Incidence Rate and Risk Factors for Anal Squamous Cell Carcinoma in a Cohort of People Living With HIV from 2004 to 2017: Implementation of a Screening Program.

BACKGROUND: Anal squamous cell carcinoma is rare, in general, but considerably higher in HIV-infected men who have sex with men. There is no consensus on the screening of at-risk populations. OBJECTIVE: This study aimed to determine the incidence rates of anal squamous cell carcinoma and the efficacy of a screening program. DESIGN: This is a cohort study (SeVIHanal/NCT03713229). SETTING: This study was conducted at an HIV outpatient clinic in Seville, Spain. PATIENTS: From 2004 to 2017, all patients with at least 1 follow-up visit were analyzed (follow-up group), including a subgroup of men who have sex with men who participated in a specialized program for screening and treating anal neoplasia (SCAN group) from 2011 onward. MAIN OUTCOME MEASURES: The primary outcome measure was the incidence rate of anal squamous cell carcinoma. RESULTS: Of the 3878 people living with HIV included in the follow-up group, 897 were transferred to the SCAN group; 1584 (41%) were men who have sex with men. Total follow-up was 29,228 person-years with an overall incidence rate for anal squamous cell carcinoma of 68.4/100,000 person-years (95% CI, 46.7-97.4). The changes in the incidence rate/100,000 person-years (95% CI) over time was 20.7 (3.40-80.5) for 2004 to 2006, 37.3 (13.4-87.3) for 2007 to 2010, and 97.8 (63.8-144.9) for 2011 to 2017 (p < 0.001). The strongest impact on the incidence of anal squamous cell carcinoma was made by the lack of immune restoration (adjusted incidence rate ratio (95% CI): 6.59 (4.24-10); p < 0.001), the Centers for Disease Control and Prevention category C (adjusted incidence rate ratio (95% CI): 7.49 (5.69-9.85); p < 0.001), and non-men who have sex with men (adjusted incidence rate ratio (95% CI): 0.07 (0.05-0.10); p < 0.001) in a Poisson analysis. From 2010 to 2017, incidence rates (95% CI) of anal squamous cell carcinoma within the SCAN group and the men who have sex with men of the follow-up group were 95.7 (39.6-202) and 201 (101-386)/100,000 person-years (adjusted incidence rate ratio (95% CI): 0.30 (0.23-0.39); p<0.001). The incidence rate ratio (95% CI) including non-men who have sex with men in the follow-up group was 0.87 (0.69-1.11); p = 0.269. LIMITATIONS: Adherence to the visits could not be quantified. CONCLUSION: Incidence rates of anal squamous cell carcinoma in people living with HIV increased significantly from 2004 to 2017, especially in men who have sex with men who were not being screened. Participation in the SCAN program significantly reduced the incidence of anal squamous cell carcinoma in men who have sex with men, in whom focus should be placed, especially on those presenting with Centers for Disease Control and Prevention category C and advanced immune suppression. See Video Abstract at http://links.lww.com/DCR/B734. TASA DE INCIDENCIA Y FACTORES DE RIESGO DEL CARCINOMA ANAL A CLULAS ESCAMOSAS EN UNA COHORTE DE PERSONAS QUE VIVEN CON EL VIH DE A IMPLEMENTACIN DE UN PROGRAMA DE DETECCIN: ANTECEDENTES:El carcinoma anal a células escamosas es generalmente raro, pero considerablemente más alto en hombres infectados por el VIH que tienen relaciones sexuales con hombres. No hay consenso sobre el cribado de poblaciones en riesgo.OBJETIVO:Este estudio tuvo como objetivo determinar las tasas de incidencia del carcinoma anal a células escamosas y la eficacia de un programa de detección.DISEÑO:Estudio de cohorte (SeVIHanal / NCT03713229).AJUSTE:Clínica ambulatoria de VIH en Sevilla, España.PACIENTES:De 2004 a 2017, se analizaron todos los pacientes con al menos una visita de seguimiento (grupo F / U), incluido un subgrupo de hombres que tenían relaciones sexuales con hombres que participaron en un programa especializado de cribado y tratamiento de neoplasias anales (SCAN-group) a partir de 2011.PRINCIPALES MEDIDAS DE RESULTADO:Tasas de incidencia del carcinoma anal a células escamosas.RESULTADOS:De las 3878 personas que viven con el VIH incluidas en el grupo F / U, 897 fueron transferidas al grupo SCAN, 1584 (41%) eran hombres que tenían relaciones sexuales con hombres. El seguimiento total fue de 29228 personas-año con una tasa de incidencia general de carcinoma anal a células escamosas de 68,4 / 100000 personas-año [intervalo de confianza del 95%: 46,7-97,4]. El cambio en las tasas de incidencia / 100000 personas-año (intervalo de confianza del 95%) a lo largo del tiempo fue 20,7 (3,40-80,5) para 2004-2006, 37,3 (13,4-87,3) para 2007-2010 y 97,8 (63,8-144,9) para 2011-2017, p <0,001. El impacto más fuerte en la incidencia del carcinoma a células escamosas anal fue la falta de restauración inmunológica [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 6,59 (4,24-10); p <0,001], categoría C de los Centros de Control de Enfermedades [índice de tasa de incidencia ajustado (intervalo de confianza del 95%): 7,49 (5,69-9,85); p <0,001] y no hombres que tenían relaciones sexuales con hombres [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,07 (0,05-0,10); p <0,001] en el análisis de Poisson. Desde 2010-2017, las tasas de incidencia (intervalo de confianza del 95%) de carcinoma anal a células escamosas dentro del grupo SCAN y los hombres que tienen relaciones sexuales con hombres del grupo F / U fueron 95,7 (39,6-202) y 201 (101- 386) / 100000 personas-año [razón de tasa de incidencia ajustada (intervalo de confianza del 95%): 0,30 (0,23-0,39); p <0,001]. La razón de la tasa de incidencia (intervalo de confianza del 95%), incluidos los no hombres que tenían relaciones sexuales con hombres en F / U, fue de 0,87 [0,69-1,11); p = 0,269].LIMITACIONES:No se pudo cuantificar la adherencia a las visitas.CONCLUSIÓNES:La tasa de incidencia del carcinoma anal a células escamosas en personas que viven con el VIH aumentó significativamente de 2004 a 2017, especialmente en hombres que tenían relaciones sexuales con hombres que no se someten a pruebas de detección. La participación en el programa SCAN redujo significativamente la incidencia de carcinoma anal a células escamosas en hombres que tenían relaciones sexuales con hombres, en quienes se debe prestar una especial atención, sobre todo en aquellos que se presentan en la categoría C de los Centros de Control de Enfermedades con inmunodeficiencia avanzada. Consulte Video Resumen en http://links.lww.com/DCR/B734.

Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum ß-lactamase-producing Escherichia coli in the community: an interrupted time-series analysis.

BACKGROUND: There is little evidence on the ecological effect and sustainability of antimicrobial stewardship programmes (ASPs) in primary-care settings. We aimed to determine whether a multimodal, educational ASP would be sustainable in the long-term and reduce the incidence of infections caused by extended-spectrum ß-lactamase-producing Escherichia coli in the community by optimising antibiotic use. METHODS: We did this quasi-experimental intervention study in 214 primary health centres of four primary health-care districts in Andalusia, Spain. Local multidisciplinary teams, comprised of general practitioners, paediatricians, primary-care pharmacists, and epidemiologists, were created in each district and implemented a multimodal, education-based ASP. The core activity of the programme consisted of regular one-to-one educational interviews between a reference interviewing physician and prescribing physicians from each centre on the appropriateness of their most recent (same or preceding day) antibiotic prescriptions based on a structured questionnaire. Appropriate prescribing was defined as compliance of all checklist items with the reference guidelines. An average of five educational interviews were scheduled per prescriber per study year. We did an interrupted time-series analysis to assess the effect of the intervention on quarterly antibiotic use (prescription and collection by the patient) and quality of prescriptions (as defined daily doses per 1000 inhabitants per day) and incidence per 1000 inhabitants of E coli producing extended-spectrum ß-lactamase (ESBL) isolated from urine samples. FINDINGS: The study was done between January, 2012, and December, 2017, in a pre-intervention period of 2012-13 and an intervention period of 2014-17. Throughout the study period, there were 1387 physicians (1116 general practicioners and 271 paediatricians) in the included health centres serving a mean population of 1 937 512 people (299 331 children and 1 638 181 adults). 24 150 educational interviews were done over the 4 years. Inappropriate antibiotic prescribing was identified in 1794 (36·5%) of 4917 educational interviews in 2014 compared with 1793 (26·9%) of 6665 in 2017 (p<0·0001). The intervention was associated with a sustained reduction in the use of ciprofloxacin (relative effect -15·9%, 95% CI -23·9 to -8·0) and cephalosporins (-22·6%, -35·9 to -9·2), and a sustained increase in the use of amoxicillin (22·2%, 6·4 to 38·0) and fosfomycin trometamol (6·1%, 2·6 to 9·6). The incidence density of ESBL-producing E coli decreased by -0·028 cases per 1000 inhabitants (95% CI -0·034 to -0·021) after the start of the programme, reversing the pre-intervention increase and leading to a relative reduction of -65·6% (-68·2 to -63·0) 4 years later. INTERPRETATION: Our data suggest that implementation of a multimodal ASP in primary care that is based on individual educational interviews improves the use of antibiotics and results in a sustained significant reduction of infections by ESBL-producing E coli in the community. This information should encourage the implementation of ASPs in primary care. FUNDING: Instituto de Salud Carlos III, Spanish Government (PI14/01523).

