Antiretroviral drug use by individuals living with HIV/AIDS and compliance with the Clinical Protocol and Therapy Guidelines / Uso de antirretrovirais por pessoas vivendo com HIV/AIDS e sua conformidade com o Protocolo Clínico e Diretrizes Terapêuticas

ABSTRACT Objective To describe antiretroviral treatment regimens prescribed and their compliance with the Clinical Protocol and Therapy Guidelines of the Ministry of Health for the management of HIV infection. Methods Observational and descriptive study. Secondary data of the state of Paraná (Brazil) on drugs, treatment regimens, lines of treatment and number of individuals on treatment, from January to June 2018, were accessed at the Antiretroviral Agents Logistic Control System. Combinations of antiretroviral drugs (treatment regimens) were compared according to the current Clinical Protocol and Therapy Guidelines and non-compliances were classified and quantified. Results In Paraná, 35,127 individuals with HIV were treated with 253 different treatment regimens. Of the prescribed regimens, 19.1% were first-line, 27.4% second-line and 48.5% third-line. Among non-compliances, the most prevalent were absence of association of protease inhibitors and ritonavir (42.8%), low efficacy triple therapy (36.9%), double therapy (26.1%), monotherapy (20.3%), and triple therapy of nucleoside analog reverse transcriptase inhibitors (17.1%). Conclusion Most individuals receiving HIV treatment in the state of Paraná are on treatment regimens established in the current Clinical Protocol and Therapy Guidelines, which contributes to successful therapy. However, associations not provided by the current Clinical Protocol and Therapy Guidelines were identified in the initial treatment lines, which could lead to ineffectiveness, virologic failure and viral resistance.

RESUMO Objetivo Descrever esquemas terapêuticos de antirretrovirais prescritos e sua conformidade com o Protocolo Clínico e Diretrizes Terapêuticas, do Ministério da Saúde, para manejo da infecção pelo HIV. Métodos Estudo observacional e descritivo. Os dados do estado do Paraná sobre medicamentos que compõem os esquemas terapêuticos, linhas de tratamento e número de pessoas em uso destes foram acessados no Sistema de Controle Logístico de Medicamentos Antirretrovirais no período de janeiro a junho de 2018. As combinações de antirretrovirais (esquemas terapêuticos) foram comparadas conforme o Protocolo Clínico e Diretrizes Terapêuticas vigente, e as inconformidades foram categorizadas e quantificadas. Resultados No Paraná, 35.127 pessoas com HIV foram tratadas com 253 esquemas terapêuticos distintos. Dentre os esquemas prescritos, 19,1% eram de primeira linha, 27,4% de segunda linha e 48,5% de terceira linha. Nas inconformidades, predominaram a não associação entre inibidores da protease e ritonavir (42,8%), terapia tripla de baixa eficiência (36,9%), terapia dupla (26,1%), monoterapia (20,3%) e terapia tripla de inibidores da transcriptase reversa análogos de nucleosídeos (17,1%). Conclusão Maior parte das pessoas em tratamento do HIV no Paraná utilizam esquemas terapêuticos previstos no Protocolo Clínico e Diretrizes Terapêuticas vigente, o que contribui para o sucesso terapêutico. Entretanto, associações não previstas foram identificadas nas linhas de tratamento iniciais, podendo ocasionar inefetividade, falha virológica e resistência viral.

Molecular biology of human epidermal receptors, signaling pathways and targeted therapy against cancers: new evidences and old challenges

ABSTRACT Human epidermal receptors (HER1/2/3/4) belong to the class of receptor-type tyrosine kinases. After binding a ligand, dimerization, it will ocurr activation of intracellular kinases after two-dimensional and cytoplasmic tail reciprocal transphosphorylation. This transphosphorylation recruits signaling pathways such as Ras/Raf/MEK/Erk1-2, PI3-K/AKT and JAK/STAT, which can affect the cell cycle, cytoskeleton reorganization, apoptosis, metastasis, differentiation, angiogenesis and transcription. HER deregulation is found in epithelial, mesenchymal and nervous neoplasms and is associated with poor prognosis and tumor severity. Since HER are promiscuous proteins when subjected to mutations, resultant modifications confer cellular metabolic superiority and activate complex, interconnected and overlapping networks of cytoplasmic signaling. Moreover, overexpression of HER1/2 is involved in tumor resistance to radiation and anti-hormone therapies. Indeed, HER2 expression is up to 100-fold higher in 25-30% of invasive breast cancers. These characteristics support the development of resistance to anti-HER1/2 chemotherapy such as monoclonal antibodies and tyrosine kinase inhibitors. Then, the challenges in research with HER-positive cancers include planning therapeutic strategies against known resistance mechanisms and identifying novel mechanisms as a way to overcome and control cell growth and malignant progression.

