Biologic treatment sequences in moderate-to-severe psoriasis.

BACKGROUND: The advent of novel biologics has led to an increase in biologic-switching as patients and clinicians pursue improved clinical outcomes. However, guidance on treatment sequencing in an Australian setting is sparse. This study examines the patterns of care across two tertiary centres in Australia and characterizes the factors contributing to biologic-switching. METHODS: A retrospective study of patients who attended the outpatient Dermatology biologic clinics across two tertiary hospitals was conducted. Data on treatment sequencing and patients' PASI at every visit from April 2006 to December 2020 were collected. Patterns of biologic-switching were examined. The speed of treatment response for each biologic was determined by the time to achieve PASI-90 and -100 for each treatment course. RESULTS: A total of 440 treatment courses were analysed. Ustekinumab and adalimumab were the most frequently prescribed first-line biologics. The highest proportion of biologic-switching was observed among patients on TNF-α inhibitors (63.8%). After 2015, more patients were prescribed IL-12/23 and IL-17 inhibitors in favour of TNF-α inhibitors. IL-17 inhibitors demonstrated the most rapid treatment response and low PASI scores relative to other biologics. Patients who did not switch biologics had lower rates of psoriatic arthritis and lower BMI, compared to patients who switched biologics. The median PASI on discontinuation generally exceeded 3.0, while on continuation, it was less than 1.2, reflecting patients' and clinicians' thresholds for biologic-switching. CONCLUSIONS: This study demonstrates an increased uptake of more novel biologics as they become available, due to improved safety profiles and clinical outcomes.

Drug survival of biologics in psoriasis: An Australian multicentre retrospective study.

BACKGROUND: Drug survival, which refers to the time from treatment initiation to discontinuation, provides a surrogate measure of the effectiveness of a biologic in a real-world setting (J Invest Dermatol, 2015, 135, 1). The aim of this study was to determine the drug survival of biologics that are currently available in Australia. We also analysed the treatment efficacy of these biologics and reasons for discontinuation. METHODS: Retrospective data from outpatient Dermatology biologic clinics in Westmead Hospital and Royal Prince Alfred Hospital (Sydney, Australia) from April 2006 to December 2020 were collected. Kaplan-Meier analysis was used to calculate drug survival. RESULTS: A total of 306 patients who underwent 566 treatment courses were analysed. Guselkumab was observed to have the longest drug survival, with cumulative drug survival rates of 94.2% ± 4.0 at 1- and 5-years. This was followed by ixekizumab which had a 1-year survival rate of 87.2% ± 4.5 and 5-year survival rate of 59.4% ± 9.5. Ixekizumab and guselkumab were also noted to have superior treatment efficacy compared with other biologics, with PASI-75 rates of 94.9% and 93.8%, respectively. The most common reasons for treatment discontinuation were a lack of initial efficacy to treatment and a loss of efficacy over time despite an initial response, respectively. CONCLUSION: To our knowledge, this is the first Australian study to report on outcomes of multiple new biologics that are currently in use for the treatment of chronic plaque psoriasis. Overall, this study provides insight into patterns of care from a local experience that may help guide the management of moderate-to-severe psoriasis.

Scoping review of systematic reviews of nursing interventions in a neonatal intensive care unit or special care nursery.

