Outcome assessment in dermatology clinical trials and cochrane reviews: call for a dermatology-specific outcome taxonomy.

BACKGROUND: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision-making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology-specific reporting strategy that uses precise and consistent outcome definitions. OBJECTIVES: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. METHODS: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology-specific outcome taxonomy. RESULTS: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology-specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non-comparable outcome measurement instruments, metrics and reporting. CONCLUSIONS: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology-specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence.

The effectiveness of two silicone dressings for sacral and heel pressure ulcer prevention compared with no dressings in high-risk intensive care unit patients: a randomized controlled parallel-group trial.

BACKGROUND: There is a high incidence of pressure ulcers in high-risk settings such as intensive care. There is emerging evidence that the application of dressings to pressure ulcer predilection areas (sacrum and heels) improves prevention strategies. OBJECTIVES: To determine whether preventive dressings, applied to the sacrum and heels of high-risk patients in intensive care units, in addition to standard prevention, reduces the incidence of pressure ulcers. METHODS: Between June 2015 and July 2018, a randomized, controlled, two-arm, superiority pragmatic study was performed with a concealed 1 : 1 allocation to the intervention and control group. Patients assigned to the intervention group had dressings applied to the sacrum and heels. RESULTS: In total, 7575 patients were screened for eligibility and 475 patients were included and allocated to both groups. Finally, 212 patients in the intervention group and 210 in the control group were analysed. The mean age was 63·5 years and the majority of patients were male (65·4%). The cumulative pressure ulcer incidence category II and above was 2·8% in the intervention, and 10·5% in the control group (P = 0·001). Compared with the control group, the relative risk in the intervention group was 0·26 [95% confidence interval (CI) 0·11-0·62] and the absolute risk reduction was 0·08 (95% CI 0·03-0·13). CONCLUSIONS: The results indicate that the application of dressings, in addition to standard prevention, in high-risk intensive care unit patients is effective in preventing pressure ulcers at the heels and sacrum. What's already known about this topic? Pressure ulcers are severe soft tissue injuries and wounds, which occur worldwide in all healthcare settings. Despite preventive interventions, pressure ulcers still develop. There is emerging evidence that dressings help to prevent pressure ulcers. What does this study add? The incidence of pressure ulcers in intensive care units among high-risk patients remains high. The application of dressings to the sacrum and heels, in addition to standard preventive measures, reduces the relative and absolute risks for the development of pressure ulcers. The application of preventive dressings at the heels and sacrum seems to be feasible in intensive care settings.

Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative.

Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG-COUSIN) supports the development of core outcomes in dermatology. In the second CSG-COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers.

Expression of the PIP/GCDFP-15 gene and survival in breast cancer.

Expression of the PIP/GCDFP-15 gene was determined by measuring PIP/GCDFP-15-mRNA in breast carcinomas of 91 patients. The patients were followed-up for an average of 47 months after initial diagnosis and treatment of the disease. There were no deaths in the group of 14 patients with tumours of high PIP/GCDFP-15-mRNA levels, while 16 of 77 patients of the group with low PIP/GCDFP-15-mRNA tumour levels died. A similar advantage for high PIP/GCDFP-mRNA expression was observed with regard to disease free survival.

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of stromelysin-3 and nm23 in breast carcinoma and related tissues.

Biological functions proposed for the ST3 and nm23 genes in tumour development and progression seem to be directly opposed. Stromelysin-3 (ST3) is a putative member of the matrix metalloproteinase family. ST3 has been implicated in the progression of epithelial malignancies, specifically with regard to an invasive (and therefore potentially metastasizing) phenotype. The nm23 gene, on the other hand, encodes a nucleoside diphosphate kinase which allegedly has a metastasis-suppressor-type function. It was therefore of interest to compare the expression of ST3 and nm23 in various surgically excised normal and neoplastic breast tissues. RNA was isolated from over 200 surgical specimens and studied by Northern blots. Normal breast tissues did not express ST3, and ST3 expression was detected in only 1 of 20 normal axillary lymph nodes. None of 7 fibroadenomas expressed ST3. In contrast, 60% of primary and metastatic breast carcinomas contained ST3-mRNA. The expression of ST3 was mainly confined to invasive carcinomas and was observed less frequently in pure ductal carcinoma in situ (DCIS) lesions. Our results support the suggestion that ST3 expression is related to the malignant process in breast cancer. The role of nm23 is far less clear-cut.

