Incidence and nature of adverse drug events in paediatric intensive care units: A prospective multicentre study.

AIMS: The aim of this study was to assess the incidence, nature, preventability and severity of adverse drug events (ADEs) across three paediatric intensive care units (PICUs) in England. METHODS: A prospective observational cohort study was conducted across three PICUs over a three-month period during 2019. Included patients were aged ≤18 years and stayed in PICU for a minimum of 24 hours. Identification of suspected ADEs was performed by trained PICU pharmacists. A multidisciplinary expert panel assessed causality, preventability and severity of events. RESULTS: A total of 302 patients were included and 62 ADEs were confirmed (definite/probable causality). One in six patients experienced one or more ADEs. The estimated incidence of ADEs were 20.5 per 100 patients (95% CI 15.3-27.5) and 16.7 per 1000 patient-days (95% CI 9.3-29.9). The majority of ADEs were judged preventable by the expert panel (36/62, 58.1%). ADEs were commonly involved with medicines prescribing (29/62, 46.8%) and caused temporary patient harm (42/62, 67.7%). Medications for the central nervous system (14/62, 22.6%), infections (13/62, 20.9%) and cardiovascular system (12/62, 19.4%) were commonly implicated with ADEs. Multivariable analysis revealed that patients who stayed in PICU for ≥7 days (OR 6.29, 95% CI 2.42-16.32) were more likely to experience an ADE compared to patients with a stay of 1-6 days. CONCLUSION: ADEs are common in English PICUs and most of them may be preventable. There is a strong association between ADE occurrence and duration of PICU stay, which represents a target for remedial interventions. Exploring contributory factors of preventable ADEs is now necessary to inform preventive policies.

Targetoid spongiotic reaction pattern: A case series of seven paediatric patients.

We present seven cases of a targetoid eruption, clinically mimicking erythema multiforme, occurring in paediatric patients aged 12 months to 14 years. All patients presented with a pruritic targetoid eruption on body and acral sites which spared mucosal areas. All patients demonstrated a spongiotic reaction pattern on histology without lichenoid change and demonstrated excellent responses to either oral prednisolone or topical corticosteroids. We propose the term 'targetoid spongiotic reaction pattern (TSRP)' for our subset of paediatric patients. We review the literature regarding targetoid eruptions in the paediatric population.

Maturity and medical students' ease of transition into the clinical environment.

BACKGROUND: Medical education has been characterized in terms of points of transition, which are accentuated by lack of relevant prior experience and can lead to extreme positive and negative emotions. AIMS: Quantify the effect of maturity on medical students' transitions into the clinical environment and identify how experiences of transition might be improved. METHOD: Eleven weeks after entering the clinical environment, 29 mature students (age over 21 at entry, median age 22) in a horizontally-integrated, predominantly undergraduate entry, problem-based curriculum offering little early clinical exposure and 58 matched non-mature students (median age 18 years) rated their experiences of transition and wrote free text comments about them. RESULTS: 62% of mature students compared with 24% of controls described 'good transitions' (odds ratio [OR] for a good transition 6.1; p = 0.002) and mature students were more likely than controls to describe how they drew on their previous years in medical school (OR 2.7, p = 0.04) and their wider life experiences in making the transition (OR 3.9, p = 0.01). They were less likely to feel confused or daunted. Whether mature or not, prior workplace experience, having learned the theory of medicine by PBL, and being confident in their knowledge and skills helped students' transitions. Both mature and non-mature students valued the support of teachers and peers and would have valued clinical experience earlier. CONCLUSIONS: The fact that just a few extra years of life experience made such a large difference to students' experiences of transition illustrates how important social factors are in the personal development of medical students. In respondents' views, early clinical experience and early skills training could ease students' passage into the clerkship phase of their education.

Refractory subacute cutaneous lupus erythematosus successfully treated with rituximab.

