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OBJECTIVE: In the context of the advancement of antiretroviral therapy and, as the characteristics of people living with HIV progress toward an aging population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12â¯years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term 'interruption' will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilized Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81,5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analyzed to the therapeutic optimization (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV ≥50â¯years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSIONS: Over the 12 years there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimization being the main reason. Integrase inhibitors-based regimens and singletablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV ≥50 years with comorbidities.
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Infecciones por VIH , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , Femenino , Persona de Mediana Edad , Adulto , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Antirretrovirales/uso terapéutico , Anciano , Privación de Tratamiento , Estudios Retrospectivos , Cumplimiento de la MedicaciónRESUMEN
INTRODUCTION: In the context of the advancement of antiretroviral therapy and as the characteristics of people living with HIV progress toward an ageing population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12â¯years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term "discontinuation" is employed synonymously with "interruption". The term "discontinuation" will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilised Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81.5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analysed to the therapeutic optimisation (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV≥50â¯years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSION: Over the 12â¯years, there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimisation being the main reason. Integrase inhibitors-based regimens and single-tablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV≥50â¯years with comorbidities.
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Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Adulto , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Antirretrovirales/uso terapéutico , Antirretrovirales/administración & dosificación , Anciano , Cumplimiento de la Medicación/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
Background and objectives: Acute kidney injury (AKI) is common among hospitalized patients with COVID-19 and associated with worse prognosis. The Spanish Society of Nephrology created the AKI-COVID Registry to characterize the population admitted for COVID-19 that developed AKI in Spanish hospitals. The need of renal replacement therapy (RRT) therapeutic modalities, and mortality in these patients were assessed. Material and method: In a retrospective study, we analyzed data from the AKI-COVID Registry, which included patients hospitalized in 30 Spanish hospitals from May 2020 to November 2021. Clinical and demographic variables, factors related to the severity of COVID-19 and AKI, and survival data were recorded. A multivariate regression analysis was performed to study factors related to RRT and mortality. Results: Data from 730 patients were recorded. A total of 71.9% were men, with a mean age of 70 years (60-78), 70.1% were hypertensive, 32.9% diabetic, 33.3% with cardiovascular disease and 23.9% had some degree of chronic kidney disease (CKD). Pneumonia was diagnosed in 94.6%, requiring ventilatory support in 54.2% and admission to the ICU in 44.1% of cases.The median time from the onset of COVID-19 symptoms to the appearance of AKI (37.1% KDIGO I, 18.3% KDIGO II, 44.6% KDIGO III) was 6 days (4-10). A total of 235 (33.9%) patients required RRT: 155 patients with continuous renal replacement therapy, 89 alternate-day dialysis, 36 daily dialysis, 24 extended hemodialysis and 17 patients with hemodiafiltration. Smoking habit (OR 3.41), ventilatory support (OR 20.2), maximum creatinine value (OR 2.41) and time to AKI onset (OR 1.13) were predictors of the need for RRT; age was a protective factor (0.95). The group without RRT was characterized by older age, less severe AKI, shorter kidney injury onset and recovery time (p < 0.05). 38.6% of patients died during hospitalization; serious AKI and RRT were more frequent in the death group. In the multivariate analysis, age (OR 1.03), previous chronic kidney disease (OR 2.21), development of pneumonia (OR 2.89), ventilatory support (OR 3.34) and RRT (OR 2.28) were predictors of mortality while chronic treatment with ARBs was identified as a protective factor (OR 0.55). Conclusions: Patients with AKI during hospitalization for COVID-19 had a high mean age, comorbidities and severe infection. We defined two different clinical patterns: an AKI of early onset, in older patients that resolves in a few days without the need for RRT; and another more severe pattern, with greater need for RRT, and late onset, which was related to greater severity of the infectious disease. The severity of the infection, age and the presence of CKD prior to admission were identified as risk factors for mortality in these patients. In addition chronic treatment with ARBs was identified as a protective factor for mortality.
