Empirical prescribing of penicillin G/V reduces risk of readmission of hospitalized patients with community-acquired pneumonia in Norway: a retrospective observational study.
挪威青霉素g/V 经验性处方降低社区获得性肺炎住院患者再入院风险: 一项回顾性观察性研究。
- 作者列表："Høgli JU","Garcia BH","Svendsen K","Skogen V","Småbrekke L
BACKGROUND:Norwegian guideline recommendations on first-line empirical antibiotic prescribing in hospitalised patients with community-acquired pneumonia (CAP) are penicillin G/V in monotherapy, or penicillin G in combination with gentamicin (or cefotaxime) in severely ill patients. The aim of this study was to explore how different empirical antibiotic treatments impact on length of hospital stay (LOS) and 30-day hospital readmission. A secondary aim was to describe median intravenous- and total treatment duration. METHODS:We included CAP patients (≥18 years age) hospitalised in North Norway during 2010 and 2012 in a retrospective study. Patients with negative chest x-ray, malignancies or immunosuppression or frequent readmissions were excluded. We collected data on patient characteristics, empirical antibiotic prescribing, treatment duration and clinical outcomes from electronic patient records and the hospital administrative system. We used directed acyclic graphs for statistical model selection, and analysed data with mulitvariable logistic and linear regression. RESULTS:We included 651 patients. Median age was 77 years [IQR; 64-84] and 46.5% were female. Median LOS was 4 days [IQR; 3-6], 30-day readmission rate was 14.4% and 30-day mortality rate was 6.9%. Penicillin G/V were empirically prescribed in monotherapy in 51.5% of patients, penicillin G and gentamicin in combination in 22.9% and other antibiotics in 25.6% of patients. Prescribing other antibiotics than penicillin G/V monotherapy was associated with increased risk of readmission [OR 1.9, 95% CI; 1.08-3.42]. Empirical antibiotic prescribing was not associated with LOS. Median intravenous- and total treatment duration was 3.0 [IQR; 2-5] and 11.0 [IQR; 9.8-13] days. CONCLUSIONS:Our findings show that empirical prescribing with penicillin G/V in monotherapy in hospitalised non-severe CAP-patients, without complicating factors such as malignancy, immunosuppression and frequent readmission, is associated with lower risk of 30-day readmission compared to other antibiotic treatments. Median total treatment duration exceeds treatment recommendations.
背景: 挪威指南关于社区获得性肺炎 (CAP) 住院患者一线经验性抗生素处方的建议是单药治疗中的青霉素g/V,或青霉素g 联合庆大霉素 (或头孢噻肟) 治疗重症患者。本研究的目的是探讨不同的经验性抗生素治疗对住院时间 (LOS) 和 30 天再入院的影响。次要目的是描述静脉和总治疗持续时间的中位数。 方法: 我们纳入了 2010 年至 2012 年期间在挪威北部住院的 CAP 患者 (≥ 18 岁) 的回顾性研究。排除胸片阴性、恶性肿瘤或免疫抑制或频繁再入院的患者。我们从电子患者记录和医院管理系统中收集了患者特征、经验性抗生素处方、治疗持续时间和临床结局的数据。我们使用有向无环图进行统计模型选择，并用多变量 logistic 和线性回归分析数据。 结果: 我们纳入了 651 例患者。中位年龄为 77 岁 [IQR; 64-84]，46.5% 为女性。中位 LOS 为 4 天 [IQR; 3-6]，30 天再入院率为 14.4%，30 天死亡率为 6.9%。青霉素g/V 在 51.5% 的患者单药治疗中经验性处方，青霉素g 和庆大霉素在 22.9% 的患者中联合使用，其他抗生素在 25.6% 的患者中使用。处方除青霉素 G/V 单药治疗外的其他抗生素与再入院风险增加相关 [OR 1.9，95% CI; 1.08-3.42]。经验性抗生素处方与 LOS 无关。静脉和总治疗持续时间中位数分别为 3.0 [IQR; 2-5] 和 11.0 [IQR; 9.8-13] 天。 结论: 我们的研究结果表明，住院非严重 CAP 患者单药治疗中使用青霉素g/V 的经验性处方，没有恶性肿瘤、免疫抑制和频繁再入院等复杂因素。与其他抗生素治疗相比，30 天再入院的风险较低。中位总治疗持续时间超过治疗建议。
METHODS:BACKGROUND AND PURPOSE:A critical role for sphingosine kinase/sphingosine-1-phosphate (S1P) pathway in the control of airway function has been demonstrated in respiratory diseases. Here, we address S1P contribution in a mouse model of mild chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH:C57BL/6J mice have been exposed to room air or cigarette smoke up to 11 months and killed at different time points. Functional and molecular studies have been performed. KEY RESULTS:Cigarette smoke caused emphysematous changes throughout the lung parenchyma coupled to a progressive collagen deposition in both peribronchiolar and peribronchial areas. The high and low airways showed an increased reactivity to cholinergic stimulation and α-smooth muscle actin overexpression. Similarly, an increase in airway reactivity and lung resistances following S1P challenge occurred in smoking mice. A high expression of S1P, Sph-K2 , and S1P receptors (S1P2 and S1P3 ) has been detected in the lung of smoking mice. Sphingosine kinases inhibition reversed the increased cholinergic response in airways of smoking mice. CONCLUSIONS AND IMPLICATIONS:S1P signalling up-regulation follows the disease progression in smoking mice and is involved in the development of airway hyperresponsiveness. Our study defines a therapeutic potential for S1P inhibitors in management of airways hyperresponsiveness associated to emphysema in smokers with both asthma and COPD.
METHODS::The interim results from this 90-day multi-dose, inhalation toxicology study with life-time post-exposure observation has shown an important fundamental difference in persistence and pathological response in the lung between brake dust derived from brake-pads manufactured with chrysotile, TiO2 or chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. In the brake dust exposure groups no significant pathological response was observed at any time. Slight macrophage accumulation of particles was noted. Wagner-scores, were from 1 to 2 (1 = air-control group) and were similar to the TiO2 group. Chrysotile being biodegradable, shows a weakening of its matrix and breaking into short fibers & particles that can be cleared by alveolar macrophages and continued dissolution. In the chrysotile exposure groups, particle laden macrophage accumulation was noted leading to a slight interstitial inflammatory response (Wagner-score 1-3). There was no peribronchiolar inflammation and occasional very slight interstitial fibrosis. The histopathology and the confocal analyses clearly differentiate the pathological response from amphibole asbestos, crocidolite and amosite, compared to that from the brake dust and chrysotile. Both crocidolite and amosite induced persistent inflammation, microgranulomas, and fibrosis (Wagner-scores 4), which persisted through the post exposure period. The confocal microscopy of the lung and snap-frozen chestwalls quantified the extensive inflammatory response and collagen development in the lung and on the visceral and parietal surfaces. The interim results reported here, provide a clear basis for differentiating the effects from brake dust exposure from those following amphibole asbestos exposure. The subsequent results through life-time post-exposure will follow.
METHODS::The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, 'hybrid' mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.