Longer than 2 hours to antibiotics is associated with doubling of mortality in a multinational community-acquired bacterial meningitis cohort

To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I2 = 90.1%, 95% CI 71.9–98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180–362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28–4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03–3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital.

Investigating the Impact of Cloud Computing Vendor on the Adoption of Cloud Computing

Cloud computing offers significant impacts on organization by changing how information systems are developed, deployed, operated, maintained, and paid for. Therefore, the adoption of cloud computing becomes the focus of relevant research; however, previous studies have mostly studied the factors affecting cloud computing adoption from the perspective of adopters, ignoring the influence of the vendors. This study defines cloud service capability and develops scale to measure it from the perspective of cloud computing vendors to empirically examine the impact of the supply-side of cloud computing. The initial scale of cloud service capability is constructed using qualitative research, and the formal scale is obtained after two rounds of pretest. The statistical results of matched data collected from 132 cloud computing vendors and their users show that cloud service capability significantly affects cloud computing adoption. This study shifts the research perspective on cloud adoption to make theoretical contributions and management insights from the perspective of cloud computing vendors.

Intrinsic Rewards for Creativity and Employee Creativity to the Mediation Role of Knowledge Sharing and Intrinsic Motivation

The purpose of this research is to examine the mediating role of knowledge sharing and intrinsic motivation on the relationship between intrinsic rewards for creativity and employee creativity and furthermore explore the mediating role of intrinsic motivation on the relationship between intrinsic rewards for creativity and knowledge sharing. A total of 400 matched data were collected from employees and their immediate supervisors of four public universities in Afghanistan. The results revealed that knowledge sharing and intrinsic motivation mediated the linkage between intrinsic rewards for creativity and employee creativity, which comprises idea generation. The results have shown that the relationship between intrinsic rewards for creativity and knowledge sharing is mediated by intrinsic task motivation. The current research contributes to the employee creativity literature by empirically examining the mediating role of knowledge sharing and intrinsic motivation in the relationship between intrinsic rewards for creativity and employee creativity in the one hand and the mediating role of intrinsic motivation in the relationship between intrinsic rewards for creativity and employee creativity in other.

Telerobotic interventions from a distance: an initial experience in 3D phantom mapping

Introduction The current COVID-19 pandemic has fostered several accelerations in “remote” patient care such as video and telephone clinics, as well as multidisciplinary collaborations using online platforms with experts consulting the local teams from a distance. The next logical step would be to also offer remote-controlled interventions which the expert operator not on site, but in support of the local team. This is especially valuable for complex interventions when either patient or expert operator can not be present at the same place. Purpose We aimed to demonstrate that an expert operator located at far distance (Austria) could directly interact with the remote magnetic navigation system in London (UK) whilst mapping a 3D phantom using an electroanatomical mapping system. Method Two experienced operators of the magnetic navigation system were tasked with creating fast anatomic maps (FAM) of the atrial and ventricular chambers of a 3D phantom using remote magnetic navigation in combination with 3D electroanatomical mapping. One was located in the control room of the magnetic catheter lab (UK) and the second one was in Tirol, Austria and connected through a secure remote desktop connection (via high speed fibre optic cable). Using a solid tip magnetic catheter connected to a mechanical drive, all interactions with the system were carried out via the Odyssey platform. Acquisitions for right and left atrium, as well as right and left ventricles plus aorta was compared with regards to mapping duration, map completeness (as judged by the average distance of surface points from 3D CT scan reconstruction), total 3D map volume and need for additional radiation exposure during the mapping process. Results Mapping time and map completeness when performed by the distant operator was not inferior to the local operator and both did not require any additional radiation exposure during the mapping process. Table 1 demonstrates the mean parameters for each chamber, respectively. Figure 1 depicts the matched data for chamber completeness as compared for the LA (green= local operator, pink= distant operator) using a contrast CT scan as the gold standard. Conclusion Telerobotic 3D mapping of a 3D phantom from a distance was equally fast delivered from the control room as compared to an operator located 1200 km away without compromising on map completeness. This demonstrates the feasibility of telerobotic interventions and stress the need for remote collaboration which is especially valuable when travel of patients and/or physician experts is restricted. Funding Acknowledgement Type of funding sources: None. Matched data for aorta

