Rural emergency medical technician pre-hospital electrocardiogram transmission.

INTRODUCTION: Emergent care of the acute heart attack patient continues to be at the forefront of quality and cost reduction strategies throughout the healthcare industry. Although the average cardiac door-to-balloon (D2B) times have decreased substantially over the past few years, there are still vast disparities found in D2B times in populations that reside in rural areas. Such disparities are mostly related to prolonged travel time and subsequent delays in cardiac catherization lab team activation. Urban ambulance companies that are routinely staffed with paramedic level providers have been successful in the implementation of pre-hospital 12-lead electrocardiogram (ECG) protocols as a strategy to reduce D2B times. METHOD: The authors sought to evaluate the evidence related to the risk and benefits associated with the replication of an ECG transmission protocol in a small rural emergency medical service. The latter is staffed with emergency medical technician-basics (EMT-B), emergency medical technician-advanced (EMT-A), and emergency medical technician-intermediate (EMT-I) level. RESULTS: The evidence reviewed was limited to studies with relevant data regarding the challenges and complexities of the ECG transmission process, the difficulties associated with ECG transmission in rural settings, and ECG transmission outcomes by provider level. CONCLUSIONS: The evidence supports additional research to further evaluate the feasibility of ECG transmission at the non-paramedic level. Multiple variables must be investigated including equipment cost, utilization, and rural transmission capabilities. Clearly, pre-hospital ECG transmission and early activation of the cardiac catheterization laboratory are critical components to successfully decreasing D2B times.

Homozygous variegate porphyria presenting with developmental and language delay in childhood.

Variegate porphyria is an autosomal dominant disorder that usually presents with photosensitivity and acute neurological crises in adulthood. It is caused by heterozygous mutations in the protoporphyrinogen oxidase gene (PPOX). A rarer variant, homozygous variegate porphyria (HVP), presents in childhood with recurrent skin blisters and scarring. More variable features of HVP are short stature, brachydactyly, nystagmus, epilepsy, developmental delay and mental retardation. We describe a child who presented with nystagmus, developmental delay and ataxia, combined with a photosensitive eruption. Analysis of porphyrins in plasma, urine and stool supported a clinical diagnosis of HVP. DNA from the patient showed that he is compound heterozygous for two novel missense mutations in the PPOX coding region: c.169G>C (p.Gly57Arg) and c.1259C>G (Pro420Arg). Interestingly, cranial magnetic resonance imaging showed an absence of myelin, a feature not previously reported in HVP, which expands the differential diagnosis of childhood hypomyelinating leucoencephalopathies.

The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey.

BACKGROUND: There is a paucity of evidence for the use of systemic agents in children with atopic eczema refractory to conventional therapy, resulting in considerable variation in patient management. OBJECTIVES: The European TREatment of severe Atopic eczema in children Taskforce (TREAT) survey was established to collect data on current prescribing practice, to identify factors influencing the use of specific systemic agents, and to inform the design of a clinically relevant intervention study. METHODS: Consultant physician members of the paediatric dermatology societies and interest groups of eight European countries were invited to participate in a web-based survey. The multiple-response format questionnaire collated data on clinical practice in general, as well as detailed information on the use of systemic agents in refractory paediatric atopic eczema. RESULTS: In total, 343/765 members (44·8%) responded to the invitational emails; 89·2% were dermatologists and 71% initiate systemic immunosuppression for children with severe atopic eczema. The first-line drugs of choice were ciclosporin (43·0%), oral corticosteroids (30·7%) and azathioprine (21·7%). Ciclosporin was also the most commonly used second-line medication (33·6%), with methotrexate ranked as most popular third choice (26·2%). Around half of the respondents (53·7%) replied that they routinely test and treat reservoirs of cutaneous infection prior to starting systemic treatment. Across the eight countries, penicillins were the first-line antibiotic of choice (78·3%). CONCLUSIONS: In the absence of a clear evidence base, the European TREAT survey confirms the wide variation in prescribing practice of systemic immunosuppression in refractory paediatric atopic eczema. The results will be used to inform the design of a randomized controlled trial relevant to patient management across Europe.

Digital reader vs print media: the role of digital technology in reading accuracy in age-related macular degeneration.

