Development of a core outcome domain set for clinical research on capillary malformations (the COSCAM project).

BACKGROUND: Due to a large variety in treatment outcomes reported in therapeutic trials and lacking patient-relevant outcomes, it is hard to adequately compare and improve current therapies for patients with capillary malformations (CMs). The Core Outcome Set for Capillary Malformations (COSCAM) project aims to develop a core outcome set (COS) for use in future CM trials, in which we will first develop a core outcome (sub)domain set (CDS). Here, we describe the methods for the development of a CDS and present the results of the first development stage. METHODS: The COSCAM project is carried out according to the recommendations of the Cochrane Skin Core OUtcomes Set INitiative (CS-COUSIN) and the Core Outcome Measures in Effectiveness Trials (COMET) initiative. During the first stage, we identified all potentially relevant outcome subdomains based on a systematic review, two focus group sessions and input from patient representatives of Dutch patient organizations and the COSCAM-founding group. In stage two, we will present the subdomains in a three-round e-Delphi study and online consensus meeting, in which CM patients, parents/caregivers and CM experts worldwide rate the importance of the proposed subdomains, hereby finalizing the core outcome (sub)domains of the CDS. RESULTS: A total of 67 potential outcome subdomains were included; sixteen were previously used in the literature, 20 were proposed by Dutch patients and their parents/caregivers (n = 13) in focus group sessions and 38 were suggested by the experts of the COSCAM-founding group. Seven were excluded because of overlap. CONCLUSION: The final CDS may serve as a minimum standard in future CM trials, thereby facilitating adequate comparison of treatment outcomes. After this CDS development, we will select appropriate outcome measurement instruments to measure the core outcome subdomains.

A systematic review of outcome reporting in laser treatments for dermatological diseases.

The standardization of outcome reporting is crucial for interpretation and comparison of studies related to laser treatment of skin disorders. In collaboration with the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN), a procedure has been proposed to find consensus on the most important generic outcome domains (what to measure) for implementation in the international Laser TrEAtment in Dermatology (LEAD) registry. As the first step in the development of a generic outcome set for the LEAD registry, we undertook a systematic review to identify outcomes, outcome measurement instruments, methods and definitions reported in recently published literature of laser treatments for skin disorders. A systematic search was conducted and generated a total of 707 papers. We assessed 150 studies including all types of studies involving laser treatments for the skin. Two researchers independently extracted the type, definition and frequency of all outcomes and used outcome measurement instruments. We identified 105 verbatim outcomes that were categorized into eight domains recommended by the COMET framework: appearance, long-term effects, physician and patient-reported physical signs, satisfaction, health-related quality of life, psychological functioning and adverse events. Heterogeneity in outcome reporting (e.g. categories and outcome measurement instruments) was high, and definitions were insufficiently reported. There was a clear under representation of life impact domains, including satisfaction (23%) quality of life (3%) and psychological functioning (1%). Outcome reporting concerning laser treatments for the skin is heterogeneous. Standardized outcomes are needed for improving evidence synthesis. Results of this review will be used in the next step to reach consensus between stakeholders on the outcome domains to be implemented in the LEAD registry.

Laser treatment of hyperpigmented lesions: position statement of the European Society of Laser in Dermatology.

BACKGROUND: Lasers and intense pulsed light sources (IPLS) are proposed for the treatment of many pigmentary disorders. They are sometimes considered as magic tools able to remove any type of lesions. Although being the best option for several hyperpigmented lesions, they can also worsen some conditions and have potential side-effects. OBJECTIVE: The aim of this review was to give evidence-based recommendations for the use of lasers and IPLS in the treatment of hyperpigmented lesions. METHODS: These recommendations were produced for the European Society of Laser Dermatology by a consensus panel made up of experts in the field of pigment laser surgery. Recommendations on the use of lasers and light treatments were made based on the quality of evidence for efficacy, safety, tolerability, cosmetic outcome, patient satisfaction/preference and, where appropriate, on the experts' opinion. RESULTS: Lasers and IPLS are very effective for treating many hyperpigmented lesions such as lentigos, dermal hypermelanocytosis or heavy metal depositions. In the other hand, they have to be considered with great caution for other disorders, such as café au lait macules, melasma or postinflammatory hyperpigmentation. After making the correct diagnosis, if lasers or IPLS are indicated, the optimal wavelengths and parameters will be chosen taking into account the skin phototype, origin and depth of the target pigments. CONCLUSION: Although potentially very effective, lasers and IPLS cannot be proposed for all types of hyperpigmented lesions. In all cases, precise recognition of the disorder is mandatory for choosing between these devices and other therapeutic approaches.

