Identification of proteins associated with development of metastasis from cutaneous squamous cell carcinomas (cSCCs) via proteomic analysis of primary cSCCs.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers capable of metastasizing. Proteomic analysis of cSCCs can provide insight into the biological processes responsible for metastasis, as well as future therapeutic targets and prognostic biomarkers. OBJECTIVES: To identify proteins associated with development of metastasis in cSCC. METHODS: A proteomic-based approach was employed on 105 completely excised, primary cSCCs, comprising 52 that had metastasized (P-M) and 53 that had not metastasized at 5 years post-surgery (P-NM). Formalin-fixed, paraffin-embedded cSCCs were microdissected and subjected to proteomic profiling after one-dimensional (1D), and separately two-dimensional (2D), liquid chromatography fractionation. RESULTS: A discovery set of 24 P-Ms and 24 P-NMs showed 144 significantly differentially expressed proteins, including 33 proteins identified via both 1D and 2D separation, between P-Ms and P-NMs. Several differentially expressed proteins were also associated with survival in SCCs of other organs. The findings were verified by multiple reaction monitoring on six peptides from two proteins, annexin A5 (ANXA5) and dolichyl-diphosphooligosaccharide-protein glycosyltransferase noncatalytic subunit (DDOST), in the discovery group and validated on a separate cohort (n = 57). Increased expression of ANXA5 and DDOST was associated with reduced time to metastasis in cSCC and decreased survival in cervical and oropharyngeal cancer. A prediction model using ANXA5 and DDOST had an area under the curve of 0·93 (confidence interval 0·83-1·00), an accuracy of 91·2% and higher sensitivity and specificity than cSCC staging systems currently in clinical use. CONCLUSIONS: This study highlights that increased expression of two proteins, ANXA5 and DDOST, is significantly associated with poorer clinical outcomes in cSCC.

Surgical tuition within Irish hospitals: a national survey.

INTRODUCTION: The General Medical Council (GMC) of the UK states that doctors have a duty to train and contribute to the education of colleagues, and that those involved in formal clinical teaching should have a teaching qualification. OBJECTIVES: We sought to evaluate the current levels of engagement of surgical trainees and recently appointed surgical consultants in clinical teaching. METHODS: All trainees who commenced a basic or higher surgical training post during or after 2007 were invited to participate. The electronic questionnaire was administered using the survey tool GetFeedback, collecting information regarding subspecialty, current role, quantity of teaching that respondents engaged in and who they taught and teaching motivations and barriers. RESULTS: There were 128 respondents out of 358 invitations to participate (36% response rate). Less than half (39%) of respondents had attended formal courses on clinical education. Over 70% of respondents engaged in clinical teaching for two or more hours each week. A lack of time and resources were noted as barriers to engaging in teaching. We found a low number of those involved in teaching seeking feedback after teaching sessions. CONCLUSION: In surgery, the apprenticeship model is still the framework for developing the surgeons of the future. In attempting to produce a highly skilled workforce for the future, we rely on those in senior positions to train those coming through; higher surgical trainees are relied on to teach the core surgical trainees and so on. Our study shows a low level of formalisation of this model.

STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin- and mucosa-derived cell types: implications in neoplastic and inflammatory skin diseases.

BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS: Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

Maternal stress and psychological distress preconception: association with offspring atopic eczema at age 12 months.