High-risk Human Papilloma Virus Testing Improves Diagnostic Performance to Predict Moderate- to High-grade Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-infected Men Who Have Sex With Men in Low-to-Absent Cytological Abnormalities.

BACKGROUND: Screening methods for anal squamous intraepithelial lesions (SILs) are suboptimal. We aimed to determine the diagnostic performance of a composite endpoint comprising anal liquid-based cytology (aLBC) and high-risk human papillomavirus (HR-HPV) testing to predict histological high-grade SILs (hHSILs). METHODS: From the SeVIHanal cohort, human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) who had an aLBC with concomitant HR-HPV testing were included. hHSILs were determined by high-resolution anoscopy (HRA)-guided biopsy. RESULTS: A total of 705 visits obtained from 426 patients were included. The prevalence of HR-HPV among aLBC results were 51.9% (133/215) normal, 87.9% (20/232) low-grade SILs (LSILs), and 90.9% (149/164) high-grade SILs; P (linear association) < .001. Low prevalence of hHSILs was only observed for the composite aLBC/HR-HPV testing endpoint "normal/noHR-HPV" (10%) and "LSIL/noHR-HPV" (4%). The prognostic values (95% confidence interval) for HR-HPV to predict hHSILs in normal cytology were positive predictive value (PPV), 29.3% (25.6%-33.3%); negative predictive value (NPV), 90.2% (82.8%-94.7%); sensitivity, 83% (69.2%-92.4%); and specificity, 44.1% (36.4%-51.9%). Corresponding figures for cytologic LSILs were PPV, 39.2% (37.4%-41.1%); NPV, 96.4% (78.9%-99.5%); sensitivity, 98.8% (93.3%-99.9%); and specificity, 17.9% (12.1%-24.9%). A positive interaction and a synergistic effect for the composite endpoint were observed (relative excess risk = 1.50, attributable proportion of histological results to interaction = 0.17, synergy index = 1.24). CONCLUSIONS: HRA should not be indicated in the setting of LSILs/noHR-HPV following aLBC-based screening. In contrast, HIV-infected MSM with normal aLBC/HR-HPV infection should be considered for HRA. CLINICAL TRIALS REGISTRATION: NCT03713229.

Estudio multicéntrico sobre la actividad in vitro de ceftarolina frente a Staphylococcus aureus aislados en España / In vitro activity of ceftaroline against Spanish isolates of Staphylococcus aureus: A multicenter study

INTRODUCCIÓN: Ceftarolina fosamil es un nuevo antibiótico de última generación del subgrupo de las cefalosporinas. Es el primer beta-lactámico comercializado que presenta actividad frente a Staphylococcus aureus resistente a la meticilina (SARM). El objetivo del presente estudio es determinar los valores in vitro de la concentración mínima inhibitoria (CMI) y de la concentración mínima bactericida (CMB) de ceftarolina frente a cepas de S. aureus, tanto sensible a la meticilina (SASM) como resistente. MATERIAL Y MÉTODOS: Se realizó un estudio multicéntrico en el que participaron 4 hospitales representativos de la geografía española. Mediante el método de microdilución en caldo se determinaron los valores de CMI y CMB de la ceftarolina frente a cepas de S. aureus (SARM y SASM). RESULTADOS: Se analizaron un total de 266 cepas de S. aureus (95 SARM y 171 SASM). En las 266 cepas analizadas, todos los valores de CMI se encontraron dentro de la categoría de sensible (valor ≤ 1 μg/ml), no detectándose ninguna cepa intermedia ni ni resistente. Las CMI50 y CMI90 para SAMR fueron de 0,25 y 0,5 μg/ml, respectivamente, con un rango de 0,125 a 1 μg/ml. Las CMI50 y CMI90 para SASM fueron de 0,125 y 0,25 μg/ml, con un rango de 0,125 a 0,5 μg/ml. Las CMB50 y CMB90 para SAMR fueron de 0,5 y 1 μg/ml, respectivamente, con un rango de 0,125 a 1 μg/ml. Las CMB50 y CMB90 para SASM fueron de 0,25 y 0,25 μg/ml, con un rango de 0,125 a 0,5 μg/ml. CONCLUSIÓN: Ceftarolina muestra una excelente actividad in vitro frente a S.aureus, incluyendo cepas SARM, por lo que podría presentarse como una alternativa prometedora en el tratamiento de infecciones causadas por esta bacteria

