Poor decision making among clinicians to transferring human immune deficiency virus (HIV) patients into second-line antiretroviral therapy (ART) has led to an increase in morbidity and mortality to people living with HIV (PLHIV). No clear barriers are known for clinicians not switching their patients. This is a descriptive qualitative research aimed to discover obstacles that influence clinicians' decision making to transferring patients into second-line ART despite higher level resistance to first-line ART. The researcher applied a participatory action research framework to solve the identified barriers with clinicians. Using the research questions the researcher explored reasons, perceived barriers and enabling factors for clinicians delay in making decision to transferring HIV patients into second-line ART. In-depth semistructured interviews were conducted with 30 participants. Six thematic areas (a) clinicians' capacity to diagnose treatment failure, (b) laboratory investigations, (c) availability, access, and tolerability to second-line ART, (d) clinicians' perceptions on ARV medicines, (e) clients' readiness for ARV medicines, and (f) adherence and retention to ARV medicines were analysed using STATA. Readiness, adherence and retention to ART, knowledge, competence and experience on ART , lack of viral load testing, and shortage of second-line ART were the common major barriers for clinicians in determining transferring patients into second-line ART. The government of Tanzania should acknowledge and create participation, responsibility, and commitment strategies to reduce the observed barriers. Findings of this study generates knowledge and provide actionable plans to help clinicians easily identify HIV patients who are in need of second-line ART.

Chlamydia trachomatis is the most common sexually transmitted bacterial disease agent worldwide, and, though frequently asymptomatic, can cause extreme pathology including infertility. Chlamydial species exhibit a unique biphasic developmental cycle. Once attached to a cell surface, infectious elementary bodies (EB) are internalized within an inclusion, the membrane-bound structure in which EB transform to noninfectious, replicable reticulate bodies (RB). After multiple rounds of division, RB condense to form EB, which are released and can infect new host cells. In culture, exposure to stressors, such as beta-lactam antibiotics, induce chlamydiae to reversibly detour from normal development into a noninfectious, viable state termed persistence. Cell culture data suggest that persistent forms are resistant to azithromycin (AZM), a front-line antibiotic, and are able to alter the host transcriptome. Though persistence has been described in culture for over 50 years, whether or not it: i) occurs in vivo; and ii) influences chlamydial pathogenesis, transmission and therapy has remained unresolved. To address these questions, we developed an animal model of persistent chlamydial infection using amoxicillin (AMX) treatment. AMX exposure decreased shedding of infectious chlamydiae in C. muridarum-infected mice without affecting chlamydial viability, demonstrating the presence of persistent chlamydiae. Shedding of infectious EB resumed following AMX cessation. Shedding data and microarray analyses suggested that host immunity might limit chlamydia’s exit from persistence in our model. Thus, we hypothesized that cyclophosphamide (CTX) treatment would increase the magnitude of chlamydial shedding observed after AMX-treatment cessation. CTX treatment increased post-AMX shedding by more than 10-fold compared to AMX-only controls. To determine whether persistent chlamydiae are resistant to antibiotic eradication in vivo, we induced persistence by administering AMX and treated mice with various AZM dosing regimes. Persistently infected mice demonstrated increased treatment failure following AZM therapy compared to productively infected controls. These data suggest that persistent chlamydiae are refractory to treatment in vivo and provide an explanation for the observation that treatment fails in some patients. In addition to creating the first fully characterized, experimentally tractable, in vivo model of chlamydial persistence, these experiments provide evidence that persistent/stressed chlamydial forms may serve as a long-term reservoir of infectious organisms in vivo.

No description available.

