Clinical manifestations and treatment outcomes in degos disease: a systematic review.

Degos disease (atrophic papulosis) is a rare vasculopathy with cutaneous and systemic manifestations. Although potentially fatal, the characteristics of and treatments for Degos disease variants are not adequately described. We conducted a systematic review to summarize cutaneous and systemic presentations, treatments and outcomes of malignant (MAP) and benign (BAP) variants of Degos disease. A comprehensive search was conducted on Embase, MEDLINE, CINAHL and CENTRAL on 27 October 2020, which yielded 254 original studies reporting cases of Degos disease. A total of 357 patients were included in the analysis. Mean age of onset was 33.9 years. MAP was most commonly reported (63.8%, n = 228/357), with 56.6% (n = 129/228) mortality. Cutaneous lesions were usually asymptomatic (26.3%, n = 81/308) and localized to the trunk (57.7%, n = 206/357) and extremities (56.8%, n = 203/357). Systemic involvement developed within 2 years on average, ranging from 0 to 28 years. Anti-platelet monotherapy had a complete resolution rate of 42.3% (n = 11/26) in BAP and 20.0% (n = 7/35) in MAP. Based on the findings of the study, most cases of Degos disease are malignant with high mortality, and even benign cutaneous cases may develop systemic disease in as late as 28 years. Anti-platelet monotherapies may prove effective against both variants. Further studies are needed to confirm these findings.

Drug Survival of IL-12/23, IL-17 and IL-23 Inhibitors for Psoriasis Treatment: A Retrospective Multi-Country, Multicentric Cohort Study.

BACKGROUND: Drug survival analysis of biologic agents in psoriasis is of extreme importance, as it allows not only the evaluation of objective clinical outcomes (such as effectiveness and safety) but also of factors that are associated with patients' adherence to treatment. The aim of this study was to evaluate and compare the drug survival of the most recent biologic agents approved for the treatment of moderate-to-severe psoriasis-ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and risankizumab-and to identify clinical predictors that can influence the drug survival of these drugs. METHODS: This retrospective multicentric cohort study from 16 dermatology centers in Portugal, Spain, Italy, Switzerland, Czech Republic, Canada, and the United States included patients that started IL-12/23, IL-17 (IL-17A and IL-17R) and IL-23 inhibitors for the treatment of psoriasis between January 1, 2012 and December 31, 2019. Survival analysis was performed using a Kaplan-Meier estimator, to obtain descriptive survival curves, and proportional hazard Cox regression models. RESULTS: A total of 3312 treatment courses (total patients: 3145) were included in the study; 1118 (33.8%) with an IL-12/23 inhibitor (ustekinumab), 1678 (50.7%) with an IL-17 inhibitor [911 (27.5%) on secukinumab, 651 (19.7%) on ixekizumab, 116 (3.5%) on brodalumab], and 516 (15.5%) with an IL-23 inhibitor [398 (12.0%) on guselkumab, 118 (3.5%) on risankizumab]. At 18 months, the cumulative probability of survival was 96.4% for risankizumab, 91.1% for guselkumab, 86.3% for brodalumab, 86.1% for ustekinumab, 82.0% for ixekizumab, and 79.9% for secukinumab. Using ustekinumab as reference, drug survival of guselkumab was higher (HR 0.609; 95% CI 0.418-0.887) and that of secukinumab was lower (HR 1.490; 95% CI 1.257-1.766). In the final multivariable model, secukinumab, female sex, higher BMI, and prior exposure to biologic agents significantly increased the risk of drug discontinuation, whereas risankizumab was protective. CONCLUSION: In this multinational cohort with 8439 patient-years of follow-up, the cumulative probability of drug survival for all drugs was >79% at 18 months. Prescribed biologic, female sex, higher BMI, and previous exposure to biologic agents were predictors of drug discontinuation. Drug survival of guselkumab and risankizumab was higher than that of ustekinumab, and secukinumab was lower.

The effects of inorganic chromium and brewer's yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes.

