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BACKGROUND: Patients hospitalized with coronavirus disease 2019 (COVID-19) are at increased risk of health care-associated infections (HAIs), especially with prolonged hospital stays. We sought to identify incidence, antimicrobial susceptibilities, and outcomes associated with bacterial/fungal secondary infections in a large cohort of patients with COVID-19. METHODS: We evaluated adult patients diagnosed with COVID-19 between 2 March and 31 May 2020 and hospitalized >24 hours. Data extracted from medical records included diagnoses, vital signs, laboratory results, microbiological data, and antibiotic use. Microbiologically confirmed bacterial and fungal pathogens from clinical cultures were evaluated to characterize community- and health care-associated infections, including describing temporal changes in predominant organisms on presentation and throughout hospitalization. Univariable and multivariable logistic regression analyses were performed to investigate risk factors for HAIs. RESULTS: A total of 3028 patients were included and accounted for 899 positive clinical cultures. Overall, 516 (17%) patients with positive cultures met criteria for infection. Community-associated coinfections were identified in 183 (6%) patients, whereas HAIs occurred in 350 (12%) patients. Fifty-seven percent of HAIs were caused by gram-negative bacteria and 19% by fungi. Antibiotic resistance increased with longer hospital stays, with incremental increases in the proportion of vancomycin resistance among enterococci and ceftriaxone and carbapenem resistance among Enterobacterales. Intensive care unit stay, invasive mechanical ventilation, and steroids were associated with HAIs. CONCLUSIONS: HAIs occur in a small proportion of patients hospitalized with COVID-19 and are most often caused by gram-negative and fungal pathogens. Antibiotic resistance is more prevalent with prolonged hospital stays. Antimicrobial stewardship is imperative in this population to minimize unnecessary broad-spectrum antibiotic use.
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PURPOSE: To share challenges and opportunities for antimicrobial stewardship programs based on one center's experience during the early weeks of the coronavirus disease 2019 (COVID-19) pandemic. SUMMARY: In the spring of 2020, New York City quickly became a hotspot for the COVID-19 pandemic in the United States, putting a strain on local healthcare systems. Antimicrobial stewardship programs faced diagnostic and therapeutic uncertainties as well as healthcare resource challenges. With the lack of effective antivirals, antibiotic use in critically ill patients was difficult to avoid. Uncertainty drove antimicrobial use and thus antimicrobial stewardship principles were paramount. The dramatic influx of patients, drug and equipment shortages, and the need for prescribers to practice in alternative roles only compounded the situation. Establishing enhanced communication, education, and inventory control while leveraging the capabilities of the electronic medical record were some of the tools used to optimize existing resources. CONCLUSION: New York City was a unique and challenging environment during the initial peak of the COVID-19 pandemic. Antimicrobial stewardship programs can learn from each other by sharing lessons learned and practice opportunities to better prepare other programs facing COVID-19 case surges.
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Gestão de Antimicrobianos , COVID-19 , Pandemias , SARS-CoV-2 , Hospitais , Humanos , Cidade de Nova IorqueRESUMO
RATIONALE AND OBJECTIVES: Two-dimensional (2D) ultrasound (US) is operator dependent, requiring operator skill and experience to selectively identify and record planes of interest for subsequent interpretation. This limits the utility of US in settings in which expert sonographers are unavailable. Three-dimensional (3D) US acquisition of an anatomic target, which enables reconstruction of any plane through the acquired volume, might reduce operator dependence by providing any desired image plane for interpretation, without identification of target planes of interest at the time of acquisition. We applied a low-cost 3DUS technology because of the wider potential application compared with dedicated 3DUS systems. We chose second trimester fetal biometric parameters for study because of their importance in maternal-fetal health globally. We hypothesized that expert and novice interpretations of novice-acquired 3D volumes would not differ from each other nor from expert measurements of expert-acquired 2D images, the clinical reference standard. MATERIALS AND METHODS: This was a prospective, blinded, observational study. Expert sonographers blinded to 3DUS volumes acquired 2DUS images of second trimester fetuses from 32 subjects, and expert readers performed interpretation, during usual care. A novice sonographer blinded to other clinical data acquired oriented 3DUS image volumes of the same subjects on the same date. Expert readers blinded to other data assessed placental location (PL), fetal presentation (FP), and amniotic fluid volume (AFV) in novice-acquired 3D volumes. Novice and expert raters blinded to other data independently measured biparietal diameter (BPD), humerus length (HL), and femur length (FL) for each fetus from novice-acquired 3D volumes. Corresponding gestational age (GA) estimates were calculated. Inter-rater reliability of measurements and GAs (expert 3D versus expert 2D, novice 3D versus expert 2D, and expert 3D versus novice 3D) were assessed by intraclass correlation coefficient (ICC). Mean inter-rater measurement differences were analyzed using one-way ANOVA. RESULTS: 3D volume acquisition and reconstruction required mean 30.4 s (±5.7) and 70.0 s (±24.0), respectively. PL, FP, and AFV were evaluated from volumes for all subjects; mean time for evaluation was 16 s (±0.0). PL, FP, and AFV could be evaluated for all subjects. At least one biometric measurement was possible for 31 subjects (97%). Agreement between rater pairs for a composite of all measures was excellent (ICCs ≥ 0.95), and for individual measures was good to excellent (ICCs ≥ 0.75). Inter-rater differences were not significant (p > .05). CONCLUSIONS: Expert and novice interpretations of novice-acquired 3DUS volumes of second trimester fetuses provided reliable biometric measures compared with expert interpretation of expert-acquired 2DUS images. 3DUS volume acquisition with a low-cost system may reduce operator dependence of ultrasound.
