Determinants of Acquisition and Clearance of Human Papillomavirus Infection in Previously Unexposed Young Women.

BACKGROUND: Global variation in human papillomavirus (HPV) prevalence and persistence may be explained by differences in risk factors, such as sexual activity, oral contraceptive use, and behavioral factors. We evaluated determinants of acquisition and clearance of HPV infection among young women previously unexposed to HPV. METHODS: Five hundred thirty-four women aged 15 to 25 years who were cytology and HPV DNA negative, and seronegative for anti-HPV-16/18 antibodies, were recruited (July 2000-September 2001) from study centers in Brazil, the United States, and Canada (NCT00689741/NCT00120848). They were followed up for 76 months. Cervical samples were HPV genotyped via polymerase chain reaction. We used multivariable (forward stepwise, P = 0.15) Cox proportional hazards regression to estimate rate ratios (RR) and 95% confidence intervals (CI), separately according to length of follow-up time. RESULTS: On short-term follow-up (0-27 months), 257 (48%; 8535.80 person-months; incidence rate = 30.11; 95% CI, 26.64-34.02) incident HPV infections were detected. Marital status, lifetime number of sex partners, history of any sexually transmitted disease, and occasional use of oral contraceptives were strongly associated with acquisition of any HPV. Having 2 or more lifetime sex partners (RR, 2.03; 95% CI, 1.37-3.02) and a history of any sexually transmitted disease (RR, 1.98; 95% CI, 1.19-3.29) were the most important determinants of high-risk HPV (hrHPV) incidence. During the entire follow-up (0-76 months), an increased hrHPV clearance was found among women in North America (RR, 1.38; 95% CI, 1.08-1.78) and black women (RR, 1.64; 95% CI, 1.04-2.60). Greater number of lifetime partners was associated with reduced clearance rates for any HPV (RR, 0.65; 95% CI, 0.43-0.98). CONCLUSIONS: We identified variation in risk of HPV acquisition and clearance among women unexposed to HPV at baseline.

Prevalence of human papillomavirus infection and associated risk factors in young women in Brazil, Canada, and the United States: a multicenter cross-sectional study.

To determine the prevalence of cervical human papillomavirus (HPV) infection and risk factors in young women from Brazil, Canada, and the USA. Cross-sectional study in 3204 healthy women, aged 15 to 25 years. Cervical samples were collected for cytology and for HPV DNA detection (SPF 10-LiPA 25 system). Serum samples were collected for the measurement of HPV-16 and HPV-18 antibodies by enzyme-linked immunosorbent assay. Risk factors were obtained through a questionnaire. Overall, 26.6% of women had DNA detected for at least 1 HPV type. The prevalence for oncogenic HPV types was 21.7% (25% in Brazil, 16.9% in Canada, and 19.1% in the USA). HPV-16 was the most prevalent oncogenic type (5.2%). The next most common oncogenic HPV types were 51 (3.3%), 52 (3.3%), 31 (2.9%), 66 (2.3%), and 39 (2.0%). Multiple oncogenic types were detected in one-third of the infections. The prevalence of HPV-16 and/or HPV-18 infections detected by DNA and/or enzyme-linked immunosorbent assay was 24.8%. The majority of women (85%) had a normal cervical cytology. Sexual behavior was the main determinant for HPV-16/18 infections and squamous intraepithelial lesions. The prevalence of HPV oncogenic infections was high and linked to sexual behavior. Strategies to reduce the burden of oncogenic HPV infection, such as prophylactic vaccination programs, are likely to impact the burden of disease due to cervical precancer and cancer.

Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs.

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45 min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30 min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis(®), however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis(®) are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization.

Incidence and duration of type-specific human papillomavirus infection in high-risk HPV-naïve women: results from the control arm of a phase II HPV-16/18 vaccine trial.

