Estimating the association between antibiotic exposure and colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria using machine learning methods: a multicentre,prospective cohort study

ObjectivesThe aim of the study was to measure the impact of antibiotic exposure on the acquisition of colonization with extended-spectrum β-lactamase-producing Gram-negative bacteria (ESBL-GNB) accounting for individual- and group-level confounding using machine-learning methods.MethodsPatients hospitalized between September 2010 and June 2013 at six medical and six surgical wards in Italy, Serbia and Romania were screened for ESBL-GNB at hospital admission, discharge, antibiotic start, and after 3, 7, 15 and 30 days. Primary outcomes were the incidence rate and predictive factors of new ESBL-GNB colonization. Random forest algorithm was used to rank antibiotics according to the risk of selection of ESBL-GNB colonization in patients not colonized before starting antibiotics.ResultsWe screened 10 034 patients collecting 28 322 rectal swab samples. New ESBL-GNB colonization incidence with and without antibiotic treatment was 22/1000 and 9/1000 exposure-days, respectively. In the adjusted regression analyses, antibiotic exposure (hazard ratio (HR) 2.38; 95% CI 1.29–4.40), age 60–69 years (HR 1.19; 95% CI 1.05–1.34), and spring season (HR 1.25; 95% CI 1.14–1.38) were independently associated with new colonization. Monotherapy ranked higher als combination therapy in promoting ESBL-GNB colonization. Among monotherapy, cephalosporins ranked first followed by tetracycline (second), macrolide (fourth) and cotrimoxazole (seventh). Overall the ranking of cephalosporins was lower when used in combination. Among combinations not including cephalosporins, quinolones plus carbapenems ranked highest (eighth). Among sequential therapies, quinolones ranked highest (tenth) when prescribed within 30 days of therapy with cephalosporins.ConclusionsImpact of antibiotics on selecting ESBL-GNB at intestinal level varies if used in monotherapy or combination and according to previous antibiotic exposure. These finding should be explored in future clinical trials on antibiotic stewardship interventions.Clinical Trial registrationNCT01208519.     

雅安市精神障碍患者就诊情况及影响因素

目的 了解雅安市精神障碍患者就诊情况及影响因素，提高雅安市精神卫生服务利用质量。方法 采用分层整群随机抽样方法抽取雅安市6县2区9 000名居民作为调查对象，实际共8 876名完成调查。其中符合《精神障碍诊断与统计手册（第5版）》（DSM-5）诊断标准共1 106例，使用精神卫生服务利用调查表对精神障碍患者的就诊情况进行调查。采用χ²检验及Logistic二元回归对患者就诊情况的影响因素进行分析。结果 1 106例精神障碍患者中，曾到精神卫生专业机构就诊共173例，就诊率为15.64%（标化就诊率为15.62%）。就诊率排名后三位的病种为：物质相关及成瘾障碍（7.92%）、创伤及应激相关障碍（6.12%）、强迫及相关障碍（0.00%）。未就诊而采用自助方式者（求神拜佛、咨询亲友）共42例，其中汉族28例，少数民族14例。居住地为城市（OR=2.36，P<0.01）对精神障碍患者就诊有正向影响，家族史阴性（OR=0.49，P<0.01）、无就诊意愿（OR=0.07，P<0.01）对精神障碍患者就诊有负向影响。结论 雅安市精神障碍患者就诊率偏低，就诊方式以精神科住院及门诊就诊为主，居住地、家族史和就诊意愿影响精神障碍患者的就诊。     

Temperature Measurement by Sublimation Rate as a Process Analytical Technology Tool in Lyophilization

Product temperature (T_b) and drying time constitute critical material attributes and process parameters in the lyophilization process and especially during the primary drying stage. In the study, we performed a temperature measurement by the sublimation rate (TMbySR) to monitor the T_b value and determine the end point of primary drying. First, the water vapor transfer resistance coefficient through the main pipe from the chamber to the condenser (C_r) was estimated via the water sublimation test. The use of C_r value made it possible to obtain the time course of T_b from the measurement of pressure at the drying chamber and at the condenser. Second, a Flomoxef sodium bulk solution was lyophilized by using the TMbySR system. The outcome was satisfactory when compared with that obtained via conventional sensors. The same was applicable for the determination of the end point of primary drying. A laboratory-scale application of the TMbySR system was evidenced via the experiment using 220-, 440-, and 660-vial scales of lyophilization. The outcome was not dependent on the loading amount. Thus, the results confirmed that the TMbySR system is a promising tool in laboratory scale.     

Influence of the Punch Speed on the Die Wall/Powder Kinematic Friction During Tableting

Influence of the compaction speed on the final tablet properties is an important challenge during the scale-up of a solid dosage form. This strain rate sensitivity is generally attributed to the time dependent deformation behavior of the powder. In this work, we studied the influence of the speed on another important factor during compaction: friction between the tablet/powder and the die. An original experimental methodology was developed to study the evolution of the kinematic friction coefficient between the tablet and the die as a function of the sliding speed of the tablet on the die wall. This methodology made it possible to separate the speed used to make the tablet from the speed used to measure the friction coefficient. Results indicate that the kinematic coefficient of friction increases with the sliding speed following a logarithmic trend. This trend was observed for 4 different pharmaceutical excipients. Moreover, it was proved that the speed dependency is an intrinsic property of the friction between a tablet and a die lubricated using magnesium stearate.     

Pharmacological and pathological modulation of cerebral physiology

Homeostatic mechanisms exist to enable the supply of oxygen and glucose for cerebral metabolism and neuronal function. In health, cerebral autoregulation, neurogenic and metabolic processes ensure that the supply of these nutrients is adequate to meet metabolic requirements, thus preventing neuronal cell damage. The goals of neuroanaesthesia are to provide optimal operating conditions and provide adequate cerebral blood flow, often in the context of a vulnerable brain which is exposed to the physiological stress of surgical trauma. This article outlines how delivery of anaesthesia and disease processes affecting the brain modulate the mechanisms that regulate cerebral blood flow and metabolism.     

Cancer Drug Dosing in Chronic Kidney Disease and Dialysis

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