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INTRODUCTION: Hypogammaglobulinemia after front-line immunochemotherapy for follicular lymphoma is a poorly studied adverse event that could be related to the appearance of severe and/or recurrent non-neutropenic infections which could affect the quality of life of the patients, even motivating a need of long-term replacement therapy with human immunoglobulins. METHODS: Observational, retrospective study aiming to estimate the incidence of hypogammaglobulinemia, as well as its severity and clinical consequences, and to explore possible predictive factors for its development. Specific immunoglobulin deficiencies were also studied. RESULTS: 76.5% of patients had hypogammaglobulinemia during or after front-line treatment, mostly grade 1-2; with 38.8% patients who developed clinically relevant infections and 20% patients requiring human immunoglobulins replacement therapy. A high-risk FLIPI score was identified as a risk factor for hypogammaglobulinemia (ods ratio: 4.51; 95% confidence interval: 1.29-15.68; p < 0.001) and basal gamma globulin level as a protective factor (odds ratio: 0.92; 95% confidence interval: 0.988-0.996; p = 0.018). Any type of immunochemotherapy regimen was associated with different risks of hypogammaglobulinemia in our study. CONCLUSIONS: Hypogammaglobulinemia appears in a high percentage of patients with follicular lymphoma in a real-world population, identifying a high-risk FLIPI score as a risk factor for its development and basal gamma globulins as a protective factor.
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Agammaglobulinemia , Linfoma Folicular , Humanos , Agammaglobulinemia/inducido químicamente , Agammaglobulinemia/epidemiología , Agammaglobulinemia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Linfoma Folicular/tratamiento farmacológico , Calidad de Vida , Estudios RetrospectivosRESUMEN
Stenotrophomonas maltophilia (S. maltophilia), an important pathogen in immuno-compromised patients, has recently gained attention in patients admitted in intensive care units (ICU). We sought to investigate clinical features of infections caused by S. maltophilia in ICU patients and identify risk factors for mortality. We conducted a retrospective study in two multivalent non-COVID-19 ICUs of tertiary-teaching hospitals in Greece and Spain, including patients with isolated S. maltophilia from at least one clinical specimen along with clinical signs of infection. A total of 103 patients (66% male) were analyzed. Median age was 65.5 (54-73.3) years and mean APACHE II and SOFA scores upon ICU admission were 18.36 (±7.22) and 18.17 (±6.95), respectively. Pneumonia was the predominant clinical syndrome (72.8%), while 22% of cases were among hemato/oncology patients. Crude 28-day mortality rate was 54.8%, even though, 14-day clinical and microbiological response was 96%. Age, APACHE II on ICU admission, hemato-oncologic disease, and multi-organ failure were initially identified as potential predictors of mortality. In the multivariable analysis, only increasing age and hemato-oncologic disease were shown to be independent risk factors for 28-day mortality. High all-cause mortality was observed in critically ill patients with predominantly respiratory infections by S. maltophilia, despite initial clinical and laboratory response after targeted treatment. The study elucidates a potentially worrisome emerging pathogen in the ICU.
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INTRODUCTION: The high pharmacotherapeutic complexity, drug interactions and lack of adherence to concomitant medication are circumstances with negative consequences in the clinical evolution of patients with HIV infection. The 3-HIT phenomenon refers to the simultaneous occurrence of these situations. The objective of the study is to determine the prevalence of the phenomenon 3-HIT in the polymedicated HIV population as well as to determine factors related to its occurrence. METHODS: Observational, retrospective and single-center study that included all elderly patients on active antiretroviral treatment in pharmacotherapeutic follow-up between January and March 2020. A logistic regression model was carried out to evaluate the factors associated with the occurrence of the 3-HIT concept with the variables significantly associated with this phenomenon and those considered clinically relevant. RESULTS: 428 patients were included, registering a prevalence of polypharmacy in 25.9% of the study sample. The 3-HIT phenomenon was detected in 6.3% of the patients. For each concomitant drug prescribed the risk of developing the phenomenon 3-HIT increases 1.5 times. CONCLUSION: Prevalence of the phenomenon 3-HIT is high in HIV patients with polymedication. A change in the pharmaceutical care model to a multidimensional setting is essential, together with pharmacotherapeutic optimization strategies to improve patient health outcomes.