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Imageamento Tridimensional , Ultrassonografia Pré-Natal , Feminino , Idade Gestacional , Humanos , Placenta/diagnóstico por imagem , Gravidez , Segundo Trimestre da Gravidez , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: The efficacy and safety of methylprednisolone in mechanically ventilated patients with acute respiratory distress syndrome resulting from coronavirus disease 2019 (COVID-19) are unclear. In this study, we evaluated the association between use of methylprednisolone and key clinical outcomes. METHODS: Clinical outcomes associated with the use of methylprednisolone were assessed in an unmatched, case-control study; a subset of patients also underwent propensity-score matching. Patients were admitted between 1 March and 12 April, 2020. The primary outcome was ventilator-free days by 28 days after admission. Secondary outcomes included extubation, mortality, discharge, positive cultures, and hyperglycemia. RESULTS: A total of 117 patients met inclusion criteria. Propensity matching yielded a cohort of 42 well-matched pairs. Groups were similar except for hydroxychloroquine and azithromycin use, which were more common in patients who did not receive methylprednisolone. Mean ventilator-free days were significantly higher in patients treated with methylprednisolone (6.21â ±â 7.45 vs 3.14â ±â 6.22; Pâ =â .044). The probability of extubation was also increased in patients receiving methylprednisolone (45% vs 21%; Pâ =â .021), and there were no significant differences in mortality (19% vs 36%; Pâ =â .087). In a multivariable linear regression analysis, only methylprednisolone use was associated with a higher number of ventilator-free days (Pâ =â .045). The incidence of positive cultures and hyperglycemia were similar between groups. CONCLUSIONS: Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort. Randomized, controlled studies are needed to further define methylprednisolone use in patients with COVID-19.
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COVID-19 , Metilprednisolona , Estudos de Casos e Controles , Humanos , Metilprednisolona/uso terapêutico , Respiração Artificial , SARS-CoV-2 , Resultado do TratamentoRESUMO
BACKGROUND: Patients with COVID-19 may be at increased risk for secondary bacterial infections with MDR pathogens, including carbapenemase-producing Enterobacterales (CPE). OBJECTIVES: We sought to rapidly investigate the clinical characteristics, population structure and mechanisms of resistance of CPE causing secondary infections in patients with COVID-19. METHODS: We retrospectively identified CPE clinical isolates collected from patients testing positive for SARS-CoV-2 between March and April 2020 at our medical centre in New York City. Available isolates underwent nanopore sequencing for rapid genotyping, antibiotic resistance gene detection and phylogenetic analysis. RESULTS: We identified 31 CPE isolates from 13 patients, including 27 Klebsiella pneumoniae and 4 Enterobacter cloacae complex isolates. Most patients (11/13) had a positive respiratory culture and 7/13 developed bacteraemia; treatment failure was common. Twenty isolates were available for WGS. Most K. pneumoniae (16/17) belonged to ST258 and encoded KPC (15 KPC-2; 1 KPC-3); one ST70 isolate encoded KPC-2. E. cloacae isolates belonged to ST270 and encoded NDM-1. Nanopore sequencing enabled identification of at least four distinct ST258 lineages in COVID-19 patients, which were validated by Illumina sequencing data. CONCLUSIONS: While CPE prevalence has declined substantially in New York City in recent years, increased detection in patients with COVID-19 may signal a re-emergence of these highly resistant pathogens in the wake of the global pandemic. Increased surveillance and antimicrobial stewardship efforts, as well as identification of optimal treatment approaches for CPE, will be needed to mitigate their future impact.
