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.

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.

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.

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.

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.

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.

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.

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.

Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans.

Melanin pigmentation protects the skin from the damaging effects of ultraviolet radiation (UVR). There are two types of melanin, the red phaeomelanin and the black eumelanin, both of which are present in human skin. Eumelanin is photoprotective whereas phaeomelanin, because of its potential to generate free radicals in response to UVR, may contribute to UV-induced skin damage. Individuals with red hair have a predominance of phaeomelain in hair and skin and/or a reduced ability to produce eumelanin, which may explain why they fail to tan and are at risk from UVR. In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin and the product of the agouti locus which antagonises this action. In mice, mutations at either the MC1R gene or agouti affect the pattern of melanogenesis resulting in changes in coat colour. We now report the presence of MC1R gene sequence variants in humans. These were found in over 80% of individuals with red hair and/or fair skin that tans poorly but in fewer than 20% of individuals with brown or black hair and in less than 4% of those who showed a good tanning response. Our findings suggest that in humans, as in other mammals, the MC1R is a control point in the regulation of pigmentation phenotype and, more importantly, that variations in this protein are associated with a poor tanning response.

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.

Repeated low-dose skin exposure is an effective sensitizing stimulus, a factor to be taken into account in predicting sensitization risk.

BACKGROUND: Contact sensitization by ingredients in personal products is an important clinical problem. It is not clear how sensitization is induced by the generally low concentrations at which they occur but it might be the result of repeated exposure. OBJECTIVES: To compare the strength of contact sensitization induced by a single exposure to 2,4-dinitrochlorobenzene (DNCB) (60 microg cm(-2)) or three repeated exposures to a subsensitizing dose (10 microg cm(-2)). METHODS: Two groups (n = 10) of healthy adult volunteers were randomized to receive either a single patch of DNCB 60 microg cm(-2) or three once-weekly applications to the same site of 10 microg cm(-2) DCNB. Four weeks after the last application, sensitization was quantified by measurement of responses (skinfold thickness) to a graded series of four challenge doses. RESULTS: All the volunteers were sensitized and the strength of the responses was virtually identical between the groups. CONCLUSIONS: The same degree of sensitization was induced by three exposures to DNCB 10 microg cm(-2) as by one exposure to 60 microg cm(-2) of DNCB. Thus repeated exposure to low doses of contact sensitizers may increase the sensitizing potency. This must be taken into account in future risk assessments.

Self-management experiences in adults with mild-moderate psoriasis: an exploratory study and implications for improved support.

BACKGROUND: Psoriasis is a long-term condition affecting 2-3% of the population. The mainstay of treatment for mild-moderate disease is the regular application of topical medication by the individual. At present little is known about how people with psoriasis self-manage and how they may best be supported in this endeavour. OBJECTIVES: To explore how adults with mild-moderate psoriasis manage their condition and to identify strategies that can support people to self-manage effectively. METHODS: A qualitative investigation was carried out using six focus groups to collect data from purposively sampled participants managed in the community (n = 22). RESULTS: Thematic data analysis generated three categories that offer new insights into how people currently manage their condition, their low expectations of health services and how self-management may be better supported. People with mild-moderate psoriasis do not always achieve what they perceive to be optimal self-management. They often do not use topical therapy systematically and frequently abandon it if rapid improvements are not seen. Factors which participants identified as likely to improve self-management included the provision of individualized education directed towards improving effective adherence techniques by medical and nonmedical personnel who have practical experience in topical application of psoriatic therapies. CONCLUSIONS: People with mild-moderate psoriasis continue to find self-management problematic; however, they can identify strategies that could enable them to become more effective in self-managing. There is a need to incorporate these strategies in 'self-management plans' in order to support individuals to self-manage as effectively as possible to help improve their skin condition and quality of life.

Sexuality and personal relationships for people with an intellectual disability. Part II: staff and family carer perspectives.

BACKGROUND: Recent ideological shifts in service provision promote appropriate sexual expression for people with an intellectual disability (ID), although there is little evidence that such advances in ideology are matched by current service provision. Part II of the current two-part study assessed the attitudes of staff and family carers to the sexuality of people with an ID. METHOD: A questionnaire survey which included case scenarios was carried out with family (n = 155) and staff carers (n = 153) of people with an ID in the west of Ireland. RESULTS: In general, staff carers were more inclined than family carers to openly discuss issues of sexuality with service users, and to suggest environmental, rather than service-user characteristics, as impediments to such discussions. Attitudinal differences emerged with significant differences between staff and family carers and between younger and older carers. Staff carers were more likely to support service-user engagement in intimate and non-intimate relationships whereas the majority of family carers (80%) showed a preference for low levels of intimacy in service-user relationships. CONCLUSION: When compared with the attitudes of family carers towards the sexuality of people with ID, the attitudes of staff carers more closely match those promoted by ideological developments. However, differences in attitudes between carer groups may lead to inconsistent approaches to the management of sexuality. As a consequence, we conclude that there is continued need to provide staff and family carers with opportunities for dialogue and an ongoing need for training in the area of sexuality.

Sexuality and personal relationships for people with an intellectual disability. Part I: service-user perspectives.

BACKGROUND: Despite a recent ideological shift towards the recognition of sexual autonomy for people with an intellectual disability (ID), there are continuing social and cultural barriers to sexual expression. Part I of the current two-part study assessed the sexual knowledge, experiences and aspirations of service users through focus groups and also examined their perceptions of impediments to achieving sexual autonomy. METHOD: Thirty-two participants (20 male, 12 female) attending an ID service participated in focus groups delineated by gender and age group (13-17 years; 18-30 years; 31+ years). RESULTS: Analysis of the focus groups showed that service users, especially those over the age of 18 years, had an understanding of their sexual rights but also identified a number of social and cultural barriers that they felt prevent them from achieving sexual autonomy. Those under the age of 18 years had only rudimentary knowledge of sexuality issues, for example pregnancy and sexual anatomy, but aspired to relationships and marriage similar to those over the age of 18 years. Family and staff attitudes appeared to be very influential in the views of respondents. All service users had received some form of sex education, although the benefits of such education appeared most enduring for those over 18 years. CONCLUSION: Service users had an understanding of their sexual rights and the social and environmental barriers that prevent them from fulfilling their rights. The provision of sex education training and promotion of positive attitudes towards appropriate sexual expression is critical to the realization of sexual autonomy for people with an ID.

Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment.

BACKGROUND: Long-term treatment for atopic dermatitis (AD) using low dose, intermittent, topical anti-inflammatory agents may control acute disease and prevent relapses. This 12-month, European, multicentre, randomized study investigated whether the proactive use of 0.1% tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations (DE). METHODS: During the initial open-label period, 257 adults with AD applied 0.1% tacrolimus ointment twice daily (b.i.d.) for up to 6 weeks to affected areas. When an Investigator Global Assessment (IGA) score of