RESUMEN
Importance: Although overall rates of opioid use have been plateauing, coprescriptions of benzodiazepines and opioids have increased greatly in recent years. It is unknown whether this combination is an independent risk factor for all-cause mortality as opposed to being more frequently used by persons with a baseline elevated risk of death. Objective: To evaluate whether benzodiazepine use, with or without opioid use, is associated with increased all-cause mortality relative to the use of low-risk antidepressants. Design, Setting, and Participants: This retrospective cohort study used a large, nationally representative US data set (the National Health and Nutrition Examination Surveys [NHANES]) from 1999 to 2015. Eight cycles of NHANES data were used, spanning 37â¯610 person-years of follow-up time among 5212 individuals. Statistical analysis was performed from August 24, 2019, through May 23, 2020. Exposures: The primary exposure variable was benzodiazepine and opioid coprescriptions. Individuals taking selective serotonin reuptake inhibitors (SSRIs) served as an active comparator reference group. Main Outcomes and Measures: All-cause mortality was obtained via linkage of NHANES to the National Death Index. Propensity scores were calculated from covariates associated with sociodemographic factors, comorbidities, and medication use for more than 1000 prescription types. Propensity score-weighted mortality hazards were calculated from Cox proportional hazards regression models. Results: Of 5212 participants aged 20 years or older (1993 men [38.2%]; mean [SD] age, 54.8 [16.9] years) followed up for a median of 6.7 years (range, 0.2-16.8 years), 101 deaths (33.0 per 1000 person-years) occurred among those receiving cotreatment, 236 deaths (26.5 per 1000 person-years) occurred among those receiving only benzodiazepines, and 227 deaths (20.2 per 1000 person-years) occurred among SSRI recipients taking neither opioids nor benzodiazepines. After propensity score weighting, a significant increase in all-cause mortality was associated with benzodiazepine and opioid cotreatment (hazard ratio, 2.04 [95% CI, 1.65-2.52]) and benzodiazepines without opioids (hazard ratio, 1.60 [95% CI, 1.33-1.92]). Subgroup analyses revealed an increased risk of mortality for individuals receiving cotreatment who were 65 years or younger but not for those older than 65 years; similar findings were observed for those receiving benzodiazepines without opioids. Conclusions and Relevance: This study found a significant increase in all-cause mortality associated with benzodiazepine use with or without opioid use in comparison with SSRI use. Benzodiazepine and opioid cotreatment, in particular, was associated with a 2-fold increase in all-cause mortality even after taking into account medical comorbidities and polypharmacy burden.
Asunto(s)
Analgésicos Opioides/uso terapéutico , Benzodiazepinas/uso terapéutico , Enfermedad Crónica , Quimioterapia Combinada , Trastornos Mentales , Enfermedad Crónica/epidemiología , Enfermedad Crónica/terapia , Estudios de Cohortes , Comorbilidad , Quimioterapia Combinada/mortalidad , Quimioterapia Combinada/estadística & datos numéricos , Femenino , Humanos , Masculino , Trastornos Mentales/tratamiento farmacológico , Trastornos Mentales/epidemiología , Persona de Mediana Edad , Mortalidad , Pautas de la Práctica en Medicina/tendencias , Medicamentos bajo Prescripción/uso terapéutico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.
Asunto(s)
Infecciones por Coronavirus , Interacciones Farmacológicas , Quimioterapia Combinada , Hidroxicloroquina , Metformina , Pandemias , Neumonía Viral , Adulto , Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Betacoronavirus/aislamiento & purificación , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/mortalidad , Femenino , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/uso terapéutico , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/uso terapéutico , Masculino , Metformina/farmacocinética , Metformina/uso terapéutico , Persona de Mediana Edad , Farmacovigilancia , Neumonía Viral/diagnóstico , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología , SARS-CoV-2RESUMEN
OBJECTIVE: Antipsychotic drugs are known to increase mortality among patients with dementia. Many patients receive concomitant treatment with other psychotropic agents. The aim of this retrospective cohort study was to investigate the impact of benzodiazepines and antidepressants on the risk of death in patients with dementia initiating antipsychotic drug treatment. METHODS: Nationwide registry data on all incident dementia cases among individuals aged 65 years and older in Denmark between 2009 and 2013 for which antipsychotic treatment was initiated were used. The 180-day mortality was evaluated by crude and adjusted hazard ratios (HRs, including adjustment for somatic and psychiatric comorbidity, other prescription drugs, nursing home residency, and time since diagnosis), comparing periods of antipsychotic treatment with periods of concomitant treatment with benzodiazepines or antidepressants. RESULTS: Among 41,494 incident dementia cases, antipsychotic treatment was initiated for 10,291 (24.8%). After 3,140 people were excluded due to recent antipsychotic drug use or hospitalization, 7,151 people were included in the analysis. The total follow-up time during current antipsychotic treatment was 1,146 person-years, and 831 died during antipsychotic treatment. Compared with antipsychotic treatment alone, the risk of death increased during antipsychotic treatment in combination with benzodiazepines (adjusted HR = 2.19; 95% CI, 1.83-2.63), while there was a decreased risk of death during antipsychotic treatment in combination with antidepressants (adjusted HR = 0.61; 95% CI, 0.50-0.74). CONCLUSIONS: The diverse impact of concomitant use of benzodiazepines and antidepressants on mortality may be due to a direct drug-related effect. Alternatively, the findings could reflect differential mortality associated with different indications for therapy. Although the results cannot prove causality, and there may be residual confounding, clinicians should be cautious when considering the combination of antipsychotics and benzodiazepines in patients with dementia.