No / To examine the safety and acceptability of providing antiretroviral therapy (ART) in a resource poor setting. DESIGN: Two-stage observational and qualitative study. SETTING: Rural hospital in Southern Africa. METHODS: Structured observation using failure modes and effects analysis (FMEA) of the drug supply, dispensing, prescribing and administration processes. The findings from the FMEA were explored further in qualitative interviews with eight health professionals involved in the delivery of ART. To obtain a patient perspective, a stratified sample of 14 patients receiving ART was also interviewed. RESULTS: Key vulnerabilities in the process of ART provision include supply problems, poor packaging and labelling, inadequate knowledge among staff and lack of staff. Key barriers to successful patient adherence include transport inconsistency in supply and personal financial difficulties. There is, however, strong evidence of patient commitment and adherence. IMPLICATIONS AND CONCLUSION: Medication safety is relatively unexplored in the developing world. This study reveals an encouraging resilience in the health system and adherence among patients in the delivery of complex ART. The vulnerabilities identified, however, undermine patient safety and effectiveness of ART. There are implications for drug manufacturers; international aid agencies funding and supplying ART; and local practitioners. FMEA can help identify potential vulnerabilities and inform safety improvement interventions.

A metformina é a droga de escolha no tratamento inicial do diabetes mellitus tipo 2 (DM2). Não existe consenso na literatura sobre qual seria a segunda melhor opção terapêutica após a falência desta em longo prazo. Objetivo: avaliar a eficácia em longo prazo de gliflozinas e gliptinas após a falência do tratamento primário com metformina no DM2. Material e métodos: foi realizada uma revisão sistemática para o maior tempo de tratamento nas bases de dados bases Embase, Pubmed (via Medline), Lilacs e Cochrane Library e metanálise em rede com as sulfoniluréias (glimepirida e glipizida) como meta comparador. Desfechos: eficácia da medicação (valor final da HbA1c e porcentagem de pacientes com HbA1c < 7%), variação de peso e frequência de pacientes com hipoglicemia. Resultados: O maior tempo de segmento foi de quatro anos. Foram selecionados um artigo com empagliflozina, um artigo com dapagliflozina e um artigo com saxagliptina com dados faltantes. Após um ano de tratamento, mais de 50% dos pacientes estavam com HbA1c > 7%. O perfil de eficácia em quatro anos da empagliflozina (23%) foi melhor que da dapagliflozina (5%) e saxagliptina (7%), porém com valores de HbA1c não estatisticamente significantes (7,4 e 7,3% entre as gliflozinas), sem dados para a saxagliptina. Entretanto, a empagliflozina foi superior à glimepirida no período de quatro anos (diferença média padronizada/DMP: 0,40, intervalo de confiança/IC95%: 0,23- 0,56). A variação de peso permaneceu estável após um ano de tratamento, com vantagem em quatro anos para a empa (DMP: 1,56, IC95%: 1,23- 1,88). A frequência de pacientes com hipoglicemia não diferiu entre empagliflozina e dapagliflozina (razão de chances: 1,53, IC95%: 0,80- 2,91) e foi significativamente menor do que em relação às sulfoniluréias. Conclusões: a falência da segunda terapia com gliflozinas ocorre em menos de um ano de tratamento ( > 50% dos pacientes com HbA1c > 7%). A empagliflozina obteve um controle glicêmico melhor em relação às sulfoniluréias, porém semelhante à dapagliflozina. A perda de peso foi mantida por quatro anos, com superioridade para empagliflozina. Houve uma baixa frequência de hipoglicemia nas gliflozinas em comparação com as sulfoniluréias. Mais estudos são necessários para avaliar a eficácia de gliptinas e gliflozinas em longo prazo, após a falência terapêutica com metformina / Metformin is the first-choice treatment in people with type 2 diabetes (TD2). There is no consensus in the medical literature about which drug would be a second-best option of treatment in the case of metformin failure in long-term. Objective: to assess the long-term efficacy of