Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler

COSTA MIGUEL, M. C.; NONAKA, C. F. W.; GERMANO, A. R.; SOUZA, L. B.; SOUZA, L. B. Oral foreign body granuloma: unusual presentation of a rare adverse reaction to permanent injectable cosmetic filler. International journal of oral and maxillofacial surgery, v. 38, p. 385-387, 2009.

A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment

Cross-sectional Study Comparing Different Therapeutic Modalities For Cystic Lymphangiomas In Children.

Here, we describe our experience with different therapeutic modalities used to treat cystic lymphangiomas in children in our hospital, including single therapy with OK-432, bleomycin and surgery, and a combination of the three modalities. We performed a retrospective, cross-sectional study including patients treated from 1998 to 2011. The effects on macrocystic lymphangiomas and adverse reactions were evaluated. Twenty-nine children with cystic lymphangiomas without any previous treatment were included. Under general anesthesia, patients given sclerosing agents underwent puncture of the lesion (guided by ultrasound when necessary) and complete aspiration of the intralesional liquid. The patients were evaluated with ultrasound and clinical examinations for a maximum follow-up time of 4 years. The proportions of patients considered cured after the first therapeutic approach were 44% in the surgery group, 29% in the bleomycin group and 31% in the OK-432 group. These proportions were not significantly different. Sequential treatment increased the rates of curative results to 71%, 74% and 44%, respectively, after the final treatment, which in our case was approximately 1.5 applications per patient. The results of this study indicate that most patients with cystic lymphangiomas do not show complete resolution after the initial therapy, regardless of whether the therapy is surgical or involves the use of sclerosing agents. To achieve complete resolution of the lesions, either multiple operations or a combination of surgery and sclerotherapy must be used and should be tailored to the characteristics of each patient.

Influence Of Cyclosporine On The Occurrence Of Nephrotoxicity After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review.

Cyclosporine, a drug used in immunosuppression protocols for hematopoietic stem cell transplantation that has a narrow therapeutic index, may cause various adverse reactions, including nephrotoxicity. This has a direct clinical impact on the patient. This study aims to summarize available evidence in the scientific literature on the use of cyclosporine in respect to its risk factor for the development of nephrotoxicity in patients submitted to hematopoietic stem cell transplantation. A systematic review was made with the following electronic databases: PubMed, Web of Science, Embase, Scopus, CINAHL, LILACS, SciELO and Cochrane BVS. The keywords used were: bone marrow transplantation OR stem cell transplantation OR grafting, bone marrow AND cyclosporine OR cyclosporin OR risk factors AND acute kidney injury OR acute kidney injuries OR acute renal failure OR acute renal failures OR nephrotoxicity. The level of scientific evidence of the studies was classified according to the Oxford Centre for Evidence Based Medicine. The final sample was composed of 19 studies, most of which (89.5%) had an observational design, evidence level 2B and pointed to an incidence of nephrotoxicity above 30%. The available evidence, considered as good quality and appropriate for the analyzed event, indicates that cyclosporine represents a risk factor for the occurrence of nephrotoxicity, particularly when combined with amphotericin B or aminoglycosides, agents commonly used in hematopoietic stem cell transplantation recipients.

Modelo de suplementação nutricional com fatores hepatotróficos aumenta proliferação celular em fígado de ratos sadios