Asunto(s)
Antidepresivos/efectos adversos , Antipsicóticos/efectos adversos , Benzodiazepinas/efectos adversos , Demencia/mortalidad , Quimioterapia Combinada/mortalidad , Sistema de Registros , Anciano , Anciano de 80 o más Años , Demencia/tratamiento farmacológico , Dinamarca/epidemiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Tigecycline (TGC) and cefoperazone/sulbactam (CPS) both have been shown good in vitro activity against carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. We aim to compare the efficacy of TGC versus CPS for CRAB infections. We conducted a retrospective cohort study of patients with CRAB at a single center in China from 2013 to 2015. Outcomes comprised in-hospital mortality, clinical and microbiological response. The method of inverse probability of treatment weighting and multivariable logistic regression analysis incorporated with propensity score were employed to estimate the effect of treatment groups. There were 130 subjects included in our study. The patients in TGC, CPS and TGC plus CPS combination group were 42, 66, and 22, respectively. After adjustment, in-hospital mortality was lower in CPS group than TGC group (weighted OR 0.173; 95% CI 0.06-0.497; P=0.001) but without differences in clinical success and microbiological eradication (P>0.05). TGC monotherapy had a similar outcome with TGC plus CPS combination group. This is the first study comparing the efficacy of tigecycline and cefoperazone/sulbactam for CRAB infections. Cefoperazone/sulbactam appears to be more efficacious than tigecycline during treatment.
Asunto(s)
Infecciones por Acinetobacter/tratamiento farmacológico , Cefoperazona/uso terapéutico , Sulbactam/uso terapéutico , Tigeciclina/uso terapéutico , Infecciones por Acinetobacter/mortalidad , Acinetobacter baumannii/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Cefoperazona/farmacología , Farmacorresistencia Bacteriana , Quimioterapia Combinada/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pentostatina/análogos & derivados , Estudios Retrospectivos , Sulbactam/farmacología , Tigeciclina/farmacologíaRESUMEN
BACKGROUND: Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. METHODS AND FINDINGS: We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ≥ 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. CONCLUSIONS: These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.
Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/mortalidad , Terapia Respiratoria/métodos , Administración por Inhalación , Adulto , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Broncodilatadores/uso terapéutico , Progresión de la Enfermedad , Quimioterapia Combinada/métodos , Quimioterapia Combinada/mortalidad , Humanos , Persona de Mediana Edad , Metaanálisis en Red , Oportunidad Relativa , Calidad de Vida , Terapia Respiratoria/mortalidadRESUMEN
The PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Antiplatelet Therapy (PRECISE-DAPT) score has been validated to predict bleeding complications in patients undergoing stent implantation and dual antiplatelet therapy. This score does not include the platelet count (PC), which has been shown to be an independent marker of mortality in patients with acute coronary syndrome (ACS). We assessed the role of the PRECISE-DAPT score calculated on admission for mortality risk prediction and evaluated whether the predictive accuracy of this score improved by adding the PC. In a retrospective cohort study of 1000 patients with ACS, after adjustment for relevant covariates, a PRECISE-DAPT score ≥25 was independently associated with mortality (hazard ratio [HR]: 7.91; 95% confidence interval [CI]: 4.37-14.30). When this score was combined with PC, compared to patients with PRECISE-DAPT <25 and PC ≥150 × 109/L, the adjusted HR was 7.2 (95% CI 2.4-21.6) for those with PRECISE-DAPT <25 and PC <150 × 109/L; 10.7 (95% CI: 5.2-21.9) for those with PRECISE-DAPT ≥25 and PC ≥150 × 109/L; and 17.9 (95% CI 7.0-45.4) for those with PRECISE-DAPT ≥25 and PC <150 × 109/L. Selecting thresholds for high-risk designation, the PRECISE-DAPT score integrated with PC had a higher prediction value, compared to the PRECISE-DAPT and Global Registry of Acute Coronary Events scores.
