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The clinical research units (CRUs) are one of the main spaces where both translational research and science take place. However, there is a lack of information about both best practices for CRU operations and, ultimately, benchmarks to evaluate CRU performance. The Research Unit Network (RUN) was created with the purpose to enable direct communication and collaboration among CRUs. An online survey was administered to further illustrate the functionality and impact of RUN. Thirty-one individual survey responses (39.2%) were included in the final analysis. The members value RUN monthly meetings (87.1%) as the most useful aspect of this network and CRU budgeting (67.7%) and staffing (61.3%) were the most relevant topics discussed. This is followed by EPIC – Research (58.1%), delegation of authority logs, unit signatures, and policies (51.6%), COVID-19 pandemic response (41.9%), the implementation of clinical trial management system (29.0%), and protocol deviations (19.4%). The intermediate goal of RUN is to identify best practices CRUs are establishing, implementing, and sharing these experiences with the goal to adopt them in different CRUs. The network’s long-term goal is to establish standard benchmarks that can be used for evaluating the performance of CRUs across the nation.
Late-life depression (LLD) is characterized by differences in resting state functional connectivity within and between intrinsic functional networks. This study examined whether clinical improvement to antidepressant medications is associated with pre-randomization functional connectivity in intrinsic brain networks.
Participants were 95 elders aged 60 years or older with major depressive disorder. After clinical assessments and baseline MRI, participants were randomized to escitalopram or placebo with a two-to-one allocation for 8 weeks. Non-remitting participants subsequently entered an 8-week trial of open-label bupropion. The main clinical outcome was depression severity measured by MADRS. Resting state functional connectivity was measured between a priori key seeds in the default mode (DMN), cognitive control, and limbic networks.
In primary analyses of blinded data, lower post-treatment MADRS score was associated with higher resting connectivity between: (a) posterior cingulate cortex (PCC) and left medial prefrontal cortex; (b) PCC and subgenual anterior cingulate cortex (ACC); (c) right medial PFC and subgenual ACC; (d) right orbitofrontal cortex and left hippocampus. Lower post-treatment MADRS was further associated with lower connectivity between: (e) the right orbitofrontal cortex and left amygdala; and (f) left dorsolateral PFC and left dorsal ACC. Secondary analyses associated mood improvement on escitalopram with anterior DMN hub connectivity. Exploratory analyses of the bupropion open-label trial associated improvement with subgenual ACC, frontal, and amygdala connectivity.
Response to antidepressants in LLD is related to connectivity in the DMN, cognitive control and limbic networks. Future work should focus on clinical markers of network connectivity informing prognosis.
Treatment for major depressive disorder (MDD) is imprecise and often involves trial-and-error to determine the most effective approach. To facilitate optimal treatment selection and inform timely adjustment, the current study investigated whether neurocognitive variables could predict an antidepressant response in a treatment-specific manner.
In the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial, outpatients with non-psychotic recurrent MDD were first randomized to an 8-week course of sertraline selective serotonin reuptake inhibitor or placebo. Behavioral measures of reward responsiveness, cognitive control, verbal fluency, psychomotor, and cognitive processing speeds were collected at baseline and week 1. Treatment responders then continued on another 8-week course of the same medication, whereas non-responders to sertraline or placebo were crossed-over under double-blinded conditions to bupropion noradrenaline/dopamine reuptake inhibitor or sertraline, respectively. Hamilton Rating for Depression scores were also assessed at baseline, weeks 8, and 16.
Greater improvements in psychomotor and cognitive processing speeds within the first week, as well as better pretreatment performance in these domains, were specifically associated with higher likelihood of response to placebo. Moreover, better reward responsiveness, poorer cognitive control and greater verbal fluency were associated with greater likelihood of response to bupropion in patients who previously failed to respond to sertraline.
These exploratory results warrant further scrutiny, but demonstrate that quick and non-invasive behavioral tests may have substantial clinical value in predicting antidepressant treatment response.