PURPOSE: To compare patient satisfaction, reading accuracy, and reading speed between digital e-readers (Sony eReader, Apple iPad) and standard paper/print media for patients with stable wet age-related macular degeneration (AMD). METHODS: Patients recruited for the study were patients with stable wet AMD, in one or both eyes, who would benefit from a low-vision aid. The selected text sizes by patients reflected the spectrum of low vision in regard to their macular disease. Stability of macular degeneration was assessed on a clinical examination with stable visual acuity. Patients recruited for the study were assessed for reading speeds on both digital readers and standard paper text. Standardized and validated texts for reading speeds were used. Font sizes in the study reflected a spectrum from newsprint to large print books. Patients started with the smallest print size they could read on the standardized paper text. They then used digital readers to read the same size standardized text. Reading speed was calculated as words per minute by the formula (correctly read words/reading time (s) ·60). The visual analog scale was completed by patients after reading each passage. These included their assessment on 'ease of use' and 'clarity of print' for each device and the print paper. RESULTS: A total of 27 patients were used in the study. Patients consistently read faster (P<0.0003) on the Apple iPad with larger text sizes (size 24 or greater) when compared with paper, and also on the paper compared with the Sony eReader (P<0.03) in all text group sizes. Patients chose the iPad to have the best clarity and the print paper as the easiest to use. CONCLUSIONS: This study has demonstrated that digital devices may have a use in visual rehabilitation for low-vision patients. Devices that have larger display screens and offer high contrast ratios will benefit AMD patients who require larger texts to read.

MBTPS2 mutation in a British pedigree with keratosis follicularis spinulosa decalvans.

Keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) is an X-linked disorder characterized by widespread hyperkeratotic follicular papules (including keratosis pilaris-like lesions), facial erythema, hypotrichosis and scarring alopecia. KFSD results from mutations in the MBTPS2 gene. Mutations in this gene also underlie ichthyosis follicularis, alopecia and photophobia syndrome. We report a British pedigree with KFSD resulting from the mutation p.Asn508Ser. This particular mutation has been reported in three other pedigrees with KFSD (Dutch, American, British) and is the only pathogenic mutation reported in this disorder to date. However, the same mutation has also been reported in a Chinese pedigree with IFAP syndrome, highlighting the clinical heterogeneity and overlapping molecular pathology of these two disorders.

Eczema and cancer risk: a critical appraisal and review of the literature.

AIM: Hwang et al. aimed to evaluate the risk of malignancy among individuals with eczema, allergic rhinitis (AR) and asthma, compared with the general Taiwanese population. HYPOTHESIS: People with atopic conditions, including eczema, have an altered risk of malignancy. SETTING AND DESIGN: This was a prospective nationwide cohort study. The authors used the Taiwanese National Health Insurance Research Database (NHIRD) to compare the incidence of cancers among people with established allergic disease relative to the risk in the general population. STUDY EXPOSURE: Exposure was the presence of one or more atopic conditions (eczema, AR or asthma). Data were extracted on 997,729 randomly selected people registered on the NHIRD at any time point between 1996 and 2008. Eczema was identified via ICD-9-CM codes with the diagnosis being made by a dermatologist, paediatrician or allergist. Follow-up was until 2008, date of first cancer or death. OUTCOMES: The outcome was a new diagnosis of malignancy, identified via catastrophic illness insurance certificates, again using ICD-9-CM diagnostic codes. PRIMARY OUTCOME MEASURE: Standardized incidence ratios (SIRs) for cancers overall and different types of malignancy among patients with eczema, AR or asthma were calculated against the expected number of cancer cases in the general population, adjusted for age and sex. RESULTS: The number of patients identified with eczema, AR and asthma was 34,263, 225,315 and 107,601, respectively. Overall cancer rates in patients with these conditions were not significantly different from those in the general population [SIR eczema = 0·97 (95% confidence interval 0·87-1·09), SIR AR = 1·02 (0·98-1·05) and SIR asthma = 1·01 (0·97-1·04)]. However, when the results for eczema were stratified by age, people aged between 20 and 39 years appeared to have a 56% increase in risk in relation to 'any cancer' [SIR = 1·56 (1·13-2·09)]. Looking at individual cancer types in patients with eczema, only the risk of brain cancer was significantly raised [SIR = 2·52 (1·15-4·79)]. Patients who had had all three allergic conditions had a reduced SIR for 'cancers overall' [SIR = 0·59 (0·37-0·88)]. This inverse association was less strong for those with eczema and asthma [SIR = 0·73 (0·55-0·97)] or asthma and AR [SIR = 0·79 (0·73-0·84)] and statistically only of borderline significance for those with eczema and AR [SIR = 0·85 (0·67-1·07)]. CONCLUSIONS: Hwang et al. conclude that the relationship between allergic diseases and cancer risk is complex and site specific. The risk of malignancy was highest in all atopic conditions in the 20-39-year age group. In patients with eczema, the incidence of brain cancer was higher than expected, which the authors note is at odds with previous studies. However, numbers were too small to allow stratification by histological subtypes. The authors warn against deriving conclusions for rarer cancers and that borderline SIRs must be interpreted with caution.