[Laser and light therapy for treatment of radiation dermatitis]. / Laser- und Lichttherapie zur Behandlung der Strahlendermatitis.

Radiation dermatitis (RD), an inflammatory skin disease that can be an unwanted side effect of medical radiation therapy (RT), most commonly occurs in patients undergoing cancer of the ENT, anal, and vulvar regions. The side effects on the skin and mucous membranes occur within a few weeks after the initiation of RT; however, late side effects can develop months to years after the RT. Therapeutically, various treatment approaches are considered such as pentoxifylline, hyperbaric oxygen therapy, laser therapy, and PBMT. In order to limit the reduced quality of life of patients with RT-induced fibrosis, supportive care consisting of pain therapy, psychological support, and wound care is necessary.

Incremental build-up food challenge--a new diagnostic approach to evaluate pseudoallergic reactions in chronic urticaria: a pilot study: stepwise food challenge in chronic urticaria.

BACKGROUND: The remission rate of patients with chronic urticaria (CU) due to elimination diets varies between 31% and 71%. However, the diagnostic value of subsequent traditional oral provocation tests with food additives in capsules remains unsatisfactory. OBJECTIVES: A newly incremental build-up food challenge (IBUF) for patients with CU was designed and implemented in an open pilot study. Primary endpoint was the percentage of patients developing urticaria during at least one step of IBUF after an initial complete remission due to a pseudoallergen-free elimination diet. METHODS: In total, 153 patients with CU were submitted for 5 weeks to a pseudoallergen-free diet. All patients with remission were included to the 6-week IBUF protocol, containing pseudoallergen-rich foods in a systematic and additive manner. The recurrence and severity of CU was evaluated by urticaria score. Subjective disturbance and quality of life were evaluated by patients' diary, visual analogue scale and quality of life questionnaire (CU-Q2oL). Subsequently, patients were followed up for 3-24 months after IBUF by a telephone interview. RESULTS: A total of 104 patients completed the pseudoallergen-free diet, whereby 51% reported partial, 17% complete and 32% no remission due to the diet. All diet responders showed a decrease in subjective impairment, urticaria and quality of life score (P<0.001 each). Eighty-six percent (12/14) of the patients reaching complete remission, showed a recurrence of urticaria symptoms during the IBUF protocol. Fifty-eight percent (7/12) of these patients still remained free of symptoms due to avoidance of IBUF-identified foods at telephone follow-up. In patients with partial remission to pseudoallergen-free diet, however, IBUF did not provide information about the cause of urticaria symptoms. CONCLUSIONS: The newly developed IBUF protocol seemed to be a promising method for identifying individually incompatible foods in some CU patients. IBUF should be verified by randomized controlled trials to gain additional evidence for its diagnostic value.

Effect of tourism and trade on intestinal parasitic infections in Guatemala.

A survey was performed to determine if infection with gastrointestinal parasites differs between the rural and urban poor inhabitants of Guatemala. A total of 317 stool samples from children in two towns, one rural and one urban, were examined using the formalin-ether concentration method. The overall prevalence of parasites in infected children was 67%, 20%, 30%, and 22%, respectively for Ascaris lumbricoides, Trichuris trichiura, Giardia duodenalis and Entamoeba histolytica in the rural town of La Mano de Leon and 49%, 14%, 15%, and 21%, respectively in the urban town of Santa Maria de Jesus. Two sub-studies were carried out to determine the effects of (1) gender and (2) age on the rate of parasitic infections. Female children in the 1-to 6-year-olds age group in Santa Maria de Jesus had more infections with A. lumbricoides and T. trichiura when compared to La Mano de Leon. A. lumbricoides was most prevalent in Santa Maria de Jesus. These results propose that accessibility to tourism and trade decreases the risk for the establishment of parasitic diseases in children of Guatemala possibly due to improvements in basic nutrition and availability of health care.

Inhibition of methionine gamma lyase deaminase and the growth of Porphyromonas gingivalis: A therapeutic target for halitosis/periodontitis.