A BIOMECHANICAL COMPARISON OF MATCHED FOUR-STRAND AND FIVE-STRAND SEMITENDINOSUS-GRACILIS GRAFTS

ABSTRACT Introduction: Recent studies have shown that the likelihood of semitendinosus-gracilis graft rupture is inversely correlated to its diameter. A graft can be prepared in a five-strand or four-strand fashion to increase its diameter. However, the biomechanical superiority of five-strand semitendinosus-gracilis grafts is still under debate. Objective: This study aimed to evaluate the biomechanical characteristics of matched four-strand and five-strand human semitendinosus-gracilis grafts. Methods: We evaluated semitendinosus-gracilis tendons harvested from ten fresh human male and female cadavers, aged 18-60 years. Four-strand or five-strand grafts were prepared with the tendons and fixed to wooden tunnels with interference screws. Each graft was submitted to axial traction at 20 mm/min until rupture; the tests were donor matched. Data were recorded in real time and included the analysis of the area, diameter, force, maximum deformation and stiffness of the grafts. Results: The diameter, area and tunnel size were significantly greater in the five-strand grafts than in the four-strand grafts. There were no significant differences in biomechanical properties. The area and diameter of the graft were positively correlated to stiffness, and inversely correlated to elasticity. There was no significant correlation between graft size and maximum force at failure, maximum deformation or maximum tension. Conclusion: Five-strand hamstring grafts have greater area, diameter and tunnel size than four-strand grafts. There were no significant differences in biomechanical properties. In this model using interference screw fixation, the increases in area and diameter were correlated with an increase in stiffness and a decrease in elasticity. Level of evidence V; biomechanical study.

Intergenerational connections to improve social well-being of older adults with ADRD: A research protocol

There is growing concern about social isolation, loneliness, and diminished emotional well-being among persons with ADRD who live in the community. Research suggests that reminiscence strategies, especially with the production of a digital story book, combined with an intergenerational approach may yield significant benefits for older adults. Reminiscence approaches are typically implemented by trained professionals. However, the use of trained volunteers is of growing interest due to the costs associated with reminiscence programs. This research protocol describes the development and testing of an intergenerational, telephone-based reminiscence program offered by trained, young adult volunteers that includes the use of digital storytelling (DST). Specifically, the study addresses three aims: 1) Quantitatively test the effectiveness in improving social and emotional well-being of older adults with ADRD; 2) Quantitatively test attitudes towards aging and knowledge and awareness of ADRD disease among the young adults; and (3) Qualitatively evaluate the usefulness of this intervention from perspectives of the dyads. A randomized control trial is used to assess the effects of the intervention using an explanatory sequential mixed methods design. The older and younger participants (n = 92 dyads) are randomly assigned to intervention (reminiscence) or sham (social visit) group, and then randomly matched. Data are collected at baseline, mid-intervention, post- intervention, 3 months-post intervention and through qualitative interviews (selected dyads). The proposed evaluation activities will allow us to determine the applicability of intergenerational reminiscence with DST as an effective intervention for supporting the social and emotional needs of persons with ADRD.

Denture Use and Cognitive Decline in Chinese Older Adults: A Propensity Score Analysis

Using data from the Chinese Longitudinal Healthy Longevity Survey (2011 to 2018), we examined the effect of denture use on cognitive decline (assessed by the Mini-Mental State Examination [MMSE]) among 1,316 cognitively normal older adults with severe tooth loss (≤9 remaining teeth) at baseline. We generated propensity scores for weighted and matched analyses using 18 covariates, classified as socio-demographics, health-related behaviors, health status, and oral health conditions. The results show that non-denture users had worse cognitive decline than denture users. In the kernel-based matched data, the difference in the declined score of cognitive function between denture and non-denture users was 2.25 (95%CI=1.37 to 3.13). In the weighted data, the difference in cognitive function score was 2.14 (95% CI=1.35 to 2.94). Using dentures is beneficial for cognitive health in older adults with severe tooth loss, suggesting that prosthodontic rehabilitation with dentures might have benefits beyond restoring oral functioning.