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COVID-19/microbiologia , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Proteínas de Bactérias/genética , COVID-19/complicações , COVID-19/epidemiologia , Enterobacteriáceas Resistentes a Carbapenêmicos/enzimologia , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Estudos de Coortes , Comorbidade , Infecções por Enterobacteriaceae/complicações , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Sequenciamento por Nanoporos , Cidade de Nova Iorque/epidemiologia , Filogenia , Estudos Retrospectivos , SARS-CoV-2 , beta-Lactamases/genética , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: Polymyxins are antimicrobials of last resort for the treatment of carbapenem-resistant Enterobacteriaceae, but resistance in 5% to >40% isolates has been reported. We conducted a genomic survey of clinical polymyxin-resistant (PR) Klebsiella pneumoniae to determine the molecular mechanisms of PR and the role of polymyxin exposure versus transmission in PR emergence. METHODS: We included 88 patients with PR K. pneumoniae from 2011-2018 and collected demographic, antimicrobial exposure, and infection data. Whole-genome sequencing was performed on 388 isolates, including 164 PR isolates. Variant calling and insertion sequence detection were performed, focusing on key genes associated with PR (mgrB, crrAB, phoPQ, and pmrAB). We conducted phylogenetic analyses of key K. pneumoniae multi-locus sequence types (ST258, ST17, ST307, and ST392). RESULTS: Polymyxin exposure was documented in 53/88 (60%) patients prior to PR detection. Through an analysis of key PR genes, we detected 129 individual variants and 72 unique variant combinations in PR isolates. This included multiple, distinct changes in 36% of patients with serial PR isolates. Insertion sequence disruption was limited to mgrB (P < .001). Polymyxin minimum inhibitory concentrations showed stepwise increases with the number of PR genes affected (P < .001). When clusters containing PR isolates in ≥2 patients were analyzed, 10/14 had multiple genetic events leading to PR. CONCLUSIONS: Molecular mechanisms leading to PR in clinical K. pneumoniae isolates are remarkably heterogenous, even within clusters or individual patients. Polymyxin exposure with de novo PR emergence led to PR in the majority of patients, rather than transmission. Optimizing polymyxin use should be a key strategy in stopping the spread of PR.
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Infecções por Klebsiella , Klebsiella pneumoniae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Colistina , Farmacorresistência Bacteriana/genética , Genômica , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Filogenia , Polimixinas/farmacologia , Estudos RetrospectivosRESUMO
The role of compassion in healthcare is receiving increased attention as emerging research demonstrates how compassionate patient care can improve health outcomes and reduce workplace stress and burnout. To date, proposals to encourage empathy, kindness, and compassion in healthcare have focused primarily on training individual care providers. This article argues that increasing the awareness and skills of individuals is necessary but insufficient. Compassionate care becomes an organizational norm only when health leaders create and nurture a "culture of compassion" that actively supports, develops, and recognizes the role of compassion in day-to-day management and practice. The article profiles four organizations that have adopted compassionate healthcare as an explicit organizational priority and implemented practical measures for building and sustaining a culture of compassion. Common principles and practices are identified. These organizations demonstrate how compassion can lead directly to improved outcomes of primary importance to healthcare organizations, including quality and safety, patient experience, employee and physician engagement, and financial performance. They show how compassion can be a powerful yet often underappreciated tool for helping organizations successfully manage current challenges.
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Atenção à Saúde/métodos , Empatia , Cultura Organizacional , Atenção à Saúde/organização & administração , Humanos , Liderança , Qualidade da Assistência à SaúdeRESUMO
We demonstrate the application of the Dynamic Mode Decomposition (DMD) for the diagnostic analysis of the nonlinear dynamics of a magnetized plasma in resistive magnetohydrodynamics. The DMD method is an ideal spatio-temporal matrix decomposition that correlates spatial features of computational or experimental data while simultaneously associating the spatial activity with periodic temporal behavior. DMD can produce low-rank, reduced order surrogate models that can be used to reconstruct the state of the system with high fidelity. This allows for a reduction in the computational cost and, at the same time, accurate approximations of the problem, even if the data are sparsely sampled. We demonstrate the use of the method on both numerical and experimental data, showing that it is a successful mathematical architecture for characterizing the helicity injected torus with steady inductive (HIT-SI) magnetohydrodynamics. Importantly, the DMD produces interpretable, dominant mode structures, including a stationary mode consistent with our understanding of a HIT-SI spheromak accompanied by a pair of injector-driven modes. In combination, the 3-mode DMD model produces excellent dynamic reconstructions across the domain of analyzed data.