Asunto(s)
Síndrome Coronario Agudo/mortalidad , Stents Liberadores de Fármacos/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Síndrome Coronario Agudo/terapia , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/complicaciones , Quimioterapia Combinada/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Recuento de Plaquetas/métodos , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Medición de RiesgoRESUMEN
BACKGROUND: Dihydroartemisinin-piperaquine is an effective and well tolerated artemisinin-based combination therapy that has been assessed extensively for the prevention and treatment of malaria. Piperaquine, similar to several structurally related antimalarials currently used, can prolong cardiac ventricular repolarisation duration and the electrocardiographic QT interval, leading to concerns about its proarrhythmic potential. We aimed to assess the risk of potentially lethal iatrogenic ventricular arrhythmias in individuals receiving dihydroartemisinin-piperaquine. METHODS: We did a systematic review and Bayesian meta-analysis. We searched clinical bibliographic databases (last on May 24, 2017) for studies of dihydroartemisinin-piperaquine in human beings. Further unpublished studies were identified with the WHO Evidence Review Group on the Cardiotoxicity of Antimalarials. We searched for articles containing "dihydroartemisinin-piperaquine" as title, abstract, or subject heading keywords, with synonyms and variant spellings as additional search terms. We excluded animal studies, but did not apply limits on language or publication date. Eligible studies were prospective, randomised, controlled trials or cohort studies in which individuals received at least one 3-day treatment course of dihydroartemisinin-piperaquine for mass drug administration, preventive therapy, or case management of uncomplicated malaria, with follow-up over at least 3 days. At least two independent reviewers screened titles, abstracts, and full texts, agreed study eligibility, and extracted information about study and participant characteristics, adverse event surveillance methodology, dihydroartemisinin-piperaquine exposures, loss-to-follow up, and any deaths after dihydroartemisinin-piperaquine treatment into a standardised database. The risk of sudden unexplained death after dihydroartemisinin-piperaquine with 95% credible intervals (CI) generated by Bayesian meta-analysis was compared with the baseline rate of sudden cardiac death. FINDINGS: Our search identified 94 eligible primary studies including data for 197â867 individuals who had received dihydroartemisinin-piperaquine: 154â505 in mass drug administration programmes; 15â188 in 14 studies of repeated courses in preventive therapies and case management of uncomplicated malaria; and 28â174 as single-course treatments of uncomplicated malaria in 76 case-management studies. There was one potentially drug-related sudden unexplained death: a healthy woman aged 16 in Mozambique who developed heart palpitations several hours after the second dose of dihydroartemisinin-piperaquine and collapsed and died on the way to hospital (no autopsy or ECG was done). The median pooled risk estimate of sudden unexplained death after dihydroartemisinin-piperaquine was 1 in 757â950 (95% CI 1 in 2â854â490 to 1 in 209â114). This risk estimate was not higher than the baseline rate of sudden cardiac death (0·7-11·9 per 100â000 person-years or 1 in 1â714â280 to 1 in 100â835 over a 30-day risk period). The risk of bias was low in most studies and unclear in a few. INTERPRETATION: Dihydroartemisinin-piperaquine was associated with a low risk of sudden unexplained death that was not higher than the baseline rate of sudden cardiac death. Concerns about repolarisation-related cardiotoxicity need not limit its current use for the prevention and treatment of malaria. FUNDING: Wellcome Trust, UK Medical Research Council, WHO, Bill & Melinda Gates Foundation, and University of Oxford.
Asunto(s)
Antimaláricos/administración & dosificación , Antimaláricos/efectos adversos , Artemisininas/administración & dosificación , Artemisininas/efectos adversos , Quimioterapia Combinada/mortalidad , Malaria/tratamiento farmacológico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Adolescente , Animales , Teorema de Bayes , Causas de Muerte , Estudios de Cohortes , Femenino , Humanos , Mozambique , Estudios ProspectivosRESUMEN
BACKGROUND: Antithrombin and recombinant human thrombomodulin (rhTM) are individually reported to improve survival in sepsis-induced disseminated intravascular coagulation (DIC). However, continuing controversy exists as to which agent is superior and whether concomitant therapy is superior to individual administration. METHODS: This post hoc analysis included adult patients with sepsis-induced DIC from a nationwide multicenter registry database in Japan. We categorized patients into 4 groups: patients who received (1) individual administration of antithrombin, (2) individual administration of rhTM, (3) both, and (4) neither. In-hospital mortality was compared between every 2 groups among the 4 groups by Cox proportional hazards model adjusted with propensity scores. RESULTS: In total, 1432 patients with sepsis-induced DIC were included. Although both antithrombin and rhTM were associated better outcome compared with no anticoagulants, mortality benefits were similar between each individual anticoagulant. Similarly, no significant difference in mortality was detected between individual administrations and concomitant therapy. CONCLUSION: Antithrombin and rhTM might have comparable efficacy in reducing mortality in patients with sepsis; however, concomitant therapy appeared to offer no additional survival benefit.