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Infecciones por VIH , Humanos , Anciano , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Polifarmacia , Estudios Retrospectivos , Antirretrovirales/uso terapéutico , Interacciones FarmacológicasRESUMEN
BACKGROUND: There is a high prevalence of multimorbidity and polypharmacy among older people, especially in people living with HIV (PLWH) with an increased life expectancy due to effective antiretroviral therapy (ART). Consequently, there is a higher risk of potentially inappropriate medications (PIM), potential drug-drug interactions (DI), and problems of non-adherence to treatment (NAC) in older PLWH. PIMDINAC criteria (potentially inappropriate medications (PIM), drug-drug interactions (DI), and non-adherence to treatment (NAC)) purport to jointly analyse these problems. The purpose of the study was to compare the prevalence of PIMDINAC criteria among elderly PLWH and non-infected patients with chronic diseases, and to determine whether HIV infection constitutes a predictor of the presence of PIMDINAC criteria, totally or partially. METHODS: A cross sectional study was conducted between February and June 2020. HIV positive patients aged ≥65 years were compared with a group of patients with chronic conditions attending the outpatient hospital pharmacy service. RESULTS: The study involved 140 patients: 47 HIV positive and 93 HIV negative, and mean age was 69 versus 73 years, respectively (p=0.062). The prevalence of total PIMDINAC criteria was similar between the groups (12.5 vs 10.8%, p=0.505). In relation to inappropriate medication, no differences were observed between groups (48.9 vs 55.9%, p=0434). Drug-drug interactions were higher in patients with chronic conditions (52.7 vs 25.5%, p=0.002) compared with non-adherence, which was higher in people with HIV (22.6 vs 65.6%, p<0.001). No differences in polypharmacy (≥6 and 11 drugs) rates were observed. CONCLUSIONS: PIMDINAC criteria were highly prevalent in older PLWH, similar to non-infected patients. HIV infection in older people was associated with a lower risk of drug-drug interactions. However, non-adherence was a risk factor compared with age matched controls. Deprescribing strategies, including a capability-motivation-opportunity pharmaceutical care model based intervention should be implemented in clinical routines.
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INTRODUCTION: Aging of people living with HIV could be related to potentially inappropiate medication prescriptions, drugs interactions and lack of drugs adherence. PIMDINAC criteria seek to jointly analyze these problems. The objective of this study is to determine the prevalence of PIMDINAC criteria in an elderly HIV population. METHODS: Observational, cross-sectional, multicenter study that included patients older than 65 years in pharmacotherapeutic follow-up between February-April 2020. The main endpoint was the percentage of PIMDINAC criteria identified in the study population. RESULTS: Forty-seven patientes were included, identifying total PIMDINAC in 12.5%. Non-adherence to concomitant treatment was detected in 65.6% of patients, potentially inappropiate medication in 48.9% and drugs interactions in 25.2%. The number of concomitant drugs and polypharmacy were associated with a higher appearance of PIMDINAC criteria. CONCLUSION: The prevalence of PIMDINAC criteria in elderly HIV patients is high.
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Infecciones por VIH , Lista de Medicamentos Potencialmente Inapropiados , Anciano , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Prescripción Inadecuada , PrevalenciaRESUMEN
BACKGROUND: Eribulin's clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. PATIENTS AND METHODS: This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. RESULTS: A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1-11.4) and 2.8 months (95% confidence interval: 2.5-3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3-4.5) versus triple negative: 2.0 (95%confidence interval: 1.7-2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6-12.5 vs. 4.8 months, 95% confidence interval: 3.4-6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1-16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8-5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. CONCLUSION: Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.