Foram avaliados dois protocolos de administração, em ratos sadios, de uma solução de fatores hepatotróficos (FH), composta por aminoácidos, vitaminas, sais minerais, glicose, insulina, glucagon e triiodotironina (T3). A solução foi administrada durante 10 dias, 40mg/kg/dia, i.p., em duas, grupo 2xFH (n=15), ou três doses, grupo 3xFH (n=15), diárias. Foram observados os efeitos na proliferação celular dos hepatócitos, na angiogênese e na matriz extracelular hepática, assim como as possíveis reações adversas. Os animais dos grupos 2xFH e 3xFH apresentaram aumento da massa hepática de 30,1% e 22,5%, respectivamente, em relação ao grupo-controle (CT; n=15). O índice de proliferação hepatocelular foi maior nos grupos 2xFH (1,4%) e 3xFH (1,2%) em relação ao grupo CT (0,53%), e a densitometria relativa do fator de crescimento do endotélio vascular pelo imunoblot não revelou diferença estatística entre os três grupos. Nos grupos 2xFH e 3xFH, houve redução do colágeno intersticial em relação ao grupo CT. A solução de FH estimulou o crescimento hepático e reduziu o volume de colágeno perissinusoidal. A administração em três doses diárias resultou em mortalidade de 26,7%, possivelmente pelo excessivo estresse da manipulação e pela menor adaptação fisiológica dos ratos, o que não ocorreu nos grupos 2xFH e CT. Para esse tipo de abordagem em ratos, o procedimento experimental mais apropriado, seguro, com melhor chance de adaptação dos animais e com resultados significativos é a aplicação dos FH em duas doses diárias.

Severity of Oral Mucositis in Patients Undergoing Hematopoietic Cell Transplantation and an Oral Laser Phototherapy Protocol: A Survey of 30 Patients

Background Data and Objective: Oral mucositis (OM) is one of the worst cytotoxic effects of chemotherapy and radiotherapy in patients undergoing hematopoietic cell transplantation (HCT), and it causes severe morbidity. Laser phototherapy has been considered as an alternative therapy for prevention and treatment of OM. The aim of this study was to describe the incidence and severity of OM in HCT patients subjected to laser phototherapy, and to discuss its effect on the oral mucosa. Patients and Methods: Information concerning patient age and gender, type of basic disease, conditioning regimen, type of transplant, absence or presence of pain related to the oral cavity, OM grade, and adverse reactions or unusual events were collected from 30 patients undergoing HCT (allogeneic or autologous). These patients were given oral laser phototherapy with a InGaAIP laser (660 nm and 40 mW) daily. The data were tabulated and their frequency expressed as percentages. Results: In the analysis of those with OM, it was observed that 33.4% exhibited grade I, 40% grade II, 23.3% grade III, and 3.3% grade IV disease. On the most critical post-HCT days (D+5 and D+8), it was observed that 63.3% of patients had grade I and 33.3% had grade II disease; no patients had grade III or IV disease in this period. This severity of OM was similar to that seen in other studies of laser phototherapy and OM. Conclusion: The low grades of OM observed in this survey show the beneficial effects of laser phototherapy, but randomized clinical trials are necessary to confirm these findings.

Rubus rosaefolius Extract as a Natural Preservative Candidate in Topical Formulations

Even though the synthetic preservatives may offer a high antimicrobial efficacy, they are commonly related to adverse reactions and regarded as having potentially harmful effects caused by chronic consumption. The development of natural preservatives provides a way of reducing the amount of synthetic preservatives normally used in pharmaceutical and cosmetic preparations. In addition, these agents have less toxic effects and represent a possible natural and safer alternative of the preservatives. The purpose of this research was to evaluate the Rubus rosaefolius Smith extract efficiency as a natural preservative in base formulations. Of the extract, 0.2% (w/w) was assayed for its effectiveness of antimicrobial protection in two different base formulations (emulsion and gel). The microbial challenge test was performed following the standard procedures proposed by The United States Pharmacopoeia 33nd, European Pharmacopoeia 6th, Japanese Pharmacopoeia 15th, and the Cosmetics, Toiletries, and Fragrance Association using standardized microorganisms. The results demonstrated that R. rosaefolius extract at the studied concentration reduced the bacterial inocula, satisfying the criterion in all formulations, even though it was not able to present an effective preservative behavior against fungi. Thus, the investigation of new natural substances with preservative properties that could be applied in pharmaceutical and cosmetic products is relevant due to the possibility of substituting or decreasing the concentration of synthetic preservatives, providing a way for the development of safer formulas for the use of consumers.

