High rate of sensitization to Kathon CG, detected by patch tests in patients with suspected allergic contact dermatitis

Abstract Background: Kathon CG, a combination of methylchloroisothiazolinone and methylisothiazolinone, is widely used as preservative in cosmetics, as well in household cleaning products, industrial products such as paints and glues. It has emerged as an important sensitizing agent in allergic contact dermatitis. Objectives: This study evaluated the reactivity to this substance in patients subjected to patch tests at the Dermatology Institute in Bauru, São Paulo from 2015 to 2017 and its correlation with other preservatives, the professional activity and location of the lesions. Methods: The patients were submitted to standard series of epicutaneous tests, standardized by the Brazilian Group Studies on Contact Dermatitis. Results: Out the 267 patients tested, 192 presented positivity to at least one substance and 29 of the patients (15.10%) presented reaction to Kathon CG, with predominance of the female gender (n = 27); main professional activity associated with Kathon CG sensibilization was cleaning (17.24%), followed by aesthetic areas (13.79%) and health care (10.34%). The most prevalent sensitizations among the substances tested were nickel sulphate (56.3%), followed by cobalt chloride (23.4%), neomycin (18.2%), potassium dichromate (17.7%), thimerosal (14.5%), formaldehyde (13.2%), paraphenylenediamine (9.3%), and fragrance mix (8.3%). Study limitations: We do not have data from patients that were submitted to patch test a decade ago in order to confront to current data and establish whether or no sensitization to Kathon CG has increased. Conclusion: High positivity to Kathon CG corroborates the recent findings in the literature, suggesting more attention to concentration of this substance, used in cosmetics and products for domestic use.

Manejo de hemorragia asociada a anticoagulantes orales directos: estado actual de las estrategias de reversión / Management of bleeding associated with direct oral anticoagulants: update on reversal strategies

Direct oral anticoagulants (DOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban have at least comparable efficacy as vitamin K antagonists along with a better safety profile, reflected by a lower incidence of intracranial hemorrhage. Specific reversal agents have been developed in recent years. Namely, idarucizumab, a specific antidote for dabigatran, is currently approved in most countries. Andexanet, which reverses factor Xa inhibitors, has been recently approved by the FDA, and ciraparantag, a universal antidote targeted to reverse all DOACs, is still under investigation. In this review we provide an update on the pharmacology of DOACs, the risk of hemorrhagic complications associated with their use, the measurement of their anticoagulant effect and the reversal strategies in case of DOAC-associated bleeding.

Increasing trend of sensitization to Methylchloroisothiazolinone/methylisothiazolinone (MCI/MI)

Recent reports have shown increased sensitization to Methylchloroisothiazolinone/methylisothiazolinone. We report a retrospective study conducted at the Hospital das Clínicas - UFMG, based on the results of patch tests with the Brazilian standard series, performed on referred patients. The positive results in 359 patients from November 2009 to October 2012 were analyzed and compared with the previous data collected from March 2006 to October 2009 (447 patients). The data showed 11.14% sensitization to Methylchloroisothiazolinone/ methylisothiazolinone during 2009-2012, contrasting with the previous period (3.35%). A positive association was found between its positivity and the period of 2009-2012.

Preventive Efficacy and Safety of Rebamipide in Nonsteroidal Anti-Inflammatory Drug-Induced Mucosal Toxicity

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.

Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone / Tranquilização rápida para pacientes agitados nos serviços de emergência psiquiátrica: um ensaio clínico randomisado de olanzapina, ziprasidona, haloperidol mais prometazina, haloperidol mais midazolam e haloperidol em monoterapia

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS: All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION: Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

