Riesgos asociados a la utilización de antimicrobianos en personas mayores

Objetivos: Describir los cambios fisiológicos más relevantes asociados al envejecimiento, las características de las infecciones en estos pacientes así como los efectos adversos más frecuentes e interacciones farmacológicas graves de los antimicrobianos en los mayores. Material y Métodos: Se realizó una revisión bibliográfica sobre los riesgos asociados al uso de antibióticos en ancianos. La información se apoyó en la actualización de la evidencia científica y la información de las Fichas Técnicas de los medicamentos. La búsqueda se limitó a los últimos 11 años, seleccionándose documentos publicados en español, inglés o francés. Se realizó una búsqueda electrónica de fuentes secundarias (revisiones sistemáticas) y una búsqueda manual “ad hoc”, partiendo de la bibliografía recuperada, estudios primarios, informes de agencias de evaluación de medicamentos, guías de práctica clínica y documentos de Sociedades Científicas. Se utilizaron como fuentes de información: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®. Resultados: Se localizaron 321 resultados, tras eliminar los que no cumplían criterios de inclusión 52 documentos, además de las fichas técnicas de todos los antibióticos citados, se incluyeron en la revisión bibliográfica. Conclusiones: Los pacientes mayores adquieren con mayor frecuencia infecciones por patógenos multi-resistentes y sufren más complicaciones graves de las infecciones. Los antibióticos son un grupo de fármacos especialmente sensibles a los cambios fisiológicos producidos por la edad, lo que puede condicionar la respuesta a los estos y exige en muchas ocasiones modificaciones posológicas con el fin de evitar intoxicaciones y/o fracasos terapéuticos. Este trabajo aporta información sobre estos cambios fisiológicos y los riesgos de los antibióticos en las personas mayores, aspectos necesarios para elegir un tratamiento adecuado.Aim: Describe the most important physiological changes associated with aging, the characteristics of infections in these patients and the most common side effects and severe interactions with antimicrobials in older people. Material and methods: We conducted a literature review on the risks associated with the use of antibiotics in the elderly. The information was based on the update of the scientific evidence and information from the drug Sheets. The search was limited to the past 11 years, selected papers published in English, Spanish or French. We performed an electronic search of secondary sources (systematic reviews) and a manual search “ad hoc” basis of the literature retrieved, primary studies, reports of drug evaluation agencies, clinical practice guidelines and documents of Scientific Societies. Information sources: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®. Results: We identified 321 results, after eliminating those who did not meet inclusion criteria 52 papers in addition to the technical specifications of all mentioned antibiotics were included in the literature review. Conclusion: Older patients can acquire infections more frequently multi-resistant pathogens and suffer more serious complications of infections. The antibiotics is a group of drugs sensitive to the physiological changes induced by aging, which may influence the response to these and often requires dosage modifications to avoid poisoning and / or therapeutic failures. This paper provides information on these physiological changes and risks of antibiotics in the elderly, aspects necessary to choose a proper treatment.Este trabajo ha sido realizado con la co- financiación de sendos proyectos de investigación: FISS PI/10/01152 y Consejería de Salud de la Junta de Andalucía PI-0160-2010