BACKGROUND: Perinatal maternal stress and low mood have been linked to offspring atopic eczema. OBJECTIVES: To examine the relation of maternal stress/mood with atopic eczema in the offspring, focusing particularly on stress/psychological distress preconception. METHODS: At recruitment in the UK Southampton Women's Survey, preconception maternal reports of perceived stress in daily living and the effect of stress on health were recorded; in a subsample, psychological distress was assessed (12-item General Health Questionnaire). Infants were followed up at ages 6 (n = 2956) and 12 (n = 2872) months and atopic eczema ascertained (based on UK Working Party Criteria for the Definition of Atopic Dermatitis). At 6 months post-partum, mothers were asked if they had experienced symptoms of low mood since childbirth and completed the Edinburgh Postnatal Depression Scale. RESULTS: Preconception perceived stress affecting health [OR 1.21 (95% CI 1.08-1.35), P = 0.001] and stress in daily living [OR 1.16 (1.03-1.30), P = 0.014] were associated with an increased risk of offspring atopic eczema at age 12 months but not at 6 months, robust to adjustment for potentially confounding variables. Findings were similar for maternal psychological distress preconception. Low maternal mood between delivery and 6 months post-partum was associated with an increased risk of infantile atopic eczema at age 12 months, but no significant association between post-natal mood and atopic eczema was seen after taking account of preconception stress. CONCLUSION AND CLINICAL RELEVANCE: Our data provide novel evidence linking maternal stress at preconception to atopic eczema risk, supporting a developmental contribution to the aetiology of atopic eczema and pointing to potentially modifiable influences.

Particulate and non-particulate steroids in spinal epidurals: a systematic review and meta-analysis.

BACKGROUND: Steroids in transforaminal epidural injections are widely used to ease radicular pain in both cervical and lumbar radiculopathy. Concerns have been articulated about the use of particulate steroids for this intervention, as a number of case reports have been published linking them with post procedural paralysis, possibly due to spinal ischaemia secondary to a steroid particulate embolism. Non-particulate, or soluble steroids, are mooted as an alternative; however, their effectiveness relative to particulate steroids has not been conclusively proven. STUDY DESIGN: We review the evidence in the published literature regarding the efficacy of non-particulate steroids in epidural injections compared to particulate steroids, and synthesise it to gauge the qualitative outcomes from level one evidence (visual analogue scales, numerical pain scores and Oswestry Disability Index) from baseline to specified follow up. METHODS: The PRISMA guidelines were utilised for this review. An internet search was performed to collate the available literature from medical databases PubMed, EMBASE, Web of Science and the Cochrane library. We used a broad search term [epidural (and) steroid] to ensure a wide capture of articles. No limitations in terms of language or date of publication were implemented. The reference lists of articles included for full text review were searched for any additional primary or review publications. RESULTS: Four online libraries were searched, with a combined total of 11,353 titles reviewed, not excluding duplicates. Post title abstract and full text review, nine articles were identified as suitable for inclusion for qualitative synthesis. Four of these were suitable for quantitative synthesis, with a total of 300 participants, 147 in the particulate group and 153 in the non-particulate group. Using a random effects model, the pooled standard mean difference of VAS score diminution was not significant between groups (0.31 in favour of particulates, 95 % CI -0.68 to 1.30). From our qualitative synthesis, there was a trend for greater improvement in pain scores within the particulate group. The type of steroid used did not appear to have an effect on the disability score given by patients. CONCLUSION: Particulate steroids are not demonstrably better in relieving pain compared to their non-particulate counterparts. In view of the concerns over the safety profile of particulate steroids, it may be prudent to switch to non particulates, or at the very least the dangers and alternatives should be flagged with the patient group as part of a shared decision making process.

Measuring the Effect of Carers on Patients' Risk of Adverse Healthcare Outcomes Using the Caregiver Network Score.

