A comparison study of clinician-rated atopic dermatitis outcome measures for intermediate- to dark-skinned patients.

BACKGROUND: Atopic dermatitis (AD) assessment is more difficult in patients with skin of colour (SOC). OBJECTIVES: To compare the reliability of commonly used outcome measures for assessing AD in patients with SOC and to evaluate a novel greyscale in this population. METHODS: Twenty-five patients with AD each attended a 1-day scoring exercise based in either Sydney or Melbourne, Australia. Each patient was scored by the same five physicians using the Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator's Global Assessment (IGA) and a novel greyscale. Patients also completed the Patient-Oriented Eczema Measure and quality-of-life measures. A Mexameter was used to measure baseline melanin indices. Ten random patients were rescored to test intrarater reliability. RESULTS: We included 11 light-skinned patients (melanin index ≤ 200) and 14 patients with SOC (melanin index > 200) in the cohort. The inter-rater intraclass correlation coefficients (ICCs) were EASI 0·83 [95% confidence interval (CI) 0·66-0·94] for light skin and 0·77 (95% CI 0·60-0·91) for SOC; oSCORAD 0·68 (95% CI 0·44-0·88) for light skin and 0·74 (95% CI 0·54-0·89) for SOC; and IGA 0·80 (95% CI 0·62-0·93) for light skin and 0·70 (95% CI 0·49-0·87) for SOC. The greyscale had an ICC of 0·78 (95% CI 0·60-0·91) when replacing the EASI's erythema scale for patients with SOC. All scores showed excellent intrarater reliability for all skin types. Erythema component analysis showed that erythema did not contribute to variability. CONCLUSIONS: EASI showed excellent reliability for patients of all skin colours, and is recommended as the optimal core measure for patients with all skin colours.

VEGF remains an interesting target in advanced pancreas cancer (APCA): results of a multi-institutional phase II study of bevacizumab, gemcitabine, and infusional 5-fluorouracil in patients with APCA.

BACKGROUND: We investigated the safety and efficacy of bevacizumab combined with gemcitabine followed by infusional 5-fluorouracil (5-FU) in patients with advanced pancreas cancer (APCA). DESIGN: Patients with untreated APCA received bevacizumab 10 mg/kg, gemcitabine 1000 mg/m(2) over 100 min, and 5-FU 2400 mg/m(2) over 48 h on days 1 and 15 of each 28-day cycle. The primary end point was the proportion of patients with progression-free survival (PFS) at 6 months from initiation of therapy. If PFS at 6 months was ≥41%, the regimen would be considered promising. RESULTS: Forty-two patients were enrolled in the study; of which, 39 were evaluable for primary end point. PFS at 6 months was 49% (95% CI 34% to 64%). Median PFS was 5.9 months (95% CI 3.5 to 8.1) and median overall survival (OS) was 7.4 months (95% CI 4.7 to 11.2). Partial response and stable disease occurred in 30% and 45% of patients, respectively. Treatment-related hypertension and normal baseline albumin correlated with an improved response rate, PFS and OS. Grade 3 to 4 toxicities included fatigue (14%), hypertension (5%), and venous thrombosis (5%). CONCLUSIONS: The study met its primary end point. Further investigation of anti-VEGF therapy in combination with fluoropyrimidine-based therapy is warranted in APCA. Treatment-related hypertension and normal baseline albumin may predict for the efficacy of bevacizumab and should be investigated in prospective studies.

Domains of importance for parents, medical professionals and youth with cerebral palsy considering treatment outcomes.