OBJECTIVES: Persistence of human papillomaviruses (HPVs) is necessary for cervical carcinogenesis. We evaluated incidence and duration of type-specific HPV infections and the influence of age and number of sexual partners. METHODS: Data were obtained from 553 women (15-25 years), who were seronegative and DNA-negative for high-risk HPV (HR-HPV) types and were enrolled in the placebo arm of a randomised trial of the HPV-16/18 vaccine (NCT00689741/NCT00120848). They were followed for 6.3 years. Cervicovaginal samples were self-collected at 3-month intervals for up to 27 months, and cervical samples were collected by clinicians at 6-month intervals until study end. Samples were tested for HPV types using a broad-spectrum PCR assay. Incidence rate ratios (RRs) and 95% CIs were used to estimate the association among age, sexual habits and HPV acquisition. RESULTS: Incidence rates (95% CI) using cervical samples were 11.8 (10.4 to 13.4) and 5.6 (4.7 to 6.6) per 1000 women-months for HR-HPVs and low-risk HPVs (LR-HPVs), respectively. Equivalent rates in combined cervicovaginal and cervical samples were 17.2 (15.4 to 19.2) and 6.9 (5.9 to 8.0), respectively. 54 per cent of HR-HPV types from combined cervicovaginal and cervical samples persisted for 1 year compared with 32.3% for LR-HPV types. The risk of acquiring any HPV infection was higher among women aged <21 years (RR=1.33, 95% CI 1.1 to 1.7) and women having >1 sexual partner (RR=1.83, 95% CI 1.4 to 2.4) at baseline. CONCLUSIONS: HR-HPV infections were more common and lasted longer on average than LR-HPV infections. HPV acquisition was more common in younger women with multiple sexual partners. TRIAL REGISTRATION NUMBER: NCT00689741, NCT00120848; Post-results.

The effect of mechanical grinding on the formation, crystalline changes and dissolution behaviour of the inclusion complex of telmisartan and ß-cyclodextrins.

Telmisartan (TEL) was entrapped into ß-cyclodextrin aiming the improvement of its biopharmaceutical properties of low solubility. A solid state grinding process was used to prepare the molecular inclusion complex (MIC) for up to 30min. The inclusion ratio of drug and ß-cyclodextrin was established as 1:2 and 1:3 (mol/mol) by phase solubility study and Job Plot. DSC, XRPD and FTIR confirmed the molecular interactions between TEL and ß-cyclodextrin. Computer molecular modeling supports the presence of hydrogen bonds between guest and host and demonstrated the most probable complexes configuration. MIC_1:2_30 and MIC_1:3_30 enhanced the dissolution rate of the drug achieving a delivery rate comparable with the reference medicine available in the market (81% and 87% in 5min, for MIC_1:3_30 and Micardis(®), respectively). These formulations showed rapid and effective antihypertensive effect against angiotensin II in rats up to 180min, with statistically significant results against placebo and control in the first 30min after administration.

Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: final analysis of a long-term follow-up study up to 9.4 years post-vaccination.

HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15-25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (-128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine.

Development and evaluation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and polycaprolactone microparticles of nimodipine.

Polymeric microparticles containing the calcium channel blocker nimodipine were successfully obtained through simple emulsion/ organic solvent evaporating method. The extended release formulations, composed by the polymers poly(3-hydroxybutyrate-co-3- hydroxyvalerate) (PHBV) and polycaprolactone (PCL), were submitted to characterization through X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), Fourier transform infrared analysis (FT-IR) and determination of the mean particle diameter. All formulations obtained revealed an amorphous characteristic, proven through XRPD and DSC results. Besides, no chemical interaction was observed between drug and polymer in polymeric microparticles. PHBV-NMP formulation showed a higher drug entrapment, a larger particle size, a thermal degradation behavior similar to that observed for nimodipine and a longer drug release time, being selected for in vivo evaluation. The PHBV-NMP polymeric microparticles were able to keep the pharmacological antihypertensive effect for a longer period of time, becoming a good alternative to control nimodipine release in hypertension treatment.

