Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

BACKGROUND: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec). METHODS: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders. RESULTS: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen. CONCLUSIONS: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment.

Características clínicas, pronóstico y factores asociados de la bacteriemia por Staphylococcus aureus en la actualidad / Clinical characteristics and prognosis of Staphylococcus aureus bacteremia

Introducción. Describimos las características de los pacientes con bacteriemia por Staphylococcus aureus en un hospital de tercer nivel y analizamos sus complicaciones, la mortalidad y los factores asociados a las mismas. Métodos. Se analizaron de manera retrospectiva los datos de los pacientes ingresados con bacteriemia por S. aureus entre marzo de 2020 y febrero de 2021 en el hospital universitario Miguel Servet de Zaragoza. Resultados. La mortalidad a los 14 días fue del 24,2% y la mortalidad a los 30 días del 40%. La aparición de complicaciones [HR 3,1 (1,2-8,05)] y la edad >65 años [HR 3,1 (IC95% 1,4-6,6)] disminuyeron la supervivencia global de manera significativa. En la regresión logística se asociaron a mayor mortalidad a los 30 días la edad >65 años [OR 6,3 (IC95% 1,7-23,1)], la presencia de sepsis [OR 19,3 (IC95% 5,4-68,7)] y solo con cierta tendencia, el número de frascos de HC (+) ≥3 [OR 5,4 (IC95% 0,8-34,1)]. Se asoció a mayor mortalidad a los 14 días el haber presentado sepsis [OR 58,2 (IC95% 5,7-592,9)], el número frascos de HC (+) ≥3 [OR 14,1 (IC95% 1,1-173,7)] y una edad >65 años [OR 1,1 (IC95% 1,03-1,1) años]. Cuando analizamos juntos aquellos con un TP ≤12 horas y un número frascos de HC (+) ≥3, la sepsis fue más frecuente [30 pacientes (66,6%) vs 15 pacientes (33,3%); OR 3,4 (IC95% 1,5-8)]. Conclusiones. La mortalidad a los 14 y a los 30 días fue elevada, observándose una peor evolución en los pacientes con mayor edad, presencia de sepsis, un mayor número de frascos de hemocultivos positivos y un tiempo hasta hemocultivos positivos ≤12 h. (AU)

Introduction. Staphylococcus aureus bacteremia patients characteristics at a tertiary hospital are described, and complications, mortality and associated factors are analyzed. Methods. Data from patients with S. aureus bacteremia admitted between March 2020 and February2021 at Miguel Servet university hospital in Zaragoza were retrospectively analyzed. Results. Results showed a 14 days mortality of 24.2% and an 30 days mortality of 40%. Overall survival decreased with complications appearance [HR 3.1 (1.2-8.05)] and age over 65 years [HR 3.1 (1.4-6.6)]. The adjusted analysis showed correlation between a higher mortality at 14 and 30 days with age over 65 years [OR 6.3 (1.7-23.1)], sepsis presence [OR 19.3 (5.4-68.7)] and number of positive (+) blood cultures ≥3 [OR 5.4 (0.8-34.1)]. Mortality at 14 days was associated with sepsis presence [OR 58.2 (5.7-592.9)], number of positive (+) blood cultures ≥3 [OR 14.1 (1.1-173.7)] and an older age [OR 1.1 (1.03-1.1)]. Analyzing time to positive blood cultures ≤12 hours and number of positive blood cultures ≥ 3 at the same time, frequency of sepsis increased [30 patients (66.6%) vs 15 patients (33.3%); OR 3.4 (IC95% 1.5-8)]. Conclusions. High 14- and 30-days mortality were found, as well as a worse evolution in older age patients, with sepsis presence, and with greater number of positive blood cultures and times to positive blood cultures ≤12 h. (AU)

Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19 / Impact of Staphylococcus aureus bacteremia in COVID-19 patients

Introducción. La enfermedad causada por SARS-CoV-2 (COVID-19) ha supuesto un desafío para los profesionales sanitarios desde su aparición. Staphylococcus aureus es uno de los principales patógenos causantes de infecciones bacterianas en pandemias virales. Sin embargo, se debe estudiar bien la co-infección por S. aureus causante de bacteriemia en pacientes con COVID-19. Métodos. Se analizaron los casos de bacteriemia por S. aureus (BSA) atendidos en el Hospital Miguel Servet (Zaragoza) desde marzo de 2020 hasta febrero de 2021. Se compararon las características clínicas, los factores de riesgo y mortalidad de los pacientes con BSA asociada a COVID-19 respecto los pacientes no-COVID-19. Resultados. Se identificaron 95 pacientes con BSA. El 27,3% fueron COVID-19 positivos. La BSA representó el 9,9% de las bacteriemias, siendo el segundo microorganismo en frecuencia tras E. coli. La bacteriemia nosocomial fue más frecuente en el grupo de pacientes con COVID-19. La fuente de BSA fue desconocida en el 46,2% de los pacientes con COVID-19. La fuente de BSA más frecuente en estos pacientes fue la respiratoria (26,9% vs 0%; P<0,001) seguida de la cutánea (15,5% vs 15,9%; P=1). El desarrollo de sepsis fue más frecuente en los pacientes con COVID-19 (61,5% vs 7,8%; P=0,336) y de ellos, los que recibieron dosis de dexametasona >6 mg/día (62,5% vs 37,5%; P< 0,05). Conclusiones. Nuestros datos sugieren que la BSA influye negativamente en la evolución de los pacientes con COVID-19. Sin embargo, se requieren más estudios y preferiblemente prospectivos para obtener datos sólidos sobre el impacto de la BSA en los pacientes con coronavirus. (AU)