OBJECTIVE: To study the effects of supplementation with organic and inorganic chromium on glucose tolerance, serum lipids, and drug dosage in type 2 diabetes patients, in the hope of finding a better and more economical method of control. METHODS: Seventy eight type 2 diabetes patients were divided randomly into two groups and given Brewer's yeast (23.3ug Cr/day), and CrCl3 (200ug Cr/day) sequentially with placebo in between, in a double blind cross-over design of four stages, each lasting 8 weeks. At the beginning and end of each stage, subjects were weighed, their dietary data and drug dosage recorded, and blood and urine samples were collected for analysis of glucose (fasting and 2 hour post 75g glucose load) fructosamine, triglycerides, total and HDL-cholesterol, and serum and urinary chromium. RESULTS: Both supplements caused a significant decrease in the means of glucose (fasting and 2 hour post glucose load), fructosamine and triglycerides. The means of HDL-cholesterol, and serum and urinary chromium were all increased. The mean drug dosage decreased slightly (and significantly in case of Glibenclamide) after both supplements and some patients no longer required insulin. No change was noted in dietary intakes or Body Mass Index. A higher percentage of subjects responded positively to Brewer's yeast chromium, which was retained more by the body, with effects on fructosamine, triglycerides, and HDL-cholesterol maintained in some subjects when placebo followed it, and mean urinary chromium remaining significantly higher than zero time mean. CONCLUSION: Chromium supplementation gives better control of glucose and lipid variables while decreasing drug dosage in type 2 diabetes patients. A larger scale study is needed to help decide on the convenient chemical form, and dosage required to achieve optimal response.

Determination of equilibrium constant of ascorbic acid and benzoic acid at different temperature and in aqueous and non-aqueous media.

Dissociation constant studies of ascorbic acid and benzoic acid has been carried out potentiometrically at various temperature from 25 to 50 degrees C and in 10, 20, 30 and 40 percent dioxane-water solvent system at 25 degrees C. Effect of temperature and solvent concentration on pKa values has been observed. The resolution of acid strength in dioxane-water relative to that in water has been determined for both compound by plotting pKa values vs percent composition of solvent. The results shows greater resolution in non-aqueous media as compare to aqueous media. Data obtained is analyzed by Computer program written in GW-Basic for calculation of pKa values for monobasic acid.

Allopurinol therapy of ischemic heart disease with infarct extension.

OBJECTIVE: Free radicals produced by the hypoxanthine-xanthine oxidase reaction in ischemia/reperfusion experiments have been proposed as contributing to myocardial cell necrosis in acute myocardial infarction. In this study, the hypothesis was tested that a commonly observed late phase of necrosis, infarct extension, could be prevented by allopurinol, an inhibitor of xanthine oxidase. STUDY DESIGN: Allopurinol, a xanthine oxidase inhibitor, was used with placebo in a double-blind randomized therapy study in 140 patients with ischemic heart disease admitted to the authors' hospital. Eighty-four had acute myocardial infarction and the remaining 56 had unstable angina. Of the 84 patients with infarction, 39 received allopurinol treatment. If xanthine oxidase production of cytotoxic free radical plays a major role in the pathogenesis of infarct extension, blockade of the reaction with allopurinol should decrease the occurrence of extension. RESULTS: Nineteen infarct extensions were observed; five (11%) in the placebo group and 14 (36%) in the allopurinol. CONCLUSIONS: The increased incidence of extension (P less than 0.007) in the treatment group does not support the hypothesis that xanthine oxidase contributes to infarct extension, which is consistent with recent reports that xanthine oxidase is not a significant component of the human myocardium. These findings indicate that allopurinol may actually be contraindicated in patients with ischemic heart disease.

Indirect sources of mercury poisoning in the Iraqi epidemic.

Secondary sources of intoxication with methylmercury poisoning other than home-made bread were explored. Mercury levels in various food items were below 0.05 mg/kg.Over 30 000 specimens of meat and internal organs of sheep were analysed because of the strong suspicion that the animals had been fed treated barley. It was found that 6-12% of the specimens analysed contained more than 0.5 mg/kg of mercury. Consumption of meat did not appear to constitute a danger of intoxication during the outbreak.

An outbreak of organomercury poisoning among Iraqi farmers.

An outbreak of organomercury poisoning due to the consumption of treated grain by farmers and their families occurred in Iraq in 1971-72. A total of 6530 cases were admitted to hospital and of these 459 died. However, there were many more with minor symptoms of poisoning who consulted outpatient departments. This outbreak constituted the largest poisoning epidemic ever recorded. No age was exempt and no pronounced sex difference was apparent. The latent period of up to 60 days between dosage and the onset of symptoms was probably the major factor contributing to the size of the epidemic. Measures taken to limit the outbreak are outlined.