Perfil epidemiológico da polifarmacoterapia e morbidades em idosos de uma cidade do interior paulista / Epidemiological profile of the health conditions of the elderly in a city in the interior of São Paulo

O processo de envelhecimento traz consigo diversas modificação no âmbito pessoal e biológico do indivíduo. Expandindo-se essas transformações, para o âmbito populacional, na questão da saúde, delimita-se um crescente prevalências das denominadas doenças crônicas não transmissíveis. Nesta lógica, um maior número de moléstias crônicas, leva os indivíduos a ingerirem uma maior quantidade de fármacos, sejam eles prescritos por via clínica ou mesmo pela própria automedicação. Em vista disso, o presente trabalho objetivou realizar um levantamento epidemiológico para se traçar o perfil de saúde dos idosos de uma cidade do interior paulista, enfocando-se a presença de doenças crônicas não transmissíveis, medicamentos utilizados, a presença de polifarmácia e a qualidade de vida. A amostra foi composta por 241 idosos residentes da cidade de Duartina, SP. Primeiramente realizou-se um questionário geral para se determinar a presença de doenças e caracterização geral da amostra. Após, os idosos passaram pelo questionário de qualidade de vida e por um questionário sobre os medicamentos utilizados. A partir dos dados deste último, através do site drugs.com determinou-se a presença e os níveis de polifarmácia. Nos resultados, pode-se observar uma considerável prevalência de diabetes, dislipidemias e hipertensão, sendo as idosas as mais afetadas. Quanto ao uso dos fármacos, 22,7% utilizam, ao menos, cinco medicamentos distintos ao dia. Na análise da polifarmácia, 30% não apresentaram interações, 68% apresentaram nível moderado e 2% elevado. Através da correlação de Pearson, identificou-se que com o aumento do número de medicamentos utilizados, houve aumento do nível da intensidade da polifarmácia (p < 0,0001 e r = 0,81). Quanto à qualidade de vida, todos as áreas apresentaram índices relativamente altos, sendo o domínio físico com a melhor média e o ambiental com pior. Na análise por questão, os piores índices ficaram com dor, dependência de medicamentos e sentimentos negativos. Com a Correlação de Spearman, determinou-se que o aumento dos índices de polifarmácia diminuem a qualidade vida (p = 0,03 e r = -0,57). Deste modo, conclui-se que, nos idosos, há uma elevada prevalência de hipertensão, diabetes e das dislipidemias, bem como um considerável uso de diferentes medicamentos diariamente. Anexo a estes dados, a qualidade de vida apresentou índices adequados, sendo afetada negativamente pelo aumento do uso diários de medicamentos.(AU)

The process of aging brings with it several modifications in the personal and biological scope of the individual. Expanding these transformations, for the population, in the health issue, delimits a growing prevalence of so-called chronic non-communicable diseases. In this logic, a greater number of chronic diseases, leads individuals to ingest a greater amount of drugs, whether they are prescribed clinically or even by self-medication. In view of this, the present study aimed to carry out an epidemiological survey to trace the health profile of the elderly in a city in the interior of the state of São Paulo, focusing on the presence of chronic noncommunicable diseases, medications used, the presence of polypharmacy and the quality of life. The sample consisted of 241 elderly residents of the city of Duartina, SP. Firstly, a general questionnaire was carried out to determine the presence of diseases and the general characterization of the sample. Afterwards, the elderly passed the quality of life questionnaire and a questionnaire about the medications used. From the data of the latter, through the website drugs.com was determined the presence and levels of polypharmacy. In the results, a considerable prevalence of diabetes, dyslipidemia and hypertension can be observed, with the elderly being the most affected. As for drug use, 22.7% use at least five different drugs a day. In the analysis of polypharmacy, 30% did not present interactions, 68% presented moderate level and 2% elevated. Through the Pearson correlation, it was identified that with the increase in the number of medications used, there was an increase in the level of polypharmacy intensity (p <0.0001 and r = 0.81). As for the quality of life, all the areas presented relatively high indexes, being the physical domain with the best average and the environmental one with worse. In the analysis by question, the worst indexes were pain, drug dependence and negative feelings. With Spearman's correlation, it was determined that the increase in polypharmacy indexes decreased the quality of life (p = 0.03 and r = -0.57). Thus, it is concluded that in the elderly, there is a high prevalence of hypertension, diabetes and dyslipidemias, as well as a considerable use of different drugs daily. Annexed to these data, the quality of life presented adequate indexes, being negatively affected by the increase in the daily use of medicines.(AU)