gliflozins and gliptins once metformin has failed as the primary treatment for TD2. Materials and methods: a systematic review was performed considering the longest period found in Embase, Pubmed (via Medline), Lilacs and Cochrane Library databases and also network meta-analyses using sulfonylureas (glimepiride and glipizide) as a meta comparator. Clinical outcomes where efficacy of medical treatment (final value of HbA1c and percentage of patients with HbA1c < 7%), weight variation and frequency of patients with hypoglycemia. Results: the longest period of the segment was 4 years. It was selected 1 article on empagliflozin, 1 article on dapagliflozin, and 1 article on saxagliptin with missing data. After one year of treatment, over 50% of the patients presented HbA1c > 7%. Efficacy rate in 4 years of empagliflozin (23%) was better than dapagliflozin (5%) and saxagliptin (7%), however presenting statistically non-significant values for HbA1c (7.4 and 7.3% between gliflozins), and missing data for the saxaglifozin. Nonetheless, empagliflozin performed better than glimepiride in the 4-year period (standardized mean difference SMD 0.4, confidence interval CI 95% 0.23 to 0.56). Weight variation remained stable after one year of treatment, presenting empagliflozin better results in the 4-year period (SMD 1.56, CI 95% 1.23 to 1.88). The frequency of patients with hyperglycemia did not vary for empagliflozin and dapagliflozin (odds ratio 1.53, CI 95% 0.8 to 2.91), and it was significantly lower when compared to the sulfonylureas. Conclusions: the failure of the secondary treatment using gliflozins occurs in less than one year of treatment (less than 50% of the patients presenting HbA1c > 7 %). Empagliflozin offered a better glycemic control compared to the sulfonylureas, but similar to dapagliflozin. The weight loss was maintained for 4 years, being empagliflozin the one with better results. There was a low frequency of hypoglycemia for the gliflozins when compared to the sulfonylureas. Further studies are required to evaluate the efficacy of gliptins and gliflozins in the long-term after metformin failure

INTRODUÇÃO: Apesar do índice de sucesso da cirurgia da ligadura ou cauterização da artéria esfenopalatina, para o tratamento da epistaxe severa, ser maior que 95%, a falha pode variar de 2% a 10%. Algumas variações anatômicas na parede lateral do nariz são relatadas, sendo referentes à localização do forame esfenopalatino (FEP), à presença de um forame acessório, à ramificação das artérias e à dimensão e morfologia do FEP. A variação anatômica dessa região assim como a escassez de estudos endoscópicos mostrando pontos de reparo para o encontro da artéria esfenopalatina e seus ramos podem justificar a falha cirúrgica em alguns casos, assim como a dificuldade técnica encontrada por alguns autores. OBJETIVO: Descrever a anatomia da região do FEP na parede lateral do nariz e as possíveis variações anatômicas, durante a dissecção endoscópica em cadáveres, e observar as possíveis diferenças entre os achados anatômicos, o gênero (masculino/feminino) e o grupo étnico/racial, assim como a simetria entre as fossas nasais. CASUÍSTICA E MÉTODOS: Estudo anatômico prospectivo realizado de setembro de 2006 a janeiro de 2007. A região do FEP de 61 cadáveres frescos (122 fossas nasais) foi cuidadosamente dissecada, sob visibilização endoscópica. Prevaleceram os cadáveres do sexo masculino (75%) e grupo étnico/racial pardo, seguidos de negros e brancos. Foram observados a presença da crista etmoidal da lâmina perpendicular do osso palatino, a localização dos forames esfenopalatino e acessório, o número de ramos arteriais emergentes pelos forames e a distância dos mesmos à espinha nasal anterior. Os dados foram analisados em relação ao gênero, grupo étnico/racial e simetria entre as fossas nasais do mesmo cadáver. Foi, ainda, avaliada a predição da presença do forame acessório em relação ao número de ramos arteriais emergentes através do FEP, à localização do FEP e à distância do FEP à espinha nasal anterior. RESULTADOS: A crista etmoidal esteve presente em 100% dos cadáveres, sendo anterior ao mesmo em 98,4% das