Background: Patients presenting to hospitals often arrive with peripherally inserted central catheters (PICC) in place upon admission. The admitting facility may not be familiar with that device’s history and the unknown risk for bloodstream infection associated with it often prompts requests for device replacement. A blanket approach to “change all lines” must be balanced with the potential for patient discomfort and insertion-related complications. To better inform our approach to prevention, we determined the incidence of central-line–associated bloodstream infection (CLABSI) in adult patients presenting to hospitals in our health system with a PICC present on admission (POA), relative to those who have a PICC placed after admission (PAA). Methods: This retrospective cohort study included all adult hospital encounters at 11 Cleveland Clinic acute-care hospitals lasting > 2 days in 2018 with electronic medical record nursing care flowsheet documentation of a PICC during the stay. Patients whose admission diagnosis was related to intravascular catheter infection, children aged <18 years, and observation unit encounters were excluded. Patients were categorized as having a PICC POA if a nurse selected that option on a PICC flowsheet, otherwise the patient was categorized has having a PICC PAA. Surveillance for CLABSI was performed in all inpatient locations at all hospitals according to the NHSN protocol. Patients with ≥1 CLABSI were matched to encounters by name and date of admission. Repeat infections occurring to the same patient were excluded. Results: Of the 8,827 eligible hospital encounters, 1,799 (20%) involved a PICC POA and 7,028 (80%) had PICCs PAA. Across 11 hospitals, the median proportion of PICC-associated encounters with a device POA was 15% (range, 8%–25%). Moreover, 23 of the 112 CLABSIs (21%) in our cohort occurred in patients with a PICC POA and 89 (79%) occurred in patients with a PICC PAA (Table 1). The overall relative risk of CLABSI, whether the PICC was placed before or after admission, was 1.00 (95% CI, 0.64–1.60). Conclusions: Patients with a PICC present on admission to our hospitals were no more likely to experience a CLABSI than patients who had a PICC placed after admission. Replacing vascular catheters that are POA may not reduce the risk of CLABSI. With up to 25% of PICC-associated encounters having the device POA, universal device replacement at admission would involve hundreds of patients per year at our multihospital health system.
Background: Weekly surveillance to identify neonatal intensive care unit (NICU) infants with methicillin-resistant S. aureus (MRSA) nasal colonization was performed using Remel Spectra MRSA chromogenic media. An increased MRSA colonization rate from baseline was detected in 2019, prompting additional review of all positive MRSA NICU screening cultures from 2019. Methods: A subset of 23 positive cultures were interrogated in detail. Species-level identification was confirmed using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) with a Bruker Biotyper. Penicillin-binding protein 2a (PBP2a) testing was performed using the Alere culture colony test, and cefoxitin and oxacillin susceptibility were assessed via Kirby-Bauer disk-diffusion methods (for the purpose of this analysis, oxacillin zone sizes 18 mm were considered susceptible). Molecular detection of mecA and mecC genes using PCR was performed. Results: All 23 isolates in the subset group were confirmed as S. aureus based on MALDI-TOF testing. Moreover, 8 isolates (35%) were confirmed as MRSA based on cefoxitin susceptibility, positive rapid PBP2a testing, and mecA PCR results. Overall, 15 isolates (65%) tested cefoxitin-susceptible and PBP2a negative with negative mecA and mecC gene testing. Of these, 1 (7%) tested oxacillin-susceptible based on disk-diffusion testing, consistent with methicillin-susceptible S. aureus (MSSA). The remaining 14 isolates (93%) tested oxacillin resistant based on oxacillin zone size. Conclusions: Our findings indicate the detection of mecA/mecC negative S. aureus isolates demonstrating oxacillin resistance and growth on Remel Spectra MRSA chromogenic media. These results have important implications for infection prevention surveillance efforts to detect MRSA and raise questions regarding optimal antibiotic therapy in patients with isolates displaying this phenotype.