Asunto(s)
Antitrombinas/administración & dosificación , Coagulación Intravascular Diseminada/tratamiento farmacológico , Quimioterapia Combinada/mortalidad , Sepsis/mortalidad , Trombomodulina/administración & dosificación , Adulto , Anciano , Coagulación Intravascular Diseminada/etiología , Femenino , Mortalidad Hospitalaria , Humanos , Japón , Masculino , Persona de Mediana Edad , Sistema de Registros , Sepsis/complicaciones , Sepsis/tratamiento farmacológicoRESUMEN
BACKGROUND: Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART) in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE), Eastern Europe (Russia and Ukraine), and Thailand. METHODS AND FINDINGS: Children with perinatal HIV aged <18 years initiating cART were followed until their 21st birthday, transfer to adult care, death, loss to follow-up, or last visit up until 31 December 2013. Rates of death and first AIDS-defining events were calculated. Baseline and time-updated risk factors for early/late (≤/>6 months of cART) death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3) years; 35% of children aged <5 years had a CD4 lymphocyte percentage <15% in 1997-2003, which fell to 15% of children in 2011 onwards (p < 0.001). Similarly, 53% and 18% of children ≥5 years had a CD4 count <200 cells/mm3 in 1997-2003 and in 2011 onwards, respectively (p < 0.001). Median follow-up was 5.6 (2.9-8.7) years. Of 94 deaths and 237 first AIDS-defining events, 43 (46%) and 100 (42%) were within 6 months of initiating cART, respectively. Multivariable predictors of early death were: being in the first year of life; residence in Russia, Ukraine, or Thailand; AIDS at cART start; initiating cART on a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen; severe immune suppression; and low BMI-for-age z-score. Current severe immune suppression, low current BMI-for-age z-score, and current viral load >400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC) disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time. CONCLUSIONS: In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART) in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.
Asunto(s)
Antirretrovirales/administración & dosificación , Progresión de la Enfermedad , Quimioterapia Combinada/estadística & datos numéricos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/mortalidad , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/mortalidad , Síndrome de Inmunodeficiencia Adquirida/virología , Adolescente , Niño , Preescolar , Estudios de Cohortes , Quimioterapia Combinada/mortalidad , Europa (Continente)/epidemiología , Infecciones por VIH/virología , Humanos , Lactante , Recién Nacido , Factores de Riesgo , Tailandia/epidemiologíaRESUMEN
: When patients on anticoagulation present with intracranial bleeding, stopping the bleeding is paramount. Despite the availability of multiple options to reverse anticoagulation, no study has directly compared the effectiveness of the procoagulants recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination, and 4-factor PCC on improving patient outcomes compared with a control. This study examined the medical records of 197 warfarin patients with intracranial hemorrhage, an initial international normalized ratio (INR) greater than 1.5, and who received rFVIIa (26), the combination (84), 4-PCC (50), or no procoagulant, the control group (37). Mortality, length of stay, location discharged, change in INR prior to and postdrug administration, plasma use, and number of thromboembolic complications were used to assess effectiveness. Although INR decreased in all groups (1.31 rFVIIa vs. 2.04 combination vs. 1.41 4-PCC vs. 1.20 control, Pâ=â0.07), the combination group had the greatest percentage to reach an INR of less than 1.3 (46.2 vs. 73.8 vs. 58.0 vs. 43.2%, Pâ=â0.004). The combination and control groups experienced a high, though nonsignificant, number of thromboembolic complications (5.6 vs. 19.0 vs. 7.7 vs. 12.9%, Pâ=â0.533). The rFVIIa group used the most plasma and had the longest length of stay. Mortality did not differ significantly among groups. Although the combination improved INR compared with control, this had a high number of complications. Judicious use of procoagulants is recommended due to their expense and lack of significant improvement in outcomes compared with control.