vezes. A localização mais freqüente do FEP foi a região de transição do meato médio e meato superior (86,9%). A distância média do FEP e do forame acessório à espinha nasal anterior foi respectivamente de 66mm e 67mm, com desvio padrão de 5,3 e 4,7mm. O forame acessório esteve presente em 9,83% dos casos. Um único tronco arterial emergia através do FEP em 67,2% das vezes e em 100% dos forames acessórios. A análise da prevalência das variáveis estudadas em relação ao gênero e grupo étnico/racial não mostrou diferenças estatisticamente significantes (p<0,05). A análise da simetria mostrou concordância boa a excelente em relação à localização do FEP (índice Kappa 0,71/ p<0,001); concordância pobre em relação ao número de ramos arteriais emergentes através do FEP (índice Kappa 0,22/p=0,03) e ausência de concordância estatisticamente significante em relação à presença de forame acessório (p=0,53). Nenhuma das variáveis de interesse apresentou associação estatisticamente significante (p>0,05) que permita predizer a presença do forame acessório. CONCLUSÕES: Existem variações anatômicas na parede lateral do nariz que devem ser levadas em consideração para o sucesso do tratamento cirúrgico endoscópico da epistaxe severa. / INTRODUCTION: Even though the success rate of sphenopalatine ligation is greater than 95%, some authors have reported some difficulties in isolating those arteries during endoscopic surgical procedure. The failure rate of the sphenopalatine artery ligation or cauterization may vary from 2% to 10%. Some anatomical variations on the nose lateral wall are reported, with reference to the sphenopalatine foramen (SPF) location, the presence of an accessory foramen, arteries ramification and SPF dimension and morphology. Anatomical variation of the region, as well as scarcity of endoscopic studies showing landmarks to find the sphenopalatine artery and its branches may justify surgical failure. OBJECTIVE: The purpose of this study was to describe the anatomy of SPF region and possible anatomical variations, during the endoscopic cadaver dissection and to observe the symmetry between nasal sides and the relationship to gender and racial group. CASUISTICS AND METHODS: It is a prospective anatomical study developed from September, 2006 to January, 2007. The SPF of 61 fresh cadavers (122 nasal fossae) was carefully endoscopic dissected. Male (75%) and mixed race cadavers prevailed. Presence of ethmoidal crest, location of sphenopalatine and accessory foramens, number of arterial branches emerging through foramens and distances from the foramens to anterior nasal spine were observed. Data were analyzed in relation to gender, racial group and symmetry of the same cadaver. Prediction of the presence of accessory foramen was evaluated in relation to number of arterial branches emerging through SPF, SPF location and distance from the SPF to the anterior nasal spine. RESULTS: Ethmoidal crest was present in 100% of cadavers, being anterior to the SPF in 98.4% of times. The most frequent SPF location was the transition region of middle and superior meatus (86.9%). Mean distance from SPF and accessory foramen to anterior nasal spine was 6.6cm and 6.7cm, respectively. Accessory foramen was present in 9.83% of cases. A single arterial stem emerged through the SPF in 67.2% of times, and 100% through accessory foramens. The prevalence analyses showed no differences statistically significant (p>0,05) between gender and racial group. The symmetry analyses showed a strong conformity (Kappa index 0,71/p<0,01) between nasal fossae in relation to the SPF location; and a poor conformity (Kappa index 0,22/p=0,03) in relation to the number of arterial branches emerging through the SPF. There was no statistically significant conformity between nasal fossae and the presence of accessory foramen (p = 0,53). None of the variables of interest presents any statistically significant (p>0,05) association with the presence of the accessory foramen. CONCLUSIONS: Anatomical variations in the lateral nose wall exist, and should be taken into account, for a well-succeeded endoscopic surgical treatment of severe epistaxis.