BACKGROUND: Although caregivers are important in the management of frail, community-dwelling older adults, the influence of different caregiver network types on the risk of adverse healthcare outcomes is unknown. OBJECTIVE: To examine the association between caregiver type and the caregiver network subtest of The Risk Instrument for Screening in the Community (RISC), a five point Likert scale scored from one ("can manage") to five ("absent/liability"). To measure the association between caregiver network scores and the one-year incidence of institutionalisation, hospitalisation and death. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: Community-dwelling adults, aged >65, attending health centres in Ireland, (n=779). PROCEDURE AND MEASUREMENTS: The caregiver network subtest of the RISC was scored by public health nurses. Caregivers were grouped dichotomously into low-risk (score of one) or high-risk (scores two-five). RESULTS: The majority of patients had a primary caregiver (582/779; 75%), most often their child (200/582; 34%). Caregiver network scores were highest, indicating greatest risk, when patients had no recognised primary caregiver and lowest when only a spouse or child was available. Despite this, patients with a caregiver were significantly more likely to be institutionalised than those where none was required or identified (11.5% versus 6.5%, p=0.047). The highest one-year incidence of adverse outcomes occurred when state provided care was the sole support; the lowest when private care was the sole support. Significantly more patients whose caregiver networks were scored high-risk required institutionalisation than low-risk networks; this association was strongest for perceived difficulty managing medical domain issues, odds ratio (OR) 3.87:(2.22-6.76). Only perceived difficulty managing ADL was significantly associated with death, OR 1.72:(1.06-2.79). There was no association between caregiver network scores and risk of hospitalisation. CONCLUSION: This study operationalizes a simple method to evaluate caregiver networks. Networks consisting of close family (spouse/children) and those reflecting greater socioeconomic privilege (private supports) were associated with lower incidence of adverse outcomes. Caregiver network scores better predicted institutionalisation than hospitalisation or death.

Mental health outcomes at age 11 of very low birth weight infants in Ireland.

Aim To compare mental health (MH) outcomes of and service use by children born under 1500 g in Ireland with a matched control group. METHOD: Using a retrospective cohort design, semi-structured and standardised MH assessments were conducted with parents, teachers and youth. RESULTS: A total of 64 of 127 surviving children from a very low birth weight (VLBW) cohort from a National Maternity Hospital participated at a mean age of 11.6 years (s.d. 1.0), along with 51 matched controls. More VLBW children received clinical or borderline scores when rated by parents [χ 2 (1, n=114)=7.3, p=0.007] or youths [χ 2 (1, n=114)=4.83, p=0.028], but not by teachers [χ 2 (1, n=114)=1.243, p=0.463]. There was no increase in the use of MH services. A main effect of birth weight remained on the parent Strengths and Difficulties Questionnaire [F (1, 88)=5.07, p<0.05) after controlling for intelligence quotient (IQ) and socio-economic status (SES), but only on hyperactivity in males. SES, rather than IQ or birth weight, predicted identification of problems by teachers [F (1, 82)=6.99, p=0.01). Interpretations Teachers miss MH difficulties and are influenced more by SES than by IQ or birth weight. This has implications for MH service access. Initial perinatal investment needs to be matched with ongoing surveillance and psychoeducation to ensure that disorders are recognised early and offered appropriate interventions.

Growth and hormone profiling in children with congenital melanocytic naevi.

BACKGROUND: Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are described in germline RASopathies, but growth and hormone status have not previously been investigated in individuals with CMN. OBJECTIVES: To explore premature thelarche, undescended testes, and a clinically abnormal fat distribution with CMN through prospective endocrinological assessment of a cohort of subjects with CMN, and a retrospective review of longitudinal growth of a larger group of patients with CMN from outpatient clinics (which included all subjects in the endocrinological assessment group). PATIENTS AND METHODS: Longitudinal growth in a cohort of 202 patients with single or multiple CMN was compared with the U.K. National Child Measurement Programme 2010. Forty-seven children had hormonal profiling including measurement of circulating luteinizing hormone, follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, growth hormone, prolactin, pro-opiomelanocortin, estradiol, testosterone, cortisol, thyroxine, insulin-like growth factor-1 and leptin; 10 had oral glucose tolerance testing 25 had dual-energy X-ray absorptiometry scans for body composition. RESULTS: Body mass index increased markedly with age (coefficient 0·119, SE 0·016 standard deviation scores per year), at twice the rate of the U.K. population, due to increased adiposity. Three per cent of girls had premature thelarche variant and 6% of boys had persistent undescended testes. Both fat and muscle mass were reduced in areas underlying large naevi, resulting in limb asymmetry and abnormal truncal fat distribution. Anterior pituitary hormone profiling revealed subtle and variable abnormalities. Oral glucose tolerance tests revealed moderate-severe insulin insensitivity in five of 10, and impaired glucose tolerance in one. CONCLUSIONS: Interpersonal variation may reflect the mosaic nature of this disease and patients should be considered individually. Postnatal weight gain is potentially related to the underlying genetic defect; however, environmental reasons cannot be excluded. Naevus-related reduction of fat and muscle mass suggests local hormonal or metabolic effects on development or growth of adjacent tissues, or mosaic involvement of these tissues at the genetic level. Premature thelarche and undescended testes should be looked for, and investigated, as for any child.

