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BACKGROUND: Carbapenem-resistant gram-negative bacteria (CRGNB) present a considerable global threat due to their challenging treatment and increased mortality rates, with bloodstream infection (BSI) having the highest mortality rate. Patients with end-stage renal disease (ESRD) undergoing renal replacement therapy (RRT) face an increased risk of BSI. Limited data are available regarding the prognosis and treatment outcomes of CRGNB-BSI in patients with ESRD in intensive care units (ICUs). METHODS: This multi-center retrospective observational study included a total of 149 ICU patients with ESRD and CRGNB-BSI in Taiwan from January 2015 to December 2019. Clinical and microbiological outcomes were assessed, and multivariable regression analysis was used to evaluate the independent risk factors for day-28 mortality and the impact of antimicrobial therapy regimen on treatment outcomes. RESULTS: Among the 149 patients, a total of 127 patients (85.2%) acquired BSI in the ICU, with catheter-related infections (47.7%) and pneumonia (32.2%) being the most common etiologies. Acinetobacter baumannii (49.0%) and Klebsiella pneumoniae (31.5%) were the most frequently isolated pathogens. The day-28 mortality rate from BSI onset was 52.3%, and in-hospital mortality was 73.2%, with survivors experiencing prolonged hospital stays. A higher Sequential Organ Failure Assessment (SOFA) score (adjusted hazards ratio [aHR], 1.25; 95% confidence interval [CI] 1.17-1.35) and shock status (aHR, 2.12; 95% CI 1.14-3.94) independently predicted day-28 mortality. Colistin-based therapy reduced day-28 mortality in patients with shock, a SOFA score of ≥ 13, and Acinetobacter baumannii-related BSI. CONCLUSIONS: CRGNB-BSI led to high mortality in critically ill patients with ESRD. Day-28 mortality was independently predicted by a higher SOFA score and shock status. In patients with higher disease severity and Acinetobacter baumannii-related BSI, colistin-based therapy improved treatment outcomes.
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BACKGROUND: The importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB. METHODS: This was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67). RESULTS: The loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan-Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups. CONCLUSIONS: The administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.
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Colistina , Pneumonia Bacteriana , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Colistina/efeitos adversos , Estado Terminal/terapia , Bactérias Gram-Negativas , Humanos , Pneumonia Bacteriana/tratamento farmacológico , Estudos RetrospectivosRESUMO
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease. Currently, therapeutic options are limited for this fatal disease. Curcumin, with its pleiotropic effects, has been studied for its potential therapeutic utilities in various diseases, including pulmonary fibrosis. However, the detailed mechanisms have not been studied comprehensively. We conducted a next-generation sequencing and bioinformatics study to investigate changes in the profiles of mRNA and microRNA after curcumin treatment in IPF fibroblasts. We identified 23 downregulated and 8 upregulated protein-coding genes in curcumin-treated IPF fibroblasts. Using STRING and IPA, we identified that suppression of cell cycle progression was the main cellular function associated with these differentially expressed genes. We also identified 13 downregulated and 57 upregulated microRNAs in curcumin-treated IPF fibroblasts. Further analysis identified a potential microRNA-mediated gene expression alteration in curcumin-treated IPF fibroblasts, namely, downregulated hsa-miR-6724-5p and upregulated KLF10. Therefore, curcumin might decrease the level of hsa-miR-6724-5p, leading to increased KLF10 expression, resulting in cell cycle arrest in curcumin-treated IPF fibroblasts. In conclusion, our findings might support the potential role of curcumin in the treatment of IPF, but further in-depth study is warranted to confirm our findings.
