Report from the fifth international consensus meeting to harmonize core outcome measures for atopic eczema/dermatitis clinical trials (HOME initiative).

This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12-14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long-term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole-group and small-group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small-group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole-group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long-term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long-term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon.

Understanding the Relationship Between Pruritus Severity and Work Productivity in Patients With Moderate-to-Severe Psoriasis: Sleep Problems Are a Mediating Factor.

BACKGROUND: Psoriasis is a debilitating skin disease associated with substantial pruritus, work impairment, and sleep disturbance. OBJECTIVE: This study evaluated associations between pruritus and work productivity, and the role of sleep problems as a possible mediator of the relationship between the two. METHODS AND MATERIALS: Data from a pruritus visual analog scale (Itch VAS), the Medical Outcomes Study Sleep Scale (MOS-SS), and the Work Productivity and Activity Impairment Questionnaire (WPAI) were collected in a phase 2 clinical trial in patients with psoriasis treated with ixekizumab or placebo. Mediating effects of sleep were tested in multiple regressions with pruritus severity (independent variable) and work productivity (dependent variable). Sobel tests evaluated the significance of sleep's effect. RESULTS: Several MOS-SS domains were significantly associated with the WPAI presenteeism, work productivity, and activity impairment scores, and decreased the effect of pruritus. Sobel tests indicated that the Sleep Problems Index I had a significant effect (P<.05) in mediating the relationship between pruritus and presenteeism, work productivity, and activity impairment. CONCLUSION: Sleep may mediate the role of pruritus on work productivity, but both factors appear to have independent negative effects on work.

Prevalence and incidence rates of cardiovascular, autoimmune, and other diseases in patients with psoriatic or psoriatic arthritis: a retrospective study using Clinical Practice Research Datalink.

BACKGROUND: Previous studies have demonstrated that patients with psoriasis have higher rates of comorbidities compared to the general population. Despite the clinical and economic burden of psoriatic disease, there have been few large-scale observational studies focused on this condition. OBJECTIVE: To assess rates of cardiovascular, autoimmune, infectious and other conditions in patients with psoriasis or psoriatic arthritis (PSA). METHODS: The data for this retrospective study were obtained from the Clinical Practice Research Datalink (CRPD). Cohorts of patients with psoriasis (n = 27,672; mild, n = 22,174, severe, n = 5498) and PSA (n = 1952) were generated based on the diagnosis made by general practitioner or specialist recorded in CPRD between 2006 and 2010. Frequencies of comorbidities at baseline and incidence rate ratios (IRR) of medical conditions occurring during follow-up were calculated and compared between groups. Cox proportional hazard models were employed to compare hazard ratios (HR) of comorbidities across the same subpopulations previously described. RESULTS: Significant differences in the unadjusted risk of cardiovascular disease, hyperlipidaemia, diabetes, skin cancer and autoimmune diseases were observed between patients with differing severity of psoriasis or between PSA and psoriasis patients. The adjusted HR analyses confirmed patients with severe psoriasis had significantly higher rates of several conditions including diabetes (1.23; 95% CI: 1.01-1.51) and rheumatoid arthritis (2.88; 95% CI: 2.25-3.67) compared to patients with mild psoriasis. Patients with PSA had significantly higher adjusted rates of hypertension (1.30; 95% CI: 1.01-1.68), rheumatoid arthritis (6.93; 95% CI: 5.45-8.80) and ankylosing spondylitis (6.98; 95% CI: 2.37-20.58) compared to those with severe psoriasis. CONCLUSION: Patients with mild psoriasis are less affected by comorbid conditions than those with severe psoriasis, and patients with psoriasis are less affected by comorbidities than those with PSA. Given the differences observed across severities of psoriasis and between psoriasis and PSA, each patient subgroup should be taken into consideration in clinical practice and future research.

Itching is a significant problem and a mediator between disease severity and quality of life for patients with psoriasis: results from a randomized controlled trial.