Identification of translational dermatology research priorities in the U.K.: results of an electronic Delphi exercise.

BACKGROUND: Translational research is the direct application of basic and applied research to patient care. It is estimated that there are at least 2000 different skin diseases; thus, there are considerable challenges in seeking to undertake research on each of these disorders. OBJECTIVES: This electronic Delphi (e-Delphi) exercise was conducted in order to generate a list of translational dermatology research questions that are regarded as a priority for further investigations. METHODS: During the first phase of the e-Delphi exercise, 228 research questions were generated by an expert panel that included clinical academic dermatologists, clinical dermatologists, nonclinical scientists, dermatology trainees and representatives from patient support groups. RESULTS: Following completion of the second and third phases, 40 questions on inflammatory skin disease, 20 questions on structural skin disorders/genodermatoses, 37 questions on skin cancer and eight miscellaneous questions were designated as priority translational dermatology research questions (PRQs). In addition to PRQs on a variety of disease areas (including multiple PRQs on psoriasis, eczema, squamous cell carcinoma and melanoma), there were a number of cross-cutting themes that identified a need to investigate mechanisms/pathogenesis of disease and the necessity to improve treatments for patients with skin disease. CONCLUSIONS: It is predicted that this list of PRQs will help to provide a strategic direction for translational dermatology research in the U.K. and that addressing this list of questions will ultimately provide clinical benefit for substantial numbers of patients with skin disorders.

TSH-secreting pituitary adenoma: benefits of pre-operative octreotide.

UNLABELLED: TSH-secreting pituitary adenomas are rare and the optimal investigation and management is uncertain. We describe a case of a 43 year-old woman with a TSH-secreting pituitary adenoma, highlighting diagnostic testing and our use, pre-operatively of somatostatin analogue therapy, which induced biochemical euthyroidism and a reduction in tumour size. LEARNING POINTS: The differential diagnosis of the syndrome of inappropriate TSH secretion is non-thyroidal illness, medications, assay interference due to heterophilic antibodies, thyroid hormone resistance and TSH-secreting pituitary adenoma.TRH stimulation test and triiodothyronine suppression test assist in differentiating thyroid hormone resistance and TSH-secreting pituitary adenoma.Somatostatin analogue therapy can induce biochemical euthyroidism and reduce tumour size.

Clinical, neuropathological and radiological evidence for a rare complication of rituximab therapy.

We report a rare case of myofasciitis and meningitis with deafness caused by systemic enterovirus infection in the setting of hypogammaglobulinaemia induced by rituximab. Whilst effective and generally safe, anti- CD 20 antibody therapy is increasingly recognised to result in unusual infectious complications to be considered in a treated patient presenting with neurological symptoms. These cases may pose diagnostic difficulties and can have atypical presentations. We present this rare complication of rituximab therapy, with histopathological confirmation of myofasciitis. In the older literature, enterovirus associated myofasciitis may have erroneously been termed dermatomyositis and we review the literature to demonstrate this important nosological point.

Limited exposure to ambient ultraviolet radiation and 25-hydroxyvitamin D levels: a systematic review.

