Impact of fixed-dose combination Cal/BD foam on the work productivity of patients with psoriasis: results from the 52-week randomized, double-blind, PSO-LONG trial.

BACKGROUND: Psoriasis contributes to unemployment, work impairment, missed workdays and substantial indirect costs due to lost productivity. Combination Cal/BD foam is the only topical that is approved for long-term maintenance treatment of plaque psoriasis for 52 weeks. This is the first known investigation of the effect of topical psoriasis therapy on productivity. OBJECTIVE: To examine the change in work productivity and activity impairment after 4 weeks of treatment with fixed-dose combination calcipotriol 50 µg/g/betamethasone dipropionate 0.5 mg/g (Cal/BD) foam and observe long-term changes after 52 weeks of long-term management (proactive or reactive treatment). METHODS: This is a post-hoc analysis of the PSO-LONG trial - a phase 3, randomized, double-blind, vehicle-controlled, parallel group, international multi-centre trial of treatment with combination Cal/BD foam. Work and activity impairment due to psoriasis were assessed by the Dermatology Life Quality Index (DLQI) and the Work Productivity and Activity Impairment Psoriasis (WPAI:PSO) questionnaire at baseline, week 4, week 28 and week 56. The improvement in hours of work productivity was translated into monthly and annual indirect cost savings estimates for patients in Italy, Sweden, United Kingdom, Canada and Germany. RESULTS: Using fixed-dose combination Cal/BD foam for four weeks significantly reduced psoriasis-related work presenteeism, total work productivity impairment (TWPI) and total activity impairment (TAI) over 56 weeks, with significant improvements observed as early as 4 weeks after the baseline visit. The proportion of patients reporting impact on work productivity (as measured by presenteeism and TWPI) and activity impairment (as measured by both DLQI-Q7b and TAI) also decreased. CONCLUSION: Fixed-dose combination Cal/BD foam used for long-term management of psoriasis significantly reduces psoriasis-related work productivity and activity impairment which may result in substantial indirect cost savings. Clinical Trial Registration NCT02899962, EudraCT number: 2016-000556-95.

A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial.

BACKGROUND: Significantly more patients with moderate-to-severe plaque psoriasis treated with the interleukin (IL)-17A inhibitor ixekizumab vs. the IL-23p19 inhibitor guselkumab in the IXORA-R head-to-head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12. OBJECTIVES: To compare skin and nail clearance and patient-reported outcomes for ixekizumab vs. guselkumab, up to week 24. METHODS: IXORA-R enrolled adults with moderate-to-severe plaque psoriasis, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran-Mantel-Haenszel test stratified by pooled site. Time-to-first-event comparisons were performed using Kaplan-Meier analysis, and P-values were generated using adjusted log-rank tests stratified by treatment group. Cumulative days at clinical and patient-reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). RESULTS: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference -2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. CONCLUSIONS: Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate-to-severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.

Efficacy and safety of ixekizumab in a randomized, double-blinded, placebo-controlled phase IIIb study of patients with moderate-to-severe genital psoriasis.

BACKGROUND: Genital psoriasis (GenPs) is a common, debilitating and difficult-to-treat manifestation of plaque psoriasis. However, few controlled, interventional studies of GenPs exist. OBJECTIVES: To determine the efficacy of ixekizumab vs. placebo in patients with moderate-to-severe GenPs with ≥ 1% involved body surface area (BSA). METHODS: Patients with moderate-to-severe GenPs, defined as a baseline static Physician's Global Assessment of Genitalia (sPGA-G) score of ≥ 3, with BSA ≥ 1% were randomized 1 : 1 to receive placebo (n = 74) or the recommended dosing of ixekizumab (n = 75). Major outcomes included the percentage of patients achieving 0 or 1 scores on the sPGA-G (primary end point), overall sPGA, GenPs Sexual Frequency Questionnaire (GenPs-SFQ) item 2, and ≥ 3-point improvement from baseline on the GenPs itch numerical rating scale. RESULTS: At week 12, ixekizumab was superior to placebo for sPGA-G 0/1 (73% vs. 8%, P < 0·001), overall sPGA 0/1 (73% vs. 3%, P < 0·001), GenPs-SFQ item 2 score of 0 or 1 (78% vs. 21%, P < 0·001) and genital itch (60% vs. 8%, P < 0·001). No candidiasis was reported, no deaths occurred and one (1%) serious adverse event was reported in a patient receiving placebo. CONCLUSIONS: Ixekizumab was superior to placebo for the treatment of moderate-to-severe GenPs with BSA ≥ 1%. The safety profile of ixekizumab was consistent with previous studies in moderate-to-severe plaque psoriasis.