Drug utilization profile in adult patients with refractory epilepsy at a tertiary referral center / Perfil de utilizacao de farmacos por pacientes adultos com epilepsia refrataria em um centro terciario de referencia

Objective To evaluate the utilization profile of antiepileptic drugs in a population of adult patients with refractory epilepsy attending a tertiary center. Method Descriptive analyses of data were obtained from the medical records of 112 patients. Other clinical and demographic characteristics were also registered. Results Polytherapies with ≥3 antiepileptic drugs were prescribed to 60.7% of patients. Of the old agents, carbamazepine and clobazam were the most commonly prescribed (72.3% and 58.9% of the patients, respectively). Among the new agents, lamotrigine was the most commonly prescribed (36.6% of the patients). At least one old agent was identified in 103 out of the 104 polytherapies, while at least one new agent was prescribed to 70.5% of the population. The most prevalent combination was carbamazepine + clobazam + lamotrigine. The mean AED load found was 3.3 (range 0.4–7.7). Conclusion The pattern of use of individual drugs, although consistent with current treatment guidelines, is strongly influenced by the public health system. .

Objetivo Avaliar o perfil de utilização de fármacos antiepilépticos em uma população de pacientes adultos com epilepsia refratária atendidos em um centro terciário. Método Análises descritivas dos dados obtidos dos registros médicos de 112 pacientes. Também foram consideradas as características clínicas e demográficas. Resultados Foram prescritas politerapias com ≥3 antiepilépticos a 60,7% dos pacientes. Em relação aos fármacos de primeira geração, carbamazepina e clobazam foram os mais frequentemente prescritos (a 72,3% e 58,9% dos pacientes, respectivamente). Dentre os novos antiepilépticos, a lamotrigina foi o mais prescrito (36,6% dos pacientes). Ao menos um antiepiléptico de primeira geração foi encontrado em 103 das 104 politerapias; ao menos um novo antiepiléptico foi prescrito a 70,5% da população. A combinação mais prevalente foi carbamazepina+clobazan+lamotrigina. A carga média de antiepilépticos foi 3.3 (0.4 a 7.7). Conclusão O padrão de utilização de antiepilépticos, embora concordante com guias atuais, é fortemente influenciado pelo sistema público de saúde. .

Comparison between the role of n-acetylcysteine alone and with silymarin in paracetamol induced acute hepatotoxicity [clinical and experimental study]

Paracetamol [APAP], a widely used analgesic and antipyretic, is known to cause hepatic injury in high doses. N-acetylcysteine [NAC] and silymarin have been used in treatment of liver diseases of varying origins. This work was conducted to compare between the role of NAC alone and with silymarin in paracetamol induced acute hepatotoxicity. This work included both clinical and experimental studies. The clinical study included 27 patients with acute paracetamol poisoning admitted to Poisoning Treatment Unit - Zagazig University Hospitals between January and July, 2011. Sixteen patients [group I] were treated with NAC alone. Another eleven patients [group II] were treated with both NAC and silymarin. Plasma paracetamol level was measured on admission and liver function tests were assessed on admission and daily for three days. The experimental study included forty two adult male albino rats were divided into 7 groups. Group [1]: negative control rats, group [2]: positive control rats received distilled water, group [3]: received 140mg/kg NAC, group [4]: received 40mg/kg silymarin, group [5]: received l000mg/kg APAP, group [6]: received APAP followed by NAC in the same previous doses/ Group [7]: received combined NAC and silymarin following APAP administration in the same previous doses. All drugs were given once by oral gavage. 24 hours after commencing the experiment liver function tests and hepatic glutathione [GSH] content were assessed. Liver specimens were submitted to histopathological examination and immunolocalization of BCL-2 and BrdU. It was found that combined treatment with NAC and silymarin induced a significant reduction of the elevated hepatic transaminases compared to treatment with NAC alone in both patients and rats especially patients presented late after 15 hours of APAP ingestion. Histopathological examination of hepatic specimens from combined treated rats revealed reappearance of the regular morphology of the hepatic lobules with strong immunoreactivity to BCL-2 and BrdU. Rats treated with NAC alone showed partial improvement where there were some areas of hepatocytes vacuolization, cellular infiltration, and sinusoidal dilatation, with moderate reaction for both BCL-2 and BrdU. This was accompanied with a significant elevation of the mean values of hepatic GSH in combined treated rats compared to those treated with NAC alone. It was concluded that both silymarin and NAC have a synergistic effect, and combined treatment with both of them could be used as a beneficial treatment for paracetamol acute hepatotoxicity especially for late presented cases