Introduction. The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. Methods. We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. Results. A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). Conclusions. Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients. (AU)

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.

Importance: The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. Objective: To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. Design, Setting, and Participants: This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. Interventions: Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or parenteral ertapenem for the comparator group after 4 days. Main Outcomes and Measures: The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. Results: Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to ∞ percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI, -∞ to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). Conclusions and Relevance: This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections. Trial Registration: ClinicalTrials.gov Identifier: NCT02142751.

Efectos adversos neuropsiquiátricos de dolutegravir en la práctica clínica real / Neuropsychiatric adverse effects of dolutegravir in real-life clinical practice

Introducción: Los inhibidores de la integrasa, y especialmente dolutegravir (DTG), son el tratamiento de primera línea antirretroviral por su eficacia y seguridad. Aunque en los ensayos pivotales la tasa de efectos adversos (EA) era baja (2-3%), en los estudios de vida real parece ser mayor, especialmente los EA neuropsiquiátricos. El objetivo fue determinar el porcentaje de EA e interrupción de DTG en nuestro centro y la relación con los antecedentes psiquiátricos. Métodos: Estudio descriptivo retrospectivo de pacientes que iniciaron DTG entre 2015-2017. Se registraron: interrupción del tratamiento, EA y enfermedad psiquiátrica. Se realizó seguimiento desde el inicio del del tratamiento con DTG y se registraron las hospitalizaciones y las visitas a urgencias y atención primaria. Fue autorizado por el Comité Ético de Investigación Clínica de Aragón. Resultados: Se incluyeron 283 pacientes, entre 11-87 años, 70% varones. El 21% naive. Interrumpieron el tratamiento con DTG el 24%, un 10% por EA. Se detectó un 5% de EA neuropsiquiátricos. Este grupo tenía más antecedentes psiquiátricos (62 vs. 41%; p=0,002) que el de pacientes que continuaron el tratamiento, y precisaron más visitas en atención primaria (18,8 vs. 8,4%; p=0,016) y urgencias (8,7 vs. 3,3%; p=0,061). Conclusión: Los pacientes que interrumpieron el tratamiento con DTG tenían más antecedentes psiquiátricos. Por ello, aunque se precisan más estudios, sería necesario valorar este antecedente previamente al tratamiento con inhibidores de la integrasa. Síntomas como ansiedad, insomnio o depresión pueden ser EA de DTG con una frecuencia mayor de la esperada. Ser identificados por los médicos de atención primaria y urgencias podría evitar una cascada de prescripción innecesaria.(AU)

Introduction: Integrase inhibitors and especially dolutegravir (DTG) are placed as a first-line antiretroviral treatment for their efficacy and safety. Although in the pivotal trials the rate of adverse effects (AEs) was low (2-3%), in real-life studies it appears to be higher, especially neuropsychiatric AEs. The objective is to determine the percentage of AEs and discontinuation of DTG in our site and the relationship with the psychiatric background. Methods: Retrospective descriptive study of patients starting DTG from 2015 to 2017. Discontinuation of treatment, AEs and previous psychiatric pathology were recorded. Follow-up is carried out since the beginning of the treatment, and hospitalizations and emergency room and primary care visits were registered. The study was authorized by the Ethics Committee for Clinical Research of Aragon. Results: Two hundred and eighty-three patients were included, between 11 and 87 years old, 70% male. 21% were naive. 24% of the patients discontinued treatment with DTG, 10% due to AEs. Neuropsychiatric AEs were detected in 5%. This group of patients had a more frequent previous psychiatric history (62 vs. 41%; P=.002) than the ongoing treatment group and they needed more visits to primary care (18.8 vs. 8.4%; P=.016) and emergency room (8,7 vs. 3.3%; P=.061). Conclusion: Patients who discontinued treatment with DTG had more psychiatric history. Although more studies are required, it is necessary to assess this background before starting treatment with integrase inhibitors. Symptoms such as anxiety, insomnia or depression can be DTG AEs more frequently than expected. Being identified by primary care and emergency physicians could avoid the unnecessary prescription of other medications.(AU)

Neuropsychiatric adverse effects of dolutegravir in real-life clinical practice. / Efectos adversos neuropsiquiátricos de dolutegravir en la práctica clínica real.