Clonal Evolution Pattern and Prognostic Significance of Clonal Architecture in KMT2A-Rearranged Acute Myeloid Leukemia

MLL (KMT2A) rearrangements are among the most frequent chromosomal abnormalities that occur in acute myeloid leukemia (AML). Mutational landscapes in KMT2A-rearranged AML have been reported; however, most studies are missing data at relapse. Therefore, matched diagnostic and relapse samples were analyzed in this study, and the clonal evolution pattern in KMT2A-rearranged AML was examined. Further, the prognostic significance of the clonal architecture was investigated. Sixty-two diagnostic and 16 relapse samples obtained from pediatric patients with KMT2A-rearranged AML enrolled in the Japan Children's Cancer Group (JCCG) AML-05/AML-99 study were analyzed for 338 genes using targeted sequencing. The data were analyzed with the published data of 105 diagnostic and 9 relapse samples with KMT2A-rearranged AML. Additionally, as a control, the mutation data of matched diagnostic and relapse samples of 107 patients with non-KMT2A-rearranged AML were collected. Among 25 patients with KMT2A-rearranged AML with matched data at diagnosis and relapse, mutations of signaling pathway genes (FLT3, KRAS, NRAS, PTPN11, CBL, and BRAF) were frequently detected in diagnostic samples (25 mutations/25 patients). However, 21 of 25 (84.0%) mutations were lost at relapse. In contrast, 7 of 19 (36.8%) mutations of other pathway genes were lost at relapse, and the percentage was significantly lower than that of mutations in the signaling pathway genes (P = 0.002). Six mutations in the signaling pathway genes and 11 mutations in other pathway genes were acquired at relapse. Particularly, mutations of transcription factor genes (WT1, SPI1, GATA2, and RUNX1) were acquired at relapse: 7 of 8 (87.5%) mutations were detected only at relapse. These results suggest that mutations of signaling pathway genes are unstable in the clonal evolution of KMT2A-rearranged AML. Mutations of other pathway genes, especially those of transcription factor genes, may contribute to relapse in patients with KMT2A-rearranged AML. Next, attention was turned to the KRAS mutations (KRAS-MT) because we have previously shown that KRAS-MT are independent adverse prognostic factors in KMT2A-rearranged AML (Blood Adv. 2020). Among 25 patients with KMT2A-rearranged AML with matched data at diagnosis and relapse, 10 (40.0%) patients harbored KRAS-MT at diagnosis. Interestingly, KRAS-MT were lost at relapse in 9 of 10 (90.0%) patients. Among 107 patients with non-KMT2A-rearranged AML with matched data at diagnosis and relapse, 10 (9.3%) patients harbored KRAS-MT at diagnosis. The frequency of KRAS-MT was significantly higher in KMT2A-rearranged AML (40.0% vs. 9.3%, P = 0.0006). This may be explained on the basis of the fact that KRAS-MT is associated with a high relapse rate in KMT2A-rearranged AML, but not in non-KMT2A-rearranged AML. KRAS-MT was lost at relapse in 5 of 10 (50.0%) patients with non-KMT2A-rearranged AML. The percentage of KRAS-MT loss at relapse was higher in KMT2A-rearranged AML. However, it was not statistically significant (90.0% vs. 50.0%, P = 0.14). Therefore, KRAS-MT may be unstable in clonal evolution regardless of disease subtypes in AML. The underlying mechanisms of the paradox between the high relapse rate in patients with KRAS-MT and frequent loss of KRAS-MT at relapse in patients with KMT2A-rearranged AML should be examined in future studies. The loss of KRAS-MT at relapse suggests that the mutations were in subclones at diagnosis. Therefore, we finally examined the prognosis of 167 patients according to the clonality of KRAS-MT at diagnosis. In patients with KMT2A-MLLT3 (n = 67), those with subclonal KRAS-MT (n = 6) had adverse 5-y event-free survival compared with both patients with wild-type KRAS (KRAS-WT) (n = 56) (KRAS-WT vs. subclonal KRAS-MT: 58.7% vs. 16.7%, P = 0.04) and patients with clonal KRAS-MT (n = 5) (clonal KRAS-MT vs. subclonal KRAS-MT: 80.0% vs. 16.7%, P = 0.07). However, 5-y overall survival (OS) was similar among the three groups. In contrast, among patients with KMT2A-MLLT10 (n = 37), those with clonal KRAS-MT (n = 5) had adverse 5-y OS compared with both patients with KRAS-WT (n = 20) (KRAS-WT vs. clonal KRAS-MT: 59.7% vs. 0.0%, P = 0.006) and patients with subclonal KRAS-MT (n = 12) (subclonal KRAS-MT vs. clonal KRAS-MT: 58.3% vs. 0.0%, P = 0.04). According to these results, the effects of the clonality of KRAS-MT on prognosis may depend on which KMT2A fusion is present. Disclosures Nannya: Otsuka Pharmaceutical Co., Ltd.: Consultancy, Speakers Bureau; Astellas: Speakers Bureau. Saito: Toshiba corporation: Research Funding. Ogawa: Kan Research Laboratory, Inc.: Consultancy, Research Funding; Otsuka Pharmaceutical Co., Ltd.: Research Funding; Dainippon-Sumitomo Pharmaceutical, Inc.: Research Funding; Eisai Co., Ltd.: Research Funding; Ashahi Genomics: Current holder of individual stocks in a privately-held company; ChordiaTherapeutics, Inc.: Consultancy, Research Funding.