Efficacy of zinc as adjuvant therapy for pneumonia in children less than five years

Pneumonia is the leading cause of morbidity and mortality in children < 5 years old. Zinc administration lowers the risk of acute lower respiratory infections in children. This study evaluated the efficacy of zinc supplementation in the treatment of pneumonia in Egyptian children aged < 5 years who were diagnosed and treated according to WHO guidelines. In a double-blind, placebo-controlled clinical trial, children with pneumonia or severe pneumonia were randomly assigned to receive zinc [n= 56] or placebo [n =56] daily till recovery and discharge from hospital as an adjuvant to antibiotics. The outcome variables were the duration of fast breathing, chest indrawing if present and fever. The following investigations were performed: complete blood picture, serum zinc. Pneumonia was diagnosed in 16 and 15 cases in zinc and placebo group respectively while severe pneumonia was present in 40 cases in zinc group and 41 in placebo group. At enrollment both groups had deficient serum zinc level. Zinc group had shorter duration of rapid breathing [45.7 +/- 1.1 vs 66.9 +/- 1.3 h], chest indrawing [26.9 +/- 1.2 vs 44.3 +/- L4 h] and fever [23.0 +/- 1.2 vs 32.8 +/- 1.1 h] and the differences between zinc and placebo groups were statistically significant [P=0.000 for each of them]. At discharge both groups had higher serum zinc concentrations than at baseline: 88.8 +/- 1.9 microg/dl for zinc and 75.3 +/- 1.1 microg/dl for placebo group. The difference between the zinc and placebo groups' discharge zinc concentrations was significant [P=0-000]. It is concluded that the use of zinc as adjuvant therapy for pneumonia or severe pneumonia in children < 5 years reduces the duration of rapid breathing, chest indrawing and fever. This study needs to be replicated in other populations, including those with and without a high prevalence of zinc deficiency

combination anti-HBV regimen using lamivudine and other agents in treatment of resistant chronic hepatitis B

Several difficulties remain in formulating treatment for chronic hepatitis B [CHB], 350 million people are chronically infected with HBV, Chronic infection with hepatitis B virus accounts for an enormous burden of disease worldwide, including up to half of all cases of cirrhosis, end stage liver disease, and hepatocellular carcinoma. To maximize the elimination of the viral infection while minimizing or preventing damage to the liver cells and tissues and development of viral resistance to more antivirals. Eighty eight patients of chronic hepatitis B virus infection with resistance to lamivudine treatment as proved by quantitative PCR [more than 200 IU/ ml]. Their age between [20-60] years, [85 males, and 3 females] were selected from the National Hepatology and Tropical Medicine Research Institute and were included in this study. The included patients were two groups, the first group 42 patients, were receiving Lamivudine, plus [Baraclude] Entecavir [tablet 0.5mg / day] treatment at the time of assessment. The second group 46 patients were receiving [Hepsera tablet 10 mg / day] Adefovir dipivoxil plus lamivudine [tablet]. All the patients were subjected to the following: thorough history and clinical examination, abdominal ultrasonography and collection of blood samples for routine liver and kidney function investigations and serological assay for HBsAg, HBsAb, HBeAg, HBeAb, HBcAb quantitative HBV DNA [PCR]. Our results revealed significant differences between the two groups of patients of CHBV infection, resistant to Lamivudine drug, the first group were higher in response to a combination between Lamivudine + [Baraclude] Entecavir, than the second group who were receiving Lamivudine + [Hepsera] Adefovir dipivoxil combination therapy. Our study concluded that the clinical benefit is apparent with high percentage after a combination regimen using Lamivudine + Entecavir than a combination regimen using Lamivudine + Adefovir dipivoxil for the treatment of resistant chronic hepatitis B virus who were treated with Lamivudine only before. Optimal management of chronic hepatitis B, that may require long-term and sometimes lifelong treatment to maintain its clinical benefit is challenging. It is important to initiate treatment with a drug that has the least potential for induction of drug resistance as sequential monotherapy which may result in selection of multidrug resistant HBV mutatants

Tratamiento de osteosarcoma en niños con quimioterapia pre y postoperatoria y resección en bloque del tumor / Preoperative chemotherapy plus postoperative adjuvant chemotherapy and block ressection in children with osteosarcona