Risks associated with the use of antimicrobials in elderly

Objetivos: Describir los cambios fisiológicos más relevantes asociados al envejecimiento, las características de las infecciones en estos pacientes así como los efectos adversos más frecuentes e interacciones farmacológicas graves de los antimicrobianos en los mayores.Material y Métodos: Se realizó una revisión bibliográfica sobre los riesgos asociados al uso de antibióticos en ancianos. La información se apoyó en la actualización de la evidencia científica y la información de las Fichas Técnicas de los medicamentos. La búsqueda se limitó a los últimos 11 años, seleccionándose documentos publicados en español, inglés o francés. Se realizó una búsqueda electrónica de fuentes secundarias (revisiones sistemáticas) y una búsqueda manual “ad hoc”, partiendo de la bibliografía recuperada, estudios primarios, informes de agencias de evaluación de medicamentos, guías de práctica clínica y documentos de Sociedades Científicas. Se utilizaron como fuentes de información: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®.Resultados: Se localizaron 321 resultados, tras eliminar los que no cumplían criterios de inclusión 52 documentos, además de las fichas técnicas de todos los antibióticos citados, se incluyeron en la revisión bibliográfica.Conclusiones: Los pacientes mayores adquieren con mayor frecuencia infecciones por patógenos multi-resistentes y sufren más complicaciones graves de las infecciones. Los antibióticos son un grupo de fármacos especialmente sensibles a los cambios fisiológicos producidos por la edad, lo que puede condicionar la respuesta a los estos y exige en muchas ocasiones modificaciones posológicas con el fin de evitar intoxicaciones y/o fracasos terapéuticos. Este trabajo aporta información sobre estos cambios fisiológicos y los riesgos de los antibióticos en las personas mayores, aspectos necesarios para elegir un tratamiento adecuado.Aim: Describe the most important physiological changes associated with aging, the characteristics of infections in these patients and the most common side effects and severe interactions with antimicrobials in older people.Material and methods: We conducted a literature review on the risks associated with the use of antibiotics in the elderly. The information was based on the update of the scientific evidence and information from the drug Sheets. The search was limited to the past 11 years, selected papers published in English, Spanish or French. We performed an electronic search of secondary sources (systematic reviews) and a manual search “ad hoc” basis of the literature retrieved, primary studies, reports of drug evaluation agencies, clinical practice guidelines and documents of Scientific Societies. Information sources: Pubmed, Embase, Iowa Drug Information Service (IDIS), WinSPIRS 5.00, Up to Date, The Cochrane Library®.Results: We identified 321 results, after eliminating those who did not meet inclusion criteria 52 papers in addition to the technical specifications of all mentioned antibiotics were included in the literature review.Conclusion: Older patients can acquire infections more frequently multi-resistant pathogens and suffer more serious complications of infections. The antibiotics is a group of drugs sensitive to the physiological changes induced by aging, which may influence the response to these and often requires dosage modifications to avoid poisoning and / or therapeutic failures. This paper provides information on these physiological changes and risks of antibiotics in the elderly, aspects necessary to choose a proper treatment

Resultados clínicos iniciales y variables pronósticas en la implementación de un Código Sepsis en un Hospital Universitario de alta complejidad

Objective: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. Methods: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. Results: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p 65 years (OR 5.33, p 3 mmol/L (OR 5,85, p 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). Conclusions: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programsObjetivo. Evaluar el impacto de un programa educativo y organizativo llamado Código Sepsis, en los primeros siete meses de su aplicación en un hospital de alta complejidad. Material y métodos. Se realizó un estudio observacional durante un período consecutivo de siete meses (Febrero 2015-Septiembre 2015). Se analizó la relación con la mortalidad de los factores de riesgo y los valores analíticos usando análisis uni y multivariante. Resultados. Se incluyeron un total de 237 pacientes. La mortalidad intrahospitalaria a los 30 días fue del 24 % y del 27% a los 60 días. La mortalidad de los pacientes ingresados en Unidades de Cuidados Críticos fue del 30%. Se encontraron diferencias significativas entre los pacientes que murieron y los que sobrevivieron en sus valores medios de creatinina (2,30 vs 1,46 mg/dL, p <0,05), ácido láctico (6,10 vs 2,62 mmol/L, p <0,05) y procalcitonina (23,27 vs 12,73 mg/dL, p <0,05). Se encontró una tendencia lineal estadísticamente significativa entre los valores de la escala SOFA y la mortalidad (p <0,05). En el análisis multivariante se identificaron otros factores de riesgo independientes asociados con la muerte: edad > 65 años (OR 5,33, p 3 mmol/L (OR 5,85, p <0,05), creatinina > 1,2 mgr/dL (OR 4,54, p <0,05) y el shock (OR 6,57, P <0,05). Conclusiones. La mortalidad en este estudio se encuentra dentro de los límites de los ensayos clínicos más recientes de sepsis. El estudio ha identificado varios marcadores que podrían ser útiles a nivel local para estimar el riesgo en pacientes sépticos. Estudios como éste son necesarios para hacer mejoras en los programas de Código Sepsi

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defned. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confrmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n=58) or allogeneic stem cell transplantation (allo-SCT) (n=65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p=0.02). Prognostic factors identifed for day 45 overall mortality (OM) by logistic regression multivariate analysis included age>70 years [odds ratio (OR) 2.1, 95% con‑ fdence interval (CI) 1.2-3.8, p=0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p<0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p=0.02) whereas the use of hidroxycloroquine did not show signifcant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P=0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of infammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3–6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin’s lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research. We thank the Spanish Society of Hematology (SEHH) for its support on the study. We sincerely want to thanks the invaluable aid of microbiology services for their commitment in SARS-CoV-2-reactive IgG antibody monitoring in these highly immunosuppressed patients from all participating centers. Finally, we also want to thank the patients, nurses, and study coordinators for their foremost contributions in this study.Peer reviewe