The Spread of Plasmidic AmpC in a General Lebanese Hospital Over Nine Consecutive Years and the Relationship With Restricted Isolation Protocols

Background: The dreaded bacterial infection by extended-spectrum β-lactamases (ESBL)-producers has always troubled the medical field whether on the public, scientific, or clinical levels. One of the lesser known β-lactamases, which is capable of hydrolyzing broad and extended-spectrum cephalosporins—i.e., cephamycins plus oxyimino-β-lactams—are the AmpC β-lactamases. This group, which has also been termed occasionally—and incorrectly—as ESBL Class C, confers resistance to β-lactamase inhibitors. The prevalence of plasmidic AmpC (pAmpC) strains is possibly still a matter of debate considering the unevenly matched data between phenotypically-detected and molecularly-detected pAmpC.Aim: In the absence of any study in Lebanon addressing the AmpC, our intention was to determine the numbers and percentages of AmpC Enterobacteriaceae isolates, notably plasmid-mediated ones, across different wards at the Centre Hospitalier du Nord (CHN), Lebanon, and highlight the importance of infection control protocols.Materials and Methods: Carriage and infection with pAmpC Enterobacteriaceae were retrospectively investigated between 2011 and 2015 and prospectively between 2016 and 2019 at the Centre Hospitalier du Nord Hospital, North Lebanon. The rise or decline in the numbers of such strains, in concordance with the allegedly intensive isolation of the patients, were analyzed.Results: Intensive care unit (ICU) data shows an initial rise in infection isolates from 2012 to 2014 and in the carriage isolates from 2012 to 2013 with later notable overall decrease in the both isolates' numbers with the application of the isolation protocols at CHN from 2014 onwards. Floors 2, 3, and 4 seemed to house the bulk of the isolates as well.Conclusion: Preventive measures, such as on-going surveillance of the hospital wards by specialized healthcare personnel and strict implementation of infection control practices, should be a top priority in any medical center in order to isolate such strains and try to put a limit for the development and the dissemination of any possible multidrug resistant strains.