Minocycline and oral pigmentation

Minocycline is a semisynthetic tetracycline used in the treatment of inflammatory acne because of its broad spectrum of activity, less common development of resistant organisms, and its anti-inflammatory effects. A number of adverse reactions are reported, including skin and oral pigmentation. This paper details the pharmacology of minocycline and describes the pigmentation and likely mechanisms active in both hard and soft tissues. Oral pigmentation usually involves the hard tissues only and presents typically as a discrete band occupying the central zone of the alveolar mucosa and palate. As with other sites, it may persist following withdrawal of the drug. Early recognition by the dental practitioner may allow an alternative form of therapy to be sought, minimizing the likelihood of a longterm aesthetic problem.

Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n = 43) or split vaccine (n = 47) Two blood samples were collected, one before and one 4-6 weeks after vaccination Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test Post-vaccine reactions were recorded over 7 days Seroconversion rates for HI NI, H3N2 and B were 65 1%. 60 4% and 83 7% for virosome vaccine, and 68 0%, 61 7% and 68 0% for split vaccine Seroprotection rates for HI NI, H3N2 e B were 100%. 97 6% and 69.7% for virosome. and 97 8%, 97 8% and 76 6% for split vaccine No severe adverse reactions were recorded Virosome and split vaccines in patients with sickle cell anemia were equally Immunogenic. with high seroconversion and seroprotection rates Both vaccines were well tolerated (C) 2009 Elsevier Ltd All rights reserved

Efficacy and Tolerability of Lodenafil Carbonate for Oral Therapy in Erectile Dysfunction: A Phase II Clinical Trial

Oral treatment with phosphodiesterase type 5 inhibitor (PDE5) is considered the first-line treatment for patients with erectile dysfunction (ED). Lodenafil carbonate (LC) is a novel PDE5. This is a phase II, prospective, randomized, double-blind, and placebo controlled clinical trial of LC. Efficacy end points were International Index of Sexual Function (IIEF) erectile domain, IIEF questions 3 and 4, and Sexual Encounter Profile (SEP) questions 2 and 3, before and after the use of LC or placebo. Seventy-two men older than 18 years, with ED for at least 6 months with stable sexual relationship were enrolled. Patients were randomized to placebo or LC 80 mg, 40 mg, or 20 mg and followed for 4 weeks. IIEF erectile domain scores before and after the use of medications were (mean +/- standard deviation [SD]): placebo: 11.9 +/- 3.4 and 12.6 +/- 5.5; LC 20 mg: 15.8 +/- 4.1 and 18.9 +/- 6.6; LC 40 mg: 11.9 +/- 4.4 and 15.4 +/- 8.1; LC 80 mg: 14.2 +/- 4.7 and 22.8 +/- 6.0 (anova P < 0.01). The SEP-2 scores before and after the use of medications were (Mean +/- SD): placebo: 71.0 +/- 33.1 and 51.2 +/- 43.1; LC 20 mg 70.3 +/- 34.2 and 75.5 +/- 31.5; LC 40 mg: 48.4 +/- 42.1 and 60.8 +/- 42.5; LC 80 mg: 68.6 +/- 33.5 and 89.6 +/- 26.0. The SEP-3 scores were: placebo 23.3 +/- 27.6 and 33.6 +/- 42.3; LC 20 mg: 32.3 +/- 38.9 and 51.2 +/- 41.7; LC 40 mg: 39.7 +/- 44.7 and 46.7 +/- 41.1; LC 80 mg* 17.2 +/- 29.5 and 74.3 +/- 36.4 (*P < 0.05 for difference to placebo). The drug was well tolerated. Adverse reactions were mild and self-limited and included headache, rhinitis, flushing, color visual disorders, and dyspepsia. This study showed that the dosage of 80 mg of LC was significantly more efficacious than placebo and well tolerated. Glina S, Toscano I, Gomatzky C, de Goes PM, Junior AN, de Almeida Claro JF, and Pagani E. Efficacy and tolerability of lodenafil carbonate for oral therapy in erectile dysfunction: A phase II clinical trial. J Sex Med 2009;6:553-557.