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Antineoplásicos , Neoplasias de la Mama , Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Capecitabina/efectos adversos , Supervivencia sin Enfermedad , Femenino , Furanos/efectos adversos , Humanos , Cetonas , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Our objective was to assess the impact on mortality, antibacterial therapy duration, and length of stay of using PCT to guide antibiotic cessation in critically ill patients with sepsis or septic shock. RESEARCH DESIGN AND METHODS: A systematic literature search was performed in PubMed, Embase, ISI Web of Knowledge, BioMed Central, ScienceDirect and the Cochrane Central Register of Controlled Trials, of clinical trials published in English before December 31, 2019. Eligible studies should be carried out in adults at ICU with sepsis, comparing the PCT-guided antimicrobial therapy with standard of care. A random effects model was used. RESULTS: Twelve studies were eligible with a total of 4292 patients included. The combined relative risk for 28-day mortality was 0.89 (95% CI: 0.79; 0.99), for the duration of antimicrobial therapy was -1.98 days (95% CI: -2.76, -1.21) and for ICU- length of stay was-1.21 days (95% CI: -4.16, 1.74). CONCLUSIONS: In critically ill adults with sepsis, a procalcitonin-guided strategy is associated with a significant shorter duration of antimicrobial therapy. This reduction was associated with a significant decrease in mortality although the length of ICU stay was not affected.
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Polipéptido alfa Relacionado con Calcitonina , Sepsis , Adulto , Algoritmos , Antibacterianos , Biomarcadores , Enfermedad Crítica/terapia , Humanos , Unidades de Cuidados Intensivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/tratamiento farmacológicoRESUMEN
Primary aim was to assess prevalence and severity of potential and real drug-drug interactions (DDIs) among therapies for COVID-19 and concomitant medications in hospitalized patients with confirmed SARS-CoV-2 infection. The secondary aim was to analyze factors associated with rDDIs. An observational single center cohort study conducted at a tertiary hospital in Spain from March 1st to April 30th. rDDIs refer to interaction with concomitant drugs prescribed during hospital stay whereas potential DDIs (pDDIs) refer to those with domiciliary medication. DDIs checked with The University of Liverpool resource. Concomitant medications were categorized according to the Anatomical Therapeutic Chemical classification system. Binomial logistic regression was carried out to identify factors associated with rDDIs. A total of 174 patients were analyzed. DDIs were detected in 152 patients (87.4%) with a total of 417 rDDIs between COVID19-related drugs and involved hospital concomitant medication (60 different drugs) while pDDIs were detected in 105 patients (72.9%) with a total of 553 pDDIs. From all 417 rDDIs, 43.2% (n = 180) were associated with lopinavir/ritonavir and 52.9% (n = 221) with hydroxychloroquine, both of them the most prescribed (106 and 165 patients, respectively). The main mechanism of interaction observed was QTc prolongation. Clinically relevant rDDIs were identified among 81.1% (n = 338) ('potential interactions') and 14.6% (n = 61) (contraindicated) of the patients. Charlson index (OR 1.34, 95% IC 1.02-1.76) and number of drugs prescribed during admission (OR 1.42, 95% IC 1.12-1.81) were independently associated with rDDIs. Prevalence of patients with real and pDDIs was high, especially those clinically relevant. Both comorbidities and polypharmacy were found as risk factors independently associated with DDIs development.
