Summary Background Recent reductions in average door-to-balloon (D2B) times have not been associated with decreases in mortality at the population level. We investigated this seemingly paradoxical ...finding by assessing components of this association at the individual and population levels simultaneously. We postulated that the changing population of patients undergoing primary percutaneous coronary intervention (pPCI) contributed to secular trends toward an increasing mortality risk, despite consistently decreased mortality in individual patients with shorter D2B times. Methods This was a retrospective study of ST-elevation myocardial infarction (STEMI) patients who underwent pPCI between Jan 1, 2005, and Dec 31, 2011, in the National Cardiovascular Data Registry (NCDR) CathPCI Registry. We looked for catheterisation laboratory visits associated with STEMI. We excluded patients not undergoing pPCI, transfer patients for pPCI, patients with D2B times less than 15 min or more than 3 h, and patients at hospitals that did not consistently report data across the study period. We assessed in-hospital mortality in the entire cohort and 6-month mortality in elderly patients aged 65 years or older matched to data from the Centers for Medicare and Medicaid Services. We built multilevel models to assess the relation between D2B time and in-hospital and 6-month mortality, including both individual and population-level components of this association after adjusting for patient and procedural factors. Findings 423 hospitals reported data on 150 116 procedures with a 55% increase in the number of patients undergoing pPCI at these facilities over time, as well as many changes in patient and procedural factors. Annual D2B times decreased significantly from a median of 86 min (IQR 65–109) in 2005 to 63 min (IQR 47–80) in 2011 (p<0·0001) with a concurrent rise in risk-adjusted in-hospital mortality (from 4·7% to 5·3%; p=0·06) and risk-adjusted 6-month mortality (from 12·9% to 14·4%; p=0·001). In multilevel models, shorter patient-specific D2B times were consistently associated at the individual level with lower in-hospital mortality (adjusted OR for each 10 min decrease 0·92; 95% CI 0·91–0·93; p<0·0001) and 6-month mortality (adjusted OR for each 10 min decrease, 0·94; 95% CI 0·93–0·95; p<0·0001). By contrast, risk-adjusted in-hospital and 6-month mortality at the population level, independent of patient-specific D2B times, rose in the growing and changing population of patients undergoing pPCI during the study period. Interpretation Shorter patient-specific D2B times were consistently associated with lower mortality over time, whereas secular trends suggest increased mortality risk in the growing and changing pPCI population. The absence of association of annual D2B time and changes in mortality at the population level should not be interpreted as an indication of its individual-level relation in patients with STEMI undergoing primary PCI. Funding National Heart, Lung, and Blood Institute.
Summary Obstructive sleep apnoea (OSA) is a common disorder in which repetitive apnoeas expose the cardiovascular system to cycles of hypoxia, exaggerated negative intrathoracic pressure, and ...arousals. These noxious stimuli can, in turn, depress myocardial contractility, activate the sympathetic nervous system, raise blood pressure, heart rate, and myocardial wall stress, depress parasympathetic activity, provoke oxidative stress and systemic inflammation, activate platelets, and impair vascular endothelial function. Epidemiological studies have shown significant independent associations between OSA and hypertension, coronary artery disease, arrhythmias, heart failure, and stroke. In randomised trials, treating OSA with continuous positive airway pressure lowered blood pressure, attenuated signs of early atherosclerosis, and, in patients with heart failure, improved cardiac function. Current data therefore suggest that OSA increases the risk of developing cardiovascular diseases, and that its treatment has the potential to diminish such risk. However, large-scale randomised trials are needed to determine, definitively, whether treating OSA improves cardiovascular outcomes.
Abstract
Recent clinical data on vancomycin pharmacokinetics and pharmacodynamics suggest a reevaluation of current dosing and monitoring recommendations. The previous 2009 vancomycin consensus ...guidelines recommend trough monitoring as a surrogate marker for the target area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC). However, recent data suggest that trough monitoring is associated with higher nephrotoxicity. This document is an executive summary of the new vancomycin consensus guidelines for vancomycin dosing and monitoring. It was developed by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists vancomycin consensus guidelines committee. These consensus guidelines recommend an AUC/MIC ratio of 400–600 mg*hour/L (assuming a broth microdilution MIC of 1 mg/L) to achieve clinical efficacy and ensure safety for patients being treated for serious methicillin-resistant Staphylococcus aureus infections.
The selection of the right antibiotic and right dose necessitates clinicians understand the contribution of pharmacokinetic variability stemming from age‐related physiologic maturation and the ...pharmacodynamics to optimize drug exposure for clinical response. The complexity of selecting the right dose arises from the multiplicity of pediatric age groups, from premature neonates to adolescents. Body size and age (which relate to organ function) must be incorporated to optimize antibiotic dosing in this vulnerable population. In the effort to optimize and individualize drug dosing regimens, clinical pharmacometrics that incorporate population‐based pharmacokinetic modeling, Bayesian estimation, and Monte Carlo simulations are utilized as a quantitative approach to understanding and predicting the pharmacology and clinical and microbiologic efficacy of antibiotics. In addition, opportunistic study designs and alternative blood sampling strategies can serve as practical approaches to ensure successful conduct of pediatric studies. This review article examines relevant literature on optimization of antibiotic pharmacotherapy in pediatric populations published within the last decade. Specific pediatric antibiotic data, including beta‐lactam antibiotics, aminoglycosides, and vancomycin, are critically evaluated.
The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative ...pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, “Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews”, and recently issued a “Call to Action” to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure—one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
Osteoarticular Infections in Children Arnold, John C; Bradley, John S
Infectious disease clinics of North America,
09/2015, Letnik:
29, Številka:
3
Journal Article
Recenzirano
For a child with a suspected bone or joint infection, knowledge of the workup and initial therapy is important to provide quality care. Fever and pain are hallmarks of a pediatric osteoarticular ...infection, although occasionally the signs and symptoms can be more subtle. The use of C-reactive protein to diagnose and validate effective management of treatment has become standard. Multiple reports confirm the success of much shorter intravenous (IV) courses than traditionally taught. The ideal IV and oral antibiotic duration, as well as defining the markers indicating need for surgical intervention, are questions yet to be answered.
Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD).
To compare myocardial infarction (MI) and mortality rates between patients with ...nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort.
Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded.
Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main LM stenosis ≥50%) and distribution (1, 2, or 3 vessel).
The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality.
Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome.
In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.
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