Vitamin D can be synthesized following exposure to ultraviolet radiation (UVR), ingested in the diet or provided through oral supplementation. The medical literature frequently states that humans obtain most of their vitamin D from sunshine and that UVR exposure is essential to maintain vitamin D levels. A systematic review was conducted to determine the requirement for UVR in maintaining adequate (> 50 nmol L(-1) ) serum 25-hydroxyvitamin D [25(OH)D] levels. Studies reporting serum 25(OH)D during situations of negligible UVR exposure were sought. Forty-one studies (from a search yielding 42 698 articles) with a total of 4211 healthy adults met the inclusion criteria, providing 56 datasets from different population groups. Over 50% of subjects had > 50 nmol L(-1) 25(OH)D in 10 of 19 datasets reporting winter levels in areas with limited UVR. In addition, > 50% of subjects had adequate 25(OH)D levels in four of 12 datasets from polar regions during periods of negligible UVR, one of nine datasets documenting clothing-related minimal UVR and two of eight datasets detailing employment-related minimal UVR. The data demonstrate that many adults maintain adequate serum vitamin D levels despite negligible UVR exposure for several months. However, we acknowledge that preceding UVR exposure leading to vitamin D storage and delayed release may account for this maintenance of adequate serum vitamin D levels. There remains a need for further research on whether UVR exposure is required for longer-term maintenance of adequate vitamin D levels.

Components of the Risk Instrument for Screening in the Community (RISC) that Correlate with Public Health Nurses' Perception of Risk.

BACKGROUND: Functional decline and frailty are common in community-dwelling older adults, leading to an increased risk of adverse outcomes. OBJECTIVE: To examine the factors that public health nurses perceive to cause risk of three adverse outcomes: institutionalisation, hospitalisation, and death, in older adults, using the Risk Instrument for Screening in the Community (RISC). DESIGN: A quantitative, correlational, descriptive design was used. SETTING AND PARTICIPANTS: A sample of 803 community-dwellers, aged over 65 years receiving regular follow-up by public health nurses. Procedure and Measurements: Public health nurses (n=15) scored the RISC and the Clinical Frailty Scale (CFS) on patients in their caseload. We examined and compared correlations between the severity of concern and ability of the caregiver network to manage these concerns with public health nurses' perception of risk of the three defined adverse outcomes. RESULTS: In total, 782 RISC scores were available. Concern was higher for the medical state domain (686/782,88%) compared with the mental state (306/782,39%) and activities of daily living (595/782,76%) domains. Concern was rated as severe for only a small percentage of patients. Perceived risk of institutionalisation had the strongest correlation with concern over patients mental state,(r=0.53), while risk of hospitalisation,(r=0.53) and death,(r=0.40) correlated most strongly with concern over the medical state. Weaker correlations were found for the other domains and RISC scores. The CFS most strongly correlated with the ADL domain,(r=0.78). CONCLUSION: Although the prevalence of concern was high, it was mostly rated as mild. Perceived risk of institutionalisation correlated most with concern over the ability of caregiver networks to manage patients' mental state, while risk of hospitalisation and death correlated with patients' medical state. The findings suggest the importance of including an assessment of the caregiver network when examining community-dwelling older adults. Validation of the RISC and public health nurses' ratings are now required.

Immunohistochemical and ultrastructural features of congenital melanocytic naevus cells support a stem-cell phenotype.