Asunto(s)
Quimioterapia Combinada , Hemorragia/prevención & control , Hemorragias Intracraneales/tratamiento farmacológico , Warfarina/efectos adversos , Anciano , Anciano de 80 o más Años , Factores de Coagulación Sanguínea/uso terapéutico , Estudios de Casos y Controles , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/mortalidad , Factor VIIa/uso terapéutico , Femenino , Hemorragia/tratamiento farmacológico , Humanos , Relación Normalizada Internacional , Hemorragias Intracraneales/inducido químicamente , Hemorragias Intracraneales/mortalidad , Tiempo de Internación , Masculino , Persona de Mediana Edad , Mortalidad , Proteínas Recombinantes/uso terapéutico , TromboemboliaRESUMEN
BACKGROUND: As part of liver transplantation, immunosuppression (suppressing the host immunity) is given to prevent graft rejections resulting from the immune response of the body against transplanted organ or tissues from a different person whose tissue antigens are not compatible with those of the recipient. The optimal maintenance immunosuppressive regimen after liver transplantation remains uncertain. OBJECTIVES: To assess the comparative benefits and harms of different maintenance immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different immunosuppressive regimens according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until October 2016 to identify randomised clinical trials on immunosuppression for liver transplantation. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adult participants undergoing liver transplantation (or liver retransplantation) for any reason. We excluded trials in which participants had undergone multivisceral transplantation or participants with established graft rejections. We considered any of the various maintenance immunosuppressive regimens compared with each other. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio (HR) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS: We included a total of 26 trials (3842 participants) in the review, and 23 trials (3693 participants) were included in one or more outcomes in the review. The vast majority of the participants underwent primary liver transplantation. All of the trials were at high risk of bias, and all of the evidence was of low or very low quality. In addition, because of sparse data involving trials at high risk of bias, it is not possible to entirely rely on the results of the network meta-analysis. The trials included mainly participants undergoing primary liver transplantation of varied aetiologies. The follow-up in the trials ranged from 3 to 144 months. The most common maintenance immunosuppression used as a control was tacrolimus. There was no evidence of difference in mortality (21 trials; 3492 participants) or graft loss (15 trials; 2961 participants) at maximal follow-up between the different maintenance immunosuppressive regimens based on the network meta-analysis. In the direct comparison, based on a single trial including 222 participants, tacrolimus plus sirolimus had increased mortality (HR 2.76, 95% CrI 1.30 to 6.69) and graft loss (HR 2.34, 95% CrI 1.28 to 4.61) at maximal follow-up compared with tacrolimus. There was no evidence of differences in the proportion of people with serious adverse events (1 trial; 719 participants), proportion of people with any adverse events (2 trials; 940 participants), renal impairment (8 trials; 2233 participants), chronic kidney disease (1 trial; 100 participants), graft rejections (any) (16 trials; 2726 participants), and graft rejections requiring treatment (5 trials; 1025 participants) between the different immunosuppressive regimens. The network meta-analysis showed that the number of adverse events was lower with cyclosporine A than with many other immunosuppressive regimens (12 trials; 1748 participants), and the risk of retransplantation (13 trials; 1994 participants) was higher with cyclosporine A than with tacrolimus (HR 3.08, 95% CrI 1.13 to 9.90). None of the trials reported number of serious adverse events, health-related quality of life, or costs. FUNDING: 14 trials were funded by pharmaceutical companies who would benefit from the results of the trial; two trials were funded by parties who had no vested interest in the results of the trial; and 10 trials did not report the source of funding. AUTHORS' CONCLUSIONS: Based on low-quality evidence from a single small trial from direct comparison, tacrolimus plus sirolimus increases mortality and graft loss at maximal follow-up compared with tacrolimus. Based on very low-quality evidence from network meta-analysis, we found no evidence of difference between different immunosuppressive regimens. We found very low-quality evidence from network meta-analysis and low-quality evidence from direct comparison that cyclosporine A causes more retransplantation compared with tacrolimus. Future randomised clinical trials should be adequately powered; performed in people who are generally seen in the clinic rather than in highly selected participants; employ blinding; avoid postrandomisation dropouts or planned cross-overs; and use clinically important outcomes such as mortality, graft loss, renal impairment, chronic kidney disease, and retransplantation. Such trials should use tacrolimus as one of the control groups. Moreover, such trials ought to be designed in such a way as to ensure low risk of bias and low risks of random errors.