BACKGROUND AND OBJECTIVES: Pathogenic infections caused by Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia can result in the production of volatile sulfur compounds (VSC's) and other toxic compounds from methionine catabolism that can lead to halitosis and periodontitis. Our aim is to block the activity of methionine gammalyase-deaminase (Mgld) of methionine catabolism to prevent halitosis/periodontitis. DESIGNS: Cloned, expressed, Mgld protein was tested for purity by SDS-PAGE and western blotting. Mgld activity was tested by UV-vis spectroscopy and DTNB assay. Effects of Mgld inhibitor propargylglycine (PGLY) was tested on P. gingivalis growth by turbidity measurements. The effects of PGLY on oral epithelial and periodontal ligament cells in culture at different concentrations and time were tested for cell viability by MTT and Live-Dead assays. Amino acid comparisons of Mgld from different oral pathogens were done using standard bioinformatics program. RESULTS: Propargylglycine (PGLY) inhibited purified Mgld activity completely. In vivo, PGLY is a potent inhibitor on the growth of the P. gingivalis over 24 h, grown at 25 °C and 37 °C. Correspondingly in vivo Mgld activity was also affected by PGLY. Amino acid comparisons of oral pathogens showed 100% identity on the key residues of Mgld catalysis. Mammalian oral cell lines with PGLY, showed no difference in cell death over untreated controls assessed by MTT and Live-Dead assays. CONCLUSIONS: PGLY arrest's VSC's production by P. gingivalis. Since initial Mgld activity is inhibited subsequent enzymatic and nonenzymatic products formed will be prevented. PGLY showed no toxicity towards cultured mammalian oral cells. Thus, PGLY can serve as a mouthwash ingredient to prevent halitosis/periodontitis.

Prevalence of yeasts in beach sand at three bathing beaches in South Florida.

The abundance and types of yeasts in the wet and dry sand of three recreational beaches in South Florida were determined. Samples were collected on 17 occasions between August 2001 and July 2002. After analyzing 102 sand samples, a total of 21 yeast species were identified by molecular methods. These isolates comprised four Basidiomycetes and 17 Ascomycetes and included eight species that had previously been reported from humans. The most frequently encountered yeasts were Candida tropicalis and Rhodotorula mucilaginosa. A greater diversity of species (16 species) was found in the dry sand above the high tide mark compared with the wet sand in the intertidal zone (11 species). Densities were also highest in the dry sand relative to wet sand (20-fold higher at Hobie beach, 6-fold higher at Fort Lauderdale Beach and 1.3-fold higher at Hollywood beach). There were no clear temporal patterns in the data and overall densities were greatest at the busiest bathing beach (Hobie Beach) where total yeasts averaged 37,720 cfu 100g(-1) dry sand and 1852 cfu 100 g(-1) in the wet sand. This concentration of yeast was significantly higher than populations at the less populated beaches. Fort Lauderdale beach had a mean count of 4130 cfu 100 g(-1) dry sand and 705 cfu 100g(-1) in the wet sand while the least populated beach, Hollywood Beach averaged 1945 cfu 100g(-1) dry sand and 1483 cfu 100g(-1) wet sand. While definitive statements cannot be made, high levels of yeasts may have a deleterious bearing on human health and the presence of such a diverse aggregation of species suggests that yeasts could have a role as indicators of beach health.

Improving diagnostic staging laparoscopy using intraperitoneal lavage of delta-aminolevulinic acid (ALA) for laparoscopic fluorescence diagnosis.

BACKGROUND: Lymph node metastases and peritoneal carcinosis, occurring as a result of gastrointestinal cancer, reduce the likelihood that conventional therapy will be adequate to remove the cancer. Although diagnostic techniques have greatly improved, it is not always possible to diagnose the entire extent of the metastases. Often, peritoneal micrometastases are not visible and may be missed during laparoscopic or open surgery. METHODS: Peritoneal carcinosis was induced in WAG-Rij rats (n = 6), by laparoscopically implanting 1,2-dimethylhydrazine-induced colon carcinoma tumor cells (CC531, 5 x 10(5)) at multiple sites within the peritoneal cavity. After 12 days of tumor growth, the animals were given delta-aminolevulinic acid (ALA) (5 mL, 3% solution in 0.17 mol/L NaHCO3) by peritoneal lavage. The tumors were visualized laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany). Fluorescence was detected by using a modified CCD camera and a special observation filter incorporated into the laparoscope. RESULTS: Peritoneal carcinoma foci ranging in size from 0.05 to 2.0 cm were clearly visible laparoscopically with conventional white light (n = 142). After blue light excitation, all 142 tumors identified with white light were also identified by fluorescence. There were an additional 30 tumors that could only be identified by blue light-induced fluorescence and were histologically confirmed to be derived from colon carcinoma tumor cells. CONCLUSIONS: Peritoneal colonic carcinoma foci were detected laparoscopically after intraperitoneal lavage with delta-aminolevulinic acid (ALA) and excitation with blue light. These experiments demonstrate that fluorescence laparoscopy is an important technique for the staging of gastrointestinal cancer, including colorectal cancer, because of the enhanced ability to detect small cancerous foci.