Sustained immunogenicity and efficacy of the HPV-16/18 AS04-adjuvanted vaccine: up to 8.4 years of follow-up.

Prophylactic human papillomavirus (HPV) vaccines are now available and vaccination programs are being widely implemented, targeting adolescent girls prior to sexual debut. Since the risk of HPV exposure persists throughout a woman's sexual life, the duration of protection provided by vaccination is critical to the overall vaccine effectiveness. We report the long-term efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine (Cervarix (®) ) up to 8.4 y after the first vaccine dose.   In an initial placebo-controlled study performed in US, Canada and Brazil, women aged 15-25 y with normal cervical cytology, HPV-16/18 seronegative by ELISA, DNA-negative for 14 oncogenic HPV types by PCR, received either the HPV-16/18 vaccine or placebo (n = 1,113). Subjects were followed up to 6.4 y after the first dose (n = 776). We report an additional 2-y follow-up for women enrolled from the Brazilian centers from the initial study (n = 436). During the current follow-up study (HPV-023, NCT00518336), no new infection or lesions associated with HPV-16/18 occurred in the vaccine group. Vaccine efficacy over the entire follow-up (up to 8.4 y) was 95.1% (84.6, 99.0) for incident infection, 100% (79.8, 100) for 6-mo persistent infection, 100% (56.1, 100) for 12-mo persistent infection and 100% (< 0, 100) for CIN2+ associated with HPV-16/18. All women in the vaccine group remained seropositive to both HPV-16/18, with antibody titers for total and neutralizing antibodies remaining several-folds above natural infection levels. The safety profile was clinically acceptable for both vaccine and control groups. This is, to date, the longest follow-up study for a licensed cervical cancer vaccine.

Hemoptysis in a referral hospital for pulmonology.

OBJECTIVE: To determine the main causes of hemoptysis and to classify this symptom, in terms of the amount of blood expectorated, in patients hospitalized at a referral hospital for pulmonology. METHODS: The study included 50 patients with hemoptysis admitted to the pulmonology ward of a general hospital in the city of Recife, Brazil, between July of 2005 and February of 2006. The data of interest were analyzed and compared with those in the literature. RESULTS: The most common cause of hemoptysis was infection--in 39 patients (78%)--mostly related to tuberculosis sequelae or active tuberculosis. Regarding the severity of hemoptysis, moderate hemoptysis, diagnosed in 28 patients (56%), was the most common. CONCLUSIONS: Our results suggest that all patients who present with hemoptysis should be investigated for infection.

Hemoptise em hospital de referência em pneumologia / Hemoptysis in a referral hospital for pulmonology

OBJETIVO: Determinar as principais causas de hemoptise e classificar esse sintoma quanto ao volume de sangue expectorado em pacientes internados em um hospital de referência em pneumologia. MÉTODOS: Foram incluídos 50 pacientes com hemoptise internados na enfermaria de pneumologia de um hospital geral na cidade do Recife (PE) no período entre julho de 2005 e fevereiro de 2006. Os dados de interesse foram analisados e comparados aos da literatura mundial. RESULTADOS: As infecções foram principais causas de hemoptise - em 39 pacientes (78 por cento) - a maioria delas relacionadas a sequelas de tuberculose pulmonar ou secundárias a tuberculose ativa. Em relação ao grau de hemoptise, as hemoptises moderadas, diagnosticadas em 28 pacientes (56 por cento), foram as mais encontradas. CONCLUSÕES: Nossos resultados sugerem que todos os pacientes com hemoptise devam ser investigados quanto a infecções.