AIM(S): To identify, synthesise and map systematic reviews of the effectiveness of nursing interventions undertaken in a neonatal intensive care unit or special care nursery. DESIGN: This scoping review was conducted according to the JBI scoping review framework. METHODS: Review included systematic reviews that evaluated any nurse-initiated interventions that were undertaken in an NICU or SCN setting. Studies that reported one or more positive outcomes related to the nursing interventions were only considered for this review. Each outcome for nursing interventions was rated a 'certainty (quality) of evidence' according to the Grading of Recommendations, Assessment, Development and Evaluations criteria. DATA SOURCES: Systematic reviews were sourced from the Cochrane Database of Systematic Reviews and Joanna Briggs Institute Evidence Synthesis for reviews published until February 2023. RESULTS: A total of 428 articles were identified; following screening, 81 reviews underwent full-text screening, and 34 articles met the inclusion criteria and were included in this review. Multiple nursing interventions reporting positive outcomes were identified and were grouped into seven categories. Respiratory 7/34 (20%) and Nutrition 8/34 (23%) outcomes were the most reported categories. Developmental care was the next most reported category 5/34 (15%) followed by Thermoregulation, 5/34 (15%) Jaundice 4/34 (12%), Pain 4/34 (12%) and Infection 1/34 (3%). CONCLUSIONS: This review has identified nursing interventions that have a direct positive impact on neonatal outcomes. However, further applied research is needed to transfer this empirical knowledge into clinical practice. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Implementing up-to-date evidence on effective nursing interventions has the potential to significantly improving neonatal outcomes. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement in this scoping review.

Secukinumab treatment showed improved quality of life in patients with chronic plaque psoriasis in Australia: Results from the HOPE study.

BACKGROUND: Psoriasis imposes a disease burden that can have a profound negative impact on patients' quality of life (QoL). HOPE was the first non-interventional study conducted in patients with severe chronic plaque psoriasis in Australia that evaluated health-related QoL in response to treatment with secukinumab. METHODS: HOPE was a prospective, open-label, single-arm, multicentre, non-interventional, exploratory study in patients with severe chronic plaque psoriasis in Australia. The study investigated the change in QoL, using the Dermatology Life Quality Index (DLQI), Assessment Quality of Life-8 Dimension questionnaire (AQoL-8D) and Psoriasis Area and Severity Index (PASI), and safety profile in response to treatment with secukinumab 300 mg SC weekly for 4 weeks followed by monthly maintenance for 58 weeks. RESULTS: At Week 14, the mean percentage reduction in total DLQI score from baseline was -82.4% (n = 65), which indicates a substantial improvement in QoL. This level of improvement was sustained up to Week ≥58, with a mean percentage change of -87.4%. The mean percentage change from baseline for AQoL-8D weighted total score decreased from Week 14 (41.1%) to Week 58 (35.2%), indicating an improvement in patients' QoL. A high proportion of patients achieved PASI 75/90/100 responses at Week 14 (97.0%/71.2%/34.8%), with rates sustained up to Week ≥58 (100%/87.9%/43.1%). The safety profile of secukinumab was favourable, with no cumulative or unexpected safety concerns. CONCLUSION: Secukinumab treatment demonstrated a striking improvement in patients' QoL in the HOPE study, the first real-world study in patients with severe chronic plaque psoriasis in the Australian clinical setting.

Novel combination biologic therapy for recalcitrant psoriasis and psoriatic arthritis in a medically complex patient.

For patients who do not achieve adequate disease control on biologic monotherapy, or monotherapy with an oral-systemic agent such as methotrexate, combination biologic therapy may be considered. To the best of our knowledge, we report the first case assessing the safety and efficacy of the combination of an interleukin-23 (IL-23) inhibitor (risankizumab) with a tumour necrosis factor-α (TNF-α) inhibitor (golimumab) in the treatment of psoriasis and psoriatic arthritis. After twelve months of treatment with risankizumab and golimumab, our patient experienced a significant improvement in his psoriasis and psoriatic arthritis without any adverse effects to date.

Chagas disease in the United Kingdom: A review of cases at the Hospital for Tropical Diseases London 1995-2018. The current state of detection of Chagas disease in the UK.