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Tratamiento Farmacológico de COVID-19 , Interacciones Farmacológicas , Hidroxicloroquina/química , Lopinavir/química , Ritonavir/química , Anciano , Analgésicos/química , Analgésicos/uso terapéutico , COVID-19/patología , COVID-19/virología , Enfermedades Cardiovasculares/tratamiento farmacológico , Estudios de Cohortes , Diuréticos/química , Diuréticos/uso terapéutico , Femenino , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Polifarmacia , Factores de Riesgo , Ritonavir/uso terapéutico , SARS-CoV-2/aislamiento & purificación , Índice de Severidad de la Enfermedad , EspañaRESUMEN
INTRODUCTION: In recent decades, HIV has become a chronic disease with which the HIV specialist pharmacist plays a fundamental role. The traditional pharmaceutical care model followed to date relied excessively on the medication, obviating the uniqueness of each patient. The purpose of this study was to determine the influence and acceptance of a Capacity-Motivation-Opportunity (CMO)-based structured pharmaceutical care (PC) intervention in a multidisciplinary team for improving healthcare results. METHODS: Prospective single-centre study of a structured health intervention with patients living with HIV who attended hospital between January 2017 and June 2018 for any cause. Pharmacotherapeutic follow-up was applied according to the CMO PC model based on three key elements, namely stratification, motivational interview and new technologies. To assess differences in the variables collected before and after the intervention, Student's t-test or Wilcoxon test, and McNemar's test were used for quantitative and dichotomous variables, respectively. RESULTS: A total of 349 patients were included, 76.1% of which were men. The acceptance of pharmacist intervention by both doctors and patients was high [336 (97.7%) and 321 (93.3%)] and the adherence rate to antiretroviral therapy before intervention was lower than that observed afterwards (85.6%±33.7% vs 96.4%±17.7%; p<0.001). No differences were found between median viral load pre- versus post-intervention [1175 (62.75-26 050) copies/mL vs 274 (76.75-5542) copies/mL], although the undetectability rate was recorded as higher after intervention compared with the previous period [294 (85.5%) vs 274 (79.7%); p<0.001]. CONCLUSIONS: Our results could help HIV pharmacy clinic specialists to recognise high-risk patients and to develop personalised follow-up care, thereby ensuring good adherence and response to treatments.
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Infecciones por VIH , Servicios Farmacéuticos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hospitales , Humanos , Masculino , Cumplimiento de la Medicación , Motivación , Farmacéuticos , Estudios Prospectivos , España/epidemiologíaRESUMEN
INTRODUCTION: Aging of people living with HIV could be related to potentially inappropriate medication prescriptions, drugs interactions and lack of drugs adherence. PIMDINAC criteria seek to jointly analyze these problems. The objective of this study is to determine the prevalence of PIMDINAC criteria in an elderly HIV population. METHODS: Observational, cross-sectional, multicenter study that included patients older than 65 years in pharmacotherapeutic follow-up between February-April 2020. The main endpoint was the percentage of PIMDINAC criteria identified in the study population. RESULTS: Forty-seven patientes were included, identifying total PIMDINAC in 12.5%. Non-adherence to concomitant treatment was detected in 65.6% of patients, potentially inappropriate medication in 48.9% and drugs interactions in 25.2%. The number of concomitant drugs and polypharmacy were associated with a higher appearance of PIMDINAC criteria. CONCLUSION: The prevalence of PIMDINAC criteria in elderly HIV patients is high.
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The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.
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Antivirales/efectos adversos , Tratamiento Farmacológico de COVID-19 , Lopinavir/efectos adversos , Lopinavir/uso terapéutico , Inhibidores de Proteasas/efectos adversos , Ritonavir/efectos adversos , Ritonavir/uso terapéutico , Anciano , Antivirales/uso terapéutico , Estudios Transversales , Combinación de Medicamentos , Interacciones Farmacológicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Proteasas/uso terapéutico , SARS-CoV-2/efectos de los fármacos , EspañaRESUMEN
INTRODUCTION: Inflammasomes are recognized as key components of the innate immune response in sepsis. We aimed to describe the transcriptional expression of nucleotide-binding domain, leucine-rich repeat-containing receptor, pyrin domain-containing-3 (NLRP3), and serum interleukin-1ß (IL-1 ß) in critically ill patients, their changes over the first week and their prognostic value in septic patients. METHODS: Prospective study including patients with sepsis based on Sepsis-3 definitions and a control group of critically ill patients without sepsis. We measured the circulating levels of IL-1ß as well as the transcriptional expression of NLRP3 at admission and on days 3 and 7. Caspase-1 and caspase-3 activation was analyzed in a matched cohort of patients with septic shock (four dead and four survivors). RESULTS: Fifty-five septic patients and 11 non-septic patients were studied. Levels on day 0 and 3 of IL-1 ß and NLRP3 inflammasome expression were significantly higher in patients with sepsis than in controls. NLRP3 was significantly higher in septic patients who survived at day 7 without significant difference between survivors and non-survivors at baseline and on day 3. In survivors, an increased caspase-1 protein expression with reduced expression caspase-3 was observed with the opposite pattern in those who died. CONCLUSIONS: NLRP3 is activated in critically ill patients but this up-regulation is more intense in patients with sepsis. In sepsis, a sustained NLRP3 activation during the first week is protective and sepsis. An increased caspase-1 protein expression with reduced expression caspase-3 is the pattern observed in septic shock patients who survive.