Asunto(s)
Terapia de Inmunosupresión/métodos , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Metaanálisis en Red , Adulto , Azatioprina/efectos adversos , Azatioprina/uso terapéutico , Teorema de Bayes , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Quimioterapia Combinada/mortalidad , Everolimus/efectos adversos , Everolimus/uso terapéutico , Glucocorticoides/efectos adversos , Glucocorticoides/uso terapéutico , Humanos , Terapia de Inmunosupresión/efectos adversos , Terapia de Inmunosupresión/mortalidad , Inmunosupresores/efectos adversos , Trasplante de Hígado/mortalidad , Ácido Micofenólico/efectos adversos , Ácido Micofenólico/uso terapéutico , Oportunidad Relativa , Retratamiento/estadística & datos numéricos , Sirolimus/efectos adversos , Sirolimus/uso terapéutico , Tacrolimus/efectos adversos , Tacrolimus/uso terapéutico , Inmunología del TrasplanteRESUMEN
With the introduction of direct-acting antivirals (DAAs), treatment against hepatitis C virus (HCV) has significantly improved. To manage and control this worldwide infectious disease better, the "best" multidrug treatment is demanded based on scientific evidence. However, there is no method available that systematically quantifies and compares the antiviral efficacy and drug-resistance profiles of drug combinations. Based on experimental anti-HCV profiles in a cell culture system, we quantified the instantaneous inhibitory potential (IIP), which is the logarithm of the reduction in viral replication events, for both single drugs and multiple-drug combinations. From the calculated IIP of 15 anti-HCV drugs from different classes [telaprevir, danoprevir, asunaprevir, simeprevir, sofosbuvir (SOF), VX-222, dasabuvir, nesbuvir, tegobuvir, daclatasvir, ledipasvir, IFN-α, IFN-λ1, cyclosporin A, and SCY-635], we found that the nucleoside polymerase inhibitor SOF had one of the largest potentials to inhibit viral replication events. We also compared intrinsic antiviral activities of a panel of drug combinations. Our quantification analysis clearly indicated an advantage of triple-DAA treatments over double-DAA treatments, with triple-DAA treatments showing enhanced antiviral activity and a significantly lower probability for drug resistance to emerge at clinically relevant drug concentrations. Our framework provides quantitative information to consider in designing multidrug strategies before costly clinical trials.
Asunto(s)
Antivirales/farmacología , Hepacivirus/fisiología , Hepatitis C/tratamiento farmacológico , Proteínas no Estructurales Virales/antagonistas & inhibidores , Replicación Viral/efectos de los fármacos , Antivirales/uso terapéutico , Células Cultivadas , Evaluación Preclínica de Medicamentos , Farmacorresistencia Viral/efectos de los fármacos , Quimioterapia Combinada/mortalidad , Hepacivirus/efectos de los fármacos , Hepatitis C/virología , HumanosRESUMEN
Abstract Background: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. Methods: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. Results: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p = 0.044). The addition of carbapenem was not associated with increased survival. Conclusion: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Carbapenémicos/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/mortalidad , Neumonía Asociada al Ventilador/mortalidad , Antibacterianos/uso terapéutico , Factores de Tiempo , Modelos Logísticos , Estudios Transversales , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Mortalidad Hospitalaria , Estadísticas no Paramétricas , Enterobacter aerogenes/efectos de los fármacos , Quimioterapia Combinada/mortalidad , Neumonía Asociada al Ventilador/microbiología , Neumonía Asociada al Ventilador/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacosRESUMEN
BACKGROUND: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. METHODS: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. RESULTS: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p=0.044). The addition of carbapenem was not associated with increased survival. CONCLUSION: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study.
Asunto(s)
Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones por Enterobacteriaceae/mortalidad , Neumonía Asociada al Ventilador/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Quimioterapia Combinada/mortalidad , Enterobacter aerogenes/efectos de los fármacos , Femenino , Mortalidad Hospitalaria , Humanos , Klebsiella pneumoniae/efectos de los fármacos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neumonía Asociada al Ventilador/tratamiento farmacológico , Neumonía Asociada al Ventilador/microbiología , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no Paramétricas , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically-ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients.While guidelines exist for the antibiotic treatment of hospital-acquired pneumonia (HAP) from the American Thoracic Society and the British Society for Antimicrobial Chemotherapy, there are many limitations in the quality of available evidence. This systematic review aimed to summarise the results of all randomised controlled trials (RCTs) that compare empirical antibiotic regimens for VAP. OBJECTIVES: The primary objective of this review was to assess the effect of different empirical antimicrobial therapies on the survival and clinical cure of adult patients with ventilator-associated pneumonia (VAP). Secondary objectives included reporting the incidence of adverse events, new superinfections, length of hospital stay, and length of intensive care unit (ICU) stay associated with these therapies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CINAHL and Web of Science to December 2015; we searched ClinicalTrials.gov to September 2016. SELECTION CRITERIA: Two review authors independently assessed RCTs comparing empirical antibiotic treatments of VAP in adult patients, where VAP was defined as new-onset pneumonia that developed more than 48 hours after endotracheal intubation. Physicians and researchers were not required to be blinded for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted study data. We pooled studies and analysed them in two ways. We examined monotherapy, or a single experimental antimicrobial drug, versus combination therapy, or multiple experimental antimicrobial drugs. We also examined carbapenem therapy versus non-carbapenem therapy. MAIN RESULTS: We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies.We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence.For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study.We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. AUTHORS' CONCLUSIONS: We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP.Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.