Se presentaron los resultados del tratamiento de cinco niños con osteosarcoma tratados en el Hospital Infantil del Estado de Sonora, en un periodo de tres años (1987-1989): cuatro de ellos tenían el tumor localizado en tercio distal de fémur y un paciente en tercio proximal de húmero. Todos ingresaron sin metástasis. Los cinco pacientes recibieron dos ciclos de quimioterapia preoperatoria intravenosa con cisplatino y adriamicina. Un paciente fallece por infección después del primer ciclo de tratamiento. De los cuatro restantes, en tres se efectuó la resección en bloque del tumor, conservándoles su miembro y a uno se practicó amputación transmedular de la extremidad. Se evaluó histológicamente el efecto de la quimioterapia preoperatoria. Posteriormente, todos recibieron quimioterapia postoperatoria con bleomicina, ciclofosfamida y actinomicina D, alternando con cisplatino y adriamicina, durante 12 meses. Uno de los tres pacientes con resección en bloque del tumor, presentó recidiva en el cabo proximal a los 12 meses del diagnóstico, por lo que se practicó desarticulación del miembro y falleció cuatro meses después por leucoencefalopatía. Los tres casos restantes viven sin evidencia de tumor 20, 26 y 31 meses después del diagnóstico y dos de ellos conservan su miembro afectado

Poliquimioterapia de la lepra. Experiencia del Hospital Nacional Baldomero Sommer / Multidrug therapy of the leprosy

En el Hospital Nacional Baldomero Sommer se evaluaron retrospectivamente 93 pacientes que completaron por lo menos 2 años de poliquimioterapia según esquema OMS. El 82,9%de los 70 pacientes clínicamente activos mejoraron. El 12,8%permanecieron estacionarios. Se negativizó la baciloscopia del 93,4%de los 43 pacientes positivos al inicio. Los estados reaccionales mejoraron en el 66%de los pacientes que los presentaron. Un 24%de los enfermos realizó tratamiento irregular. La tolerancia fue buena en el 89%de los casos. Sólo se registraron efectos colaterales menores. Se observó una tasa de recaídas del 3,5%por año. Se discute el significado de estos hallazgos

Estudio comparativo de 7 tratamientos antifungicos en un modelo experimental de criptococosis murina (1* parte) / Comparative study of 7 antifungal treatment in experimental model of murine cryptococcosis

Se realizó un estudio comparativo de 7 tratamientos antifúngicos en un modelo experimental de criptococosis murina. Fueron inoculados por vía intraperitoneal con 10 células de Cryptococcus neoformans var. neoformans, 100 ratones Balb C, divididos en 10 grupos de 10 animales cada uno. Cinco días después de la infección, 7 grupos recibieron los siguientes tratamientos, durante 2 semanas: anfotericina B (6 mg/kg%día por medio, por vía intraperitoneal), itraconazol, fluconazol y Sch 39.304 (todos ellos a razón de 16 mg/kg/día por gastrocisis), 5-fluorocitosina sola (300 mg/kg/día) y en combinación con anfotericina B y con fluconazol, en iguales dosis y por iguales vías que cuando fueron administradas solas. Los 3 grupos restantes fueron usados como control y recibieron los solventes de las drogas. El tiempo de sobrevida, el aspecto macroscópico de cerebro, higado, pulmones y bazo, la presencia de levaduras capsuladas en el examen microscópico de estos mismos órganos y la siembra masiva de pulmones y cerebro, fueron tomados como parámetros de efectividad de las drogas. La combinación de anfotericina B y 5-fluorocitosina fue el tratamiento más efectivo, ya que produjo la negativización de los exámenes macro y microscópicos como también del 90%de las siembras masivas y prolongó el tiempo de sobrevida más allá de 60 días en todos los animales. La anfotericina B sola fue superior a los compuestos azólicos; con tiempos de sobrevida similares a los de la combinación de anfotericina B con 5-fluorocitosina y negativizó los exámenes macroscópicos, en el 60%de los ratones tratados. El Sch 39.304 mostró los tiempos de sobrevida más largos entre los derivados azólicos. Ninguno de los componentes de este grupo modificó los restantes parámetros estudiados. La asociación de 5-fluorocitosina con fluconazol no mostró mayor efectividad que cuando ambas drogas se administraron separadamente

Seguimiento de pacientes hansenianos con esquema multidroga de la OMS (modificado) / Follow-up of hanseniasis patients with a modified multidrug (OMS) scheme

Se evalúa la aplicación a lo largo de seis años del MDT en 120 pacientes hansenianos, comprobando que se trata de un esquena útil con aceptables resultados. Se cuestiona si la duración del tratamiento en las formas multibacilares y su alta, sin control hispopatológico previo, son adecuadas. Los autores prefieren continuar indefinidamente con dos drogas.