Hormone-regulated genes (pS2, PIP, FAS) in breast cancer and nontumoral mammary tissue.

Expression of the hormone-regulated genes, pS2, prolactin-inducible protein (PIP) and fatty acid synthetase (FAS), was investigated by Northern blotting in primary breast carcinoma, metastatic breast cancer in axillary lymph nodes, in uninvolved breast tissue from mastectomies and in normal lymph nodes. There were considerable differences in expression of the genes between the tissues. The proportion of tissues containing PIP-mRNA decreased from uninvolved breast tissue to primary breast carcinoma to metastatic carcinoma. The reverse applied to FAS-mRNA which was found more often in metastatic cancer than in primary cancer, and least frequently in uninvolved breast tissue. Yet another pattern was observed for pS2 expression. The highest proportion of tissues demonstrating gene expression was found in primary breast cancer with both metastatic tumor and uninvolved breast tissue expressing the gene less frequently. pS2-mRNA and PIP-mRNA could only rarely be detected in trace amounts in normal lymph nodes. In contrast, FAS-mRNA was present in about one third of normal lymph nodes. Only pS2-mRNA showed an association with estrogen and progesterone receptor status.

Expression of the pS2 gene in normal breast tissue.

pS2 expression in normal breast tissue removed for cosmetic reasons was significantly lower than in uninvolved breast tissues from mastectomies for breast carcinomas. It is speculated that the presence of the carcinoma, or factors related to its development, could be the reason for this difference.

Stromelysin-3 expression in breast cancer biopsies: clinico-pathological correlations.

Stromelysin-3 expression was studied by Northern blotting in 222 tissue samples including primary and metastatic breast carcinoma and normal breast tissue. Uninvolved breast tissue from mastectomy specimens, normal breast tissue from reduction mammoplasties and normal lymph nodes did not contain stromelysin-3 mRNA. About 62% of primary and metastatic breast carcinomas, but only 1 of 10 in situ ductal carcinomas, expressed stromelysin-3. Stromelysin-3 mRNA was found more often in estrogen-receptor-positive carcinomas and in histological grade-1 carcinomas. There was no significant correlation between stromelysin-3 expression and other prognostic factors, including tumor size, lymph-node involvement, age of patient, vascular invasion and cathepsin-D.

Expression of the pS2 gene in breast cancer--a comparison of pS2 protein radioimmunoassay and immunohistochemistry.

pS2 expression was studied in a series of 82 primary breast carcinomas using and comparing a radioimmunoassay (RIA) technique and immunohistochemistry (IPOX). There was close correlation of the results obtained with each technique. Accurate and reliable determination of pS2 status in breast cancer can be made on the basis of immunohistochemistry using formalin fixed paraffin embedded sections. Immunohistochemical determination of pS2 status may be used in situations where the RIA technique cannot be applied, i.e. instances when fresh tumor tissue is not available.

Detection of estradiol-induced messenger RNA (pS2) in uninvolved breast tissue from mastectomies for breast cancer.

pS2 mRNA was estimated in uninvolved breast tissue and breast carcinoma from the same patients. pS2 mRNA was clearly detected in 14 of 59 uninvolved breast tissues and in 30 of 58 breast carcinomas. pS2 mRNA was found more frequently in uninvolved breast tissue of premenopausal women than in that of postmenopausal women.

Expression of the pS2 gene in breast tissues assessed by pS2-mRNA analysis and pS2-protein radioimmunoassay.

The expression of the pS2 gene in breast tissues was assessed by measuring pS2-protein using a radioimmunoassay, and by determining pS2-mRNA using Northern blotting. There was a good correlation between the two measurements, indicating that expression of the pS2 gene in breast tissues may be assessed by either method. Since radioimmunoassay is technically easier and more efficient than Northern blotting, radioimmunoassay will be the method of choice in routine applications.

Detection of pS2 messenger RNA in gynecological cancers.