Asunto(s)
Antibacterianos/uso terapéutico , Neumonía Asociada al Ventilador/tratamiento farmacológico , Adulto , Antibacterianos/efectos adversos , Carbapenémicos/uso terapéutico , Causas de Muerte , Quimioterapia Combinada/mortalidad , Investigación Empírica , Humanos , Neumonía Asociada al Ventilador/mortalidad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Antiplatelet therapy after coronary artery bypass graft (CABG) has been used. Little is known about the predictors and efficacy of clopidogrel in this scenario. OBJECTIVE: Identify predictors of clopidogrel following CABG. METHODS: We evaluated 5404 patients who underwent CABG between 2000 and 2009 at Duke University Medical Center. We excluded patients undergoing concomitant valve surgery, those who had postoperative bleeding or death before discharge. Postoperative clopidogrel was left to the discretion of the attending physician. Adjusted risk for 1-year mortality was compared between patients receiving and not receiving clopidogrel during hospitalization after undergoing CABG. RESULTS: At hospital discharge, 931 (17.2%) patients were receiving clopidogrel. Comparing patients not receiving clopidogrel at discharge, users had more comorbidities, including hyperlipidemia, hypertension, heart failure, peripheral arterial disease and cerebrovascular disease. Patients who received aspirin during hospitalization were less likely to receive clopidogrel at discharge (P≤0.0001). Clopidogrel was associated with similar 1-year mortality compared with those who did not use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however, an interaction between the use of cardiopulmonary bypass and clopidogrel, with lower 1-year mortality in patients undergoing off-pump CABG who received clopidogrel, but not those undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032). CONCLUSION: Clopidogrel was used in nearly one-fifth of patients after CABG. Its use was not associated with lower mortality after 1 year in general, but lower mortality rate in those undergoing off-pump CABG. Randomized clinical trials are needed to determine the benefit of routine use of clopidogrel in CABG.
Asunto(s)
Puente de Arteria Coronaria/rehabilitación , Revascularización Miocárdica/rehabilitación , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complicaciones Posoperatorias/mortalidad , Ticlopidina/análogos & derivados , Aspirina/administración & dosificación , Aspirina/uso terapéutico , Puente Cardiopulmonar/rehabilitación , Clopidogrel , Puente de Arteria Coronaria/métodos , Quimioterapia Combinada/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica/métodos , North Carolina , Alta del Paciente/estadística & datos numéricos , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/normas , Cuidados Posoperatorios/mortalidad , Complicaciones Posoperatorias/tratamiento farmacológico , Periodo Posoperatorio , Prevalencia , Pronóstico , Tasa de Supervivencia , Ticlopidina/administración & dosificación , Ticlopidina/normas , Ticlopidina/uso terapéuticoRESUMEN
Anti-thymocyte globulin (ATG) is a key drug in immunosuppressive therapy for patients with aplastic anemia. The mainstay of ATG therapy had been a horse ATG (hATG) formulation, Lymphoglobulin or ATGAM, but Lymphoglobulin was recently discontinued, and Thymoglobulin, a rabbit ATG (rATG) formulation, is currently used as the first-line drug in many countries, including Japan. However, a recent randomized clinical trial reported significantly unfavorable outcomes associated with the use of rATG regimens. We retrospectively analyzed clinical outcomes of adult patients with moderate to severe aplastic anemia who were treated with 3.5 mg/kg of Thymoglobulin (n = 22) or 15 mg/kg of Lymphoglobulin (n = 25) in our facility. The estimated overall response rates in the rATG and hATG groups were 64.6 versus 56.0 % at 6 months, and 76.4 versus 69.2 % at 12 months, respectively; and there was no statistical difference between the two groups (P = 0.32). Overall survival at 24 months was not significantly different: rATG 89.8 % versus hATG 96.0 % (P = 0.39). Early phase infection was observed in 37.5 % of cases in the rATG and 14.8 % in the hATG group, but the frequency was not statistically different (P = 0.107). Our data indicate that Thymoglobulin at a dose of 3.5 mg/kg is a viable alternative when hATG is not available.
