Evaluation of the ELISA-F29 test as an early marker of therapeutic efficacy in adults with chronic Chagas disease

This work compared the time at which negative seroconversion was detected by conventional serology (CS) and by the ELISA-F29 test on a cohort of chronic chagasic patients treated with nifurtimox or benznidazole. A retrospective study was performed using preserved serum from 66 asymptomatic chagasic adults under clinical supervision, and bi-annual serological examinations over a mean follow-up of 23 years. Twenty nine patients received trypanocide treatment and 37 remained untreated. The ELISA-F29 test used a recombinant antigen which was obtained by expressing the Trypanosoma cruzi flagellar calcium-binding protein gene in Escherichia coli. Among the untreated patients, 36 maintained CS titers. One patient showed a doubtful serology in some check-ups. ELISA-F29 showed constant reactivity in 35 out of 37 patients and was negative for the patient with fluctuating CS. The treated patients were divided into three groups according to the CS titers: in 13 they became negative; in 12 they decreased and in four they remained unchanged. ELISA-F29 was negative for the first two groups. The time at which negativization was detected was significantly lower for the ELISA-F29 test than for CS, 14.5 ± 5.7 and 22 ± 4.9 years respectively. Negative seroconversion was observed in treated patients only. The results obtained confirm that the ELISA-F29 test is useful as an early indicator of negative seroconversion in treated chronic patients.

Vulvar Lichen Sclerosus: Efficacy of Photodynamic Therapy Under Conscious Sedation with Inhaled 50% Nitrous Oxide and Oxygen Mixture

Anogenital lichen sclerosus is a chronic, inflammatory, mucocutaneous disorder of significant morbidity. Common symptoms include pruritus, pain, dysuria, and dyspareunia, frequently of difficult control. Photodynamic therapy (PDT) may be an effective therapeutic option in selected cases refractory to first--‐line treatment options. However, procedure--‐related pain is a limiting factor in patient adherence to treatment. Conscious sedation and analgesia with a ready--‐to--‐use gas mixture of nitrous oxide and oxygen is useful in short--‐term procedures. It provides a rapid, effective, and short--‐lived effect, without the need for anesthesiology support. A 75--‐year--‐old woman presented with a highly symptomatic, histologically confirmed vulvar lichen sclerosus, with at least 15 years of evolution. Pain, pruritus, and dysuria were intense and disabling. Treatment with ultrapotent topical corticosteroids proved to be ineffective despite patient compliance. She was then referred for PDT. A total of 3 sessions were performed, held at a mean interval of 9 weeks, and under the analgesic and sedative effect of nitrous oxide/oxygen gas. Response to treatment was evaluated through a daily, self--‐reported pain rating scale. Dysuria remitted completely after the first PDT session. An 80% reduction in pruritus and pain was observed after the third session, and has been sustained for the past six months without further need for topical corticotherapy. Treatment sessions were well tolerated and pain-- free, with no side effects to report. PDT appears to be effective in the symptomatic treatment of vulvar lichen sclerosus. To the authors’ knowledge this is the first case reporting the use of inhaled nitrous oxide/oxygen gas mixture during PDT performed in the genital area. Its analgesic and sedative effects may increase patients’ adherence to this painful procedure. Furthermore, given its safety, it can be easily managed in outpatient clinics by trained dermatologists.

Prophylaxis in Hemophilia A Patients with Inhibitors

The development of antibodies to factor VIII is one of the most serious complications of haemophilia treatment. Approximately 30% of patients with severe haemophilia develop neutralizing inhibitors to replacement FVIII. Although most patients with inhibitors do not bleed more frequently than patients without inhibitors, bleeding is more difficult to control and this patients suffer more severe bleeding and have greater morbidity and mortality. Patients with persistent high-titer inhibitor who are not candidates or fail ITI, pose a great challenge to haemophilia management. The efficacy and safety of prophylaxis with bypassing agents in reducing bleeding tendency, has been described in numerous studies. Patients and methods: We report tree adult severe haemophilia A patients, two with persistent high-titre inhibitors and one who failed ITI, on prophylactic treatment after several significant musculoskeletal and life-threatening haemorrhagic episodes (intrabdominal/intramuscular) and pseudotumor haemorrhage. Treatment regimens consisted of APCC (Feiba®) in doses of 60-70UKg-1, 2-3 times per week, according underlying bleeding phenotype. Breakthrough bleeds were treated with either APCC (Feiba®) or rFVIIa (NovoSeven®). Results and Conclusion: There was reduction in total bleeding episodes in two patients (43% to 80%) and one patient remained stable, while receiving prophylaxis. Absence of severe and life threatening bleeding episodes, as well as inpatient stays, contributing to a better quality of life in those patients, was observed. APCC (Feiba®) was well tolerated and no thrombotic events were observed.