OBJETIVO: Comparar a eficácia da olanzapina, ziprasidona, haloperidol associado ao midazolam, haloperidol associado à prometazina e haloperidol isoladamente por via intramuscular como primeira escolha no tratamento de pacientes em agitação e agressividade. MÉTODO: Cento e cinquenta pacientes com agitação psicomotora por transtorno psicótico ou transtorno bipolar foram recrutados para estudo duplo-cego e receberam olanzapina, ziprasidona, haloperidol associado a midazolam, haloperidol associado a prometazina ou haloperidol isoladamente. Foram aplicadas as escalas Overt Agitation Severity Scale, Overt Aggression Scale e Ramsay Sedation Scale no período de 12 horas após a primeira aplicação. RESULTADOS: Todas as medicações foram capazes de acalmar os pacientes após uma hora da administração. Apenas a olanzapina e o haloperidol reduziram a agitação para menos de 10 pontos e apenas a olanzapina reduziu a agressividade para menos de quatro pontos nesse período. Doze horas depois, apenas o haloperidol com midazolam apresentou valores altos para a agitação e agressividade, e também esteve relacionado com maior proporção de efeitos colaterais. A ziprasidona, a olanzapina e o haloperidol apresentaram resultados mais estáveis para o controle da agitação e a ziprasidona, haloperidol associado a prometazina e olanzapina para o controle da agressividade. CONCLUSÃO: A olanzapina, a ziprasidona, o haloperidol associado a prometazina, o haloperidol associado ao midazolam e o haloperidol isoladamente foram efetivos no controle da agitação e da agressividade secundária a transtornos mentais dentro de 12 horas. Todas as drogas apresentaram vantagens e desvantagens, exceto pela associação haloperidol e midazolam que demonstrou os piores resultados em todos os parâmetros.

Risk Factors of Drug Interaction between Warfarin and Nonsteroidal Anti-Inflammatory Drugs in Practical Setting

Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to interact with the oral anticoagulant warfarin and can cause a serious bleeding complication. In this study, we evaluated the risk factors for international normalized ratio (INR) increase, which is a surrogate marker of bleeding, after addition of an NSAID in a total of 98 patients who used warfarin. Patient age, sex, body mass index, maintenance warfarin dose, baseline INR, coadministered medications, underlying diseases, and liver and kidney functions were evaluated for possible risk factors with INR increase > or =15.0% as the primary end-point. Of the 98 patients, 39 (39.8%) showed an INR elevation of > or =15.0% after adding a NSAID to warfarin therapy. Multivariate analysis showed that high maintenance dose (>40 mg/week) of warfarin (P=0.001), the presence of coadministered medications (P=0.024), the use of meloxicam (P=0.025) and low baseline INR value (P=0.03) were the risk factors for INR increase in respect to NSAID-warfarin interaction. In conclusion, special caution is required when an NSAID is administered to warfarin users if patients are taking warfarin >40 mg/week and other medications interacting with warfarin.

Meloxicam e prednisona: efeitos do tratamento oral de curto prazo sobre os níveis de pressão intraocular em cães / Meloxican and prednisone: the effects of orally short term treatment on the intra-ocular pressure levels in dogs

Para possível observação da hipertensão ocular com o uso de antiinflamatórios, foram selecionados 28 cães da raça Beagle. Para avaliação da pressão intra-ocular antes do tratamento, no dia 0 (zero) todos os animais tiveram a pressão intra-ocular avaliada às 08 horas e às 16 horas. No dia seguinte dez cães receberam meloxicam na dose de0,2 mg/kg, e 0,1mg/kg nos restantes quatro dias. Nove cães receberam prednisona na dose de 1,0 mg/kg durante cinco dias. Nove cães receberam somente porção de ração úmida. No quinto dia do tratamento todos os animais tiveram novamente a pressão intra-ocular avaliada às 08 horas e às 16 horas. Em todos os grupos, incluindo o grupo-controle, as maiores médias de pressão intra-ocular foram observadas no dia 5 (cinco). A diferença dos valores de pressão intra-ocular observada entre as medições das 08 horas e das 16 horas foi significativa, independente do tratamento e do dia considerado. O uso dos anti-inflamatórios esteroidal e não-esteroidal não foi capaz de causar hipertensão ocular e alguns fatores podem ser incriminados, como via de administração, dose e duração do tratamento utilizado, além da ausência de doença glaucomatosa nos cães selecionados