Asunto(s)
Anemia Aplásica/tratamiento farmacológico , Quimioterapia Combinada/métodos , Adulto , Animales , Suero Antilinfocítico/administración & dosificación , Ciclosporina/administración & dosificación , Quimioterapia Combinada/mortalidad , Quimioterapia Combinada/normas , Caballos , Humanos , Inmunoglobulinas/administración & dosificación , Inmunosupresores/uso terapéutico , Conejos , Resultado del TratamientoRESUMEN
Abstract Introduction: Antiplatelet therapy after coronary artery bypass graft (CABG) has been used. Little is known about the predictors and efficacy of clopidogrel in this scenario. Objective: Identify predictors of clopidogrel following CABG. Methods: We evaluated 5404 patients who underwent CABG between 2000 and 2009 at Duke University Medical Center. We excluded patients undergoing concomitant valve surgery, those who had postoperative bleeding or death before discharge. Postoperative clopidogrel was left to the discretion of the attending physician. Adjusted risk for 1-year mortality was compared between patients receiving and not receiving clopidogrel during hospitalization after undergoing CABG. Results: At hospital discharge, 931 (17.2%) patients were receiving clopidogrel. Comparing patients not receiving clopidogrel at discharge, users had more comorbidities, including hyperlipidemia, hypertension, heart failure, peripheral arterial disease and cerebrovascular disease. Patients who received aspirin during hospitalization were less likely to receive clopidogrel at discharge (P≤0.0001). Clopidogrel was associated with similar 1-year mortality compared with those who did not use clopidogrel (4.4% vs. 4.5%, P=0.72). There was, however, an interaction between the use of cardiopulmonary bypass and clopidogrel, with lower 1-year mortality in patients undergoing off-pump CABG who received clopidogrel, but not those undergoing conventional CABG (2.6% vs 5.6%, P Interaction = 0.032). Conclusion: Clopidogrel was used in nearly one-fifth of patients after CABG. Its use was not associated with lower mortality after 1 year in general, but lower mortality rate in those undergoing off-pump CABG. Randomized clinical trials are needed to determine the benefit of routine use of clopidogrel in CABG.
Asunto(s)
Humanos , Masculino , Femenino , Complicaciones Posoperatorias/mortalidad , Ticlopidina/análogos & derivados , Inhibidores de Agregación Plaquetaria/uso terapéutico , Puente de Arteria Coronaria/rehabilitación , Revascularización Miocárdica/rehabilitación , Alta del Paciente/estadística & datos numéricos , Cuidados Posoperatorios/mortalidad , Complicaciones Posoperatorias/tratamiento farmacológico , Periodo Posoperatorio , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/normas , Puente Cardiopulmonar/rehabilitación , Aspirina/administración & dosificación , Aspirina/uso terapéutico , North Carolina , Puente de Arteria Coronaria/métodos , Tasa de Supervivencia , Quimioterapia Combinada/mortalidad , Clopidogrel , Revascularización Miocárdica/métodosRESUMEN
The IMPROVE-IT study has demonstrated a significant reduction of LDL-C when ezetimibe was given in addition to statins. Although the number of strokes and MI was reduced after 7 to 10 years of this treatment, mortality was unaffected, however. Additive ezetimibe treatment can be recommended only, if a better or longer life has been proved - which is not the case.
Asunto(s)
Azetidinas/administración & dosificación , LDL-Colesterol/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Hipercolesterolemia/prevención & control , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/prevención & control , Anticolesterolemiantes/administración & dosificación , Comorbilidad , Quimioterapia Combinada/mortalidad , Medicina Basada en la Evidencia , Ezetimiba , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/mortalidad , Prevalencia , Factores de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Tigecycline is an antibiotic with a broad spectrum of activity. Similar to tetracycline antibiotics, tigecycline exerts bacteriostatic activity. Earlier studies documented the safety and efficacy of tigecycline for complicated intra-abdominal and complicated skin and skin-structure infections, which led to its approval. Recent systematic reviews and meta-analyses have suggested increased risk of death in patients receiving tigecycline compared to other antibiotics. The Food and Drug Administration has warned clinicians about increased risk for death in patients who received tigecycline with certain severe infections and have issued a black box warning. The increased mortality risk with tigecycline is most apparent in patients treated for hospital-acquired pneumonia, particularly ventilator-associated pneumonia. The cause of excess deaths in these trials is uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection. Further experience with tigecycline for serious infections with drug-resistant pathogens is currently warranted.