EFFICACY OF NITAZOXANIDE AGAINST Toxocara canis: LARVAL RECOVERY AND HUMORAL IMMUNE RESPONSE IN EXPERIMENTALLY INFECTED MICE

SUMMARY The efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

EVALUATION OF THE THERAPEUTIC EFFICACY OF LEVAMISOLE HYDROCHLORIDE ON THIRD-STAGE LARVAE OF Lagochilascaris minor IN EXPERIMENTALLY INFECTED MICE

Lagochilascariosis, a disease caused by Lagochilascaris minor, affects the neck, sinuses, tonsils, lungs, the sacral region, dental alveoli, eyeballs and the central nervous system of humans. A cycle of autoinfection may occur in human host tissues characterized by the presence of eggs, larvae and adult worms. This peculiarity of the cycle hinders therapy, since there are no drugs that exhibit ovicidal, larvicidal and vermicidal activity. Given these facts, we studied the action of levamisole hydrochloride on third-stage larvae in the migration phase (G1) and on encysted larvae (G3) of L. minor. To this end, 87 inbred mice of the C57BL/6 strain were divided into test groups comprising 67 animals (G1-37; G3-30) and a control group (G2-10; G4-10) with 20 animals. Each animal was inoculated orally with 2,000 infective eggs of the parasite. The animals of the test groups were treated individually with a single oral dose of levamisole hydrochloride at a concentration of 0.075 mg. The drug was administered either 30 minutes prior to the parasite inoculation (G1 animals) or 120 days after the inoculation (G3 animals). The mice in the control groups were not treated with the drug. After the time required for the migration and the encysting of L. minor larvae, all the animals were euthanized and their tissues examined. The data were analyzed using the Student's unpaired t-test and the Levene test. The groups showed no statistically significant difference. Levamisole hydrochloride was ineffective on third-stage larvae of L. minor. These findings explain the massive expulsion of live adult worms, as well as the use of long treatment schemes, owing to the persistence of larvae and eggs in human parasitic lesions.

Atorvastatin versus Bezafibrate in Mixed Hyperlipidaemia : Randomised Clinical Trial of Efficacy and Safety (the ATOMIX Study)

OBJECTIVE: Combined hyperlipidaemia is a common and highly atherogenic lipid phenotype with multiple lipoprotein abnormalities that are difficult to normalise with single-drug therapy. The ATOMIX multicentre, controlled clinical trial compared the efficacy and safety of atorvastatin and bezafibrate in patients with diet-resistant combined hyperlipidaemia. PATIENTS AND STUDY DESIGN: Following a 6-week placebo run-in period, 138 patients received atorvastatin 10mg or bezafibrate 400mg once daily in a randomised, double-blind, placebo-controlled trial. To meet predefined low-density lipoprotein-cholesterol (LDL-C) target levels, atorvastatin dosages were increased to 20mg or 40mg once daily after 8 and 16 weeks, respectively. RESULTS: After 52 weeks, atorvastatin achieved greater reductions in LDL-C than bezafibrate (percentage decrease 35 vs 5; p < 0.0001), while bezafibrate achieved greater reductions in triglyceride than atorvastatin (percentage decrease 33 vs 21; p < 0.05) and greater increases in high-density lipoprotein-cholesterol (HDL-C) [percentage increase 28 vs 17; p < 0.01 ]. Target LDL-C levels (according to global risk) were attained in 62% of atorvastatin recipients and 6% of bezafibrate recipients, and triglyceride levels <200 mg/dL were achieved in 52% and 60% of patients, respectively. In patients with normal baseline HDL-C, bezafibrate was superior to atorvastatin for raising HDL-C, while in those with baseline HDL-C <35 mg/dL, the two drugs raised HDL-C to a similar extent after adjustment for baseline values. Both drugs were well tolerated. CONCLUSION: The results show that atorvastatin has an overall better efficacy than bezafibrate in concomitantly reaching LDL-C and triglyceride target levels in combined hyperlipidaemia, thus supporting its use as monotherapy in patients with this lipid phenotype.