INTRODUCTION: Integrase inhibitors and especially dolutegravir (DTG) are placed as a first-line antiretroviral treatment for their efficacy and safety. Although in the pivotal trials the rate of adverse effects (AEs) was low (2-3%), in real-life studies it appears to be higher, especially neuropsychiatric AEs. The objective is to determine the percentage of AEs and discontinuation of DTG in our site and the relationship with the psychiatric background. METHODS: Retrospective descriptive study of patients starting DTG from 2015 to 2017. Discontinuation of treatment, AEs and previous psychiatric pathology were recorded. Follow-up is carried out since the beginning of the treatment, and hospitalizations and emergency room and primary care visits were registered. The study was authorized by the Ethics Committee for Clinical Research of Aragon. RESULTS: Two hundred and eighty-three patients were included, between 11 and 87 years old, 70% male. 21% were naive. 24% of the patients discontinued treatment with DTG, 10% due to AEs. Neuropsychiatric AEs were detected in 5%. This group of patients had a more frequent previous psychiatric history (62 vs. 41%; P=.002) than the ongoing treatment group and they needed more visits to primary care (18.8 vs. 8.4%; P=.016) and emergency room (8,7 vs. 3.3%; P=.061). CONCLUSION: Patients who discontinued treatment with DTG had more psychiatric history. Although more studies are required, it is necessary to assess this background before starting treatment with integrase inhibitors. Symptoms such as anxiety, insomnia or depression can be DTG AEs more frequently than expected. Being identified by primary care and emergency physicians could avoid the unnecessary prescription of other medications.

Bacteriemia por Staphylococcus aureus sensible a penicilina. Importancia epidemiológica, clínica y posibles implicaciones terapéuticas / Penicillin-susceptible Staphylococcus aureus bacteremia: Epidemiological and clinical relevance. Possible therapeutic implications

INTRODUCCIÓN: El aumento de la sensibilidad a penicilina en Staphylococcus aureus (SA-PenS) podría tener relevancia terapéutica. Pretendemos conocer esta situación en nuestro medio. MATERIAL Y MÉTODOS: Se analizaron bacteriemias por SA en un hospital durante 2,5 años (2015-2017). Estudiamos la sensibilidad a antimicrobianos, genes de resistencia a beta-lactámicos (blaZ, mecA) y presencia de leucocidina de Panton-Valentine. En aislados SA-PenS-blaZnegativo se determinó el tipo de spa, MLST y genes de resistencia a antimicrobianos no-beta-lactámicos. RESULTADOS: Hubo 84 pacientes con bacteriemia por SA (35,7% SARM y 64,3% SASM), se analizaron 77. El 22% de los SASM estudiados (n = 11) fueron PenS-blaZnegativo (CMI-Pen ≤ 0,3 μg/ml), correspondiendo al 14,3% del total de SA. En SASM-PenS-blaZnegativo se detectaron 8 tipos-spa y 7 complejos clonales. CONCLUSIÓN: Detectamos alta prevalencia de SARM/SA y de SASM-PenS-blaZnegativo/SASM en hemocultivos. Una CMI-Pen ≤ 0,3 μg/ml se correspondió con SASM-PenS-blaZnegativo. Esta situación plantea opciones terapéuticas que deberán reevaluarse con estudios más amplios y ensayos clínicos

INTRODUCTION: The increase in penicillin susceptibility among Staphylococcus aureus (SA-PenS) might have therapeutic relevance. We aimed to study the current situation in our environment. MATERIAL AND METHODS: Over a 2.5 years period, all SA isolates from bacteraemia in one hospital were analysed. For all isolates, antimicrobial susceptibility profile, beta-lactam resistance genes (blaZ, mecA) and Panton-Valentine leucocidine encoding-genes were studied. For SA-PenS-blaZnegative isolates, spa-type, MLST and the presence of other resistance genes were studied. RESULTS: Among 84 patients with SA bacteraemia (35.7% MRSA and 64.3% MSSA), 77 were analysed; 22.2% of MSSA isolates were PenS and blaZnegative (Pen-MIC ≤ 0.03 μg/ml) corresponding to 14.3% of the total SA. In MSSA-PenS-blaZnegative isolates, eight spa-types and 7 clonal-complexes were detected. CONCLUSION: A high prevalence of MRSA/SA and MSSA-PenS-blaZnegative/MSSA was detected in blood cultures. Pen-MIC ≤ 0,3 μg/ml corresponded to MSSA-PenS-blaZnegative. This situation raises therapeutic options which should be further evaluated in larger studies and clinical trials

Penicillin-susceptible Staphylococcus aureus bacteremia: Epidemiological and clinical relevance. Possible therapeutic implications. / Bacteriemia por Staphylococcus aureus sensible a penicilina. Importancia epidemiológica, clínica y posibles implicaciones terapéuticas.

