Real-World Characterization of the Portuguese Population Living with HIV who Initiated Raltegravir Based-Regimens: The REALITY Study.

INTRODUCTION: Although raltegravir has been available since 2007, data are lacking on the Portuguese population living with HIV who initiated this antiretroviral therapy. Hence, this study aimed to characterize the patients who initiated raltegravir-based regimens between January 2015 and December 2017, on sociodemographics, clinical features, and treatment satisfaction. MATERIAL AND METHODS: Observational, retrospective, multicentre study conducted at 11 reference sites. Sociodemographic and clinical data were collected retrospectively from hospital medical records. For participants continuing raltegravir at study inclusion, the HIV Treatment Satisfaction Questionnaire was administered to assess satisfaction with raltegravir-based therapy. Descriptive statistics were performed. Treatment-naïve and treatment-experienced subgroups were compared for demographic and clinical variables. RESULTS: A total of 302 patients were included; mostly men (69.5%) with a mean age of 49 years old. Approximately half of the patients had at least one non-AIDS-related comorbidity at baseline (53.3%), such as hypercholesterolemia, arterial hypertension, diabetes mellitus, and depression. Moreover, 52.3% were treatment-experienced patients with up to two treatments prior to raltegravir. Across the study time points, there was a reduction in the viral load and improvement in CD4 counts in both the treatment-naïve and treatment-experienced subgroups. Continuing users of raltegravir reported high treatment satisfaction (55.4 ± 7.2 points). CONCLUSION: Raltegravir-based regimens seem like a valid therapeutic option in heterogeneous populations of HIV-infected patients, in patients with previous ART experience and as part of first-line therapeutic options alongside with the latest generation of drugs from its class.

Introdução: Apesar de o raltegravir estar disponível desde 2007, os dados na população portuguesa com VIH que iniciou esta terapêutica antirretroviral são escassos. Deste modo, este estudo teve por objetivo caracterizar os doentes que iniciaram um regime terapêutico baseado em raltegravir entre janeiro de 2015 e dezembro de 2017, relativamente a dados sociodemográficos, características clínicas e satisfação com o tratamento. Material e Métodos: Estudo observacional, retrospetivo, multicêntrico conduzido em 11 centros de referência. Os dados sociodemográficos e clínicos foram recolhidos retrospetivamente nos processos clínicos. Os participantes que continuaram o regime com raltegravir após a inclusão no estudo preencheram o HIV Treatment Satisfaction Questionnaire para avaliar a satisfação com a terapêutica. Foram efetuadas análises de estatística descritiva e comparações para as variáveis sociodemográficas e clínicas nos subgrupos de doentes naïve de tratamento e de doentes com experiência terapêutica. Resultados: Foram incluídos 302 doentes, maioritariamente do sexo masculino (69,5%) com idade média de 49 anos. Aproximadamente metade dos doentes tinha pelo menos uma comorbilidade não relacionada com SIDA no início do estudo (53,3%), tais como hipercolesterolemia, hipertensão arterial, diabetes mellitus ou depressão. Adicionalmente, 52,3% eram doentes com experiência terapêutica com até dois tratamentos anteriores ao raltegravir. Ao longo do estudo verificou-se uma redução na carga viral e uma melhoria nas contagens de CD4 em ambos os subgrupos de doentes (doentes naïve de tratamento e doentes com experiência terapêutica). Os doentes com uso continuado de raltegravir reportaram uma elevada satisfação com o tratamento (55,4 ± 7,2 pontos). Conclusão: Os regimes terapêuticos baseados em raltegravir parecem ser uma opção terapêutica válida em populações heterogéneas de doentes infetados com VIH, em doentes com experiência em ART e como tratamento de primeira linha, em paralelo com outras terapêuticas de última geração.

Linezolid for therapy of Staphylococcus aureus meningitis: a cohort study of 26 patients.

BACKGROUND: Linezolid has good penetration to the meninges and could be an alternative for treatment of Staphylococcus aureus meningitis. We assessed the efficacy and safety of linezolid therapy for this infection. METHODS: Retrospective multicenter cohort study of 26 adults treated with linezolid, derived from a cohort of 350 cases of S. aureus meningitis diagnosed at 11 university hospitals in Spain (1981-2015). RESULTS: There were 15 males (58%) and mean age was 47.3 years. Meningitis was postoperative in 21 (81%) patients. The infection was nosocomial in 23 (88%) cases, and caused by methicillin-resistant S. aureus in 15 cases and methicillin-susceptible S. aureus in 11. Linezolid was given as empirical therapy in 10 cases, as directed therapy in 10, and due to failure of vancomycin in 6. Monotherapy was given to 16 (62%) patients. Median duration of linezolid therapy was 17 days (IQR 12-22 days) with a daily dose of 1,200 mg in all cases. The clinical response rate to linezolid was 69% (18/26) and microbiological response was observed in 14 of 15 cases evaluated (93%). Overall 30-day mortality was 23% and was directly associated with infection in most cases. When compared with the patients of the cohort, no significant difference in mortality was observed between patients receiving linezolid or vancomycin for therapy of methicillin-resistant S. aureus meningitis (9% vs. 20%; p = .16) nor between patients receiving linezolid or cloxacillin for therapy of methicillin-susceptible S. aureus meningitis (20% vs 14%; p = .68). Adverse events appeared in 14% (3/22) of patients, but linezolid was discontinued in only one patient. CONCLUSIONS: Linezolid appears to be effective and safe for therapy of S. aureus meningitis. Our findings showed that linezolid may be considered an adequate alternative to other antimicrobials in meningitis caused by S. aureus.

Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group).

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.

Currículo opcional: diversidad y desafíos a la formación pregraduada / 'Elective': enhancing heterogeneity and challenges to pregraduate curriculum

Introducción: La unidad curricular opcional proporciona al estudiante la oportunidad de profundizar en un área clínica de libre elección o en una realidad asistencial diferente, promoviendo un currículo personalizado. Sujetos y métodos: Estudio descriptivo de los intercambios clínicos en el período 2012-2017 del último año de licenciatura y comparativa entre nacionales e internacionales. Al finalizar el intercambio, el estudiante responde a un formulario onlineque incluye múltiples variables: demográficas, de proceso y de resultados, cuyo análisis es el objetivo de este estudio. Resultados: Un total de 253 intercambios realizados por 154 estudiantes, siendo un 55% mujeres, con una edad media de 28 años. Más de la mitad (59%) optaron por destinos internacionales, destacando Reino Unido (8,3%) y Brasil (7,5%), y apenas un 11% permaneció en la región. Los centros de destino fueron mayoritariamente hospitales terciarios, desarrollando actividades clínico-observacionales (66%), y hasta un 47% en áreas no abordadas en el currículo oficial. Las especialidades más solicitadas globalmente fueron salud internacional y medicina tropical (15%), anestesia (8,3%) y pediatría (8%). La planificación y los costes son asumidos por el estudiante, con apoyos externos prácticamente inexistentes. La autoevaluación final fue de 4,46 puntos (sobre 5) y el 99% lo recomendaba a sus colegas. Conclusiones: Individualmente, la unidad curricular opcionalpermite al estudiante probar sus competencias y su capacidad de adaptación a otras realidades asistenciales y sociales, confrontándolo con potenciales elecciones profesionales

Introduction: 'Elective' is an opportunity to deepen clinical competences and/or work in a different assistance reality and promotes personal curriculum. Subjects and methods: A descriptive analysis of the elective internships carried from 2012 to 2017 at the last year of course and compare international and national ones. The students complete an online survey regarding the activities which include demographic, development and outcomes variables. Results: 253 clinical internships carried out by 154 medical students with a mean age of 28 years and 55% were women. The majority (59%) chosen to carry out international internship, particularly United Kingdom (8.3%) and Brazil (7.5%), and only 11% stayed in Algarve region. Half of the internships were carried out in tertiary hospitals being observational-practical (66%). Until half of students (47%) chose medical specialties not included in official curriculum being preference areas: international health (15%) and anesthesiology (8.3%). The majority of internships (66%) were observational-practical. The students are responsible for all the necessary arrangements, being external financial support practically no existent). The final internship rank student was 4.46, on a scale of 0-5, and 99% would recommend the experience to their colleagues. Conclusions: The 'elective' aims to promote students ability to adapt a new professional and social realities, test their competences and sometimes confront themselves with their potential future professional choice

Methicillin-resistant Staphylococcus aureus meningitis in adults: a multicenter study of 86 cases.

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is an uncommon disease, and little is known about its epidemiology, clinical features, therapy, and outcome. We performed a multicenter retrospective study of MRSA meningitis in adults. Eighty-six adult patients were included and the following data were obtained: underlying diseases, clinical presentation, analytical and microbiologic data, response to therapy, and outcome.There were 56 men (65%) and the mean age was 51.5 years; 54 of them (63%) had severe comorbidities. There were 78 cases of postoperative meningitis and 8 of spontaneous meningitis. The infection was nosocomial in 93% (80/86) of the cases. Among the 78 patients with postoperative meningitis, the most common predisposing conditions were cerebrospinal fluid (CSF) devices (74%), neurosurgery (45%), CSF leakage (17%), and head trauma (12%). Most patients had fever (89%), altered mental status (68%), headache (40%), and meningeal signs (29%). The most common CSF findings were pleocytosis (90%), elevated protein level (77%), and hypoglycorrhachia (30%). CSF Gram stain and blood cultures were positive in 49% (32/65) and 36% (16/45) of cases, respectively. An associated MRSA infection and polymicrobial meningitis appeared in 33% (28/86) and 23% (20/86) of cases, respectively. Antimicrobial therapy was given to 84 patients. Most of them received vancomycin (92%) either as monotherapy (64%) or in combination with other antibiotics (28%), for a median of 18 days. Overall 30-day mortality was 31% (27/86). Multivariate study identified 2 independent factors associated with mortality: spontaneous meningitis (odds ratio [OR], 21.4; 95% confidence interval [CI], 2.3-195.4; p = 0.007), and coma (OR, 9.7; 95% CI, 2.2-42.3; p = 0.002).In conclusion, MRSA is a relatively uncommon but serious disease. Although most cases are nosocomial infections appearing in neurosurgical patients, spontaneous meningitis may present as a community-onset infection in patients with severe comorbidities requiring frequent contact with the health care system. Most patients have a favorable response to vancomycin, but the beneficial effect of combined and intraventricular therapy, or alternative drugs, remains unclear. MRSA meningitis is associated with a high mortality, and the presence of spontaneous infection and coma are the most important prognostic factors.