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

A study of CP violation in B-+/- -&gt; DK +/- and B-+/- -&gt; D pi(+/-) decays with D -&gt; (KSK +/-)-K-0 pi(-/+) final states

A first study of CP violation in the decay modes $B^\pm\to [K^0_{\rm S} K^\pm \pi^\mp]_D h^\pm$ and $B^\pm\to [K^0_{\rm S} K^\mp \pi^\pm]_D h^\pm$, where $h$ labels a $K$ or $\pi$ meson and $D$ labels a $D^0$ or $\overline{D}^0$ meson, is performed. The analysis uses the LHCb data set collected in $pp$ collisions, corresponding to an integrated luminosity of 3 fb$^{-1}$. The analysis is sensitive to the CP-violating CKM phase $\gamma$ through seven observables: one charge asymmetry in each of the four modes and three ratios of the charge-integrated yields. The results are consistent with measurements of $\gamma$ using other decay modes

Measurement of Upsilon production in collisions at root s=2.76 TeV

The production of $\Upsilon(1S)$, $\Upsilon(2S)$ and $\Upsilon(3S)$ mesons decaying into the dimuon final state is studied with the LHCb detector using a data sample corresponding to an integrated luminosity of 3.3 $pb^{-1}$ collected in proton-proton collisions at a centre-of-mass energy of $\sqrt{s}=2.76$ TeV. The differential production cross-sections times dimuon branching fractions are measured as functions of the $\Upsilon$ transverse momentum and rapidity, over the ranges $p_{\rm T} Upsilon(1S) X) x B(Upsilon(1S) -> mu+mu-) = 1.111 +/- 0.043 +/- 0.044 nb, sigma(pp -> Upsilon(2S) X) x B(Upsilon(2S) -> mu+mu-) = 0.264 +/- 0.023 +/- 0.011 nb, sigma(pp -> Upsilon(3S) X) x B(Upsilon(3S) -> mu+mu-) = 0.159 +/- 0.020 +/- 0.007 nb, where the first uncertainty is statistical and the second systematic

Successful improvement of antibiotic prescribing at Primary Care in Andalusia following the implementation of an antimicrobial guide through multifaceted interventions: An interrupted time-series analysis.

BACKGROUND:Most effective strategies designed to improve antimicrobial prescribing have multiple approaches. We assessed the impact of the implementation of a rigorous antimicrobial guide and subsequent multifaceted interventions aimed at improving antimicrobial use in Primary Care. METHODS:A quasi-experimental study was designed. Interventions aimed at achieving a good implementation of the guide consisted of the development of electronic decision support tools, local training meetings, regional workshops, conferences, targets for rates of antibiotic prescribing linked to financial incentives, feedback on antibiotic prescribing, and the implementation of a structured educational antimicrobial stewardship program. Interventions started in 2011, and continued until 2018. Outcomes: rates of antibiotics use, calculated into defined daily doses per 1,000 inhabitants-day (DID). An interrupted time-series analysis was conducted. The study ran from January 2004 until December 2018. RESULTS:Overall annual antibiotic prescribing rates showed increasing trends in the pre-intervention period. Interventions were followed by significant changes on trends with a decline over time in antibiotic prescribing. Overall antibiotic rates dropped by 28% in the Aljarafe Area and 22% in Andalusia between 2011 and 2018, at rates of -0.90 DID per year (95%CI:-1.05 to -0.75) in Aljarafe, and -0.78 DID (95%CI:-0.95 to -0.60) in Andalusia. Reductions occurred at the expense of the strong decline of penicillins use (33% in Aljarafe, 25% in Andalusia), and more precisely, amoxicillin clavulanate, whose prescription plummeted by around 50%. Quinolones rates decreased before interventions, and continued to decline following interventions with more pronounced downward trends. Decreasing cephalosporins trends continued to decline, at a lesser extent, following interventions in Andalusia. Trends of macrolides rates went from a downward trend to an upward trend from 2011 to 2018. CONCLUSIONS:Multifaceted interventions following the delivering of a rigorous antimicrobial guide, maintained in long-term, with strong institutional support, could led to sustained reductions in antibiotic prescribing in Primary Care