INTRODUCTION: Ceftaroline fosamil is a new-generation antimicrobial agent of cephalosporins subgroup. It is the first commercially available beta-lactam antibiotic that exhibits activity against methicillin-resistantStaphylococcus aureus (MRSA). The aim of this study is to determine the in vitro Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of ceftar oline against S. aureus strains (including MRSA). MATERIAL AND METHODS: A multicenter study involving four hospitals representative of the Spanish geography was performed. MIC and MBC values against both the methicillin-resistant and sensitive strains of S. aureus (MRSA and methicillin-sensitive S. aureus [MSSA]) were determined using a broth microdilution method. RESULTS: A total of 266 S. aureus strains were analyzed (95 MRSA and 171 MSSA). Ceftaroline bacterial sensitivity showed a mean MIC of 0.227 μg/ml (SD=0.146; range, 0.06 to 1μg/ml). All MIC values of the 266 strains tested belonged to the sensitive category (value ≤1μg/ml). Intermediate or resistant strains were not detected. MIC50 and MIC90 values for MRSA were 0.25 and 0.5μg/ml, respectively (range = 0.125-1 μg/ml). MSSA strains showed MIC50 and MIC90 values of 0.125 and 0.25 μg/ml, respectively (range = 0.125-0.5 μg/ml). MBC50 and MBC90 values for MRSA were 0.5 and 1μg/ml, respectively (range = 0.125-1μg/ml). MSSA strains showed MBC50 and MBC90 values of 0.25 and 0.25 μg/ml, respectively (range = 0.125-0.5 μg/ml). CONCLUSIÓN: Ceftaroline shows excellent in vitro activity against S.aureus, including MRSA strains. Therefore, this antibiotic may be a promising alternative for the treatment of infections caused by this bacterium

[In vitro activity of ceftaroline against Spanish isolates of Staphylococcus aureus: a multicenter study]. / Estudio multicéntrico sobre la actividad in vitro de ceftarolina frente a Staphylococcus aureus aislados en España.

INTRODUCTION: Ceftaroline fosamil is a new-generation antimicrobial agent of cephalosporins subgroup. It is the first commercially available beta-lactam antibiotic that exhibits activity against methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study is to determine the in vitro Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of ceftaroline against S.aureus strains (including MRSA). MATERIAL AND METHODS: A multicenter study involving four hospitals representative of the Spanish geography was performed. MIC and MBC values against both the methicillin-resistant and sensitive strains of S.aureus (MRSA and methicillin-sensitive S.aureus [MSSA]) were determined using a broth microdilution method. RESULTS: A total of 266 S.aureus strains were analyzed (95 MRSA and 171 MSSA). Ceftaroline bacterial sensitivity showed a mean MIC of 0.227 µg/ml (SD=0.146; range, 0.06 to 1 µg/ml). All MIC values of the 266 strains tested belonged to the sensitive category (value ≤ 1 µg/ml). Intermediate or resistant strains were not detected. MIC50 and MIC90 values for MRSA were 0.25 and 0.5 µg/ml, respectively (range=0.125-1 µg/ml). MSSA strains showed MIC50 and MIC90 values of 0.125 and 0.25 µg/ml, respectively (range=0.125-0.5 µg/ml). MBC50 and MBC90 values for MRSA were 0.5 and 1 µg/ml, respectively (range=0.125-1 µg/ml). MSSA strains showed MBC50 and MBC90 values of 0.25 and 0.25 µg/ml, respectively (range=0.125-0.5 µg/ml). CONCLUSION: Ceftaroline shows excellent in vitro activity against S.aureus, including MRSA strains. Therefore, this antibiotic may be a promising alternative for the treatment of infections caused by this bacterium.