Risk of Potential Drug-Drug Interactions among Brazilian Elderly A Population-Based, Cross-Sectional Study

Background: Drug-drug interactions (DDIs) are one of the main causes of adverse reactions related to medications, being responsible for up to 23% of hospital admissions. However, only a few studies have evaluated this problem in elderly Brazilians. Objectives: To determine the prevalence of potential DDIs (PDDIs) in community-dwelling elderly people in Brazil, analyse these interactions with regard to severity and clinical implications, and identify associated factors. Methods: A population-based cross-sectional study was carried out involving 2143 elderly (aged 60 years) residents of the metropolitan area of Sao Paulo, Brazil. Data were obtained from the SABE (Saude, Bem estar e Envelhecimento [Health, Well-Being, and Aging]) survey, which is a multicentre study carried out in seven countries of Latin America and the Caribbean, coordinated by the Pan-American Health Organization. PDDIs were analysed using a computerized program and categorized according to level of severity, onset, mechanism and documentation in the literature. The STATA software statistical package was used for data analysis, and logistic regression was conducted to determine whether variables were associated with PDDIs. Results: Analysis revealed that 568 (26.5%) of the elderly population included in the study were taking medications that could lead to a DDI. Almost two-thirds (64.4%) of the elderly population exposed to PDDIs were women, 50.7% were aged >= 75 years, 71.7% reported having fair or poor health and 65.8% took 2-5 medications. A total of 125 different PDDIs were identified; the treatment combination of an ACE inhibitor with a thiazide or loop diuretic (associated with hypotension) was the most frequent cause of PDDIs (n=322 patients; 56.7% of individuals with PDDIs). Analysis of the PDDIs revealed that 70.4% were of moderate severity, 64.8% were supported by good quality evidence and 56.8% were considered of delayed onset. The multivariate analysis showed that the risk of a PDDI was significantly increased among elderly individuals using six or more medications (odds ratio [OR] 3.37) and in patients with hypertension (OR 2.56), diabetes mellitus (OR 1.73) or heart problems (OR 3.36). Conclusions: Approximately one-quarter of the elderly population living in Sao Paulo could be taking two or more potentially interacting medicines. Polypharmacy predisposes elderly individuals to PDDIs. More than half of these drug combinations (57.6%, n = 72) were part of commonly employed treatment regimens and may be responsible for adverse reactions that compromise the safety of elderly individuals, especially at home. Educational initiatives are needed to avoid unnecessary risks.

Safety and Immunogenicity of Varicella Vaccine in Patients With Juvenile Rheumatic Diseases Receiving Methotrexate and Corticosteroids

Objective. To evaluate the safety and immunogenicity of varicella vaccine (VV) in susceptible patients with juvenile rheumatic diseases receiving methotrexate and corticosteroids. Methods. Twenty-five patients with juvenile rheumatic diseases (ages 2-19 years) and 18 healthy children and adolescents (ages 3-18 years) received a single dose of VV. All 25 patients were receiving methotrexate; 13 were also receiving prednisone and 5 were also receiving other disease-modifying antirheumatic drugs. None of the vaccinated patients or controls had a previous history of varicella. Anti-varicella-zoster virus IgG antibody (anti-VZV-IgG) titers were measured by enzyme-linked immunosorbent assay immediately before, 4-6 weeks after, and 1 year after vaccination. The patients were monitored prospectively for adverse reactions related to the vaccine, exposure, and occurrence of varicella. Disease activity was assessed 3 months before and 3 months after VV. Results. Twenty patients and all of the controls had negative preimmunization titers of VZV-IgG, and 5 patients had equivocal levels. Positive VZV-IgG titers were detected in 10 (50%) of 20 seronegative patients and 13 (72.2%) of 18 controls 4-6 weeks after VV (P = 0.2). One year after vaccination, 8 of 10 patients maintained positive VZV-IgG titers. No overt varicella episodes and no severe adverse reactions were observed during the followup period. No worsening of clinical parameters and no flares of juvenile rheumatic diseases or changes in doses of medications used were detected after vaccination. In fact, the number of active joints in patients with juvenile idiopathic arthritis was significantly lower after VV (P = 0.009). Conclusion. VV appears to be safe in patients with juvenile rheumatic diseases receiving methotrexate, as long as continuous prospective vigilance for side effects is performed.