Clinical experience with diffusion-weighted MR in patients with acute stroke.

PURPOSE: Our purpose was to evaluate the clinical efficacy, sensitivity, and specificity of echo-planar diffusion-weighted MR imaging in patients with acute infarction. METHODS: We retrospectively analyzed 194 cases of acute ischemic stroke diagnosed clinically within 24 hours of onset and studied with echo-planar diffusion-weighted MR imaging. Examinations were considered to be positive for infarction when an increase in signal was noted on images acquired at a high b value but absent on images with a low b value. A final clinical diagnosis of acute stroke was used as the standard of reference. A subset of 48 patients scanned within 6 hours was also analyzed. RESULTS: Diffusion-weighted MR imaging studies were positive in 133 of 151 cases of infarction (88% sensitivity) and negative in 41 of 43 cases with no infarction (95% specificity). Two cases identified as positive on diffusion-weighted images had nonischemic diagnoses (1.5% false-positive rate). Diffusion-weighted imaging had a positive predictive value of 98.5% and a negative predictive value of 69.5%. Use of T2-weighted sequences as well as diffusion-weighted imaging produced no false-positive findings. Of the negative scans, 69.5% corresponded to transient ischemic attacks or infarcts (mostly small brain stem infarcts). When only cases scanned within 6 hours of onset were considered, the sensitivity rose to 94% and the specificity to 100%. CONCLUSION: Despite bias due to dependence between diffusion-weighted imaging and the final diagnosis, this analysis suggests high sensitivity and specificity for echo-planar diffusion-weighted imaging in the diagnosis of acute cerebral infarction, although negative scans did not rule out an ischemic pathogenesis.

Effect of dietary zinc on larval burdens, tissue eosinophil numbers, and lysophospholipase activity of Ascaris suum infected mice.

The effect of dietary zinc on larval burdens, tissue eosinophil numbers, and lysophospholipase (LPL) activity in the lungs and livers of BALB/c mice infected with Ascaris suum was evaluated. A suum larval numbers were increased in both liver and lungs in low zinc groups during primary and secondary infection as assessed at days 2 and 7 after egg administration. In the same groups, LPL activity and eosinophil numbers were reduced at both time points and in both tissues, with the exception of lung eosinophils in nonimmunized mice, since these animals did not develop an eosinophil response during primary infection.

The effects of chronic exercise on metabolic and reproductive functions in male rats.

Previous studies concerning the effects of swimming on various endocrine gland functions have been performed. Our study was thus designed to analyze the effects of chronic exercise (swimming) on the resting metabolic rates (RMR) of adult rats. Most of the protocols used a water temperature of 33 C. It is our contention that such a protocol is not exclusively an exercise stress, but also a hypothermic stress. The protocol of our study was designed in a way that hypothermic stress was not part of the exercise stress. Male rats were swam in 36 C water for 3 hours a day, 5 days a week for 4 months. RMR of the animals were determined 24 h after the next to last swim session. Plasma hormone levels and epididymal sperm concentrations were determined in animals sacrificed 24 h after the last swim period. Exercising animals had a RMR 16% greater than that of control animals (p < 0.02), yet total and free thyroxine and total and free triiodothyronine were not significantly elevated. Neither plasma testosterone nor epididymal sperm counts were significantly reduced in the exercising animals. It appears that chronic exercise produces an elevation in RMR which is unrelated to thyroid gland activity and does not suppress the hypothalamic-pituitary-gonadal axis.

Seminal vesicle growth induced by Ascaris suum infection.

This study was designed to determine the effect of Ascaris suum infection upon growth of mouse vesicular glands. Mice were infected with varying dosages of A. suum eggs and killed after six weeks. Results indicated a dose dependent increase in seminal vesicle weight, independent of total body weight.