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Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Anciano , Caspasa 1/metabolismo , Caspasa 3/metabolismo , Enfermedad Crítica , Humanos , Interleucina-1beta/metabolismo , Persona de Mediana Edad , Estudios Prospectivos , Reacción en Cadena en Tiempo Real de la Polimerasa , Sepsis/metabolismo , Sepsis/patologíaRESUMEN
BACKGROUND: Graft-versus-host disease (GvHD) is the main life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty to 80% of GvHD patients do not respond to first-line treatment and a second-line treatment is not universally established. Based on their immunomodulatory properties, mesenchymal stromal cells (MSC) have been proposed for the prevention and the treatment of GvHD in patients undergoing HSCT. Unfortunately, previous studies reported conflicting results regarding the prophylactic and therapeutic effects of MSC for GvHD. Consequently, we carried out a meta-analysis to clarify whether MSC administration can improve the dismal outcome of these patients. METHODS: We carried out a systematic review and selected studies (2004-2019) reporting data about the administration of allogeneic MSC for the prevention (n = 654 patients) or treatment of acute (n = 943 patients) or chronic (n = 76 patients) GvHD after HSCT. Our primary outcome was overall survival at the last follow-up. The secondary outcomes were the response and development of GvHD. Subgroup analyses included age, MSC dose, first infusion day after HSCT, number of organs and organ-specific involvement, acute GvHD grade (I-IV), and chronic GvHD grade (limited or extensive). RESULTS: Patients infused with MSC for GvHD prophylaxis showed a 17% increased overall survival (95% CI, 1.02-1.33) and a reduced incidence of acute GvHD grade IV (RR = 0.22; 95% CI, 0.06-0.81) and chronic GvHD (RR = 0.64; 95% CI, 0.47-0.88) compared with controls. Overall survival of acute GvHD patients (0.50; 95% CI, 0.41-0.59) was positively correlated with MSC dose (P = 0.0214). The overall response was achieved in 67% (95% CI, 0.61-0.74) and was complete in 39% (95% CI, 0.31-0.48) of acute patients. Organ-specific response was higher for the skin. Twenty-two percent (95% CI, 0.16-0.29) of acute patients infused with MSC developed chronic GvHD. Sixty-four percent (95% CI, 0.47-0.80) of chronic patients infused with MSC survived; the overall response was 66% (95% CI, 0.55-0.76) and was complete in 23% (95% CI 0.12-0.34) of patients. CONCLUSIONS: Our meta-analysis indicates that allogeneic MSC could be instrumental for the prophylaxis and treatment of GvHD. Future trials should investigate the effect of the administration of MSC as an adjuvant therapy for the treatment of patients with GvHD from the onset of the disease.