Diagnosis and control of polypharmacy in the elderly

The article had the purpose of commenting on studies on polypharmacy in the elderly, focusing on diagnosis and control. Polypharmacy is defined as the use of a number of medications at the same time and the use of additional drugs to correct drug adverse effects. The fact that the elderly take more medications for the treatment of several diseases makes them more susceptible to the occurrence of adverse reactions. Prophylactic actions such as balanced prescriptions are vital to reduce the incidence of these reactions and prevent longer hospital stay, increased costs and aggravation of the elderly health condition.

Readability of medicinal package leaflets: a systematic review

OBJECTIVE To review studies on the readability of package leaflets of medicinal products for human use.METHODS We conducted a systematic literature review between 2008 and 2013 using the keywords “Readability and Package Leaflet” and “Readability and Package Insert” in the academic search engine Biblioteca do Conhecimento Online,comprising different bibliographic resources/databases. The preferred reporting items for systematic reviews and meta-analyses criteria were applied to prepare the draft of the report. Quantitative and qualitative original studies were included. Opinion or review studies not written in English, Portuguese, Italian, French, or Spanish were excluded.RESULTS We identified 202 studies, of which 180 were excluded and 22 were enrolled [two enrolling healthcare professionals, 10 enrolling other type of participants (including patients), three focused on adverse reactions, and 7 descriptive studies]. The package leaflets presented various readability problems, such as complex and difficult to understand texts, small font size, or few illustrations. The main methods to assess the readability of the package leaflet were usability tests or legibility formulae. Limitations with these methods included reduced number of participants; lack of readability formulas specifically validated for specific languages (e.g., Portuguese); and absence of an assessment on patients literacy, health knowledge, cognitive skills, levels of satisfaction, and opinions.CONCLUSIONS Overall, the package leaflets presented various readability problems. In this review, some methodological limitations were identified, including the participation of a limited number of patients and healthcare professionals, the absence of prior assessments of participant literacy, humor or sense of satisfaction, or the predominance of studies not based on role-plays about the use of medicines. These limitations should be avoided in future studies and be considered when interpreting the results.

Sub-notificação de reacções adversas medicamentosas : um problema com solução? : contribuição para o conhecimento da sub-notificação de RAMs em Portugal e implementação de medidas minimizadoras do impacte

