical impact of our DTx solution in managing stress and promoting mental health. Furthermore, in the assessment of our intervention cohort, we observed a significant increase in perceived enjoyment, with a notable 22% higher score and 10.69% increase in positive attitudes toward the application compared to the control group. These metrics underscore our DTx solution's effectiveness in improving user engagement and fostering a positive disposition toward digital therapeutic efficacy. Although current technology poses challenges in seamlessly incorporating machine learning into mobile platforms, our model demonstrated superior effectiveness and user experience compared to existing solutions. We believe this result demonstrates the potential of our user-centric machine learning techniques, such as gamified and affordance-based approaches with MFCC, which could contribute significantly to the field of mobile mental healthcare.