In order to observe a possible ocular hypertension associated with the use of anti-inflammatory drugs, 28 beagle dogs were selected. For evaluation of intraocular pressure before treatment, the totality of animals had their intraocular pressure measured at 8 a.m. and 4 p.m.on day 0 (zero). On the following day 10 animals received meloxican on dose of 0.2 mg/Kg and 0.1 mg/Kg on the four remaining days. Nine dogs received prednisone on dose of 1,0 mg/Kg during five days. Nine dogs received only wet feeding. On the fifth day of treatment the totality of dogs had their intraocular pressure measured at 8 a.m.and 4 p.m. For all groups, including control-group, the highest average values of intraocular pressure were observed on day 5 (five). The difference between the two evaluations of intra-ocular pressure (8a.m. and 4 p.m) was significant, independent of treatment and of the considered day. The use of both steroidal or non-steroidal antiinflammatory were not capable of causing ocular hypertension and some factors can be pointed out, such as route of administration, dosage and duration of therapy chosen, besides absence of glaucomatous disorder between the selected dogs

Multi-drug overdose risperidone, ziprasidone, valproate, trihexyphenidyl, and clonazepam.

Risperidone and ziprasidone are commonly used as first line drugs for the treatment of psychotic disorders and overdose with these agents is increasingly being reported. Relatively few of these reports have involved co-ingestion of multiple psychotropic agents. We report a case of overdose with risperidone, ziprasidone, valproate, trihexyphenidyl and clonazepam in a 25 years female, who recovered uneventfully with supportive management. Notwithstanding the benign outcome in this instance, age, co-ingested drugs, active metabolites and medical co-morbidity are critical issues in overdose with atypical antipsychotics. As prescription of these drugs continues to increase in developing countries, systematic studies evaluating their clinical toxicity and management are necessary. The issues associated with overdose of multiple psychotropic agents and appropriate management policies are highlighted.

Comparison of endoscopic gastric mucosa features after administration of piroxicam to meloxicam and their correlation with dyspepsia symptoms in elderly patient with knee osteoarthritis.

AIM: to know the effect of piroxicam (COX-1 and COX-2 inhibitor NSAID) and meloxicam (selective COX-2 inhibitor NSAID) against the gastric mucosa. METHODS: a random, double-blind-parallel study and repeat measurement against 20 elderly-patients with knee-OA was conducted. Patients were divided into 2 equal groups, every group got piroxicam 20 mg/day or meloxicam 15 mg/day for 3 weeks. On the second group, sukralfat 2 x 1 g/day were given. To examine the difference before and after treatment, we used Wilcoxon signed rank test, to examine the difference within those groups we used Mann-whitney U test, to examine the correlation between endoscopic score and dyspepsia, we used the Spearman correlation test with significant correlation interpretation by Guilford rules. RESULTS: one of piroxicam group was resigned, so that there was 19 person left to complete this study. Piroxicam has caused elevation of endoscopic score in 78% subject compared to the beginning of study, and 22% of the subject has developed ulcers. Alteration of endoscopic feature after administration of this piroxicam was statistically significant (p< 0,05). Mild dyspepsia symptoms after piroxicam administration were positive on 67% subjects (p< 0,05). After administration of meloxicam, 40% subjects have elevated endoscopic score compared to beginning of the study (p< 0,05). Mild dyspepsia symptoms after meloxicam administration were positive on 40% subjects (p> 0,05). Meloxicam has less elevation of endoscopic score compared to the piroxicam (p< 0,05). By statistics, both of groups showed no difference in dyspepsia symptoms (p> 0,05). There was no significant correlation between elevation of endoscopic score and dyspepsia on both of groups. Nevertheless, it tends to have weak positive correlation (piroxicam group r= 0,306, p> 0,05, meloxicam group r= 0,330, p> 0,05). CONCLUSION: on this study, we conclude that the administration of either piroxicam or meloxicam in elderly-patient with knee-OA has caused the gastric mucosa impairment. The impairment after meloxicam administration is milder than piroxicam. There is no significant difference of dyspepsia symptoms in both of groups. There is correlation between endoscopic gastric mucosa features with the dyspepsia symptoms.