Efficacy of azithromycin in the treatment of cutaneous leishmaniasis

The present open pilot study was conducted to assess the efficacy of azithromycin for the treatment of patients with cutaneous leishmaniasis in Araçuaí and Varzelândia, MG. Twenty-four patients with less of six months of disease evolution were treated after clinical examination, Montenegro test and a biopsy. The treatment schemes consisted of oral doses of 500 mg per day for 3, 5 and 10 days and of 1000 mg for two days. A clinical control was performed monthly and treatment cycles were repeated when necessary until full reepithelialization of the lesions. On the occasion of the final evaluation, 20 patients had completed the study and 17 of them (85%) were cured. The time to obtain a cure was 60 days ifor 6 (30%) patients, 90 days for 7 (35%), and 120 for 4 (20%). The three patients with treatment failure received a pentavalent antimonial for 20 days. No adverse reactions to the medication were observed and a 14 month follow-up did not show recurrence in any patient. These results suggest that azithromycin can be a good therapeutic option for the treatment of cutaneous leishmaniasis caused by Leishmania Viannia brasiliensis.

Efficacy of sulfadoxine-pyrimethamine and mefloquine for the treatment of uncomplicated Plasmodium falciparum malaria in the Amazon basin of Peru

In vivo antimalarial drug efficacy studies of uncomplicated Plasmodium falciparum malaria at an isolated site in the Amazon basin of Peru bordering Brazil and Colombia showed >50% RII/RIII resistance to sulfadoxine-pyrimethamine but no evidence of resistance to mefloquine.

Assessing the efficacy of the Mental Health Gap Action Programme (mhGAP) training for non-specialized health workers in Ethiopia

RESUMO: A OMS lançou em 2008, o Programa de Acção do Gap em Saúde Mental (mhGAP) para suprir a falta de cuidados, especialmente em países de rendimento baixo e médio, para as pessoas que sofrem de perturbações mentais, neurológicas e de uso de substâncias (MNS). Um componente crucial do mhGAP é representado pelo esforço no sentido da integração da saúde mental nos cuidados de saúde primários. Na Etiópia, o mhGAP foi monitorizado durante 3 anos, graças a um projeto de demonstração implementado em clínicas selecionadas em quatro regiões do país. A fase de demonstração de mhGAP na Etiópia traduziu-se principalmente na formação de profissionais de saúde não especializados, fornecendo-lhes orientação e supervisão apoiada para a utilização de medicamentos psicotrópicos essenciais e na coordenação com o Ministério Etíope Federal da Saúde, Hospital Amanuel de Saúde Mental e as Secretarias Regionais de Saúde ( RHBs ). O presente trabalho investigou a eficácia do pacote de formação mhGAP através de uma análise das pontuações dos participantes no pré- e pós-testes. A análise estatística mostrou - com uma exceção - que a melhoria dos formandos é estatisticamente significativa, o que sugere que os conhecimentos dos participantes é melhorada na fase de pós-teste. A eficácia do pacote de formação mhGAP para profissionais de saúde não especializados é uma evidência promissora de que os mesmos podem ser treinados com sucesso para realizar um pacote básico de intervenções para a prestação de cuidados e tratamento para pessoas com perturbações mentais, neurológicas e de uso de substâncias. Este trabalho destaca, também, várias limitações não apenas inerentes ao próprio projecto de investigação tais como o número limitado de respostas que foram analisadas e a falta de dados de uma das quatro regiões onde mhGAP foi testado na Etiópia. As principais limitações decorrem de facto da abordagem global limitar as intervenções de saúde mental ao programa de formação e supervisão dos trabalhadores de cuidados de saúde primários . Este processo só será bem sucedido se, juntamente com outras intervenções - que vão desde o desenvolvimento de currículos para o desenvolvimento de uma legislação de saúde mental -, fôr incluído numa estratégia mais abrangente para a reforma da saúde mental e desafiar o status quo.-----------ABSTRACT:In 2008, WHO launched the Mental Health Gap Action Programme (mhGAP) to address the lack of care, especially in low- and middle- income countries, for people living with mental, neurological and substance use (MNS) disorders. A crucial component of mhGAP is represented by the endeavor towards integration of mental health into primary health care. In Ethiopia, mhGAP has been piloted for 3 years thanks to a demonstration project implemented in selected clinics in 4 regions of the country. The demonstration phase of mhGAP in Ethiopia has mainly translated into training of non-specialized health workers, providing them with mentorship and supportive supervision, availing essential psychotropic medications and coordinating with the Ethiopian Federal Ministry of Health, Amanuel Mental Health Hospital and the Regional Health Bureaus (RHBs). The present paper investigated the efficacy of the mhGAP training package through an analysis of the participants’ scores at pre-test and post-test. The statistical analysis showed - with one exception - that the improvement of trainees is statistically significant, therefore suggesting that the knowledge of participants is improved in the post-test phase. The efficacy of the mhGAP training package on non-specialized health workers is promising evidence that non-specialized health-care providers can be successfully trained to deliver a basic package of interventions for providing care and treatment for people with mental, neurological and substance use disorders. However, this paper also highlights several limitations, which are not only inherent to the research itself, such as the limited number of scores that was analyzed, or the lack of data from one of the four regions where mhGAP has been piloted in Ethiopia; major limitations occur in fact in the overall approach of confining mental health interventions to training and supervising primary health care workers. This process will only be successful if coupled with other interventions – ranging from curricula development to development of a mental health legislation - and if it is included in a more comprehensive strategy to reform mental health and challenge the status quo.