Epidemiology of organomercury poisoning in Iraq. I. Incidence in a defined area and relationship to the eating of contaminated bread.

A survey was carried out in a defined area in rural Iraq where there had been many cases of organomercury poisoning following the consumption of bread contaminated by mercury, in order to determine the true incidence of the disorder. The results were compared with those obtained from a similar rural area from which few cases had been reported. A questionnaire was used to determine the amount of contaminated bread eaten and the frequency of symptoms; a simple clinical examination was performed and blood and hair samples were collected for estimation of total mercury concentration. Of 700 people over the age of 5 years in the high-exposure area, 66% admitted to having eaten contaminated bread, while none of the 864 persons in the low exposure area had done so. The mean period during which contaminated bread was eaten was 32 days, but some people had eaten it for as long as 3 months. A mean of 121 loaves was eaten, the maximum being 480 loaves. For the mean number of loaves the intake of methylmercury was likely to have been between 80 mg and 250 mg, but the people who had consumed the largest amount of contaminated bread may have ingested up to 1 000 mg of methylmercury over a 3-month period. Of those with signs of alkylmercury poisoning at the time of the survey, 80% had eaten more than 100 loaves, and 53 (71%) out of 75 persons who had eaten more than 200 loaves showed some evidence of poisoning.The incidence rate for poisoning was estimated at 271 per 1 000; this figure includes a mortality rate of 59 per 1 000, 32 per 1 000 cases with severe disability, 41 per 1 000 cases with mild or moderate disability and 138 per 1 000 cases with only subjective evidence of poisoning at the time of the study.

Epidemiology of organomercury poisoning in Iraq. II. Relationship of mercury levels in blood and hair to exposure and to clinical findings.

In the survey described by Al-Mufti et al. (see page 23) blood and hair samples were analysed for total mercury by modified atomic absorption spectrophotometry. The hair samples were divided into 2.5-cm segments and analysed consecutively. The mean blood levels were 34 ng/ml and 7 ng/ml, respectively in those who had and those who had not eaten contaminated bread.Corresponding mean maximum hair mercury values were 136 mug/g and 5 mug/g, respectively. Hair mercury values provided a better discrimination between different categories of exposure than blood mercury values at the time the survey was performed, some months after the end of the outbreak. Those persons who had not eaten contaminated bread but who lived in the area of high exposure had hair mercury values between the values of those who had eaten and those who had not eaten contaminated bread and who lived in the area of low exposure. Sequential estimation of mercury in 2.5-cm segments of hair in women gave information on the period of accumulation of mercury more than 1 year before the time of collection of the samples. It was possible to show an approximate relationship between the maximum hair mercury value and the amount of contaminated bread eaten. The match between the blood mercury level and the severity of poisoning was poor, owing to the length of time that had elapsed between the onset of poisoning and the sampling. With hair mercury, while the group results showed a good relation to the severity of poisoning, in individual cases the match was less good, especially in those persons where an insufficient length of hair was available for analysis. Biological variation in sensitivity to methylmercury was also likely to have been an important factor.

Epidemiology of organomercury poisoning in Iraq. III. Clinical features and their changes with time.

Three categories of mercury poisoning were defined in the survey described by Al-Mufti et al. (see page 23) and the age-specific incidence rates for these are given. Persons with physical signs consistent with a diagnosis of organomercury poisoning were allocated to categories of severe disability or mild/moderate disability. However, the largest category consisted of persons who had symptoms but no readily elicitable physical signs at the time of the survey. These symptoms followed a consistent pattern with paraesthesia involving the lips and/or circumoral region or trunk and difficulty with walking, described as weakness or unsteadiness of the legs, and in some cases repeated falls, forming the most commonly occurring symptom complex. Mean maximum hair mercury levels differentiated this group very clearly from the group with no symptoms of mercury poisoning. Very few people in the area of low exposure complained of such symptoms; where they did occur they were less well related to the time of the outbreak and showed little tendency to improve. Most people reported improvement in their symptoms by the time of the survey, with more improvement in some symptoms than in others. However, it is not known whether those people with symptoms only at the time of the survey had had at an earlier stage mild signs which had cleared. It was thought unlikely that further substantial improvement would occur in those persons with disability at the time of the survey.