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OBJECTIVE To assess antimicrobial prescriber knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship (AS) and associated barriers to optimal prescribing. DESIGN Cross-sectional survey. SETTING Online survey. PARTICIPANTS A convenience sample of 2,900 US antimicrobial prescribers at 5 acute-care hospitals within a hospital network. INTERVENTION The following characteristics were assessed with an anonymous, online survey in February 2015: attitudes and practices related to antimicrobial resistance, AS programs, and institutional AS resources; antimicrobial prescribing and AS knowledge; and practices and confidence related to antimicrobial prescribing. RESULTS In total, 402 respondents completed the survey. Knowledge gaps were identified through case-based questions. Some respondents sometimes selected overly broad therapy for the susceptibilities given (29%) and some "usually" or "always" preferred using the most broad-spectrum empiric antimicrobials possible (32%). Nearly all (99%) reported reviewing antimicrobial appropriateness at 48-72 hours, but only 55% reported "always" doing so. Furthermore, 45% of respondents felt that they had not received adequate training regarding antimicrobial prescribing. Some respondents lacked confidence selecting empiric therapy using antibiograms (30%), interpreting susceptibility results (24%), de-escalating therapy (18%), and determining duration of therapy (31%). Postprescription review and feedback (PPRF) was the most commonly cited AS intervention (79%) with potential to improve patient care. CONCLUSIONS Barriers to appropriate antimicrobial selection and de-escalation of antimicrobial therapy were identified among front-line prescribers in acute-care hospitals. Prescribers desired more AS-related education and identified PPRF as the most helpful AS intervention to improve patient care. Educational interventions should be preceded by and tailored to local assessment of educational needs. Infect Control Hosp Epidemiol 2018;39:316-322.
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Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Atitude do Pessoal de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Farmacêuticos/psicologia , Médicos/psicologia , Competência Clínica , Estudos Transversais , Hospitais , Humanos , Prescrição Inadequada , Cidade de Nova Iorque , Padrões de Prática Médica , Inquéritos e QuestionáriosRESUMO
A retrospective study was conducted in hospitalized patients receiving intravenous polymyxin B who underwent therapeutic drug monitoring during treatment. The aim of this study was to assess the population pharmacokinetics (PK) of intravenous polymyxin B in patients with variable total body weights and create a population model for clinical use. Nonlinear mixed-effects modeling analyses were performed. A total of 43 patients were included, and 70% of these patients were male. The median age was 58 years, and the median weight was 78 kg. The median polymyxin B dose was 180 mg/day or 2.8 mg/kg/day. A one-compartment model described the polymyxin B PK well with conditional mean parameter estimates of a clearance (CL) of 2.37 liters/h and a volume of distribution of 34.4 liters and can be employed for clinical population modeling. Total body weight was not significantly associated with CL (Akaike information criterion, 361.6 for the weight-based model versus 359.5 for the non-weight-based model). These data suggest that dosing according to patient body weight requires further exploration. Greater study is needed to assess the relationships between polymyxin B exposures and efficacy and toxicity.
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Polimixina B/administração & dosagem , Polimixina B/farmacocinética , Administração Intravenosa , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Polymyxin B (PB) has reemerged as a common treatment against multidrug-resistant Gram-negative pathogens. However, nephrotoxicity remains a significant dose-limiting side effect, and contemporary pharmacokinetic (PK) data are limited. This study sought to evaluate PB exposure differences in various loading and nonloading strategies according to total body weight (TBW) and adjusted body weight (ABW). Patients treated with PB had plasma samples obtained for clinical care and analyzed using liquid chromatography-tandem mass spectrometry. Compartmental PK models with linear and allometric scaling of TBW were explored. Semiparametric Monte Carlo simulation evaluated the total (i.e., protein bound plus unbound) area under the plasma concentration-time curve (AUCtotal) during the first 24 h of therapy and at 96 h posttherapy for each regimen at the 10th, 50th, and 90th percentiles of TBW and ABW in the derivation cohort. Literature-based values of the 24-h total AUC/MIC ratio (AUC/MICtotal) of ≥50 defined efficacy, and literature-based values of the 72- to 96-h AUCtotal of ≥100 µg · h/ml defined toxicity. Fifty-two patients contributed 156 PB plasma samples. A two-compartment model with allometric scaling of TBW produced a comparable fit (Akaike information criterion [AIC] = 376.7) to that achieved with linear scaling (AIC = 378). The regimen of a loading dose of 2.5 mg/kg of body weight plus a fixed dose of 100 mg every 12 h had the highest probability of achieving a 24-h AUC/MICtotal of ≥50 with the lowest probability of toxicity in all groups at 24 h, aside from those with the lowest 10th percentile of body weight. This is the first study to suggest that a weight-based loading and fixed maintenance (i.e., weight-independent) dosing strategy for polymyxin B may maximize efficacy while balancing toxicity concerns for most patients.