INTRODUCTION: The increase in penicillin susceptibility among Staphylococcus aureus (SA-PenS) might have therapeutic relevance. We aimed to study the current situation in our environment. MATERIAL AND METHODS: Over a 2.5 years period, all SA isolates from bacteraemia in one hospital were analysed. For all isolates, antimicrobial susceptibility profile, beta-lactam resistance genes (blaZ, mecA) and Panton-Valentine leucocidine encoding-genes were studied. For SA-PenS-blaZnegative isolates, spa-type, MLST and the presence of other resistance genes were studied. RESULTS: Among 84 patients with SA bacteraemia (35.7% MRSA and 64.3% MSSA), 77 were analysed; 22.2% of MSSA isolates were PenS and blaZnegative (Pen-MIC≤0.03µg/ml) corresponding to 14.3% of the total SA. In MSSA-PenS-blaZnegative isolates, eight spa-types and 7 clonal-complexes were detected. CONCLUSION: A high prevalence of MRSA/SA and MSSA-PenS-blaZnegative/MSSA was detected in blood cultures. Pen-MIC≤0,3µg/ml corresponded to MSSA-PenS-blaZnegative. This situation raises therapeutic options which should be further evaluated in larger studies and clinical trials.

Oportunidades perdidas en el diagnóstico de la infección por el virus de inmunodeficiencia humana en la Comunidad de Aragón. Importancia del diagnóstico tardío / Missed opportunities in the diagnosis of human immunodeficiency virus infection in the Region of Aragon. Late diagnosis importance

Introducción: El diagnóstico tardío (DT) de la infección por el virus de la inmunodeficiencia humana (VIH) (linfocitos CD4<350/μl al diagnóstico de la enfermedad) empeora el pronóstico de los afectados y aumenta las probabilidades de transmisión. El objetivo del presente trabajo fue analizar la prevalencia de DT, identificar las oportunidades diagnósticas perdidas (ODP) y averiguar el nivel asistencial donde se produjeron. Métodos: Estudio retrospectivo, observacional, descriptivo de la población diagnosticada de infección por VIH/sida en el periodo 2011-2015 en Aragón. Se identificaron las ODP durante los 3 años previos al diagnóstico de la enfermedad en todos los niveles asistenciales, así como la frecuentación asistencial. Se analizaron las condiciones indicadoras (CI) que generaron más ODP, según las últimas recomendaciones para el diagnóstico precoz del VIH en el medio sanitario. Resultados: Se analizaron 435 nuevos casos de VIH/sida. El 45,1% fueron diagnosticados en Atención Primaria (AP). El 49,4% presentaron criterios de DT y el 61,1% se contagiaron vía heterosexual. La mayor parte de ODP (68,5%) se dieron en AP. Las CI que generaron más ODP fueron la dermatitis seborreica/exantema (19,4%) y la fiebre sin causa aparente (10,3%). Sin embargo, las CI que se asociaron a mayor DT fueron la neumonía adquirida en la comunidad y la pérdida de peso injustificada. Conclusión: En Aragón, la prevalencia de DT es elevada, la principal vía de transmisión es la heterosexual y la mayor parte de las CI pasan desapercibidas en AP. La difusión de las guías actuales para solicitar una prueba de VIH orientada por CI y el screening VIH en todo preoperatorio es una medida eficaz para disminuir el DT

Introduction: Late Diagnosis (LD) of Human Immunodeficiency Virus (HIV) infection (CD4 lymphocytes <350/μl at diagnosis of the disease), deteriorates the condition of those affected and increases the probability of transmission. The objective of the present study was to analyse the prevalence of LD, to identify missed diagnostic opportunities (MDO) and to find out which level of the health care delivery system they took place. Methods: Retrospective, observational and descriptive study of the population diagnosed with infection of HIV/AIDS in the period 2011-2015 in Aragon. MDO were identified during the 3 years prior to diagnosis of the disease in all levels of the health care delivery system as well as frequentation of consultations. The indicator conditions (IC) that generated more MDO were analysed according to the latest recommendations for early diagnosis of HIV in the health care setting. Results: 435 newly diagnosed HIV/AIDS cases were analysed. 45.1% were diagnosed in Primary Healthcare (PH). 49.4% presented criteria of LD and 61.1% were infected through heterosexual contact. The majority of MDO (68.5%) were given in PH. The IC that generated the most MDO were seborrheic dermatitis/exanthema (19.4%) and fever of unknown origin (10.3%). However, the IC that were associated with higher LD were pneumonia acquired in the community and unjustified weight loss. Conclusion: In Aragon, prevalence of LD is high, the main route of infection is heterosexual and most of MDO go unnoticed in PH. The dissemination of current guidelines for requesting IC guided HIV testing and HIV screening across the preoperative period will result in an effective measure to decrease the LD

Missed opportunities in the diagnosis of human immunodeficiency virus infection in the Region of Aragon. Late diagnosis importance. / Oportunidades perdidas en el diagnóstico de la infección por el virus de inmunodeficiencia humana en la Comunidad de Aragón. Importancia del diagnóstico tardío.