BACKGROUND: The aim of this study was to assess the domains of importance in therapeutic intervention for cerebral palsy (CP) using categories of the International Classification of Functioning, Disability, and Health - Children and Youth Version (ICF-CY). METHODS: A total of 17 youth, 19 parents and 39 medical professionals responded to the open-ended query: 'What are the things you find most important to consider when you evaluate the effects of an intervention for yourself/your child/your patient with cerebral palsy?' Surveys were either mailed or conducted on-line. Responses were coded by two reviewers using the ICF-CY and discrepancies were resolved. RESULTS: Responses were distributed across the ICF-CY domains of Body Functions and Structures, Activities and Participation, and Environmental Factors, as well as non-ICF-CY concepts including quality of life. The most common responses overall were pain, motor function, mobility, community life and public services. Youth identified strength, gait pattern, hand/arm use and use of assistive technologies as priorities whereas parents were concerned with motor function, communication, mobility and provision of public services. Medical professionals listed pain, function, mobility, community life and participation most often. CONCLUSIONS: All surveyed groups indicate a desire to see changes in body functions and structures (pain, mental function, strength, movement), activities and participation (communication, hand/arm use, walking, school, recreation/community life) and quality of life following therapeutic interventions for CP. These results demonstrate the multiple, varied concerns regarding CP across the spectrum of functioning and health.

Quality of life evaluation in epidermolysis bullosa (EB) through the development of the QOLEB questionnaire: an EB-specific quality of life instrument.

BACKGROUND: Epidermolysis bullosa (EB) has a profound effect on quality of life (QOL); however, generic QOL assessments are poor indicators of the impact of EB. OBJECTIVES: To develop a valid and reliable EB-specific QOL tool for use in measuring the effects of disease impact and interventions. METHODS: Open, nonstructured interviews were conducted with 26 patients with EB, along with 33 family members and 11 health professionals (70 individuals) for item generation. A pilot questionnaire was compiled, refined and distributed to 130 patients with EB. From the 115 returned questionnaires a principal axis factor analysis was undertaken producing a 17-item final questionnaire. Discriminative validity was assessed by differences in scores between EB subtypes. Content validity was assessed by expert ranking of items in terms of importance. Construct validity was evaluated by correlation with existing QOL tools. Test-retest reliability and internal consistency were evaluated. Factor analysis was performed. RESULTS: A 17-item questionnaire was developed: the QOLEB questionnaire. This gave distinguishing QOL scores to different EB subtypes, and correlated highly with existing QOL instruments. CONCLUSIONS: The QOLEB questionnaire is the first EB-specific QOL measurement tool, and is a valid and reliable measurement tool for the quantification of QOL in patients with various subtypes of EB. In addition, the QOLEB has potential as a sensitive instrument to monitor QOL, and to identify dimensions of QOL as targets for interventions and research.

Podophyllin reaction mimicking Bowen's disease in a patient with delusions of verrucosis.

A 40-year-old woman presented with a delusion of warts on the forehead, for which she was applying podophyllin toxin. A skin biopsy was taken, which showed prominent mitotic figures in the basal and suprabasal layers of the epidermis and apoptotic keratinocytes. Histopathologically Bowen's disease was suspected, but was discounted after clinicopathological correlation was obtained and showed absence of epidermal atypia or disorganization. This case demonstrates the histological resemblance of podophyllin reaction to Bowen's disease. Differentiation of self-inflicted from organic skin disease may be difficult, especially where histopathological findings are confounded by cutaneous application of toxins.

Phase II clinical trial of 13-cis-retinoic acid and interferon-alpha-2a in patients with advanced esophageal carcinoma.

BACKGROUND: Interferon in combination with 5-fluorouracil has been shown to be active in squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the esophagus. 13-cis-retinoic acid (CRA) has chemopreventive activity in SCC of the head and neck, and, in combination with interferon, has antitumor activity in SCC of the skin and cervix. METHODS: The activity and toxicity of CRA and interferon-alpha-2a (IFN) in patients with advanced esophageal carcinoma was evaluated in a Phase II single institution trial. Patients had unresectable or metastatic AC or SCC of the esophagus. One prior chemotherapy regimen was allowed. IFN was given by daily subcutaneous injection at a dose of 3 million U and CRA was taken orally at a dose of 1 mg/kg/day in 2 divided doses. Treatment was given in cycles of 4 weeks and continued until documented disease progression. RESULTS: Of the 19 patients entered, 15 were evaluable for response and toxicity. One patient was evaluable for response only and one patient was evaluable for toxicity only. Evaluable patients were predominantly male (15 patients), and had AC (13 patients). All had AJCC Stage IV disease and 12 were pretreated. Patients completed an average of two cycles of therapy (range, one to six cycles) prior to progression of disease. National Cancer Institute Common Toxicity Criteria Grade 3/4 toxicity was notable for nausea (25%) and fatigue (31%). No major objective responses were recorded. Eleven patients with AC and 3 patients with SCC had rapid progression of disease. One patient with AC was found to have a minor response for 22 weeks and 1 patient with AC had stable disease for 45 weeks. CONCLUSIONS: This regimen had no significant activity in patients with advanced AC of the esophagus. Further evaluation of IFN plus CRA, using this dose and schedule, is not recommended. In comparison with prior trials of this therapy, a surprising amount of severe nausea and fatigue was observed in this trial.