Impact of ixekizumab on facial psoriasis and related quality of life measures in moderate-to-severe psoriasis patients: 12-week results from two phase III trials.

BACKGROUND: Facial psoriasis was reported in 17-68% of patients with psoriasis and shown to have a negative impact on patients' personal and health-related quality of life (HRQoL). OBJECTIVES: To explore the association of facial psoriasis with patients' HRQoL and to assess the relationship between ixekizumab (IXE) and improvement in facial psoriasis and changes in HRQoL. METHODS: This work reports the combined results of two phase III multicentre, randomized, double-blind, placebo-controlled, active-comparator trials in patients with moderate-to-severe psoriasis. Patients received placebo, etanercept (ETN; 50 mg twice weekly) or IXE [80 mg every 4 weeks (Q4W) or every 2 weeks (Q2W)] for up to 12 weeks following an initial 160-mg dose. HRQoL parameters were analysed based on facial psoriasis status at baseline using analysis of covariance models. Improvement was assessed as percentage of patients with no facial psoriasis. RESULTS: The combined database included 1133 patients with facial psoriasis and 1437 without. Patients treated with IXE whose facial psoriasis cleared had improved Dermatology Life Quality Index 0.1 responses (P < 0.01) compared with patients with facial psoriasis at Week 12. At Week 12, clearance of facial psoriasis compared with the presence of facial psoriasis was independently associated with significantly better improvement in Psoriasis Skin Appearance Bothersomeness scores in the IXE Q2W treatment group (P < 0.01). At Week 12, facial clearance and overall Psoriasis Area Severity Index (PASI) improvement were observed in significant numbers of patients treated with IXE compared with ETN and placebo. Facial psoriasis clearance at Week 12 in patients treated with IXE or ETN was positively associated with PASI75 and PASI90 achievement. CONCLUSION: Facial psoriasis had a larger negative impact on HRQoL than no facial psoriasis. Facial psoriasis clearance was associated with improved HRQoL. Significantly more IXE-treated patients had rapid facial clearance vs. ETN and PBO, which led to better clinical outcomes.

Impact of ixekizumab treatment on skin-related personal relationship difficulties in moderate-to-severe psoriasis patients: 12-week results from two Phase 3 trials.

BACKGROUND: Psoriasis symptoms may decrease quality of life for patients. Skin-related personal relationship difficulties in psoriasis patients are common, under-reported and poorly understood. OBJECTIVE: To assess the effect of ixekizumab (IXE) treatment on skin-related personal relationship difficulties in patients with moderate-to-severe psoriasis. METHODS: Pooled data (N = 2570) on skin-related relationship problems were obtained from two large phase 3 trials (UNCOVER-2 and UNCOVER-3) in patients with moderate-to-severe plaque psoriasis randomized to subcutaneous placebo (PBO, N = 361), etanercept (ETN; 50 mg twice weekly, N = 740), or 80 mg IXE as one injection every 4 (IXEQ4W, N = 733) or 2 weeks (IXEQ2W, N = 736) for 12 weeks, following a 160-mg initial dose. The Dermatology Life Quality Index (DLQI) Personal Relationships Domain (PRD) (Items 8 and 9) was used to assess how much the skin caused any personal relationship difficulties at weeks 0, 2, 4 and 12. Improvement was compared for IXE vs PBO and ETN using logistic models. Factors associated with improvement were assessed using multiple linear regressions. DLQI Item 9, assessing sexual difficulties, was also analysed separately. RESULTS: PRD scores (mean ± standard deviation) at baseline were similar across all treatment groups (PBO: 1.8 ± 1.9; ETN: 1.7 ± 1.8; IXEQ4W: 1.6 ± 1.8; IXEQ2W: 1.7 ± 1.8). Treatment with IXE rapidly and significantly improved the mean PRD score compared to PBO and ETN (P < 0.001 at all time points). Baseline PRD score was the strongest negative predictor of improvement. IXE enabled significantly more patients with moderate-to-severe plaque psoriasis to reduce their skin-related sexual difficulties at Week 12 compared to PBO (P < 0.001) or ETN (P < 0.001). CONCLUSION: Ixekizumab improves patient-reported skin-related PRD difficulties in patients with moderate-to-severe psoriasis.