INTRODUCTION: Late Diagnosis (LD) of Human Immunodeficiency Virus (HIV) infection (CD4 lymphocytes <350/µl at diagnosis of the disease), deteriorates the condition of those affected and increases the probability of transmission. The objective of the present study was to analyse the prevalence of LD, to identify missed diagnostic opportunities (MDO) and to find out which level of the health care delivery system they took place. METHODS: Retrospective, observational and descriptive study of the population diagnosed with infection of HIV/AIDS in the period 2011-2015 in Aragon. MDO were identified during the 3 years prior to diagnosis of the disease in all levels of the health care delivery system as well as frequentation of consultations. The indicator conditions (IC) that generated more MDO were analysed according to the latest recommendations for early diagnosis of HIV in the health care setting. RESULTS: 435 newly diagnosed HIV/AIDS cases were analysed. 45.1% were diagnosed in Primary Healthcare (PH). 49.4% presented criteria of LD and 61.1% were infected through heterosexual contact. The majority of MDO (68.5%) were given in PH. The IC that generated the most MDO were seborrheic dermatitis/exanthema (19.4%) and fever of unknown origin (10.3%). However, the IC that were associated with higher LD were pneumonia acquired in the community and unjustified weight loss. CONCLUSION: In Aragon, prevalence of LD is high, the main route of infection is heterosexual and most of MDO go unnoticed in PH. The dissemination of current guidelines for requesting IC guided HIV testing and HIV screening across the preoperative period will result in an effective measure to decrease the LD.

Limitación del esfuerzo terapéutico en pacientes con bacteriemia / Limitation of therapeutic effort in patients with bacteremia

Introducción: La limitación del esfuerzo terapéutico (LET) depende de factores médicos, éticos e individuales. Describimos las características de los pacientes con bacteriemia en los que se decidió limitar el esfuerzo terapéutico. Métodos: Estudio prospectivo de las bacteriemias en un hospital comunitario durante el año 2011. Se recogieron variables de los pacientes (edad, sexo, índice de Barthel, comorbilidades, índice de Charlson y factores exógenos) y del episodio infeccioso (etiología, foco, lugar de adquisición, expresividad clínica, LET y mortalidad hospitalaria). Se comparó el grupo en el que se realizó LET con el que no. Resultados: Se recogieron 233 episodios de bacteriemia en 227 pacientes. Se realizó LET en 19 pacientes (8,2%). Los pacientes en los que se realizó LET eran de mayor edad (80,7 vs. 72,6 años, p= 0,014), tenían más comorbilidad (índice de Charlson 4,6 vs. 2,1, p<0,001) y con más frecuencia sufrían discapacidad grave (57,9% vs. 18,8%, p<0,001). No se encontró asociación con el sexo, el lugar de adquisición ni con la expresividad clínica de la infección. El foco clínico más frecuente en los casos de LET fue el urinario (42,1%) y predominaron los grampositivos (63,2%). El tratamiento empírico fue precoz en un 73,7%. Todos los pacientes excepto uno fallecieron. Conclusión: La LET se planteó en un número importante de los pacientes con bacteriemia, especialmente en aquellos con más edad, más comorbilidad y mayor dependencia funcional. El conocimiento de sus características diferenciales nos ayuda a comprender la toma de dicha decisión

Introduction: The limitation of therapeutic effort (LTE) depends on medical, ethical and individual factors. We describe the characteristics of patients with bacteremia in which it was decided to limit the therapeutic effort Method: Prospective study of bacteremia in a community hospital in 2011. We collected information regarding patient variable (age, sex, Barthel index, comorbidities, Charlson Index and exogenous factors) as well as regarding the infectious episode (etiology, focus, place of adquisition, clinical expressivity, LTE and hospital mortality). The group in which LTE was performed was compared to the one that was not. Results: We collected 233 episodes of bacteremia in 227 patients. We performed LTE in 19 patients (8.2%). Patients with LTE were older (80.7 vs. 72.6 years, p=.014), had more comorbidity (Charlson index 4.6 vs. 2.1, p<.001 and most frequently were severe dependents (57.9% vs. 18.8%, p<.001). We found no association with sex, place of adquisition or clinical expressivity. The commonest clinical focus in patients with LTE was the urinary (42.1%) and there was a predominance of gram positive bacteria (63.2%). The empirical treatment was started early in 73.7% of cases. All patients except one died. Conclusion: LTE is considered in an important number of patients with bacteremia. They usually are older, with more comorbidity and functional dependence, bad functional basal status and important comorbidity. Knowing their differential characteristics allow us to understand this decision

[Limitation of therapeutic effort in patients with bacteremia]. / Limitación del esfuerzo terapéutico en pacientes con bacteriemia.