A metformina é a droga de escolha no tratamento inicial do diabetes mellitus tipo 2 (DM2). Não existe consenso na literatura sobre qual seria a segunda melhor opção terapêutica após a falência desta em longo prazo. Objetivo: avaliar a eficácia em longo prazo de gliflozinas e gliptinas após a falência do tratamento primário com metformina no DM2. Material e métodos: foi realizada uma revisão sistemática para o maior tempo de tratamento nas bases de dados bases Embase, Pubmed (via Medline), Lilacs e Cochrane Library e metanálise em rede com as sulfoniluréias (glimepirida e glipizida) como meta comparador. Desfechos: eficácia da medicação (valor final da HbA1c e porcentagem de pacientes com HbA1c < 7%), variação de peso e frequência de pacientes com hipoglicemia. Resultados: O maior tempo de segmento foi de quatro anos. Foram selecionados um artigo com empagliflozina, um artigo com dapagliflozina e um artigo com saxagliptina com dados faltantes. Após um ano de tratamento, mais de 50% dos pacientes estavam com HbA1c > 7%. O perfil de eficácia em quatro anos da empagliflozina (23%) foi melhor que da dapagliflozina (5%) e saxagliptina (7%), porém com valores de HbA1c não estatisticamente significantes (7,4 e 7,3% entre as gliflozinas), sem dados para a saxagliptina. Entretanto, a empagliflozina foi superior à glimepirida no período de quatro anos (diferença média padronizada/DMP: 0,40, intervalo de confiança/IC95%: 0,23- 0,56). A variação de peso permaneceu estável após um ano de tratamento, com vantagem em quatro anos para a empa (DMP: 1,56, IC95%: 1,23- 1,88). A frequência de pacientes com hipoglicemia não diferiu entre empagliflozina e dapagliflozina (razão de chances: 1,53, IC95%: 0,80- 2,91) e foi significativamente menor do que em relação às sulfoniluréias. Conclusões: a falência da segunda terapia com gliflozinas ocorre em menos de um ano de tratamento ( > 50% dos pacientes com HbA1c > 7%). A empagliflozina obteve um controle glicêmico melhor em relação às sulfoniluréias, porém semelhante à dapagliflozina. A perda de peso foi mantida por quatro anos, com superioridade para empagliflozina. Houve uma baixa frequência de hipoglicemia nas gliflozinas em comparação com as sulfoniluréias. Mais estudos são necessários para avaliar a eficácia de gliptinas e gliflozinas em longo prazo, após a falência terapêutica com metformina / Metformin is the first-choice treatment in people with type 2 diabetes (TD2). There is no consensus in the medical literature about which drug would be a second-best option of treatment in the case of metformin failure in long-term. Objective: to assess the long-term efficacy of gliflozins and gliptins once metformin has failed as the primary treatment for TD2. Materials and methods: a systematic review was performed considering the longest period found in Embase, Pubmed (via Medline), Lilacs and Cochrane Library databases and also network meta-analyses using sulfonylureas (glimepiride and glipizide) as a meta comparator. Clinical outcomes where efficacy of medical treatment (final value of HbA1c and percentage of patients with HbA1c < 7%), weight variation and frequency of patients with hypoglycemia. Results: the longest period of the segment was 4 years. It was selected 1 article on empagliflozin, 1 article on dapagliflozin, and 1 article on saxagliptin with missing data. After one year of treatment, over 50% of the patients presented HbA1c > 7%. Efficacy rate in 4 years of empagliflozin (23%) was better than dapagliflozin (5%) and saxagliptin (7%), however presenting statistically non-significant values for HbA1c (7.4 and 7.3% between gliflozins), and missing data for the saxaglifozin. Nonetheless, empagliflozin performed better than glimepiride in the 4-year period (standardized mean difference SMD 0.4, confidence interval CI 95% 0.23 to 0.56). Weight variation remained stable after one year of treatment, presenting empagliflozin better results in the 4-year period (SMD 1.56, CI 95% 1.23 to 1.88). The frequency of patients with hyperglycemia did not vary for empagliflozin and dapagliflozin (odds ratio 1.53, CI 95% 0.8 to 2.91), and it was significantly lower when compared to the sulfonylureas. Conclusions: the failure of the secondary treatment using gliflozins occurs in less than one year of treatment (less than 50% of the patients presenting HbA1c > 7 %). Empagliflozin offered a better glycemic control compared to the sulfonylureas, but similar to dapagliflozin. The weight loss was maintained for 4 years, being empagliflozin the one with better results. There was a low frequency of hypoglycemia for the gliflozins when compared to the sulfonylureas. Further studies are required to evaluate the efficacy of gliptins and gliflozins in the long-term after metformin failure