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Biologia Computacional , Curcumina/farmacologia , Fibroblastos/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Pulmão/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , Fases de Leitura Aberta/genética , Mapas de Interação de Proteínas/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
In phase II clinical trials, patients are recruited sequentially and consequently the time required to complete the clinical trial will become long if the accrual rate is low. To speed up the drug development process and account for ethical issues, stochastically and non-stochastically curtailed two-stage designs have been proposed in single-arm phase II clinical trials. More recently, randomized phase II clinical trials are being increasingly recommended to avoid biased evaluation of the treatment effect when compared with a historical control. The current patient population and the historical one may be quite heterogeneous. Moreover, it is impossible to randomly assign patients for treatments. Consequently, various two-stage designs have been presented for comparing two arms. Since the sample size required in a randomized phase II trial is usually larger than that required in a single-arm phase II trial, we introduce the concept of curtailed sampling procedure to develop curtailed two-stage design for two-armed, randomized phase II clinical trials. The proposed design does not require pairwise patient response comparison, yet it allows a trial to be stopped early as soon as the difference in therapeutic effect of the experimental therapy and the standard at the end of a trial is foreknown.
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Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Ensaios Clínicos Fase II como Assunto/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Tamanho da AmostraRESUMO
OBJECTIVE: To investigate efficacy of repetitive transcranial magnetic stimulation (rTMS) on attention-deficit/hyperactivity disorder (ADHD). METHODS: Randomized sham-controlled trials (RCTs) were identified from major databases from the inception date of January 1990 to January 2023. Primary outcome was improvement in total symptoms of ADHD. Subgroup analysis focused on rTMS efficacy targeting different brain regions. Secondary outcomes were associations of rTMS with improvements in different symptoms of ADHD. Outcomes were expressed as effect size (ES) based on standardized mean difference (SMD) (continuous data), and odds ratios (ORs) with 95% confidence interval (CI) (categorical data). RESULTS: Meta-analysis of six RCTs involving 169 participants demonstrated no difference in total ADHD symptoms between rTMS-treated participants and sham controls (SMD=-0.24,p=0.17). Subgroup analysis revealed better efficacy of rTMS than sham controls when targeting right prefrontal cortex (rPFC) (SMD=-0.49,p=0.03), but not left prefrontal cortex (lPFC) (SMD= 0.01,p=0.67). rTMS treatment correlated with better improvement in symptoms of inattention (SMD=-0.76,p=0.0002), but not hyperactivity (p=0.86), impulsivity (p=0.41), and depression (p=0.95). The apparently higher risk of dropout in the rTMS group than sham controls was not statistically significant (OR=1.65,p=0.26). CONCLUSIONS: Our study only supported the therapeutic efficacy of rTMS targeting rPFC for the symptoms of ADHD, especially inattention, but not that targeting lPFC. Further large-scale randomized sham-controlled trials are required to verify our findings.
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Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is common worldwide. Despite carbapenem resistance, standard-dose carbapenems are still used in clinical practice. Hence in this study, we aimed to compare the efficacy and outcomes of a regimen containing standard-dose carbapenems with those of a regimen lacking carbapenems during the treatment of critically ill patients with CRAB nosocomial pneumonia in the intensive care unit (ICU). Initially, 735 patients were recruited for this multicentre retrospective cohort study. After exclusion, time-window bias adjustment, and propensity score matching, multiple clinical outcomes were compared between the carbapenem-containing (CC) (n = 166) and no carbapenem-containing (NCC) (n = 166) groups. The CC group showed a higher risk of clinical failure on day 7 than the NCC group (44.6% vs. 33.1%, P = 0.043). The lengths of ICU stay (21 and 16 days, P = 0.024) and hospital stay (61 and 44 days, P = 0.003) were longer in the CC group than in the NCC group. Multivariate analysis showed that the CC regimen was associated with higher clinical failure (adjusted odds ratio (aOR) = 1.64, 95% CI = 1.05-2.56, P = 0.031) and lower microbiological eradication (aOR = 0.48, 95% CI = 0.23-1.00, P = 0.049) at day 7 than the NCC group. Thus, a regimen containing a standard dose of carbapenem should be prescribed with caution for treating CRAB nosocomial pneumonia in the ICU.
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Infecções por Acinetobacter , Acinetobacter baumannii , Infecção Hospitalar , Pneumonia Associada a Assistência à Saúde , Humanos , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Unidades de Terapia Intensiva , Pontuação de Propensão , Estudos RetrospectivosRESUMO
OBJECTIVES: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU. METHODS: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed. RESULTS: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs 45.9%, P < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, P < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, P = < 0.001). Spearman's rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777). CONCLUSIONS: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation.