Alterations in Ascaris suum larval burdens, eosinophil numbers, and lysophospholipase activity associated with low levels of dietary iron.

The effect of various amounts of dietary iron on the immune response was investigated using BALB/cAnNCr/BR mice infected with Ascaris suum. Changes in numbers of larvae, numbers of eosinophils, and levels of lysophospholipase (LPL) activity in lung or liver tissues were analyzed from nonimmune and immunized mice at 2 and 7 days postinfection (PI). Various iron diets did not influence the numbers of tissue larvae, eosinophils, or the LPL activity in lungs or livers of nonimmunized mice at various times after infection. Lung and liver LPL activity was reduced in immunized mice without significant changes in larval numbers at 2 days PI. At 7 days PI, lung and liver LPL activity, eosinophil numbers, and numbers of larvae were increased in immunized mice receiving low iron diets. Results confirm that low iron diets affect the host response to A. suum.

A study of risk factors associated with the prevalence of Cryptosporidium in villages around Lake Atitlan, Guatemala.

Cryptosporidium parvum is an endemic, zoonotic coccidian parasitosis that is highly prevalent in third-world countries where waterborne fecal contamination of food and drink or person-to-person contact with oocysts are the most common methods of transmission of the enteric protozoan. This type of transmission of the parasite made the villages around Lake Atitlan, Guatemala a unique site to compare environmental risk factors with the level of Cryptosporidium infections in the local residents. The study was carried out in two villages, San Antonio Palopo and Santa Catarina Palopo, located in the highlands above the shores of the lake. Smears from stool specimens of patients with gastroenteritis were processed using Kinyoun's modified acid-fast stain and observed with light microscopy. Of the 100 residents examined from the two villages, 32% had Cryptosporidium infections. Female children had the highest prevalence of infection (44% in San Antonio Palopo and 46% in Santa Catarina Palopo, p<0.05), and they also had significantly higher infection rates than males, 50% vs. 17%, respectively. The prevalence rate was not influenced by the season of the year or by the location of the residents. We found differences in prevalence rates due to age and gender, and we suggest that the high infection rates of specific groups are associated with their exposure to the contaminated water supply from Lake Atitlan.

Protection against Pasteurella pneumotropica during infection with Angiostrongylus cantonensis.

Lung infections of specific-pathogen-free rats were studied to determine cross-immunity between infections with Pasteurella pneumotropica and Angiostrongylus cantonensis. Rats were found to have differences in mortality due to pneumonic infections with P pneumotropica and A cantonensis and to coinfections of P pneumotropica and A cantonensis. Single infections of P pneumotropica were not dosage-dependent in their lethality for specific-pathogen-free rats. The mortality of coinfection with P pneumotropica and A cantonensis was significantly lower than that of a monoinfection with P pneumotropica, demonstrating a cross-protective phenomenon.

Seminal vesicle and coagulating gland growth induced by intraperitoneal inoculation of fungi in mice.

The effect of fungi on the growth of body organs in mice was investigated. Single, intraperitoneal injections of yeasts (Cryptococcus albidus, Saccharomyces cerevisiae, Schizosaccharomyces octosporus) or molds (Aspergillus niger, Geotrichum candidum, Mucor haemalis) induced an increase in the mass of seminal vesicles and coagulating glands independent of whole body weight changes in mice.

Medical readiness training exercise in El Salvador, Central America, 1996.

Medical Readiness Training Exercises (MEDRETEs) can be a valuable training tool for U.S. Army personnel in remote areas of deployment. We report our experience of the MEDRETE in El Salvador in 1996. Working with foreign physicians of the host country was a positive experience in which we learned local customs and mutual cooperation. Evaluation and treatment of nearly 6,000 patients increased goodwill in the community and provided an opportunity for teamwork for Army Reserve medical units, including increased discussions of public health issues. We also report on the field applicability of the advanced laboratory and pharmacy equipment we included in our training.

Evaluation of Army field sanitation during Blazing Trails '87.

US medical personnel serving in Ecuador analyzed how the field sanitation procedures of troops employed in Blazing Trails '87 had impact on living conditions and overall health of the troops. Such a situation allowed evaluation of USAR troop training and preparedness in field sanitation. Results indicate that field sanitation training needs to be improved at the unit level.