BACKGROUND: Multiple congenital melanocytic naevi (CMN) in one individual are caused by somatic mosaicism for NRAS mutations; however, the lineage of the mutated cells remains uncertain. OBJECTIVES: To test the hypothesis that CMN may be derived from cutaneous stem cells. METHODS: Sixty-six CMN samples from 44 patients were stained for immunohistochemical (IHC) markers of melanocytic differentiation (TYR, TRP1, TRP2, LEF1, MITF, cKit), pluripotency (nestin, fascin, CD133, CD20, CD34), monocyte/macrophage lineage (CD68, CD163, CD14), proliferation (Ki67) and MTOR/Wnt-signalling pathway activation (pS6, ß-catenin). Semiquantitative scoring compared samples with naevus cell nesting (group 1) with those with only diffuse dermal infiltration (group 2). Transmission electron microscopy (TEM) was performed on 10 samples. RESULTS: A normal melanocyte population was seen overlying many dermal CMN. Group 1 samples were significantly more likely to express melanocytic differentiation markers than group 2, and expression decreased significantly with depth. Expression of these markers was correlated with each other, and with nestin and fascin. CD20 staining was positive in a substantial proportion and was stronger superficially. Expression of ß-catenin and pS6 was almost universal. Some samples expressed monocyte/macrophage markers. TEM revealed variable naevus cell morphology, striking macromelanosomes, double cilia and microvilli. CONCLUSIONS: Congenital melanocytic naevi development frequently coexists with normal overlying melanocyte development, leading us to hypothesize that in these cases CMN are likely to develop from a cell present in the skin independent of, or remaining after, normal melanocytic migration. IHC and TEM findings are compatible with CMN cells being of cutaneous stem-cell origin, capable of some degree of melanocytic differentiation superficially.

In vitro diagnostic assays are effective during the acute phase of delayed-type drug hypersensitivity reactions.

BACKGROUND: Previous reports have suggested that drug-specific lymphocyte proliferation assays (LPA) can be used retrospectively to confirm the culprit drug following delayed-type drug hypersensitivity reactions (DHR). However, only limited evidence supports their use in aiding acute clinical management. The aim of this study was to compare the LPA against combination cytokine assays for potential use in the acute setting. METHODS: A total of 43 patients with DHR (19 during the acute reaction, 20 after recovery, four during acute and after recovery) and 14 control subjects without DHR were investigated using ex vivo analysis of drug-specific proliferation, and interferon (IFN)-γ and interleukin (IL)-4 production. RESULTS: Healthy controls showed negative drug-specific proliferation and cytokine release in contrast to individuals with a known sensitivity (P < 0·0001). The assays demonstrated a test specificity of 95% (LPA), 83% (IFN-γ) and 92% (IL-4). The sensitivity of combined measurement of drug-specific IFN-γ and IL-4 cytokines during acute DHR was better than LPA (82% vs. 50%), but all assays were less sensitive during the recovery phase. The correlation between LPA and IFN-γ assays was strong (r = 0·7, P < 0·0001), whereas the IL-4 assay did not correlate as well with either of these assays. In contrast to LPA, drug enzyme-linked immunosorbent spot assays showed positive responses in patients concurrently taking immunosuppressive medication. CONCLUSIONS: In vitro assays of drug-specific IFN-γ and IL-4 production offer potential for use as rapid diagnostic tests. Cytokine detection offers distinct advantages over the LPA, including a shorter assay time, a greater sensitivity and effectiveness in testing immunosuppressed patients.

High incidence of skin cancer in the Channel Islands.

BACKGROUND: Previous studies looking at rates of malignant melanoma (MM) and nonmelanoma skin cancer (NMSC) in the UK have documented one of the highest rates in the southwest of England; however, the incidence of these tumours in Guernsey and Jersey, two of the Channel Islands, has not previously been reported. AIMS: To determine the incidence of cutaneous MM and NMSC in the Channel Islands. METHODS: Data for the period 2005-2009 were obtained from clinical and histopathological records for all MMs excised in the Channel Islands, and from the South-west Cancer Registry for MMs excised in the southwest of England and for NMSCs in both areas. The age-standardized incidence rate (ASRs) per 100,000 of the population in the Channel Islands were compared with those with the southwest of England, the UK and the rest of Europe where available. The MM characteristics of the Channel Islands were then compared with the southwest of England using standardized incidence ratios (SIRs). RESULTS: The ASR/100,000 for cutaneous MM for 2005-2009 was 30 for the Channel Islands (31.3 for Jersey, 28.2 for Guernsey), 20.3 for the southwest of England, and 15.6 for the UK. Comparison with the rest of Europe indicated that the incidence of MM in the Channel Islands is one of the highest in Europe. The highest incidence of MM was in the over 65 years age group on both Guernsey and Jersey, and when divided into 5-year age bands, the 70-74 years age group had the highest rate. This suggests that this particular age group may have previously received greater exposure to some environmental factor that promotes MM development. The ASR/100,000 for NMSC was also higher for the Channel Islands (263.3) than for the southwest of England (174.6) for 2005-2009, and for the UK in 2009 (104.9). CONCLUSIONS: This study indicates that the Channel Islands have a high incidence of skin cancer (both MM and NMSC). In addition, the data show that the ASRs in older people in this population group differ from those in mainland UK, showing higher rates in the over 65 years age group.