Pulsed intravenous cyclophosphamide and methylprednisolone therapy in refractory pemphigus.

BACKGROUND: Pemphigus is a rare autoimmune blistering disorder. The mainstay of current treatment is high-dose oral corticosteroid therapy in combination with a steroid-sparing agent. Adjuvant therapy is important for disease control and to reduce the iatrogenic effects of oral prednisolone. Pulsed therapy with intravenous methylprednisolone and cyclophosphamide (PPC) has been shown to be an effective treatment but there are currently few data on its use in patients who have failed to respond to conventional immunosuppression. OBJECTIVES: To report the clinical and immunological responses of 21 patients with pemphigus refractory to prednisolone and azathioprine or mycophenolate mofetil treated in our department with a standard protocol of monthly PPC. METHODS: Patients with pemphigus were identified who had undergone PPC therapy during the period between 1997 and 2006. Initial clinical severity and response to treatment was assessed. In addition, change in intercellular antibody titres and desmoglein 1 and 3 antibodies to PPC therapy was also recorded. RESULTS: Of the 21 patients treated, seven had an excellent response, two a good response, five a moderate response, six a minimal response and one patient had no clinical response. Four patients achieved complete clinical remission and the number of pulses for these patients varied between 11 and 22. We observed significant reductions in indirect immunofluorescence titres for normal human skin substrate (P = 0.0078) and antidesmoglein 1 and 3 autoantibody levels (P = 0.007 and P = 0.0085, respectively) from pre-PPC therapy to 1 year after the last pulse. All patients were able to reduce their prednisolone dose from a pre-pulsing median dose of 40-10 mg at the last pulse with a median dose reduction of 66% (P < 0.001). The most common adverse effect was transient lymphopenia (12 patients); nonlife-threatening sepsis (seven patients) and premature ovarian failure (two patients) also occurred. CONCLUSIONS: PPC can be an effective treatment for refractory pemphigus but its adverse effects should be considered prior to therapy and closely monitored in patients on treatment.

Imiquimod and lentigo maligna: a search for prognostic features in a clinicopathological study with long-term follow-up.

BACKGROUND: Melanoma in situ/lentigo maligna (LM) is a potential precursor of LM melanoma. It occurs most commonly in elderly individuals on sun-exposed skin of the head and neck. Although surgical excision is the treatment of choice, this may not be desirable or feasible for large lesions at functionally or cosmetically important sites. Imiquimod is a topical immunomodulator which can generate a local cytotoxic response with potentially antiviral and antitumour effects. OBJECTIVES: To present our experience of LM treated with imiquimod. METHODS: A retrospective review was performed of all patients with facial LM treated in our unit with topical imiquimod between January 2001 and December 2006. Pretreatment diagnostic biopsies were also reviewed and histologically graded. RESULTS: Forty-eight patients were treated with imiquimod. There were 37 responders and 11 treatment failures (of whom two were 'partial responders'). Of the 37 responders, 31 showed a clinical inflammatory response to imiquimod. One patient in whom treatment failed subsequently developed invasive disease. The mean follow-up duration was 49 months. We could not identify histological features of prognostic significance. However, the ability to develop an inflammatory reaction to imiquimod was a strong predictor of therapeutic benefit. CONCLUSIONS: We consider imiquimod to have a role in the treatment of LM in patients in whom surgery may be contraindicated or for those in whom the cosmetic or functional consequences may be considerable. Until better characterized, its use should probably be confined to centres with experience in the detection and treatment of LM and melanoma.

Infliximab for severe, treatment-resistant psoriasis: a prospective, open-label study.