Ixekizumab treatment improves fingernail psoriasis in patients with moderate-to-severe psoriasis: results from the randomized, controlled and open-label phases of UNCOVER-3.

BACKGROUND: Fingernail psoriasis is difficult to treat. OBJECTIVE: The objective was to evaluate the effect of ixekizumab, a monoclonal antibody selectively targeting IL-17A, on fingernail psoriasis. METHODS: This Phase 3, double-blind trial (UNCOVER-3) randomized patients to placebo, etanercept (50-mg twice weekly), or 80 mg ixekizumab as one injection every 4 (IXE Q4W) or 2 weeks (IXE Q2W) after a 160-mg starting dose. At Week 12, ixekizumab patients received open-label IXE Q4W through Week 60; placebo patients received a 160-mg starting ixekizumab dose and etanercept patients a 4-week placebo washout before starting IXE Q4W. Efficacy was assessed by mean per cent Nail Psoriasis Severity Index (NAPSI) improvement at Weeks 12 and 60. RESULTS: Of 1346 patients in the UNCOVER-3 trial, this subgroup analysis included only patients with baseline fingernail psoriasis: 116 (60.1%) placebo, 236 (61.8%) etanercept, 228 (59.1%) IXE Q4W and 229 (59.5%) IXE Q2W. At Week 12, greater mean per cent NAPSI improvements were achieved in IXE Q4W (36.7%) and IXE Q2W (35.2%) vs. placebo (-34.3%, P < 0.001 each comparison) and etanercept (20.0%, P = 0.048 vs. Q4W, P = 0.072 vs. Q2W). At Week 60, mean per cent NAPSI improvement was >80% regardless of initial treatment. At Week 12 (nonresponder imputation), complete resolution (NAPSI = 0) was achieved in 19.7% (IXE Q4W), 17.5% (IXE Q2W), 4.3% (placebo, P < 0.001 each comparison) and 10.2% (etanercept, P < 0.05 each comparison) of patients. By Week 60, >50% of patients achieved complete resolution. CONCLUSIONS: At Week 12, significant improvements in fingernail psoriasis were achieved with ixekizumab therapy. With IXE Q4W maintenance dosing, additional improvement was demonstrated through 60 weeks, and >50% of patients achieved complete resolution. Registered at clinicaltrials.gov: NCT01646177.

Current management of scalp psoriasis.

The scalp is involved in up to 80% of individuals with psoriasis. Eighty percent of those with scalp psoriasis experience a negative impact on quality of life. Topical treatment with corticosteroids with or without vitamin D3 analogues is the mainstay of treatment. Topical therapy most suitable for the scalp is formulated as a solution, lotion, gel, foam, spray, oil, or shampoo. Twice weekly maintenance in frequent relapsers may decrease the time to first relapse. Intralesional steroids, phototherapy and the excimer laser are occasionally used for resistant cases. In patients with moderate-to-severe psoriasis, apremilast, adalimumab and etanercept have been shown to significantly improve scalp psoriasis. They should be considered in patients who have failed topical therapy.

Non-melanoma skin cancer in Canada chapter 1: introduction to the guidelines

BACKGROUND: Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma, represents the most common malignancy. OBJECTIVE: The aim of this document is to provide guidance to Canadian health care practitioners on NMSC management. METHODS: After conducting a literature review, the group developed recommendations for prevention, management, and treatment of basal cell carcinomas, squamous cell carcinomas, and actinic keratoses. These tumour types are considered separately in the accompanying articles. The Grading of Recommendations Assessment, Development and Evaluation system was used to assign strength to each recommendation. RESULTS: This introduction describes the scope and structure of the guidelines and the methods used to develop them. The epidemiology of NMSC is reviewed, as are the pathophysiologic changes occurring with damage to the skin, which lead to the formation of actinic keratoses and invasive squamous or basal cell carcinomas. CONCLUSIONS: This introduction describes the need for primary prevention and offers an overview of treatment options that are discussed in later chapters of the guidelines.(AU)

Review of current therapy of pancreatic pseudocysts.