INTRODUCTION: The limitation of therapeutic effort (LTE) depends on medical, ethical and individual factors. We describe the characteristics of patients with bacteremia in which it was decided to limit the therapeutic effort. METHOD: Prospective study of bacteremia in a community hospital in 2011. We collected information regarding patient variable (age, sex, Barthel index, comorbidities, Charlson Index and exogenous factors) as well as regarding the infectious episode (etiology, focus, place of adquisition, clinical expressivity, LTE and hospital mortality). The group in which LTE was performed was compared to the one that was not. RESULTS: We collected 233 episodes of bacteremia in 227 patients. We performed LTE in 19 patients (8.2%). Patients with LTE were older (80.7 vs. 72.6 years, p=.014), had more comorbidity (Charlson index 4.6 vs. 2.1, p<.001 and most frequently were severe dependents (57.9% vs. 18.8%, p<.001). We found no association with sex, place of adquisition or clinical expressivity. The commonest clinical focus in patients with LTE was the urinary (42.1%) and there was a predominance of gram positive bacteria (63.2%). The empirical treatment was started early in 73.7% of cases. All patients except one died. CONCLUSION: LTE is considered in an important number of patients with bacteremia. They usually are older, with more comorbidity and functional dependence, bad functional basal status and important comorbidity. Knowing their differential characteristics allow us to understand this decision.

Implementación de un sistema de alarmas automático para la detección precoz de los pacientes con sepsis grave / Implementation of an automatic alarms system for early detection of patients with severe sepsis

OBJETIVO: Valorar la utilidad de una herramienta informática integrada en el programa de historia clínica de urgencias en el momento del triaje, para detectar de forma precoz pacientes con sepsis grave, y su posible repercusión en reducir las cifras de mortalidad en los pacientes atendidos. MÉTODO: El estudio constaba de 2 muestras comparativas. La selección de pacientes se realizó de forma retrospectiva en los 2 grupos utilizando los códigos CIE-9 al alta de urgencias y hospitalaria 038.9, 995.91 para la sepsis, 995.92 para sepsis grave y 785.52 para shock séptico. La muestra denominada «alarmas» constaba de los pacientes estudiados tras implantar el sistema de alarmas de sepsis en el sistema informático de urgencias. Se definieron 2 tipos de alarmas, una de gravedad y otra de alerta en función de las constantes vitales alteradas. La muestra histórica, denominada «sin alarmas», constaba de pacientes atendidos en el servicio de urgencias durante el año previo a la implantación del sistema de alarmas. RESULTADOS: El porcentaje de cumplimiento del paquete de tratamiento de la sepsis fue mayor en la muestra de alarmas, comparativamente con la muestra sin alarmas, respectivamente, para los hemocultivos 96,3% frente a 80,9% (p < 0,001), antibiótico menor a 1 h 62,9% frente a 39,3% (p < 0,001), determinación de ácido láctico 91,4% frente a 77,9% (p < 0,001) y la aplicación de volumen adecuado 57,7% frente a 54,3% (p = 0,54). La mortalidad durante el ingreso se redujo en términos absolutos del 25% de la muestra sin alarmas al 13,6% en la muestra con alarmas. La supervivencia a los 30 días fue mayor en la muestra de alarmas (log rank = 0,004). CONCLUSIONES: Un sistema electrónico de identificación de pacientes con sepsis permite una mayor precocidad en la actuación, un cumplimiento mejor de las medidas básicas y por tanto una disminución de la estancia y la mortalidad

OBJECTIVE: The objective of this study was to assess the usefulness of a software tool integrated into the medical electronic history at the time of emergency triage. The aim was the early detection of patients with severe sepsis, and the potential impact of this software tool on reducing the mortality rate in patients treated. METHOD: The study consisted of two comparative samples. Patient selection was performed retrospectively into two groups using ICD-9 codes from the hospital and emergency department discharge reports. The codes were 038.9, 995.9 and 995.92 for sepsis, and 785.52 for severe sepsis and septic shock. The sample called «alarms» consisted of patients studied after implementing the sepsis alarm system in the Emergency Department computer system. There were two types of alarms, a serious one and an alert one depending on the on vital signs defined. The historical sample called «no alarms» consisted of patients seen in the Emergency Department during the year before the introduction of the alarm system. RESULTS: The compliance rate of the sepsis treatment package was higher in the «alarms» sample, compared to the sample without alarms, with blood cultures, 96.3% versus 80.9% (P < .001), antibiotic treatment in less than one hour, 62.9% vs. 39.3% (P < .001), determination of lactic acid, 91.4% vs. 77.9% (P < .001), and applying appropriate volume, 57.7% vs 54.3% (P = .052), respectively. The hospital mortality was reduced in absolute terms from 25% in the sample without alarms to 13.6% in the sample with alarms. Survival at 30 days was higher in the sample with alarms (Log Rank = .004). CONCLUSIONS: There were no studies that evaluated the effectiveness of an alarm system in our literature search. An electronic identification system for patients with sepsis allows acting earlier, better compliance with basic measures, and a reduction in hospital stay and mortality