BACKGROUND: Infliximab, a mouse-human chimeric monoclonal antibody directed against tumour necrosis factor-alpha, has been shown to be effective for moderate to severe psoriasis, but there are few data published on its use in recalcitrant, treatment-resistant disease or in combination with other antipsoriatic therapies. OBJECTIVES: To report our experience with infliximab in the treatment of patients attending a tertiary referral service with severe recalcitrant disease. METHODS: All patients attending a tertiary referral service for severe psoriasis who were treated with infliximab between 2002 and July 2005 were entered into a prospective, open-label study. Details on disease phenotype, clinical course and adverse events were recorded together with measures of disease severity [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, clinical photography] at baseline, weeks 2 and 6, and then at 2-monthly intervals throughout the treatment period. RESULTS: Twenty-three patients were treated with infliximab during the study; one patient had pustular psoriasis and was therefore excluded from statistical analysis. All had severe disease (baseline PASI 26.5+/-6.7, mean+/-SD, n=22) and had received at least two systemic therapies for psoriasis in the past; 16 were taking one or more concomitant therapies at the time of treatment initiation. At week 10, 95% had achieved a 50% or greater improvement in baseline PASI (PASI 50), and 77% had achieved a 75% or greater improvement (PASI 75). Efficacy was sustained in the longer term, with eight of 10 patients on treatment for more than 11 months maintaining at least a PASI 50. Only one patient had treatment withdrawn due to lack of efficacy, two suffered severe systemic infections including extrapulmonary tuberculosis (splenic abscess) and cellulitis, and six have discontinued due to adverse effects including infusion reactions (two), severe thrombocytopenia (one), hepatitis (one) and malignancy (two). CONCLUSIONS: Data from this open-label study suggest that infliximab is a rapidly effective treatment for patients with severe, treatment-resistant disease, although approximately 25% of patients had to discontinue therapy due to the development of serious adverse effects. Long-term follow-up, continued pharmacovigilance, and further controlled comparative studies will be required to evaluate fully the risks associated with infliximab in the context of this already difficult to treat population.

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity.

BACKGROUND: Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. OBJECTIVES: To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. METHODS: Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). RESULTS: Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to beta4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. CONCLUSIONS: Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP.

Collagen XVII/BP180: a collagenous transmembrane protein and component of the dermoepidermal anchoring complex.

Collagen XVII, or BP180, is a collagenous transmembrane protein and a structural component of the dermoepidermal anchoring complex. Molecular studies reveal that it has a globular cytosolic amino-terminal domain and flexible-rod extracellular carboxyterminal domain. The extracellular portion of collagen XVII is constitutively shed from the cell surface by ADAMs (proteinases that contain adhesive and metalloprotease domains). Cell biological analyses suggest that collagen XVII functions as a cell-matrix adhesion molecule through stabilization of the hemidesmosome complex. This concept is supported by investigations into human diseases of the dermoepidermal junction, in which collagen XVII is either genetically defective or absent (as in some forms of nonlethal junctional epidermolysis bullosa). Autoantibodies against collagen XVII (BP180) are seen in bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, linear IgA disease, lichen planus pemphigoides and pemphigoid nodularis. In vivo and in vitro studies provide evidence for a pathogenic role of these autoantibodies, and suggest that the serum level and epitope specificity of these antibodies influences disease severity and phenotype. This review summarizes the structural and biological features of collagen XVII and its role in diseases of the basement membrane zone.

Discoid lupus erythematosus with secondary amyloidosis.

BACKGROUND: Secondary localized cutaneous amyloidosis is a clinically unapparent phenomenon associated with various cutaneous pathologies, usually tumours of epidermal origin. The amyloid is thought to be derived from keratinocytes. OBJECTIVES: To characterize the amyloid deposition observed incidentally within lesional biopsies from three patients with discoid lupus erythematosus (DLE), and retrospectively to study the phenomenon within DLE skin samples. METHODS: Localized amyloid deposition was observed in three cases of DLE by immunofluorescence studies, and these cases were further studied by histology and immunohistochemistry using a monoclonal anticytokeratin antibody. Retrospective histological review of DLE tissue specimens archived over 12 months was performed to look for evidence of previously undetected amyloid. RESULTS: Amyloid deposition was confirmed histologically in the three index cases by staining with Congo red and thioflavin T. Positive staining with an anticytokeratin antibody demonstrated the epidermal origin of the amyloid protein. Of the 18 archived cases reviewed amyloid was retrospectively detected in one sample. CONCLUSIONS: Secondary cutaneous amyloidosis of keratinocyte origin can be seen in DLE lesions. It may be a not infrequent occurrence and may remain under-reported. We discuss the possible role of disease chronicity and colloid body degradation in the pathogenesis of amyloidosis.