INTRODUÇÃO: Apesar do índice de sucesso da cirurgia da ligadura ou cauterização da artéria esfenopalatina, para o tratamento da epistaxe severa, ser maior que 95%, a falha pode variar de 2% a 10%. Algumas variações anatômicas na parede lateral do nariz são relatadas, sendo referentes à localização do forame esfenopalatino (FEP), à presença de um forame acessório, à ramificação das artérias e à dimensão e morfologia do FEP. A variação anatômica dessa região assim como a escassez de estudos endoscópicos mostrando pontos de reparo para o encontro da artéria esfenopalatina e seus ramos podem justificar a falha cirúrgica em alguns casos, assim como a dificuldade técnica encontrada por alguns autores. OBJETIVO: Descrever a anatomia da região do FEP na parede lateral do nariz e as possíveis variações anatômicas, durante a dissecção endoscópica em cadáveres, e observar as possíveis diferenças entre os achados anatômicos, o gênero (masculino/feminino) e o grupo étnico/racial, assim como a simetria entre as fossas nasais. CASUÍSTICA E MÉTODOS: Estudo anatômico prospectivo realizado de setembro de 2006 a janeiro de 2007. A região do FEP de 61 cadáveres frescos (122 fossas nasais) foi cuidadosamente dissecada, sob visibilização endoscópica. Prevaleceram os cadáveres do sexo masculino (75%) e grupo étnico/racial pardo, seguidos de negros e brancos. Foram observados a presença da crista etmoidal da lâmina perpendicular do osso palatino, a localização dos forames esfenopalatino e acessório, o número de ramos arteriais emergentes pelos forames e a distância dos mesmos à espinha nasal anterior. Os dados foram analisados em relação ao gênero, grupo étnico/racial e simetria entre as fossas nasais do mesmo cadáver. Foi, ainda, avaliada a predição da presença do forame acessório em relação ao número de ramos arteriais emergentes através do FEP, à localização do FEP e à distância do FEP à espinha nasal anterior. RESULTADOS: A crista etmoidal esteve presente em 100% dos cadáveres, sendo anterior ao mesmo em 98,4% das vezes. A localização mais freqüente do FEP foi a região de transição do meato médio e meato superior (86,9%). A distância média do FEP e do forame acessório à espinha nasal anterior foi respectivamente de 66mm e 67mm, com desvio padrão de 5,3 e 4,7mm. O forame acessório esteve presente em 9,83% dos casos. Um único tronco arterial emergia através do FEP em 67,2% das vezes e em 100% dos forames acessórios. A análise da prevalência das variáveis estudadas em relação ao gênero e grupo étnico/racial não mostrou diferenças estatisticamente significantes (p<0,05). A análise da simetria mostrou concordância boa a excelente em relação à localização do FEP (índice Kappa 0,71/ p<0,001); concordância pobre em relação ao número de ramos arteriais emergentes através do FEP (índice Kappa 0,22/p=0,03) e ausência de concordância estatisticamente significante em relação à presença de forame acessório (p=0,53). Nenhuma das variáveis de interesse apresentou associação estatisticamente significante (p>0,05) que permita predizer a presença do forame acessório. CONCLUSÕES: Existem variações anatômicas na parede lateral do nariz que devem ser levadas em consideração para o sucesso do tratamento cirúrgico endoscópico da epistaxe severa. / INTRODUCTION: Even though the success rate of sphenopalatine ligation is greater than 95%, some authors have reported some difficulties in isolating those arteries during endoscopic surgical procedure. The failure rate of the sphenopalatine artery ligation or cauterization may vary from 2% to 10%. Some anatomical variations on the nose lateral wall are reported, with reference to the sphenopalatine foramen (SPF) location, the presence of an accessory foramen, arteries ramification and SPF dimension and morphology. Anatomical variation of the region, as well as scarcity of endoscopic studies showing landmarks to find the sphenopalatine artery and its branches may justify surgical failure. OBJECTIVE: The purpose of this study was to describe the anatomy of SPF region