External validation of the PROFUND index in polypathological patients from internal medicine and acute geriatrics departments in Aragón.

The objective of the study was to validate externally and prospectively the PROFUND index to predict survival of polypathological patients after a year. An observational, prospective and multicenter study was performed. Polypathological patients admitted to an internal medicine or geriatrics department and attended by investigators consecutively between March 1 and June 30, 2011 were included. Data concerning age, gender, comorbidity, Barthel and Lawton-Brody indexes, Pfeiffer questionnaire, socio-familial Gijon scale, delirium, number of drugs and number of admissions during the previous year were gathered for each patient. The PROFUND index was calculated. The follow-up lasted 1 year. A Cox proportional regression model was calculated, and was used to analyze the association of the variables to mortality and C-statistic. 465 polypathological patients, 333 from internal medicine and 132 from geriatrics, were included. One-year mortality is associated with age [hazard ratio (HR) 1.52 95 % CI 1.04-2.12; p = 0.01], presence of neoplasia [HR 2.68 95 % CI 1.71-4.18; p = 0.0001] and dependence for basic activities of daily living [HR 2.34 95 % CI 1.61-3.40; p = 0.0009]. In predicting mortality, the PROFUND index shows good discrimination in patients from internal medicine (C-statistics 0.725 95 % CI 0.670-0.781), but a poor one in those from geriatrics (0.546 95 % CI 0.448-0.644). The PROFUND index is a reliable tool for predicting mortality in internal medicine PP patients.

[Implementation of an automatic alarms system for early detection of patients with severe sepsis]. / Implementación de un sistema de alarmas automático para la detección precoz de los pacientes con sepsis grave.

OBJECTIVE: The objective of this study was to assess the usefulness of a software tool integrated into the medical electronic history at the time of emergency triage. The aim was the early detection of patients with severe sepsis, and the potential impact of this software tool on reducing the mortality rate in patients treated. METHOD: The study consisted of two comparative samples. Patient selection was performed retrospectively into two groups using ICD-9 codes from the hospital and emergency department discharge reports. The codes were 038.9, 995.9 and 995.92 for sepsis, and 785.52 for severe sepsis and septic shock. The sample called «alarms¼ consisted of patients studied after implementing the sepsis alarm system in the Emergency Department computer system. There were two types of alarms, a serious one and an alert one depending on the on vital signs defined. The historical sample called «no alarms¼ consisted of patients seen in the Emergency Department during the year before the introduction of the alarm system. RESULTS: The compliance rate of the sepsis treatment package was higher in the «alarms¼ sample, compared to the sample without alarms, with blood cultures, 96.3% versus 80.9% (P<.001), antibiotic treatment in less than one hour, 62.9% vs. 39.3% (P<.001), determination of lactic acid, 91.4% vs. 77.9% (P<.001), and applying appropriate volume, 57.7% vs 54.3% (P=.052), respectively. The hospital mortality was reduced in absolute terms from 25% in the sample without alarms to 13.6% in the sample with alarms. Survival at 30 days was higher in the sample with alarms (Log Rank=.004). CONCLUSIONS: There were no studies that evaluated the effectiveness of an alarm system in our literature search. An electronic identification system for patients with sepsis allows acting earlier, better compliance with basic measures, and a reduction in hospital stay and mortality.

Factors associated with onset of delirium among internal medicine inpatients in Spain.

BACKGROUND: Delirium increases mortality and length of stay among hospital inpatients. Little is known about the incidence of delirium among inpatients receiving care in internal medicine nursing units in Spain. OBJECTIVES: The aim of this study was to estimate frequency of delirium onset among internal medicine inpatients and identify factors associated with delirium onset using nursing records and administrative databases. METHODS: Retrospective cohort study of 744 patients hospitalized in an internal medicine department in October 2010 and January, May, and October 2011. Data concerning occurrence of delirium, age, gender, living in a nursing residence, Barthel Index of activities of daily living, Norton scale for pressure ulcer risk, intravenous fluid therapy, urinary catheterization, presence of pressure ulcers, major diagnostic category at discharge, length of stay, and mean weight in the diagnosis-related group were gathered for each patient. Backward stepwise logistic regression was used to identify factors associated with onset of delirium. RESULTS: Ninety-seven (13%) patients experienced delirium. Factors associated with delirium were age (OR = 1.03, 95% CI [1.01, 1.06]), Barthel Index (OR = 0.99. 95% CI [0.98, 0.99]), and urinary catheterization (OR = 2.00, 95% CI [1.19, 3.68]). CONCLUSION: Increased age and presence of a urinary catheter were associated with increased onset of delirium, whereas higher levels of independence in activities of daily living were protective.