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Antibacterianos/farmacocinética , Polimixina B/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Peso Corporal , Estado Terminal , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Polimixina B/farmacologia , Polimixina B/uso terapêuticoRESUMO
Occurrences of patient harm in healthcare represent a significant burden, with serious implications for patients and families and for the capacity of health systems to manage patient access, flow, and wait times. Interest in the science of high reliability, developed originally in industries such as commercial airlines that have demonstrated exceptional safety records, is an emerging trend in healthcare with the potential to help organizations and systems achieve the ultimate goal of zero patient harm. This article argues that zero patient harm is a fundamental imperative, and that high-reliability science can help to accelerate and sustain progress toward this vital goal. Although the practices used in other industries are not readily transferable to healthcare, and no single proven model for High Reliability Organizations in healthcare is yet available, leading organizations are beginning to demonstrate effective healthcare-specific strategies. Experience from Studer Group's international network of partner organizations is used to illustrate and understand these early efforts. Studer Group's Evidence-Based LeadershipSM framework is applied in diverse healthcare settings to provide a foundation of culture transformation and change management to support high reliability. It offers an approach and resources for moving forward toward the goal of zero patient harm, with concurrent benefits related to the efficient use of our valuable healthcare resources.
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Atenção à Saúde/organização & administração , Cultura Organizacional , Segurança do Paciente , Qualidade da Assistência à Saúde/organização & administração , Atenção à Saúde/normas , HumanosRESUMO
Les préjudices que subissent les patients recevant des soins de santé représentent un fardeau considérable et peuvent avoir de graves répercussions sur les patients et les familles ainsi que sur la capacité des systèmes de santé de gérer l'accès des patients, leurs déplacements dans le système et les temps d'attente. L'intérêt pour la science de la haute fiabilité, mise au point à l'origine dans des secteurs comme l'aviation commerciale, qui ont un bilan exceptionnel en matière de sécurité, est une nouvelle tendance en soins de santé qui pourrait aider les organisations et les systèmes à atteindre le but ultime : zéro préjudice subi par les patients. Cet article fait valoir que zéro préjudice au patient est un impératif fondamental et que la science de la haute fiabilité peut aider à accélérer et à soutenir les progrès vers ce but vital. Bien que les pratiques utilisées dans d'autres secteurs ne soient pas facilement transférables aux soins de santé et qu'il n'existe pas encore un seul modèle éprouvé pour les organisations à haute fiabilité en santé, des organisations de premier plan commencent à faire la démonstration de stratégies efficaces propres aux soins de santé. L'expérience du réseau international d'organisations partenaires du groupe Studer est utilisée pour illustrer et comprendre ces premiers efforts. Le cadre Evidence-Based LeadershipSM (leadership fondé sur les données probantes) du groupe Studer est appliqué dans différents milieux de soins de santé pour transformer la culture et la gestion du changement visant à favoriser une haute fiabilité. Il propose une démarche et des ressources pour progresser vers le but zéro préjudice subi par les patients et tous les avantages liés à l'utilisation efficiente de nos précieuses ressources en soins de santé.
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Atenção à Saúde/organização & administração , Cultura Organizacional , Segurança do Paciente , Qualidade da Assistência à Saúde/organização & administração , Atenção à Saúde/normas , HumanosRESUMO
In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of ampC alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at ≥72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older (P = 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of ampC genes revealed the presence of ampC in isolates with cefoxitin MICs below 16 µg/ml, in particular in Serratia spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing Enterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.