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Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriemia , Carbapenêmicos , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Humanos , Estudos Retrospectivos , Masculino , Bacteriemia/microbiologia , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Feminino , Acinetobacter baumannii/efeitos dos fármacos , Fatores de Risco , Infecções por Acinetobacter/mortalidade , Infecções por Acinetobacter/microbiologia , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/tratamento farmacológico , Pessoa de Meia-Idade , Idoso , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Antibacterianos/uso terapêutico , Pneumonia Associada a Assistência à Saúde/microbiologia , Pneumonia Associada a Assistência à Saúde/epidemiologia , Pneumonia Associada a Assistência à Saúde/mortalidade , Infecção Hospitalar/microbiologia , Infecção Hospitalar/epidemiologiaRESUMO
Background: Malposition may occur during peripherally inserted central catheter insertion. Accurately measuring the length of a peripherally inserted central catheter is crucial to preventing malposition, including "long peripherally inserted central catheter placement," in which the tip of a peripherally inserted central catheter is deeper than the target position. The traditional method of measuring peripherally inserted central catheter length involves measuring from the insertion site to the parasternal notch and down to the third or fourth intercostal space, which may result in overestimation because of the thickness of the pectoralis major and anterior chest wall. To avoid this overestimation, the authors developed and tested a modified method for reducing long peripherally inserted central catheter placement. Methods: This study employed a retrospective design. Chest X-rays were used to examine the peripherally inserted central catheter tip positions in 48 patients in the medical intensive care unit who had undergone peripherally inserted central catheter insertion. The traditional and modified measurement methods were used to measure the peripherally inserted central catheter length in 17 and 31 patients, respectively. Fisher's exact test was used to examine between-group differences in the incidence of different types of peripherally inserted central catheter malposition. Results: The peripherally inserted central catheter tip position was near the target position in five patients (29.41%) in the traditional measurement group and 17 patients (54.84%) in the modified measurement group (p = 0.132), whereas long peripherally inserted central catheter placement occurred in six patients (35.29%) in the traditional measurement group and one patient (3.23%) in the modified measurement group (p = 0.006). However, the incidence of other types of peripherally inserted central catheter malposition did not differ significantly between the groups. Conclusions: The results of this study that the proposed modified measurement method may be able to reduce the incidence of long peripherally inserted central catheter placement among medical intensive care unit patients. The method must be further evaluated in prospective studies and studies with larger sample sizes in the future.
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Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.
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Infecções por Acinetobacter , Acinetobacter baumannii , Pneumonia Associada à Ventilação Mecânica , Humanos , Colistina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Acinetobacter baumannii/genética , Carbapenêmicos/uso terapêutico , Estudos Retrospectivos , Prevalência , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , Diálise Renal , Suscetibilidade a Doenças , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). METHODS: This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. RESULTS: We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p < 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28-0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47-0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30-0.74) at 28 days. Kaplan-Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen. CONCLUSIONS: In this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates.
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Background: Therapeutic efficacies of probiotics in improving neurocognitive functions in infants and young children remained unclear. This meta-analysis focused on different cognitive outcomes in this population. Methods: Major databases were searched electronically from inception to October 2023 to identify randomized controlled trials (RCTs) that investigated the therapeutic efficacy of probiotics in enhancing cognitive functions assessed by standardized tasks. The overall effect size was calculated as standardized mean difference (SMD) based on a random effects model. Results: Nine RCTs with 3,026 participants were identified. Both our primary and secondary results demonstrated no significant difference in neurocognitive outcomes between infants/children treated with probiotics and those receiving placebos. However, our subgroup analysis of studies that offered a probiotics treatment course of over six months demonstrated a significantly better neurocognitive outcome than placebos (SMD = 0.21, p = 0.03, two studies with 451 participants), but this finding was based on only two RCTs. Conclusion: Despite lack of significant therapeutic effects of probiotics on neurocognitive outcomes, our finding of a positive impact of probiotics on neurocognitive development in those undergoing treatment for over six months may provide an important direction for further investigations into the enhancement of therapeutic effects of probiotics on neurocognitive development in infants and young children. Systematic review registration: PROSPERO CRD42023463412.