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Enfermedad Injerto contra Huésped/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas/metabolismo , Acondicionamiento Pretrasplante/efectos adversos , Femenino , Humanos , MasculinoRESUMEN
PURPOSE: Information about immunocompromised patients infected with influenza A (H1N1) virus and requiring admission to the ICU is lacking. Our objective was to know the clinical characteristics of these patients and to identify treatment-related variables associated with mortality. MATERIAL AND METHODS: A prospective multicenter observational cohort study was based on data from a Spanish registry (2009-2015) collected by 148 Spanish ICUs. All patients admitted to the ICU with the diagnosis of influenza A (H1N1) virus infection were included. Immunosuppression was clearly defined. Factors associated with mortality in immunocompromised patients were assessed by conventional logistic regression analysis and by a propensity score (PS) adjusted-multivariable analysis. RESULTS: Of 1899 patients with influenza A (H1N1) infection, 238 (12.5%) were classified as immunocompromised. Mortality was significantly higher in immunosuppressed patients. Four variables independently associated with mortality were identified: SOFA score, need of vasopressor, use of corticosteroids, and acute renal failure, AKIN 3 stage. In the PS-adjusted model, corticosteroid therapy remained as an independent factor associated with increased mortality (OR 2.25;95%CI, 1.15-4.38;pâ¯=â¯0.017). In the subgroup of hematological patients (nâ¯=â¯141), corticosteroid therapy was also associated with increased mortality (OR 3.12; 95%CI, 1.32-7.41; pâ¯=â¯0.010). CONCLUSION: Immunocompromised individuals with influenza A (H1N1) admitted to the ICU have a poor outcome. In this population, the use of corticosteroids is strongly discouraged.
Asunto(s)
Huésped Inmunocomprometido , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/mortalidad , Adulto , Anciano , Estudios de Cohortes , Femenino , Hospitalización , Humanos , Unidades de Cuidados Intensivos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , EspañaRESUMEN
INTRODUCTION: Our objectives were to describe the incidence, clinical characteristics, and risk factors for Clostridium difficile infection (CDI) in critically ill patients and to determine C. difficile PCR-ribotypes. METHODS: Prospective, observational study in 26 Spanish ICUs. Patients with diarrhea meeting ESCMID criteria for CDI were included. Molecular characterization of isolates was performed using PCR ribotyping. RESULTS: Of 4258 patients admitted to the ICUs, 190 (4.5%) developed diarrhea. Only 16 patients (8.4%) were diagnosed with CDI. Ribotype 078/126 (25.0%) was the most frequently identified. The mortality rate was similar in patients with ICD compared to patients with diarrhea not caused by C. difficile (p=0.115). Chronic renal insufficiency was identified as the only factor independently associated with the development of CDI (OR 5.87, 95% CI 1.24-27.83; p=0.026). CONCLUSIONS: The incidence of CDI in Spanish ICUs is low. Only chronic renal insufficiency was observed to be a risk factor for CDI development.
Asunto(s)
Infecciones por Clostridium/epidemiología , Anciano , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Infecciones por Clostridium/diagnóstico , Enfermedad Crítica , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ribotipificación , Factores de Riesgo , España/epidemiologíaRESUMEN
BACKGROUND: The global crisis of bacterial resistance urges the scientific community to implement intervention programs in healthcare facilities to promote an appropriate use of antibiotics. However, the clinical benefits or the impact on resistance of these interventions has not been definitively proved. METHODS: We designed a quasi-experimental intervention study with an interrupted time-series analysis. A multidisciplinary team conducted a multifaceted educational intervention in our tertiary-care hospital over a 5-year period. The main activity of the program consisted of peer-to-peer educational interviews between counselors and prescribers from all departments to reinforce the principles of the proper use of antibiotics. We assessed antibiotic consumption, incidence density of Candida and multidrug-resistant (MDR) bacteria bloodstream infections (BSIs) and their crude death rate per 1000 occupied bed days (OBDs). RESULTS: A quick and intense reduction in antibiotic consumption occurred 6 months after the implementation of the intervention (change in level, -216.8 defined daily doses per 1000 OBDs; 95% confidence interval, -347.5 to -86.1), and was sustained during subsequent years (average reduction, -19,9%). In addition, the increasing trend observed in the preintervention period for the incidence density of candidemia and MDR BSI (+0.018 cases per 1000 OBDs per quarter; 95% confidence interval, -.003 to .039) reverted toward a decreasing trend of -0.130 per quarter (change in slope, -0.029; -.051 to -.008), and so did the mortality rate (change in slope, -0.015; -.021 to -.008). CONCLUSIONS: This education-based antimicrobial stewardship program was effective in decreasing the incidence and mortality rate of hospital-acquired candidemia and MDR BSI through sustained reduction in antibiotic use.