[Nosocomial diarrhea outbreak due to Clostridium difficile in a vascular surgery department]. / Brote nosocomial de diarrea por Clostridium difficile en un servicio de cirugía vascular.

INTRODUCTION: Clostridium difficile is considered the most common cause of nosocomial-acquired diarrhea. In Spain this condition is rarely reported. METHODS: Over a five-month period, 35 episodes of C. difficile diarrhea were diagnosed by toxin A detection in stool samples. Case-control studies were designed to assess risk factors for the outbreak. Twelve cases from the vascular surgery department were compared with 24 randomized controls, patients admitted to the same ward during this period, but without diarrhea. Statistical comparisons (SPSS software) were performed with the Student's t and X2 tests (OR with 95% CI). RESULTS: Overall incidence was 3.42 episodes: 48 episodes/1000 admissions to vascular surgery. Among the total, 80% had received antibiotics before admission and the mean number of antibiotics administered was 2.91 per patient. Comparative analyses disclosed that the cases had received a larger number of antibiotics during hospitalization (p 5 0.000) and in the two months before admission (p 5 0.031) than the controls. Clindamycin administered alone (p 5 0.001) or associated with aztreonam (p 0.000) were the most frequently used antibiotic treatments. CONCLUSIONS: C. difficile diarrhea is common in our setting. Diagnosis requires a high index of suspicion. We attribute the nosocomial outbreak in our vascular surgery department to broad-spectrum antibiotic use (clindamycin and aztreonam). Surveillance, together with restriction of antibiotic use was effective for control.

Brote nosocomial de diarrea por Clostridium difficileen un servicio de cirugía vascular / Nosocomial diarrhea outbreak due to Clostridium difficile in a vascular surgery department

Introducción: El uso indiscriminado de antibióticos se ha asociado a un aumento de resistencias y constituye el factor de riesgo más importante para el desarrollo de diarrea asociada a Clostridium difficile, que se aísla entre el 10 y el 30 por ciento de los pacientes con diarrea nosocomial1, con grandes problemas para su erradicación y elevados costes en términos de morbimortalidad2,3.Intuitivamente tenemos la impresión de estar ante un problema infradiagnosticado debido a la dificultad para la confirmación de laboratorio que exige la demostración de toxina de C. difficile en un contexto clínico adecuado4. Desde el primer caso publicado por Finney5, se han publicado gran número de brotes epidémicos nosocomiales en hospitales generales y residencias de enfermos crónicos1,2,3,6, de grandes dimensiones, uno declarado en un hospital dublinés que afectó a 139 pacientes con 4 muertes7.En España se le ha dedicado escasa atención publicándose casos aislados y dos brotes epidémicos; de 6 y 5 casos, respectivamente8,9.Se describe un período de 5 meses en el que se detectó un aumento de la incidencia de diarrea por C. difficile y las INTRODUCCIÓN. La infección por Clostridium difficile es una causa de diarrea nosocomial poco descrita en España. MÉTODOS. En un período de 5 meses se detectaron 35 episodios de diarrea por C. difficile diagnosticados por la detección de toxina A en heces líquidas. Se compararon 12 casos de cirugía vascular con 24 controles aleatorizados, sin diarrea. El análisis estadístico (SPSS) utilizó para las comparativas t de Student y chi cuadrado (odds ratio con intervalo de confianza del 95 por ciento).RESULTADOS. La incidencia global fue 3,42 frente 48 casos/1.000 ingresos en cirugía vascular. El 80 por ciento recibieron antibióticos antes del ingreso y la media durante el ingreso fue de 2,91 antibióticos/paciente. El estudio casos-controles se diseñó para estudiar los factores de riesgo del brote de vascular. El análisis reveló que los casos recibieron un mayor número de antibióticos antes (p 0,0031) y durante el ingreso (p 0,000), siendo la clindamicina sola (p 0,001) o asociada a aztreonam (p 0,000) los más utilizados. CONCLUSIONES. La diarrea por C. difficile es frecuente en nuestro medio, su diagnóstico exige un elevado índice de sospecha. Se publica un brote atribuido al uso de clindamicina y/o aztreonam. Las medidas de control y la restricción en el uso de antibióticos fueron efectivos (AU)

Osteomielitis vertebral por Streptococcus agalactiae / Vertebral osteomyelitis due to Streptococcus agalactiae

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