BACKGROUND AND AIMS: Therapeutic interventions for complicated pancreatitis, especially in pseudocysts and walled-off necroses as a sequel of necrotizing pancreatitis, have a long history. Originally a stronghold of classical surgery and radiology, in the last two decades this was increasingly supplemented by endoscopy, often with adjuvant percutaneous drainage, mostly reducing open surgery to a salvage intervention in case of failure and complication. This study aims to evaluate and compare the current therapeutic options for pancreatic fluid collections, especially pseudocysts. METHODS: Systematic literature search via MedLine and Pubmed was performed with comprehensive tabulations of original publications of the endoscopic, surgical and percutaneous therapeutic interventions in pancreatic pseudocysts and WON in the last 27 years. Only studies including more than 10 cases were further analysed. The results with regard to complications, outcome, recurrence and mortality were analysed for each approach, the risk of bias was assessed and a conclusive statement was made. RESULTS: The initial literature search identified 46 studies. 12 studies had to be excluded because the number of individuals included was too low. 34 endoscopic, 8 surgical and 8 percutaneous studies were further analysed, leading to a number of 2485 patients in this review. The short-term clinical success was 85 % for the endoscopic approach, 83 % for surgery and 67 % for the percutaneous intervention. The complication rates were 16 %, 45 % and 34 % for endoscopic, surgical and percutaneous therapy, respectively. Typical complications were hemorrhage, infection, perforation and, especially in the percutaneous approach, pancreatocutaneous fistulisation. CONCLUSION: According to the high success and low complication rates the endoscopic intervention appears as the most efficient method. But each method has its own indications, restrictions and therefore patient groups. Therefore it is reasonable to consider all the available methods in a productive interdisciplinary manner for the ultimate benefit of the patient in the future.

Wear testing of crosslinked polyethylene: wear rate variability and microbial contamination.

The wear performance of two types of crosslinked polyethylene (Marathon™ and XLK™, DePuy Synthes Inc., Warsaw, IN) was evaluated in a pin-on-disc wear tester, a hip wear simulator, and a knee wear simulator. Sodium azide was used as the microbial inhibitor in the calf serum-based lubricant. In the pin-on-disc wear tester, the Marathon wear rate of 5.33±0.54mm(3)/Mc was significantly lower (p=0.002) than the wear rate of 6.43±0.60mm(3)/Mc for XLK. Inversely, the Marathon wear rate of 15.07±1.03mm(3)/Mc from the hip wear simulator was 2.2-times greater than the XLK wear rate of 6.71±1.03mm(3)/Mc from the knee wear simulator. Differences in implant design, conformity, GUR type, and kinematic test conditions were suggested to account for the difference between the wear rates generated in the different types of wear testing apparati. In all wear tests, sodium azide was ineffective at inhibiting microbial growth in the lubricant. Eight different organisms were identified in the lubricant samples from the wear tests, which suggested the necessity of using an alternative, more effective microbial inhibitor. Careful sample preparation and thorough cleaning has shown to improve the consistency of the wear results. The wear rates generated in the hip and knee wear simulators closely reflected the wear behaviour of Marathon and XLK reported in published data that were tested under similar conditions.

Performance assessment of femoral knee components made from cobalt-chromium alloy and oxidized zirconium.

BACKGROUND: The surface characteristics of the femoral component affect polyethylene wear in modular total knee replacements. In the present retrieval study, the surface characteristics of cobalt-chromium (CoCr) alloy and oxidized zirconium (OxZr) femoral components were assessed and compared. METHODS: Twenty-six retrieved CoCr alloy femoral components were matched with twenty-six retrieved OxZr femoral components for implantation period, body-mass index, patient gender, implant type, and polyethylene insert thickness. The surface damage on the retrieved femoral components was evaluated using a semi-quantitative assessment method, scanning electron microscopy, and contact profilometry. RESULTS: The retrieved CoCr alloy femoral components showed less posterior surface gouging than OxZr femoral components; however, at a higher magnification, the grooving damage features on the retrieved CoCr alloy femoral components confirmed an abrasive wear mechanism. The surface roughness values Rp, Rpm, and Rpk for the retrieved CoCr alloy femoral components were found to be significantly higher than those of the retrieved OxZr femoral components (p≤0.031). The surface roughness values were higher on the medial condyles than on the lateral condyles of the retrieved CoCr alloy femoral components; such a difference was not observed on the retrieved OxZr femoral components. CONCLUSIONS: The surface roughness of CoCr alloy femoral components increased while the surface roughness of the OxZr femoral components remained unchanged after in vivo service. Therefore, the OxZr femoral components' resistance to abrasive wear may enable lower polyethylene wear and ensure long-term durability in vivo. LEVEL OF EVIDENCE: Level IV.