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Cognição , Probióticos , Pré-Escolar , Humanos , Lactente , Probióticos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.
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Acinetobacter baumannii , Pneumonia Associada à Ventilação Mecânica , Humanos , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Estado Terminal , Estudos Retrospectivos , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Ventiladores Mecânicos/efeitos adversosRESUMO
When phase I clinical trials were found to be unable to precisely estimate the frequency of toxicity, Brayan and Day proposed incorporating toxicity considerations into two-stage designs in phase II clinical trials. Conaway and Petroni further pointed out that it is important to evaluate the clinical activity and safety simultaneously in studying cancer treatments with more toxic chemotherapies in a phase II clinical trial. Therefore, they developed multi-stage designs with two dependent binary endpoints. However, the usual sample sizes in phase II trials make these designs difficult to control the type I error rate at a desired level over the entire null region and still have sufficient power against reasonable alternatives. Therefore, the curtailed sampling procedure summarized by Phatak and Bhatt will be applied to the two-stage designs with two dependent binary endpoints in this paper to reduce sample sizes and speed up the development process for drugs.
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Ensaios Clínicos Fase I como Assunto/métodos , Ensaios Clínicos Fase II como Assunto/métodos , Projetos de Pesquisa , Desenho de Fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Determinação de Ponto Final/métodos , Humanos , Tamanho da Amostra , Fatores de TempoRESUMO
Nosocomial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a growing threat due to the limited therapeutic choices and high mortality rate. The aim of this study was to evaluate the prognostic factors for mortality in patients with nosocomial pneumonia caused by CRGNB and the impact of colistin-based therapy on the outcomes of intensive care unit (ICU) patients. We conducted a retrospective study of the ICUs in five tertiary teaching hospitals in Taiwan. Patients with nosocomial pneumonia caused by CRGNB from January 2016 to December 2016 were included. Prognostic factors for mortality were analyzed using multivariate logistic regression. The influence of colistin-based therapy on mortality and clinical and microbiological outcomes were evaluated in subgroups using different severity stratification criteria. A total of 690 patients were enrolled in the study, with an in-hospital mortality of 46.1%. The most common CRGNB pathogens were Acinetobacter baumannii (78.7%) and Pseudomonas aeruginosa (13.0%). Significant predictors (odds ratio and 95% confidence interval) of mortality from multivariate analysis were a length of hospital stay (LOS) prior to pneumonia of longer than 9 days (2.18, 1.53-3.10), a sequential organ failure assessment (SOFA) score of more than 7 (2.36, 1.65-3.37), supportive care with vasopressor therapy (3.21, 2.26-4.56), and escalation of antimicrobial therapy (0.71, 0.50-0.99). There were no significant differences between the colistin-based therapy in the deceased and survival groups (42.1% vs. 42.7%, p = 0.873). In the subgroup analysis, patients with multiple organ involvement (> 2 organs) or higher SOFA score (> 7) receiving colistin-based therapy had better survival outcomes. Prolonged LOS prior to pneumonia onset, high SOFA score, vasopressor requirement, and timely escalation of antimicrobial therapy were predictors for mortality in critically ill patients with nosocomial CRGNB pneumonia. Colistin-based therapy was associated with better survival outcomes in subgroups of patients with a SOFA score of more than 7 and multiple organ involvement.
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Acinetobacter baumannii , Infecção Hospitalar , Pneumonia Associada a Assistência à Saúde , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Colistina/uso terapêutico , Estado Terminal , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Bactérias Gram-Negativas , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Humanos , Estudos RetrospectivosRESUMO
The association between sleep apnea (SA) and depression had been reported in a few previous studies. However, whether SA increases the risk of major depressive disorder (MDD) has not been studied comprehensively in a large-scale study. We performed this population-based cohort study to assess the association between SA and MDD. We identified adult patients having SA from the Taiwan National Health Insurance Research Database and excluded those having MDD before SA diagnosis. Thirty control subjects were randomly selected to match to each SA patient by age and sex. Totally, 10,259 SA patients were matched to 102,590 control subjects. The incidence rate and cumulative incidence of MDD were significantly higher in SA patients than in the control subjects (both p < 0.0001). Multivariable Cox regression analysis showed that SA remained an independent risk factor for incident MDD after adjusting for age, sex, residency, income level, and comorbidities (hazard ratio = 2.9 [95% CI 2.8-3.1], p < 0.0001). In summary, SA patients have an increased risk to develop MDD. Physicians caring for SA patients must pay attention to their psychosocial health status.