Evaluación de la nitazoxanida en dosis única y por tres días en parasitosis intestinal / Nitazoxanide vs albendazole against intestinal parasites in a single dose and for three days

OBJETIVO: Evaluar la utilidad de nitazoxanida en dosis habitual con esquema de tres días y en dosis única, para la erradicación masiva de parásitos intestinales en la población pediátrica, comparando su efecto con el del albendazol en dosis única. MATERIAL Y MÉTODOS: Se realizó un ensayo clínico aleatorizado, en tres comunidades rurales de la región central de México, durante el periodo 2001-2003, para incluir tres posibles alternativas de tratamiento en 786 sujetos de entre 5 y 11 años de edad, de los cuales 92 tuvieron un examen parasitológico positivo (15.1 por ciento). El grupo 1 incluyó 27 pacientes que recibieron 400 mg de albendazol en dosis única; el grupo 2 incluyó 34 pacientes a quienes se administró nitazoxanida en dosis de 15 mg/kg/día durante tres días consecutivos; y el grupo 3 incluyó 31 pacientes que recibieron 1.2 g de nitazoxanida en dosis única. Se evaluó diferencia de proporciones mediante prueba exacta de Fisher. RESULTADOS: No existieron diferencias estadísticamente significativas en la efectividad de los tres esquemas de tratamiento: (80.5 por ciento) con albendazol, comparado con las dos alternativas adicionales de nitazoxanida (67.6 por ciento y 71 por ciento, respectivamente). Se observó una mayor prevalencia de efectos secundarios con nitazoxanida por kg /día (26.5 por ciento) y en dosis única (32.2 por ciento), en comparación con la dosis única de albendazol (7.4 por ciento). CONCLUSIONES: Las evidencias en cuanto a la efectividad y elevada prevalencia de efectos secundarios de la nitazoxanida no justifican aún su utilización como quimiopreventivo masivo para el control de parasitosis intestinal en áreas endémicas. En países con elevada prevalencia de parasitosis intestinal las medidas de prevención primaria que continúan vigentes, y que deben priorizarse, están relacionadas con sanidad pública, introducción de agua potable y drenaje, cloración de agua y manejo adecuado de excretas de animales domésticos, así como educación para la salud.

Safety and efficacy of meloxicam 7.5 mg in the treatment of osteoarthritis in Thai patients.

A prospective, open trial to evaluate the safety and efficacy of oral meloxicam 7.5 mg once daily over a period of 28 days in Thai patients with osteoarthritis was conducted in 3 major hospitals in Bangkok, Thailand. A total of 137 patients were enrolled and completed the study protocol. The mean age of the patients was 57.6 years and 88 per cent were female. Pain on movement and pain at rest evaluated after treatment by visual analog scale (VAS) were significantly improved with respect to the baseline status (p<0.001). The final efficacy was reported as satisfactory or good in 97 per cent and 94 per cent as determined by patients and physicians respectively. Patient status evaluated at the end of the study reported improvement of their arthritic condition in 84 per cent. Drug tolerability assessed by patients and physicians and was good or satisfactory in 99 per cent and 98 per cent. GI adverse event was reported in 8.8 per cent. Other adverse events were itching/rash in 2.0 per cent and headache/insomnia in 1.5 per cent of patients. No patients withdrew from the study due to adverse events. No GI bleeding or perforation were observed. No hospitalization was observed during the study. There was no significant change of blood chemistry and hematological profile between pre and post treatment examination. Results from this study suggest that oral meloxicam 7.5 mg for 28 days is a safe and effective treatment regimen with high GI tolerability profile for the treatment of osteoarthritis in Thai patients.