Impact of ustekinumab on health-related quality of life and sexual difficulties associated with psoriasis: results from two phase III clinical trials.

BACKGROUND: Ustekinumab, a human anti-interleukin-12/23 monoclonal antibody, has been shown to effectively treat moderate-to-severe psoriasis which significantly affects health-related quality of life (HRQoL), including patients' sexual lives. OBJECTIVES: The aim of this study was to determine if sexual difficulties associated with psoriasis are related to disease severity and whether sexual difficulties improve with skin disease during ustekinumab treatment. METHODS: In phase III PHOENIX 1 and 2 trials, psoriasis patients were randomized to ustekinumab (n=1334) at weeks 0 and 4 and q12 weeks thereafter or placebo (n=662) at weeks 0 and 4 with crossover to ustekinumab at week 12. Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) were used to assess psoriasis severity and patient-reported HRQoL respectively. Based on DLQI Question #9, impaired sexual function was defined as 'very much' or 'a lot' of sexual difficulties. RESULTS: At baseline, mean DLQI was 12.0, indicating a very large negative effect on patients' lives. Impaired sexual function was reported by 22.6% (women=27.1%; men=20.8%) and was significantly associated with increased psoriasis severity. At week 12, ustekinumab-treated patients had a greater mean improvement in DLQI (-9.13 vs. -0.53 with placebo, P<0.001) and the proportion of patients with impaired sexual function decreased from 22.4% to 2.7% compared with no change with placebo (P<0.001). Patients with greater PASI improvement experienced a greater reduction of sexual difficulties due to psoriasis. A similar pattern of improved sexual function was observed at weeks 24-28 in placebo crossover patients. CONCLUSIONS: Ustekinumab treatment is associated with significant improvement in HRQoL and sexual difficulties due to psoriasis.

Treatment of palmoplantar psoriasis with infliximab: a randomized, double-blind placebo-controlled study.

BACKGROUND: Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. OBJECTIVE: To study the safety and efficacy of infliximab in non-pustular palmoplantar psoriasis. METHODS: Patients with non-pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m-PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. RESULTS: Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m-PPPASI 75 and m-PPPASI 50 respectively compared to 8.3% for both m-PPPASI 75 (P = 0.317) and m-PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). CONCLUSIONS: This pilot study did not reach its primary endpoint of m-PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m-PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.

Successful retreatment with alitretinoin in patients with relapsed chronic hand eczema.

BACKGROUND: Patients with severe chronic hand eczema (CHE) often respond to therapy with oral alitretinoin (9-cis retinoic acid). However, the efficacy of alitretinoin after disease relapse has not been demonstrated. OBJECTIVES: To assess the efficacy and safety of a second course of oral alitretinoin in patients with severe CHE who relapsed after achieving 'clear' or 'almost clear' hands following a previous course of alitretinoin. METHODS: The double-blind study included 117 patients with CHE who had responded to therapy in an earlier clinical trial and subsequently relapsed. Patients were randomized to receive their previous treatment or placebo. Treatment was alitretinoin 30 mg or 10 mg or placebo given once daily for 12-24 weeks. Response was defined as an overall Physician's Global Assessment rating of 'clear' or 'almost clear' hands at the end of therapy. RESULTS: Response rates were 80% in patients retreated with 30 mg alitretinoin compared with 8% for placebo (P < 0.001). In patients retreated with 10 mg alitretinoin response rates were 48%, compared with 10% in the placebo group. Alitretinoin was well tolerated. Adverse reactions comprised typical retinoid class effects, and no late-arising side-effects were observed during this second course of treatment. CONCLUSIONS: The majority of patients with CHE who previously achieved 'clear' or 'almost clear' hands following treatment with alitretinoin 30 mg per day also responded to a second course of treatment. Retreatment was well tolerated. Intermittent treatment with alitretinoin is suitable for the long-term management of CHE.