OBJECTIVE: To determine the main causes of hemoptysis and to classify this symptom, in terms of the amount of blood expectorated, in patients hospitalized at a referral hospital for pulmonology. METHODS: The study included 50 patients with hemoptysis admitted to the pulmonology ward of a general hospital in the city of Recife, Brazil, between July of 2005 and February of 2006. The data of interest were analyzed and compared with those in the literature. RESULTS: The most common cause of hemoptysis was infection-in 39 patients (78 percent)-mostly related to tuberculosis sequelae or active tuberculosis. Regarding the severity of hemoptysis, moderate hemoptysis, diagnosed in 28 patients (56 percent), was the most common. CONCLUSIONS: Our results suggest that all patients who present with hemoptysis should be investigated for infection.

O que falta na luta contra o câncer de colo uterino / What is missing in the fight against cervical cancer

A vacina contra o HPV está aprovada no Brasil. Mas só é indicada para jovens mulheres que ainda não tenham iniciado sua vida sexual", disse o diretor-geral do Inca. Segundo o especialista, cerca de 80% das mulheres com atividade sexual estão contaminadas pelo HPV, e para pessoas contaminadas a vacina não surte efeito.A prevenção secundária do câncer do colo do útero, através do exame de Papanicolaou, é método acessível atualmente que deve aplicar-se massivamente na população feminina, inclusive nas mulheres que tenham recebido a vacina contra o HPV. Consideramos bem-vinda essa vacina, contudo, existem boas razões para sermos cautelosos e prudentes, pois ainda não temos evidências suficientes de sua total efetividade e inocuidade.7,8 Eu pessoalmente acredito que deveremos ter, no futuro, uma vacina profilática multivalente, que englobe todos os tipos virais de alto risco oncogênico, e outra vacina de ação terapêutica para tratar as pacientes infectadas e com lesões de alto grau a progredir para malignidade. E que essas vacinas sejam efetivas, com segurança comprovada e com custos acessíveis para as mulheres em risco de países em desenvolvimento.

Prevalência de más oclusões e alterações funcionais entre escolares assistidos pelo Programa Saúde da Família em Juazeiro do Norte, Ceará, Brasil / Prevalence of malocclusions and functional alterations among students seem by Health Family Program in Juazeiro do Norte, Ceará, Brazil

OBJETIVOS: determinar a prevalência de más oclusões e alterações funcionais entre escolares assistidos pelo Programa Saúde da Família em Juazeiro do Norte. METODOLOGIA: realizou-se um estudo transversal na área assistida pela Unidade de Saúde da Família (USF) nº 20 de Juazeiro do Norte. A partir de uma população de 704 crianças de ambos os gêneros com idades entre 6 e 12 anos, calculou-se a amostra utilizando-se um intervalo de confiança de 95 por cento. Avaliou-se, clinicamente, os padrões oclusal e funcional do sistema estomatognático de 84 crianças, as quais foram convocadas aleatoriamente por agentes comunitárias de saúde. Os padrões foram classificados em: normal (oclusão e funções normais) ou alterado (presença de má oclusão e/ou alteração funcional). A oclusão dividia-se nas relações: vertical, transversal e ântero-posterior. As funções analisadas foram: respiração e deglutição. Para a análise estatística, utilizaram-se os testes Qui-quadrado e de Fisher. RESULTADOS: 77,3 por cento e 72,6 por cento da amostra apresentaram más oclusões e padrão funcional alterado, respectivamente; 59,52 por cento apresentaram ambas as alterações; 45,2 por cento apresentaram alterações oclusais verticais; 60,7 por cento alterações transversais e 20,2 por cento alterações ântero-posteriores; 60,7 por cento alterações respiratórias e 47,6 por cento deglutição alterada. Houve associação estatisticamente significativa entre a relação vertical e as duas funções avaliadas (p<0,001) e entre a relação transversal e a função respiratória (p<0,05). CONCLUSÕES: as prevalências de más oclusões e de alterações funcionais foram elevadas, 77,3 por cento e 72,6 por cento, respectivamente. Houve uma forte associação entre a relação oclusal vertical e as funções avaliadas (respiração e deglutição).