BACKGROUND: In patients with moderate-to-severe psoriasis, health-related quality of life (HRQOL) has been shown to improve in parallel with improvement in disease severity. OBJECTIVES: To evaluate the role of pruritus (itch) in mediating the relationship between improvements in disease severity and HRQOL. METHODS: Data from a phase 2 clinical trial, in which 142 patients with moderate-to-severe plaque psoriasis received ixekizumab or placebo, were used for this posthoc analysis. Relationships between improvement in Psoriasis Area and Severity Index (PASI), Itch Visual Analogue Scale (VAS) and Dermatology Life Quality Index (DLQI), as well as in individual DLQI domains (symptoms and feelings, treatment, work and school, daily activities, leisure, and personal relationships) from baseline to week 16 were determined. Multiple hierarchical linear regressions and Sobel tests were conducted to evaluate the results. RESULTS: Improvement in PASI was highly correlated with pruritus improvement and improvements in DLQI total and domain scores at week 16 (P < 0·01). Multiple hierarchical linear regression analyses showed a statistically significant (P < 0·01) association between improvement in pruritus and improvement in DLQI total score and each of the six DLQI domain scores after adjusting for improvement in PASI. Sobel tests indicated that pruritus had a significant mediation effect (P < 0·05) on the association of PASI improvement with improvement in DLQI total score and all domains except the personal relationships score. CONCLUSIONS: Pruritus appears to be an important mediator of the association between improvements in disease severity and HRQOL in patients with moderate-to-severe psoriasis.

[Thirty-five cases of tuberculosis in childhood].

Thirty five children with tuberculosis admitted to the Hokkaido University Hospital from 1970 through 1984 wer reviewed. They were 7 cases of meningeal tuberculosis, 8 of military tuberculosis, 15 of primary tuberculosis and 5 of adult type pulmonary tuberculosis. Fifteen (43%) of the 35 cases were below 2 years, and over half of these younger cases were hematogenous spread such as meningeal and military types. Instead of hematogenic spread in these cases, erythrocyte sedimentation rate and CRP stayed in moderate values. Thirty one (91.2%) of the 34 cases having precise record had no history of BCG inoculation. Over half of the cases were infected from adults in the immediate household, and the sources of infection were found after the diagnosis of childhood tuberculosis in about half of these cases. Although incidence of the childhood tuberculosis are decreasing in recent years, childhood tuberculosis resulting hematogenous spread with poor prognosis in advanced state still exists, so it is important to remark the childhood tuberculosis at out patient clinics.

Rat lymphoid cell lines with HTLV-I production. III. Transmission of HTLV-I into rats and analysis of cell surface antigens associated with HTLV-I.

Newborn WKA rats given a single intraperitoneal injection of MMC treated TARS-1, a rat T cell line producing HTLV-I, were shown to accumulate high titred antibodies specific for HTLV-I. Adult WKA rats rejected TARS-1 transplant with transient appearance of anti-HTLV-I antibodies. However, rats maintained under daily administration of Bredinin, an immunosuppressive drug after TARS-1 transplant showed continuous production of antibodies specific for HTLV-I by aging. Type-C virus particles similar to HTLV-I were demonstrated by electronmicroscopy in the short-term cultured spleen cells of these rats. The evidence indicates that HTLV-I can be transmitted into newborn and immunosuppressed adult rats and they may provide a suitable animal model of ATL and related conditions in man, especially for elucidating the virus-host interactions involved in the leukemogenesis of HTLV-I. By using monoclonal antibodies, cell surface antigens associated with HTLV-I were also analysed.

Rat lymphoid cell lines with human T cell leukemia virus production. I. Biological and serological characterization.

Cocultivation of spleen cells, lymph node cells, and thymocytes of female Wistar-King-Aptekman rats with short-term cultured male adult T cell leukemia (ATL) cells in the presence of 5-bromo-2'-deoxyuridine (BrdUrd) resulted in the establishment of rat lymphoid cell lines, TARS-1, TARL-2, and TART-1. Cytogenetic analysis of the three cell lines showed a female rat karyotype with 42 chromosomes. The surface phenotypes of TARS-1 and TART-1 were those of rat T cells. TARL-2 was only positive for rat Ia and leukocyte common antigens. The cell lines continuously produced a type C retrovirus, human T cell leukemia virus (HTLV) and expressed ATL-associated antigens. TARS-1 and TART-1, but not TARL-2 were transplantable into newborn syngeneic rats and nude mice. These results strongly indicate that HTLV not only immortalizes, but also transforms rat T cells in vitro. Adult rats immunized with either TARS-1 or TARL-2 produced antibodies specific for HTLV. The biochemical analysis of the antigens that reacted with rat sera revealed that they are the two HTLV-specific polypeptides, p24 and p28.