RESUMO - Introdução: As Reacções Adversas Medicamentosas (RAMs) constituem um grave problema de Saúde Pública em termos da mortalidade e morbilidade provocadas, tendo também um impacto económico considerável nos Sistemas de Saúde. Os Sistemas de Notificacão Espontânea de RAMs são considerados como o método de vigilância de medicamentos mais eficaz, sendo a sub-notificação de RAMs uma das suas maiores limitações. Em termos globais, foi estimado que apenas 6% de todas as reacções adversas são notificadas. Portugal apresenta uma taxa de notificação de RAMs relativamente baixa quando comparada com os países mais notificadores da Europa. São objectivos deste estudo: 1) caracterizar as atitudes e os comportamentos dos médicos, dos farmacêuticos e dos enfermeiros em Portugal Continental relativamente à notificação de RAMs; e 2) caracterizar a efectividade de intervenções educacionais destinadas a reduzir a sub-notificação de RAMs. Métodos: Numa primeira fase será efectuado um estudo de caso-controlo em médicos, farmacêuticos e enfermeiros de Portugal Continental, a exercer actividade no Servico Nacional de Saúde (SNS), de modo a caracterizar as suas atitudes e comportamentos relativamente à notificação de RAMs. Como casos serão considerados os Profissionais de Saúde que notificaram pelo menos uma RAM num determinado período e os controlos os Profissionais de Saúde que não notificaram qualquer RAM nesse mesmo período, sendo estes útimos seleccionados aleatoriamente. O estudo será conduzido através de um questionário de auto-resposta, em que as questões relativas às atitudes e comportamentos são baseadas nos “sete pecados mortais” de Inman. Será utilizada uma Escala Visual Analógica para registar as respostas, podendo estas ir de zero (totalmente em desacordo) até 10 (totalmente de acordo). Será utilizada uma análise de regressão logística para determinar o odds ratio ajustado (ORadj) da notificação de RAMs para uma mudança de exposição correspondente ao range interquartil para cada atitude. Numa segunda fase, será efectuado ensaio aleatorizado controlado de cluster, para caracterizar a efectividade das intervenções educacionais realizadas sobre as causas identificadas na primeira parte do trabalho, com o intuito de reduzir a sub-notificação de RAMs. Com base em informacão de 2007 foram identificados 43 clusters dispersos pelas várias Regiões de Saúde. As intervenções educacionais são compostas por uma apresentação com uma hora de duração complementada por um folheto recordatório. Serão ainda realizados dois sub-estudos, em que o V1.0, Final 28Set09 viii Sub-notificação de RAMs em Portugal – Um problema com solução ? primeiro tentará caracterizar o efeito de contaminação entre Profissionais de Saúde e o segundo pretende caracterizar a duração do efeito das intervenções educacionais. Resultados a atingir: Pretende-se, com a implementação deste projecto, aumentar o número de notificações de RAMs pelos médicos, farmacêuticos e enfermeiros em cerca de 110%, de modo a atingir-se uma taxa de notificação de aproximadamente 300 notificações por milhão de habitantes por ano (i.e., multiplicar por 2,1 o número notificações existentes). -------------------ABSTRACT - Introduction: The Adverse Drug Reactions (ADRs) are a serious Public Health problem in terms of mortality and morbidity caused, being also an economic burden for the health systems. The Spontaneous Adverse Event Reporting Systems are considered as the most effective drug surveillance methods, in which the ADR under-reporting represents one of its biggest limitations. It was estimated that only 6% of all adverse reactions are notified globally. When comparing with high ADR reporting rate countries Portugal shows a low ADR reporting rate. This study aims to: 1) characterize the physicians, pharmacists and nurses attitudes and behaviours related to ADR under-reporting; 2) characterize the educational interventions effectiveness to decrease the ADRs under-reporting. Methods: During a first phase a case-control study will be conducted in physicians, pharmacists and nurses in Continental Portugal working in the National Health System (NHS) in order to characterize their attitudes and behaviours related to ADR reporting. The Healthcare Professionals that have reported at least one ADR during a determined period will be considered as the cases and those that have not reported any ADR during the same period will be considered as the controls. The controls will be randomly selected. The study will be conducted through a self-administered questionnaire in which the questions related to the attitudes and behaviours are based in the Inmans’s “seven mortal sins”. A Visual Analogue Scale will be used to record the responses. The responses can range from 0 (totally disagree) to 10 (totally agree). Logistic regression will be used to determine the ADR reporting adjusted odds ratio (ORadj) for a change in the exposure corresponding to the interquartile range for each attitude. In the second phase of the study a cluster-randomized controlled trial will be conducted to characterize the educational interventions effectiveness focused on the first phase identified causes with the aim to decrease the ADRs under-reporting. Based in 2007’s information 43 clusters have been identified throughout the several Health Regions. The educational interventions are composed of one hour presentation complemented by an informational leaflet. Two sub-studies will be also conducted in which the first one will try to characterize the contamination effect between the Healthcare Professionals and the second to characterize the educational interventions effect duration. V1.0, Final 28Set09 x Sub-notificação de RAMs em Portugal – Um problema com solução ? Outcome: With the project implementation an increase of the ADR notifications performed by the physicians, pharmacists and nurses by 110% is aimed in order to obtain approximately 300 notifications per million habitants per year (i.e., multiply by 2,1 the existent notifications).