Beta4 integrin promotes osteosarcoma metastasis and interacts with ezrin.

The development of pulmonary metastasis is the major cause of death in osteosarcoma, and its molecular basis is poorly understood. In this study, we show that beta4 integrin is highly expressed in human osteosarcoma cell lines and tumor samples. Furthermore, highly metastatic MNNG-HOS cells have increased levels of beta4 integrin. Suppression of beta4 integrin expression by shRNA and disruption of beta4 integrin function by transfection of dominant-negative beta4 integrin was sufficient to revert this highly metastatic phenotype in the MNNG-HOS model without significantly affecting primary tumor growth. These findings suggest a role for beta4 integrin expression in the metastatic phenotype in human osteosarcoma cells. In addition, we identified a previously uncharacterized interaction between beta4 integrin and ezrin, a membrane-cytoskeletal linker protein that is implicated in the metastatic behavior of osteosarcoma. The beta4 integrin-ezrin interaction appears to be critical for maintenance of beta4 integrin expression. These data begin to integrate ezrin and beta4 integrin expression into a model of action for the mechanism of osteosarcoma metastases.

Treatments for scalp psoriasis with emphasis on calcipotriol plus betamethasone dipropionate gel (Xamiol).

Scalp psoriasis occurs in 50%-75% of patients with plaque psoriasis. It may be the only area of the body affected, or it may be associated with disease elsewhere, including psoriatic arthritis. Most cases are treated topically, usually with steroids and/or calcipotriol. In 2008, Health Canada and the US FDA approved a stable, once-daily 2-compound gel containing calcipotriol and betamethasone dipropionate (Xamiol, LEO Pharma; Taclonex Scalp, Warner Chilcott). This once-daily therapy improves patient quality of life with a quick onset of action and greater efficacy than monotherapy with either ingredient or twice daily treatment with calcipotriol 0.005% (Dovonex, LEO Pharma) scalp solution. The gel vehicle was developed for ease of use, improved cosmetic acceptability and absorption on the scalp. By 2 weeks, approximately 60%, and by 8 weeks, approximately 70% of patients have controlled disease (i.e., absent or very mild disease). At 8 weeks, the calcipotriol and betamethasone dipropionate gel formulation has a safety profile comparable with betamethasone dipropionate and is associated with significantly fewer adverse events than calcipotriol. Xamiol may be safely used for up to 52 weeks. No cases of atrophy, striae, or steroid purpura were noted in two 52-week studies.

Pancreas oxygenation is limited during preservation with the two-layer method.

BACKGROUND: The two-layer method (TLM) for pancreas preservation reportedly improves islet yield and transplantation outcome relative to previous methods. Increased ATP concentrations support the hypothesis that these improvements are related to better oxygenation from the perfluorocarbon solution. However, there are limited direct measurements of oxygen partial pressure, (pO(2)) in pancreata preserved with the TLM. Theory predicts that only a small fraction of a human pancreas can be oxygenated externally. In this report we examine pancreas oxygenation with the TLM using theory and direct pO(2) measurements. METHODS: pO(2) profiles in cylindrical pancreata were calculated at various temperatures with a diffusion-reaction model. The pO(2) was measured using fiber optic sensors in the core of porcine pancreatic tissue preserved with the TLM in media saturated with 100% oxygen. RESULTS: The model predicts that at 8 degrees C, even in the absence of an external pO(2) gradient, oxygen penetration depth is about 1 mm and insensitive to pancreas diameter, while the oxygenated volume fraction is about 15% for a 2.5-cm-diameter pancreas. Experimental measurements verified that pO(2) is virtually zero in the core of a 1-cm-thick pancreatic piece preserved with the TLM. Penetration of solution around the sensor may be responsible for the observed lag and for the previously reported nonzero pO(2) measurements. Reoxygenation of heat-treated tissue took several hours. CONCLUSIONS: The TLM can oxygenate only a small volume fraction of a human pancreas. Pancreas oxygenation through the native vasculature should be explored to further improve yield of viable islets.