and possible anatomical variations, during the endoscopic cadaver dissection and to observe the symmetry between nasal sides and the relationship to gender and racial group. CASUISTICS AND METHODS: It is a prospective anatomical study developed from September, 2006 to January, 2007. The SPF of 61 fresh cadavers (122 nasal fossae) was carefully endoscopic dissected. Male (75%) and mixed race cadavers prevailed. Presence of ethmoidal crest, location of sphenopalatine and accessory foramens, number of arterial branches emerging through foramens and distances from the foramens to anterior nasal spine were observed. Data were analyzed in relation to gender, racial group and symmetry of the same cadaver. Prediction of the presence of accessory foramen was evaluated in relation to number of arterial branches emerging through SPF, SPF location and distance from the SPF to the anterior nasal spine. RESULTS: Ethmoidal crest was present in 100% of cadavers, being anterior to the SPF in 98.4% of times. The most frequent SPF location was the transition region of middle and superior meatus (86.9%). Mean distance from SPF and accessory foramen to anterior nasal spine was 6.6cm and 6.7cm, respectively. Accessory foramen was present in 9.83% of cases. A single arterial stem emerged through the SPF in 67.2% of times, and 100% through accessory foramens. The prevalence analyses showed no differences statistically significant (p>0,05) between gender and racial group. The symmetry analyses showed a strong conformity (Kappa index 0,71/p<0,01) between nasal fossae in relation to the SPF location; and a poor conformity (Kappa index 0,22/p=0,03) in relation to the number of arterial branches emerging through the SPF. There was no statistically significant conformity between nasal fossae and the presence of accessory foramen (p = 0,53). None of the variables of interest presents any statistically significant (p>0,05) association with the presence of the accessory foramen. CONCLUSIONS: Anatomical variations in the lateral nose wall exist, and should be taken into account, for a well-succeeded endoscopic surgical treatment of severe epistaxis.

Objectif : Les traitements répétés des lésions précancéreuses du col utérin (HSIL), nécessaires en cas d’échecs de traitement, sont associés à des issues obstétriques négatives, telle qu’une augmentation de la mortalité néonatale. Nous avons investigué l’association entre un grand nombre de facteurs de risque potentiels pour l’échec de traitement des HSIL dans le but d’identifier des prédicteurs potentiellement modifiables de l’échec de traitement. Méthodes : La population source était constituée de 1 548 femmes canadiennes qui ont subi un premier traitement pour HSIL. L’échec de traitement a été défini comme étant un diagnostic histologique de HSIL ou cancer au cours des deux années suivant le traitement. Nous avons mené une étude cas-témoins nichée incluant les 101 cas d’échec de traitement ainsi que les témoins appariés 1 :1 par centre de traitement et par date d’échec. Nous avons calculé des rapports de cotes (OR) et intervalles de confiance (CI) à 95% à l’aide de régressions logistiques conditionnelles, pour les associations entre l’échec de traitement et l’âge, le nombre d’accouchements, le statut tabagique, le nombre de partenaires sexuels, l’utilisation du condom, la méthode de contraception, les marges, le nombre de passages, le diagnostic sur le spécimen de traitement, le génotype du VPH, et le nombre de types. Nous avons aussi estimé l’association entre la charge virale et les variants du VPH16 et du VPH18 et l’échec de traitement. Résultats : Les marges positives vs négatives (OR ajusté=4.05, 95% CI 1.57-10.48), la positivité pour le VPH16/18 vs autres types (OR ajusté=2.69, 95% CI 1.32-5.49), et avoir un variant similaire au prototype du VPH16 vs le prototype (OR ajusté=2.49, 95% CI 1.07-5.83) étaient des prédicteurs de l’échec de traitement des HSIL. Être plus âgé, avoir des lésions plus sévères, avoir une infection monotype, et avoir une variation à la position 7521 chez celles avec le VPH16 pourraient augmenter le risque d’échec de traitement, mais les associations n’étaient pas statistiquement significatives. Les estimations pour les autres facteurs étaient proches de la valeur nulle. Nous n’avons pas observé de modification d’effet du génotype sur le risque de l’échec de traitement par le