A 48-year-old woman presented with pruritic, scaly, annular plaques over her upper back and chest that were clinically, serologically and histologically characteristic of subacute cutaneous lupus erythematosus (SCLE). She failed to respond to conventional treatment, which included high-dose hydroxychloroquine, methotrexate, prednisolone, chloroquine, acitretin, thalidomide, dapsone and azathioprine. Subsequently treated with intravenous rituximab 375 mg/m(2) weekly for 4 weeks, she remained on adjuvant oral hydrochloroquine 600 mg daily and topical clobetasol propionate 0.05% ointment as required. Clearing of annular plaques was noted 8 weeks after the initial course of rituximab. By 12 weeks there were no new lesions and only post-inflammatory hyperpigmentation remained. Both hyper- and hypopigmentation, which is more common, are consistent with SCLE lesion regression. Skin lesions recurred 11 months later; however, no further lesions occurred after re-introduction of rituximab therapy. The treatment was well tolerated. A maintenance regimen of rituximab, 375 mg/m(2) every 8 weeks for 2 years, was commenced 3 months after completing the second course of treatment, with ongoing disease remission. Rituximab appears to have activity in refractory SCLE and clinical trials are required to further assess this potential therapy.

Successful surgical management of lipoedematous alopecia.

A 67-year-old Caucasian woman presented with an area of alopecia over the right occipital scalp, which had slowly expanded over the last 10 years. The skin beneath the alopecia felt soft and boggy although the epidermis looked unremarkable. Ultrasound showed thickening of the underlying subcutaneous tissue. Scalp histology showed enlarged fat lobules within the subcutis that infiltrated along fibrous tracts into the mid-dermis. There was a complete loss of hair follicles. These findings were consistent with lipoedematous alopecia of the scalp. Surgical debulking with scalp reduction produced an acceptable result in our patient with no evidence of relapse after 12 months.

Distinct clinical and pathological features are associated with the BRAF(T1799A(V600E)) mutation in primary melanoma.

The BRAF(T1799A) mutation encodes BRAF(V600E) that leads to activation of the mitogen-activated protein kinase pathway. This study aimed to assess the clinico-pathological features of primary invasive melanomas containing the BRAF(T1799A) mutation. Patients (n=251) with invasive primary melanomas from Australia were interviewed and examined with respect to their melanoma characteristics and risk factors. Independent review of pathology, allele-specific PCR for the BRAF(T1799A) mutation, immunohistochemical staining with Ki67, and phospho-histone-H3 (PH3) were performed. The BRAF(T1799A) mutation was found in 112 (45%) of the primary melanomas. Associations with the BRAF(T1799A) mutation (P<0.05) were as follows: low tumor thickness (odds ratio (OR)=3.3); low mitotic rate (OR=2.0); low Ki67 score (OR=5.0); low PH3 score (OR=3.3); superficial spreading melanoma (OR=10.0); pigmented melanoma (OR=3.7); a lack of history of solar keratoses (OR=2.7); a location on the trunk (OR=3.4) or extremity (OR=2.0); a high level of self-reported childhood sun exposure (OR=2.0); < or =50 years of age (OR=2.5); and fewer freckles (OR=2.5). We conclude that the BRAF(T1799A) mutation has associations with host phenotype, tumor location, and pigmentation. Although implicated in the control of the cell cycle, the BRAF(T1799A) mutation is associated with a lower rate of tumor proliferation.

Clinical and histological spectrum of elastotic changes induced by penicillamine.

A 79-year-old-man with cystinuria requiring long-term penicillamine therapy presented with a 6-month history of itchy annular lesions in both axillae. Clinical examination revealed lesions consisting of crusted keratotic papules coalescing in an annular distribution. Associated findings included generalized skin laxity accentuated on the upper trunk and arms, as well as small yellowish papules on the neck. Histological evaluation revealed short, thick, eosinophilic elastic fibres with nodular protrusions. Transepidermal elimination of abnormal elastic fibres was also evident. We discuss the histological and clinical spectrum of penicillamine-induced elastotic changes and compare these changes to those seen in primary elastotic disorders.