Estrogen-inducible pS2 mRNA was previously detected in human cancer cell lines the growth of which was sensitive to estrogen. In the present study, the expression of the pS2 gene was analyzed in 111 gynecological carcinomas. The pS2 message was detected in greatest abundance in 6 primary carcinomas of the ovary (6 of 29), 4 of these being mucinous cystadenocarcinomas. A secondary carcinoma of the ovary, and another of the omentum (1 of 4), also contained detectable levels of pS2 mRNA. Weak pS2 mRNA signals were occasionally observed in endometrial (2 of 55) and cervical carcinomas (2 of 33) as well. There was a poor correlation between estrogen receptor and pS2 mRNA in ovarian carcinomas.

Hormone-sensitive gene expression in breast tumours.

The expression of genes specifically induced by estrogens (pS2), prolactin (PIP) or progestins (Pg8) was measured in primary breast tumours. A highly augmented pS2 gene expression was evident in 55% of estrogen receptor (ER)+, progesterone receptor (PR)+ tumours but was absent in ER- PR- tumours. There was no clear cut correlation between augmented levels of PIP and Pg8 mRNAs in tumours and ER and PR status. Tumours from premenopausal patients were more likely to contain high levels of Pg8 mRNA (P less than 0.038), whereas tumours from postmenopausal patients tended to have augmented levels of PIP mRNA (P less than 0.053).

Estrogen and progesterone receptor assays, by the EIA method (Abbott), of low-speed supernates of breast-cancer homogenates.

Estrogen receptor (ER) and progesterone receptor (PR) assays were performed by solid-phase enzyme immunoassays (Abbott) on low-speed (2600 x g) and high-speed (100,000 x g) supernates of breast-cancer homogenates. The results were similar, indicating that ultracentrifugation is not essential for ER and PR assays with the Abbott kit.

Urinary steroid profiles in pregnancy by capillary column gas chromatography.

A qualitative and quantitative method for the estimation of urinary steroids during pregnancy by capillary column gas chromatography has been developed. Steroid conjugates were hydrolysed by enzymes and free steroids isolated by extraction using SEP-PAK C18 cartridges. Methoxime-trimethylsilyl derivatives of the steroids were characterized by packed column gas chromatography-mass spectrometry and subsequently by their retention indices on capillary column gas chromatography. Of the 48 peaks resolved on the profiles about 35 were identified as steroids. The retention indices of reference steroids were very reproducible in the short term showing a mean coefficient of variation of 0.015%. The columns allowed 95% valley resolution of steroids whose retention indices differed by only 7 units. The use of an on-column injection technique contributed to the high precision for replicate injections (coefficient of variation less than 1%) while for reference steroids, and well-resolved peaks in the urine profile, the mean coefficient of variation for the complete assay was less than 10%. To the best of our knowledge this is the first report concerning the quantitation, with good precision, of a large number of steroids in pregnancy urine.

[Perioperative antibiotic prevention in colon and rectum surgery. A randomized study on the value of single dose prevention]. / Perioperative Antibiotikaprophylaxe in der Kolon- und Rektumchirurgie. Eine randomisierte Studie zum Wert der 'single-dose' Prophylaxe.

In a prospective randomized trial clinical results of one-shot-prophylaxis with Tinidazole (Group I, n = 50) versus 9 doses of Metronidazole (Group II, n = 50) as perioperative short-time-prophylaxis were compared. The rate of postoperative wound infections was not significantly different in the groups (p = 0,09). (1/50 in Group I = 2%, 5/50 in Group II = 10%). Postoperative complications clearly occurred less frequently in the first group than in the second one (12% versus 34%, p0,01). Our investigation indicates that prophylactic treatment with Tinidazole as a preoperative high and single dose is important for preventing postoperative infection in patients undergoing bowel surgery.

Prenatal diagnosis of X-linked ichthyosis.

Prenatal diagnosis of X-linked ichthyosis in a case of steroid sulfatase deficiency was made at 16 weeks by the demonstration of (1) high levels of dehydroepiandrosterone sulfate in amniotic fluid; (2) gross deficiency of steroid sulfatase activity in cultured amniotic fluid cells; (3) very low estriol concentrations in maternal blood and urine; (4) increased maternal plasma dehydroepiandrosterone sulfate; and (5) a characteristic maternal urinary steroid profile with greatly increased levels of 16 alpha-hydroxydehydroepiandrosterone. The latter method is particularly useful since it requires no invasive procedures for the patient and is very specific.