Efficacy of voriconazole in experimental rat paracoccidioidomycosis

INTRODUCTION: Amphotericin B, azole or sulfamide drugs are used for treatment of patients with paracoccidioidomycosis. Among the azole drugs, voriconazole was active in vitro against Paracoccidioides brasiliensis and showed efficacy in the treatment of patients infected with this fungus.In the present study the antifungal activity of voriconazole and of other drugs was compared in a rat model of paracoccidioidomycosis. METHODS: Wistar rats were inoculated intravenously with the BOAS strain of P. brasiliensis and antifungal drugs were administered to the animals by gavage at the following doses (mg/kg weight/day): voriconazole (5 to 20), ketoconazole (12 to 15), fluconazole (6), itraconazole (4), and sulfamethoxazole-trimethoprim (120 to 150). The antifungal activity of the drugs was assessed by determining the P. brasiliensis colony forming units in the lungs and spleen of the animals at the end of treatment and by a survival study. RESULTS: Voriconazole reduced the total tissue fungal burden of P. brasiliensis, particularly at doses of ≥10mg/kg weight/day but its antifungal activity was less intense than that of fluconazole, itraconazole and sulfamethoxazole-trimethoprim. The mean survival of animals treated with the last three drugs, 29.1±10.7, 26.1± 10.1 and 28.4±9.6 days, respectively, was higher than that achieved with voriconazole 10mg/kg weight/day (18.5±8.3 days) and that observed in untreated animals (15.7±3.6 days). CONCLUSIONS: At doses similar to those used for clinical treatment, voriconazole showed lower antifungal activity in experimental rat paracoccidioidomycosis than that obtained with itraconazole and sulfamethoxazole-trimethoprim.

The efficacy of the old way/new way methodology on the correction of an automated technical error and its impact on the athlete’s psychological skills : Case study in tennis

The aim of this study was to evaluated the efficacy of the Old Way/New Way methodology (Lyndon, 1989/2000) with regard to the permanent correction of a consolidated and automated technical error experienced by a tennis athlete (who is 18 years old and has been engaged in practice mode for about 6 years) in the execution of serves. Additionally, the study assessed the impact of intervention on the athlete’s psychological skills. An individualized intervention was designed using strategies that aimed to produce a) a detailed analysis of the error using video images; b) an increased kinaesthetic awareness; c) a reactivation of memory error; d) the discrimination and generalization of the correct motor action. The athlete’s psychological skills were measured with a Portuguese version of the Psychological Skills Inventory for Sports (Cruz & Viana, 1993). After the intervention, the technical error was corrected with great efficacy and an increase in the athlete’s psychological skills was verified. This study demonstrates the methodology’s efficacy, which is consistent with the effects of this type of intervention in different contexts.

Efficacy and tolerability of two single-day regimens of triclabendazole for fascioliasis in Peruvian children

Abstract:INTRODUCTION:The therapeutic scheme of triclabendazole (TCBZ), the recommended anthelmintic against Fasciola hepatica , involves 10mg/kg of body weight administered in a single dose; however, clinical trials in children are scarce. We evaluated the efficacy and tolerability of 2 schemes of TCBZ.METHODS: Eighty-four Peruvian children with F. hepatica eggs in their stools were allocated into 2 groups: 44 received 2 dosages of 7.5mg/kg each with a 12-h interval (Group I), and 40 received a single 10-mg/kg dose (Group II). Evaluation of efficacy was based on the presence of eggs in stools, and tolerability was based on the presence of symptoms and signs post-treatment.RESULTS: A parasitological cure was obtained in 100% of individuals from Group I and 95% of individuals from Group II. The most common adverse event was biliary colic.CONCLUSIONS: The tested scheme was efficacious and tolerable, and it might be an optimal scheme in the region. To the best of our knowledge, this represents the largest series of children treated with TCBZ in a non-hospital setting.