Province of residence and active syphilis infection among Zambian men and women: new evidence from population-based data.

This study examined the risk factors for active syphilis infection in a subset of nationally-representative population-based survey of Zambian men and women. Syphilis prevalence was 6.5% for women = 2107) and 7.4% for men (N = 1745). In the multivariate model, province was a strong risk factor for active syphilis infection, with Copperbelt, Eastern, Luapula, Lusaka, North-Western and Western Provinces presenting significantly higher risk for women, and Copperbelt, Eastern and Lusaka Provinces presenting significantly higher risk for men compared to the Northern Province. In addition to province, age, education, age at first intercourse, marital status, history of genital sore or discharge, and having ever paid for sex were independent predictors of syphilis infection. Given the ongoing HIV-1 epidemic in Zambia, more aggressive diagnosis and treatment of active syphilis infections, particularly in high-risk provinces, are important strategies to reduce reproductive morbidity and curb HIV-1 transmission.

Evaluation of a BP180-NC16a enzyme-linked immunosorbent assay in the initial diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal immunobullous disease, characterized by circulating IgG autoantibodies targeting BP180 and BP230 hemidesmosomal proteins. Several immunological studies have demonstrated that the membrane proximal noncollagenous domain NC16a of BP180 is the immunodominant region targeted by BP autoantibodies. Recently, a commercial BP180 NC16a-specific enzyme-linked immunosorbent assay (ELISA) has become available for detecting pathogenic anti-BP180 autoantibodies in BP sera. However, it remains unclear whether the diagnostic potential of the ELISA is equivalent to that of the 'gold-standard' diagnostic technique of immunofluorescence (IF). OBJECTIVES: To examine the usefulness of a commercially available BP180-NC16a ELISA in the initial serodiagnosis of BP. METHODS: Sera from a large cohort of patients with BP (n = 102) and control subjects (age- and sex-matched normal volunteers, n = 60; pemphigus foliaceus, n = 18; pemphigus vulgaris, n = 16) were assayed by BP180-NC16a ELISA. All BP sera were obtained at presentation before initiation of systemic immunosuppressive therapy. The values of IgG antibody levels measured by ELISA were compared with those measured by indirect IF on salt-split skin. Results Receiver operating characteristic analysis was used to calculate the cut-off value for the ELISA in the diagnosis of BP which maximizes both sensitivity and specificity, and to estimate the diagnostic accuracy of the ELISA as represented by the area under the curve (AUC = 0.965). A cut-off value of 9 was associated with a sensitivity of 89% (91 of 102 BP sera showed a positive result) and a specificity of 98%. Fifty-eight of 60 normal controls and all the pemphigus sera showed a negative result. There was a correlation between the mean ELISA values and indirect IF titres (Spearman rank correlation 0.286; P = 0.004). CONCLUSIONS: Our results suggest that the BP180-NC16a ELISA is a useful tool for the detection of pathogenic anti-BP180 IgG autoantibodies at the initial disease stage of BP. Because it is not only highly sensitive and specific, but is also easy to perform, is objective, and semiquantitative, the ELISA may provide valuable information for the accurate and reliable serodiagnosis of BP.

Paraneoplastic pemphigus secondary to fludarabine evolving into unusual oral pemphigus vegetans.

We report a patient with chronic lymphocytic leukaemia who developed paraneoplastic pemphigus (PNP) soon after the initiation of fludarabine therapy. He presented with severe oral and cutaneous erosions. Initially, he had high titres of circulating autoantibodies as detected by indirect immunofluorescence (IF) on multiple epithelial substrates (normal human skin, monkey oesophagus, and rat bladder) and by desmoglein 1 and 3 enzyme-linked immunosorbent assays (ELISAs). His oral erosions have subsequently progressed into unusual hyperplastic papillomatous lesions affecting the inner aspect of lips and buccal mucosae, histologically consistent with pemphigus vegetans. Desmoglein 1 antibodies and IF on rat bladder substrate have become negative after 18 months of therapy. Several agents had been initiated to bring the disease under control originally, but a partial remission was achieved and maintained with mycophenolate mofetil and low-dose prednisolone.