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Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Enterobacteriaceae/enzimologia , Ácido Penicilânico/análogos & derivados , beta-Lactamases/metabolismo , Idoso , Bacteriemia/microbiologia , Proteínas de Bactérias/genética , Estudos de Casos e Controles , Enterobacteriaceae/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Penicilânico/uso terapêutico , Fenótipo , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/genética , beta-Lactamases/genéticaRESUMO
OBJECTIVE A better understanding of the effects of chronically delivering compounds to the substantia nigra and nearby areas is important for the development of new therapeutic approaches to treat alpha-synucleinopathies, like Parkinson's disease. Whether chronic intranigral delivery of an infusate could be achieved without causing motor dysfunction or marked pathology remains unclear. The authors evaluated the tolerability of continuously delivering an infusate directly into the rhesus monkey substantia nigra via a programmable pump coupled to a novel intraparenchymal needle-tip catheter surgically implanted using MRI-guided techniques. METHODS The MRI contrast agent gadopentetate dimeglumine (Magnevist, 5 mM) was used to noninvasively evaluate catheter patency and infusion volume associated with 2 flow rates sequentially tested in each of 3 animals: 0.1 µl/min for 14 days into the right substantia nigra and 0.1 µl/min for 7 days plus 0.2 µl/min for an additional 7 days into the left substantia nigra. Flow rate tolerability was assessed via clinical observations and a microscopic examination of the striatum and midbrain regions. RESULTS Evaluation of postsurgical MRI indicated that all 6 catheters remained patent throughout the study and that the volume of distribution achieved in the left midbrain region at a rate of up to 0.2 µl/min (2052 ± 168 mm3) was greater than that achieved in the right midbrain region at a constant rate of 0.1 µl/min (1225 ± 273 mm3) by nearly 2-fold. Both flow rates provided sufficient infusate coverage of the rhesus (and possibly the human) midbrain region. There were no indications of observable deficits in behavior. Histopathological evaluations confirmed that all catheter tips were placed in or near the pars compacta region of the substantia nigra in all animals. There was no evidence of infection at any of the 6 catheter sites. Mild to moderate microglial reactions were observed at most catheter track sites and were comparable between the 2 infusion rates. Finally, there was neither observable decrease of tyrosine hydroxylase staining in the striatum nor detectable necrosis of neurons in the pars compacta region of the substantia nigra in any of the animals. CONCLUSIONS The data from this study support the feasibility of using a pump-and-catheter system for chronic intranigral infusion and lay the foundation for using this approach to treat Parkinson's disease or other related degenerative diseases that would benefit from targeted drug delivery to the substantia nigra or to other brainstem regions.
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Bombas de Infusão , Substância Negra , Animais , Cateteres de Demora , Meios de Contraste , Estudos de Viabilidade , Feminino , Gadolínio DTPA , Macaca mulatta , Imageamento por Ressonância Magnética , Modelos Animais , Segurança do Paciente , Substância Negra/diagnóstico por imagem , Substância Negra/patologiaRESUMO
Two-photon laser-induced fluorescence measurements were performed on the helicity injected torus (HIT-SI3) device to determine the density and temperature of the background neutral deuterium population. Measurements were taken in 2 ms long pulsed plasmas after the inductive helicity injectors were turned off. Attempts to measure neutrals during the main phase of the plasma were unsuccessful, likely due to the density of neutrals being below the detection threshold of the diagnostic. An unexpectedly low density of atomic deuterium was measured in the afterglow; roughly 100 times lower than the theoretical prediction of 1017 m-3. The neutral temperatures measured were on the order of 1 eV. Temporally and spatially resolved neutral density and temperature data are presented.
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Improving patient experience has emerged as an important healthcare policy priority across Canada. Tools and systems for monitoring patient experience metrics are becoming increasingly refined and standardized, and the trend toward greater accountability for improvements that are sustainable and affordable is well underway. For many healthcare professionals, this represents a renewed focus on core patient needs and priorities, following decades during which structural and technological changes have dominated healthcare agendas. Improving patient experience in our contemporary healthcare environment presents major challenges-and opportunities-for Canadian health leaders. The experience of Studer Group partner organizations in Canada is relevant and instructive in this context. These organizations have adopted a model known as Evidence-Based Leadership (EBL) that enables and supports the alignment of all activities and behaviours toward specific organizational goals, including measurable patient experience improvements. This article reviews case studies of organizations that have adopted EBL. These organizations are demonstrating rapid progress in patient experience indicators while simultaneously making gains in critical areas such as clinical outcomes, safety, physician and staff engagement, and financial performance. Emerging evidence concerning the factors and processes that underlie these improvements is also discussed.