BACKGROUND: Chagas disease (CD), is a parasitic disease endemic in Latin America. Presentation in non-endemic areas is either in the asymptomatic indeterminate phase or the chronic phase with cardiac and/or gastrointestinal complications. METHODS: The Hospital for Tropical Diseases (HTD) based in central London, provides tertiary care for the management of CD. We reviewed all cases managed at this centre between 1995 and 2018. RESULTS: Sixty patients with serologically proven CD were identified. Most were female (70%), with a median age at diagnosis of 41 years. Three quarters of the patients were originally from Bolivia. 62% of all patients were referred to the HTD by their GP. Nearly half of the patients were asymptomatic (47%). Twelve patients had signs of cardiac involvement secondary to CD. Evidence of gastrointestinal damage was established in three patients. Treatment was provided at HTD for 31 patients (47%). Most patients (29) received benznidazole, five of them did not tolerate the course and were switched to nifurtimox. Of the seven patients receiving this second line drug, five completed treatment, whilst two interrupted it due to side effects. CONCLUSIONS: Despite the UK health system having all the resources required to diagnose, treat and follow up cases, there is lack of awareness of CD, such that the vast majority of cases remain undiagnosed and therefore do not receive treatment. We propose key interventions to improve the detection and management of this condition in the UK, especially in pregnant women and neonates.

Clinical and Diagnostic Features of 413 Patients Treated for Imported Strongyloidiasis at the Hospital for Tropical Diseases, London.

This study describes the clinical features of a cohort of imported cases of strongyloidiasis and the performance of standard diagnostic techniques for this condition. A total of 413 cases were identified, of whom 86 had microscopically proven infection. In proven cases, 23% had normal eosinophil counts, 19% had negative Strongyloides-specific serology, and 9.3% had normal blood counts and were seronegative. Serological testing was less sensitive for returning travelers (46.2%) than for migrants (89.7%). Immunosuppression, including human T-cell lymphotropic virus 1, was significantly associated with proven infection after controlling for age, presence of symptoms, duration of infection, and eosinophilia (OR 5.60, 95% CI 1.54-20.4). Patients with proven infection had lower serology values than those diagnosed with strongyloidiasis on the basis of positive serology and eosinophilia alone (P = 0.016). Symptomatic patients were significantly younger, had a shorter presumed duration of infection, and lower serology values. These data suggest a correlation between immunologic control of strongyloidiasis and the amplitude of the humoral response.

Immune Toxicity with Checkpoint Inhibition for Metastatic Melanoma: Case Series and Clinical Management.

Immune checkpoint inhibitors (anti-PD-1 and anti-CTLA-4 antibodies) are a standard of care for advanced melanoma. Novel toxicities comprise immune-related adverse events (irAE). With increasing use, irAE require recognition, practical management strategies, and multidisciplinary care. We retrospectively evaluated the incidence, kinetics, and management of irAE in 41 patients receiving anti-PD-1 antibody therapy (pembrolizumab) for advanced melanoma. 63% received prior anti-CTLA-4 antibody therapy (ipilimumab). IrAE occurred in 54%, most commonly dermatological (24%), rheumatological (22%), and thyroid dysfunction (12%). Thyroiditis was characterised by a brief asymptomatic hyperthyroid phase followed by a symptomatic hypothyroid phase requiring thyroxine replacement. Transplant rejection doses of methylprednisolone were necessary to manage refractory hepatotoxicity. A bullous pemphigoid-like skin reaction with refractory pruritus responded to corticosteroids and neuropathic analgesia. Disabling grade 3-4 oligoarthritis required sulfasalazine therapy in combination with steroids. The median interval between the last dose of anti-CTLA-4 antibody and the first dose of anti-PD-1 therapy was 2.0 months (range: 0.4 to 22.4). Toxicities may occur late; this requires vigilance and multidisciplinary management which may allow effective anticancer therapy to continue. Management algorithms for thyroiditis, hypophysitis, arthralgia/arthritis, colitis, steroid-refractory hepatitis, and skin toxicity are discussed.

Comparison of skin cancers in liver and renal transplant recipients: Results of a prospective study in an Australian tertiary referral centre.