A pilot randomized controlled trial to examine the feasibility and efficacy of an educational nursing intervention to improve self-management practices in patients with mild-moderate psoriasis.

BACKGROUND: Large numbers of people are expected to self-manage their skin condition, but limited attention has been given to studies of self-management in psoriasis, neither clearly highlighting the challenge nor seeking to develop interventions to support its effectiveness. OBJECTIVES: 1. To test the feasibility of a new educational intervention to enable people with psoriasis to self-manage more effectively an adequately powered multi-centred trial design through piloting. METHOD: Pilot randomized controlled trial with adults (n = 64) with mild-moderate psoriasis in Primary Care in the United Kingdom. Both groups continued with usual treatment. A theory-based educational intervention was designed. The primary outcome measure was the Dermatology Life Quality Index (DLQI). Secondary measures included the Psoriasis Area and Severity Index (PASI) and qualitative feedback from participants. Assessment of the feasibility of the intervention included recruitment and acceptability to participants. RESULTS: Delivery of the intervention was feasible and positively evaluated. Recruitment strategies and the intervention need minor modification. As a pilot study there was insufficient power to detect significant score changes. Sub group analysis of participants with a PASI or DLQI of >6 indicated a modest reduction in PASI in the intervention group which demonstrates a trend that may indicate that this intervention has potential value for people with moderate psoriasis when combined with qualitative data. CONCLUSION: This study highlights the feasibility of delivering a self-efficacy based educational intervention for people with mild-moderate psoriasis in primary care establishing the numbers and design required for an adequately powered multi-centred trial.

Cost-effectiveness of tacrolimus ointment in adults and children with moderate and severe atopic dermatitis: twice-weekly maintenance treatment vs. standard twice-daily reactive treatment of exacerbations from a third party payer (U.K. National Health Service) perspective.

BACKGROUND: A twice-weekly maintenance treatment regimen with tacrolimus ointment for atopic dermatitis (AD) significantly delayed and reduced the number of disease exacerbations over a 12-month period compared with the standard reactive treatment regimen. OBJECTIVES: To determine the cost-effectiveness of tacrolimus ointment used in the maintenance treatment regimen vs. the standard reactive treatment regimen for the management of moderate and severe AD in adults and children. METHODS: Data from two pivotal phase III studies conducted in adults and children receiving 0·1% and 0·03% tacrolimus ointment, respectively, were used to populate a decision-analytic model. The costs and benefits associated with maintenance vs. reactive use of tacrolimus ointment were calculated over a 12-month period based on the clinical and quality of life data from the clinical trials. The analysis was conducted from the perspective of the U.K. National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. RESULTS: For both adults and children with moderate and severe AD, twice-weekly maintenance treatment with tacrolimus ointment was shown to be a more effective and less costly (dominant) treatment regimen than the standard treatment regimen. Sensitivity analyses demonstrated that the model was robust and largely insensitive to changes in model parameters. CONCLUSIONS: Maintenance treatment with tacrolimus ointment for the management of moderate and severe AD provides incremental health benefits at a lower cost compared with the reactive treatment regimen.