Melatonin reduces locomotor activity and circulating cortisol in goldfish.

The present study focused on the effects of a subchronic melatonin treatment on locomotor activity and cortisol plasma levels in goldfish. We compared two different administration routes: peripheral (10 microg/g body weight) versus central (1 microg/microl) injections of melatonin for 7 or 4 days, respectively. Daily locomotor activity, including both diurnal and nocturnal activities, food anticipatory activity and circulating cortisol at 11:00 (under 24 h of food deprivation and 17 h postinjection) were significantly reduced after repeated intraperitoneal injections with melatonin for 7 days, but not after intracerebroventricular treatment. Taking in mind the anoretic effect of melatonin in this species, we investigated if such feeding reduction is directly responsible for the reduction in motor activity induced by melatonin treatment. Food restriction (50%) for 10 days did not significantly modify either daily locomotor activity or plasma cortisol levels in goldfish, indicating that the peripheral action of melatonin diminishing locomotor activity in goldfish is not a direct consequence of its anoretic action. In summary, our results indicate that, as previously described in other vertebrate species, melatonin can regulate locomotor activity and cortisol levels in goldfish, suggesting a sedative effect of this hormone in this teleost.

Melatonin reduces body weight in goldfish (Carassius auratus): effects on metabolic resources and some feeding regulators.

The objective of the present study was to analyze the effects of chronic melatonin (10 microg/g body weight) on body weight and the main energetic reserves, particularly hepatic and muscle content of proteins, lipids and glycogen in goldfish. In addition, we studied plasma leptin and ghrelin, and hypothalamic content of neuropeptide Y (NPY) and monoamines after chronic melatonin treatment in order to elucidate a possible interplay between melatonin and these feeding regulators on the body weight regulation in this species. Body weight gain and specific growth rate were reduced (74% and 76%, respectively) after chronic (10 days) intraperitoneal (i.p.) treatment with melatonin. The carbohydrate and lipid metabolism was regulated by melatonin in goldfish, because this indoleamine reduced muscle glycogen stores and increased lipid mobilization. A suppressive trend, but not statistically significant, in circulating ghrelin was observed after chronic treatment with melatonin. Chronic melatonin administration significantly reduced noradrenergic metabolism and increased dihydroxiphenylacetic acid content in the hypothalamus, without significant modifications in the serotoninergic system. Thus, it could be suggested that melatonin may mediate its action on energy balance in fish, at least in part, via interactions with hypothalamic catecholaminergic system. Plasma leptin and hypothalamic NPY remained unaltered after melatonin treatment, suggesting that these feeding regulators may not be involved in the effects of melatonin on energy homeostasis in fish.

Inflamción del tobillo poco habitual en el ámbito deportivo / An inusual form of ankle inflamation in a sporting context

La inflamación articular en el ámbito deportivo no siempre está relacionada con un contexto traumático. En otras ocasiones, podemos estar ante el inicio de un reumatismo inflamatorio o de otras enfermedades con repercusión articular

Inflammation of the joints within sports-related injuries is not always associated with trauma. At times it may occur at the onset of inflammatory rheumatism or other problems which can affect the joint

Adaptive branchial mechanisms in the sturgeon Acipenser naccarii during acclimation to saltwater.

Variations of Na(+)/K(+)-ATPase activity and fatty-acid composition in the gills of the sturgeon Acipenser naccarii subjected to progressive acclimation to full seawater (35 ppt) were determined in relation to the hypo-osmoregulatory capacity of this species in the hyperosmotic medium. Blood samples were taken and gills arches were removed at intermediate salinity levels between 0 and 35 ppt and after 20 days at constant salinity (35 ppt). Plasma osmolality and Na(+)/K(+)-ATPase activity increased significantly with growing environmental salinity. Total saturated fatty acids (SFAs) decreased, while total polyunsaturated fatty acids (PUFAs) increased significantly with increasing salinity due mainly to changes in n-3 PUFAs (20:5n-3 and 22:6n-3). The n-3/n-6 ratio increased significantly during the acclimation process. The results show a direct relationship between salinity, increased gill Na(+)/K(+)-ATPase activity and ultrastructural changes of the gill chloride cells. Changes in the fatty-acid composition in gills of A. naccarii during progressive acclimation to full seawater suggest that variations of gill fatty acids may also have a role in osmoregulatory mechanisms.