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Transtorno Depressivo Maior/epidemiologia , Síndromes da Apneia do Sono/epidemiologia , Adulto , Algoritmos , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/patologia , Taiwan/epidemiologiaRESUMO
Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.
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OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.
Assuntos
Antibacterianos/uso terapêutico , Colistina/uso terapêutico , Infecções por Bactérias Gram-Negativas , Pneumonia Associada a Assistência à Saúde , Pneumonia Bacteriana , Carbapenêmicos/uso terapêutico , Estado Terminal , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Pneumonia Associada a Assistência à Saúde/tratamento farmacológico , Pneumonia Associada a Assistência à Saúde/mortalidade , Humanos , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/mortalidade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The effects of tiotropium bromide soft mist inhalers (SMIs) in patients with chronic obstructive pulmonary disease (COPD) receiving mechanical ventilation remain unexplored. This study investigated the dynamic effects of a tiotropium SMI on lung mechanics and gas exchange in these patients. We analyzed 11 mechanically ventilated and hemodynamically stable patients with COPD who experienced acute exacerbation and were ready to be weaned from the ventilator. Two puffs of tiotropium (2.5 µg/puff) were administered with a T-adaptor connected to the ventilator circuit. Lung mechanics-peak inspiratory pressure, plateau pressure, mean airway pressure, maximum respiratory resistance (Rrs), and gas exchange function-were analyzed. The two-puff tiotropium SMI treatment led to the greatest reduction in Rrs at 6 h, with the Rrs returning to baseline gradually, and significantly improved the PaO2/FiO2 ratio at 24 h. Compared with baseline values, tiotropium SMI had the strongest effect on Rrs between hours 3 and 6 but did not significantly affect hemodynamic parameters. Tiotropium SMI administration in mechanically ventilated patients with COPD achieved the greatest reduction in Rrs at 6 h and significantly improved the PaO2/FiO2 ratio at 24 h. Future studies should investigate whether the bronchodilation effect can be improved with increased dosage or frequency.
RESUMO
Resting-state functional magnetic resonance imaging (MRI) has been used to investigate the brain activity related to autism spectrum disorder (ASD). In this study, we applied information from a large-scale dataset, the Autism Brain Imaging Data Exchange (ABIDE), to clinical applications. We recruited 21 patients with ASD and 23 individuals with neurotypical development (TD). We applied ASD biomarkers derived from ABIDE datasets and subsequently investigated the relationship between the MRI biomarkers and indicators from clinical screening questionnaires, the social responsiveness scale (SRS), and the Swanson, Nolan, and Pelham Questionnaire IV. The results indicated that the biomarkers generated from the default mode and executive control networks significantly differed between the participants with ASD and TD. In particular, the biomarkers derived from the default mode network were negatively correlated with the raw scores and model factors of the SRS. In summary, this study transferred the efforts of the global autism research community to clinical applications and identified connectivity-based biomarkers in ASD.
Assuntos
Transtorno Autístico/metabolismo , Biomarcadores/metabolismo , Bases de Dados Factuais , Adolescente , Criança , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
When the accrual rate is low and the treatment period is long, a long observational period is required before information concerning the primary end point, such as binary response, becomes available in the study. Simon's two-stage designs are often employed in Phase II clinical trials to avoid giving patient an ineffective drug. Thus, if the new drug is ineffective then this design would certainly accelerate the process of drug discovery and development. However, for a promising new drug this design may still require a long observational period. Therefore, when drug safety is not a primary concern, this paper proposes curtailed two-stage designs to shorten the drug development process as soon as the treatment either shows lack of efficacy or is very effective. The proposed design is superior to Simon's two-stage designs in terms of savings in expected sample size and is much easier to implement in practice than stochastically curtailed Simon's designs.