Biomarker assessment of the effects of coal strip-mine contamination on channel catfish.

A suite of biomarkers was used to evaluate acute (1-day) to semichronic (3-month) heavy metal-induced toxicity in channel catfish, lctalurus punctatus, caged at an abandoned strip mine and a noncontaminated reference site. Assays performed include indicators of metabolic, hematological, osmoregulatory, and genotoxic stress. Two cage designs were used to evaluate the importance of exposure routes: one excluding contact with the sediments and the other allowing contact with water and sediments. Significant DNA strand breakage was observed in catfish exposed to both exposure regimens, but evidence of DNA repair was observed only in water-exposed catfish. Transient increases in hemoglobin, delta-aminolevulinic acid dehydratase, and hematocrit levels were observed at 1 month's exposure for both exposure regimens, followed by a return to control levels for the duration of the study. Environmental conditions (i.e., weather-related changes in water quality) may have contributed to the variable plasma chloride and glucose levels observed in all catfish exposed to strip-mine wastes. The transient changes in biomarkers followed by a return to reference values represent an initial stress and an acclimation to normal levels.

Biomarker assessment of the effects of petroleum refinery contamination on channel catfish.

A suite of biomarkers was used to evaluate acute (1- and 7-day) heavy metal-induced toxicity in channel catfish, Ictalurus punctatus, caged at an abandoned petroleum refinery and a non-contaminated reference site. Assays performed include indicators of metabolic, hematological, osmoregulatory, and genotoxic stress. Two cage designs were utilized to evaluate the importance of exposure routes: one allowing exclusive contact with the water column and the other allowing contact with water and sediments. Data collected at 1 and 7 days postexposure indicated that the experimental fish were stressed, having significant increases in blood glucose. After 7 days of exposure, two hemodynamic parameters, hemoglobin and delta-aminolevulinic acid dehydratase, were significantly increased. There were no significant differences observed in other parameters measured.

Clinical evaluation of autotransfusion during liver transplantation.

The clinical suitability of intraoperative autotransfusion was evaluated in 25 patients undergoing orthotopic liver transplantation using a Cell Saver #4 (Haemonetics) with acid-citrate-dextrose anticoagulation. In the first 14 patients (phase 1), biochemical, hematologic, coagulation, and semiquantitative bacteriologic studies were performed from the collected blood, processed blood, and patients' blood before and after 500 mL of autotransfusion. The acid-citrate-dextrose solution produced adequate anticoagulation, and the system effectively removed most of the potassium, red blood cell fragments, plasma free hemoglobin, bilirubin, coagulation factors, platelets, and fibrin degradation products. Autotransfusion (500 mL) did not alter coagulation, electrolyte balance, and hematologic findings in recipients except for a clinically insignificant increase in plasma free hemoglobin. Seventeen of 56 samples of the collected blood or processed blood were positive for coagulase (-) Staphylococcus (occasional or rare), but blood cultures before and after autotransfusion were negative in all patients. In the next 11 patients (phase 2), a quantitative bacteriologic study was performed from the collected blood, processed blood, skin, bile duct stump, peritoneal cavity, and room air using a mock reservoir. The processed blood was not transfused. All blood cultures from the patients were sterile. However, coagulase (-) Staphylococcus or Bacillus sp was seen in two cultures from skin, three from the processed blood, and three from air, suggesting that room air and skin were the sources of contamination. When the patients of the two phases of study were compared, postoperative blood cultures were all sterile, and renal function was similar. Therefore, autotransfusion appears to be clinically acceptable during liver transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)