tabagisme, ni par les marges. Conclusion : Seules les marges positives, la positivité pour le VPH16/18 et avoir un variant similaire au prototype étaient des prédicteurs d’un échec de traitement au cours des deux années suivant le traitement. Malgré l’aspect non-modifiable des prédicteurs identifiés, ils sont informatifs et pourront éclairer la prise en charge et le suivi clinique. / Objective: Repeated treatments for high-grade squamous intraepithelial lesions (HSIL), which are necessary in the case of treatment failure, are associated with negative obstetric outcomes, such as an increased risk of neonatal death. We investigated the association between a large number of potential risk factors and HSIL treatment failure in an effort to identify potentially modifiable predictors of treatment failure. Methods: The source population included 1,548 Canadian women who received a first treatment for HSIL. Treatment failure was defined as the histological diagnosis of HSIL or cancer within the two years following treatment. We conducted a nested case-control study that included all 101 cases of treatment failure and controls that were matched 1:1 on treatment center and date of failure. We used conditional logistic regression to calculate the odds ratios (OR) and 95% confidence intervals (CI) between treatment failure and age, parity, smoking status, number of sexual partners, condom use, method of contraception, margins, number of passes, diagnosis on the treatment specimen, HPV genotype and number of types. We also estimated the association between HPV16 and HPV18 viral loads and variants and HSIL treatment failure. Results: Having positive vs. negative margins (adjusted OR=4.05, 95% CI 1.57-10.48), being positive for HPV16 and/or HPV18 vs. any other type (adjusted OR=2.69, 95% CI 1.32-5.49), and having a prototype-like variant of HPV16 vs. the prototype (adjusted OR=2.49, 95% CI 1.07-5.83) were predictors of HSIL treatment failure. Older age, more severe lesions, single-type infections and a variation at the 7521 position of the HPV16 genetic sequence may lead to a higher risk of treatment failure but were not statistically significant. Estimates for all other factors were near the null value. The effect of genotype on the risk of treatment failure was not modified by smoking status, nor by margin status. Conclusion: Only positive margins, HPV16/18 positivity, and having a prototype-like variant of HPV16 were predictors for HSIL treatment failure within two years of treatment. Despite being non-modifiable, the identified predictors are clinically significant in regards to management and follow-up of patients.

No / AIMS/HYPOTHESIS: We previously demonstrated that animals fed a high-fat (HF) diet for 10 weeks developed insulin resistance and behavioural inflexibility. We hypothesised that intervention with metformin would diminish the HF-feeding-evoked cognitive deficit by improving insulin sensitivity. METHODS: Rats were trained in an operant-based matching and non-matching to position task (MTP/NMTP). Animals received an HF (45% of kJ as lard; n = 24), standard chow (SC; n = 16), HF + metformin (144 mg/kg in diet; n = 20) or SC + metformin (144 mg/kg in diet; n = 16) diet for 10 weeks before retesting. Body weight and plasma glucose, insulin and leptin were measured. Protein lysates from various brain areas were analysed for alterations in intracellular signalling or production of synaptic proteins. RESULTS: HF-fed animals developed insulin resistance and an impairment in switching task contingency from matching to non-matching paradigm. Metformin attenuated the insulin resistance and weight gain associated with HF feeding, but had no effect on performance in either MTP or NMTP tasks. No major alteration in proteins associated with insulin signalling or synaptic function was detected in response to HF diet in the hypothalamus, hippocampus, striatum or cortex. CONCLUSIONS/INTERPRETATION: Metformin prevented the metabolic but not cognitive alterations associated with HF feeding. The HF diet protocol did not change basal insulin signalling in the brain, suggesting that the brain did not develop insulin resistance. These findings indicate that HF diet has deleterious effects on neuronal function over and above those related to insulin resistance and suggest that weight loss may not be sufficient to reverse some damaging effects of poor diet.