BACKGROUND/OBJECTIVES: Organ transplant recipients (OTR) have an increased risk of skin cancers compared with the general population. METHODS: A prospective study of renal (RTR) and liver transplant recipients (LTR) was conducted in a single New South Wales tertiary referral centre over 60 months. Initial and subsequent visit data were recorded in our transplant database. Only patients with a minimum of 11 months follow up were included. RESULTS: Altogether 142 RTR and 88 LTR were included in the analysis. Compared with RTR, the median age of liver transplant recipients was higher (64 vs 57 years), more men were patients (73 vs 60%) and there were higher rates of high-risk skin types (54 vs 33%) and heavy sun exposure (43 vs 30%). RTR developed 304 non-melanoma skin cancers (NMSC) with a squamous cell carcinoma:basal cell carcinoma ratio of 1.7:1. LTR developed 205 NMSC with a squamous cell carcinoma:basal cell carcinoma ratio of 1.6:1. The odds ratio of developing NMSC in LTR:RTR was 1.8:1 (95% CI: 1.02-3.11, P = 0.044) on univariate analysis but there was no difference on multivariate analysis. A previous history of NMSC, age, time from transplant from first visit, skin phenotype and previous sun exposure were significant risk factors for developing NMSC. CONCLUSIONS: Liver transplant recipients are not at a lower risk of NMSC than RTR. Our study supports routine and regular post-transplant skin surveillance of all LTR, like other OTR.

Chemical peels: A review of current practice.

Chemical peels belong to a group of cutaneous resurfacing procedures that are used in the treatment of photoageing, inflammatory dermatoses, epidermal proliferations, pigmentary disorders and scarring. This review describes best current practice, highlights recent advances in chemical peel technology and discusses the recommended uses for different peel types. It also presents the results of a survey of the chemical peeling practices of 30 Australian dermatologists.

The changing aetiology of eosinophilia in migrants and returning travellers in the Hospital for Tropical Diseases, London 2002-2015: An observational study.

INTRODUCTION: Determining the cause of eosinophilia in patients returning from the tropics continues to present a diagnostic challenge. The history, symptoms and degree of eosinophilia are often poor predictors of eventual diagnosis, but helminths are an important cause. The current British Infection Association recommendations use travel history to guide investigation of eosinophilia. However the global burden of helminth disease and travel patterns have changed over the last 3 decades and guidelines based on previous epidemiology need to be reviewed in the light of current data. METHODS: Consecutive patients presenting with, or referred for, investigation of eosinophilia were identified prospectively. Case notes, laboratory results and electronic records were reviewed for demographic and clinical data. Patients with an eosinophil count ≥0.50 × 109/L were included, and grouped based on lifetime history of travel to: West Africa, elsewhere in Africa, and the rest of the world. Results were compared to published data from 1997 to 2002 collected at the same centre. RESULTS: Of 410 patients who met the inclusion criteria, 407 had a documented travel history. Average yearly referrals for eosinophilia fell from 58 per year between 1997 and 2002, to 33 per year (2002-2015). The proportion of eosinophilia cases diagnosed with a parasitic cause fell from 64% to 50%, and yields for all parasitological investigations fell, the largest reduction in stool microscopy (20% yield to 9%) and day bloods for microfilariae (14% yield to 3%). Strongyloides stercoralis was the commonest diagnosis overall in our cohort, accounting for 50% of the total parasites diagnosed, and was present in 38% of patients from West Africa, 19% from rest of Africa, and 34% from rest of world; a relative increase compared to previous data. Schistosomiasis is slightly less common in those who had travelled to West Africa than the rest of Africa, and overall point prevalence has fallen from 33% (1997-2002) to 17% (2002-2015). Travellers were significantly less likely than patients who had immigrated to the UK to be diagnosed with any parasite (OR 0.54 95% CI 0.378-0.778 p = 0.0009). DISCUSSION: A parasitic cause will still be found in half of people returning from the tropics with an eosinophilia, but we observed a fall in the overall prevalence of parasitic diagnoses when compared with the earlier data. This may, in part, be explained by the impact of control programmes on the prevalence of parasites globally, especially filarial disease. S. stercoralis now represents the majority of parasites diagnosed in our cohort from all continents. We identified significantly higher rates of strongyloidiasis in immigrants than returning travellers. Despite the falling yields of stool microscopy and filarial serology the current guidelines based on travel history remain relevant with adequate yield.