Decisions on the use of nature reflect the values and rights of individuals, communities and society at large. The values of nature are expressed through cultural norms, rules and legislation, and they can be elicited using a wide range of tools, including those of economics. None of the approaches to elicit peoples’ values are neutral. Unequal power relations influence valuation and decision-making and are at the core of most environmental conflicts. As actors in sustainability thinking, environmental scientists and practitioners are becoming more aware of their own posture, normative stance, responsibility and relative power in society. Based on a transdisciplinary workshop, our perspective paper provides a normative basis for this new community of scientists and practitioners engaged in the plural valuation of nature.
Several reports have shown that doctoral and postdoctoral trainees in biomedical research pursue diverse careers that advance science meaningful to society. Several groups have proposed 3-tier career taxonomy to showcase these outcomes. This 3-tier taxonomy will be a valuable resource for institutions committed to greater transparency in reporting outcomes, to not only be transparent in reporting their own institutional data but also to lend greater power to a central repository.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Objectives: The aim of this study was to illustrate the contribution of stakeholder engagement to the impact of health technology assessment (HTA) using an Irish HTA of a national public access defibrillation (PAD) program.
Background: In response to draft legislation that proposed a PAD program, the Minister for Health requested that Health Information and Quality Authority undertake an HTA to inform the design and implementation of a national PAD program and the necessary underpinning legislation. The draft legislation outlined a program requiring widespread installation and maintenance of automatic external defibrillators in specified premises.
Methods: Stakeholder engagement to optimize the impact of the HTA included one-to-one interviews with politicians, engagement with an Expert Advisory Group, public and targeted consultation, and positive media management.
Results: The HTA quantified the clinical benefits of the proposed PAD program as modest, identified that substantial costs would fall on small/medium businesses at a time of economic recession, and that none of the programs modeled were cost-effective. The Senator who proposed the Bill actively publicized the HTA process and its findings and encouraged participation in the public consultation. Participation of key stakeholders was important for the quality and acceptability of the HTA findings and advice. Media management promoted public engagement and understanding. The Bill did not progress.
Conclusions: The HTA informed the decision not to progress with legislation for a national PAD program. Engagement was tailored to ensure that key stakeholders including politicians and the public were informed of the HTA process, the findings, and the advice, thereby maximizing acceptance. Appropriate stakeholder engagement optimizes the impact of HTA.
Two methods were used to obtain the sensitivity of chemical leaching depth to variations in the input parameters of the Pesticide Root Zone Model (PRZM). First a Plackett-Burman (PB) screening design was used to vary 35 PRZM inputs over seven ranges around a nominal value. Six of the seven ranges were approximately 0.1, 0.25, 0.5, 1.0, 5.0, and 15%, the seventh range was chosen to cover a range appropriate for a soybean herbicide applied preemergence in the Midwestern region defined by the USDA–SCS land resource region M. Next, Fourier amplitude sensitivity testing (FAST) was then used to vary from 19 to 25 parameters over four of the ranges previously tested. For the smaller parameter ranges the two methods typically gave equivalent results but the PB method required far fewer simulations. For the simulation of the Midwestern region where some parameter varied by larger amounts the relative magnitudes of the sensitivity coefficients obtained by the two methods were similar but the magnitude of the coefficients obtained using FAST were smaller than those obtained using PB.
Tsunamis and storms instigate sedimentological and geomorphological changes to the coastal system, both long-term and ephemeral. To accurately predict future coastal hazards, one must identify the records that are generated by the processes associated with these hazards and recognize what will be preserved. Using eyewitness accounts, photographs, and sedimentology, this study documents pre- and post-tsunami conditions and constrains the timing and process of depositional events during and following the 11 March 2011 Tohoku tsunami in the coastal system at El Garrapatero, Galapagos Islands. While the tsunami acted as both an erosional and depositional agent, the thick, fan-like sand sheet in El Garrapatero was primarily emplaced by overwash deposition during high tide from swell waves occurring between 19–25 March and 17–22 April 2011. The swell waves were only able to access the terrestrial coastal system via a channel carved by the 2011 Tohoku tsunami through the barrier sand dune. This combined deposit could result in an overestimation of the hazard if interpreted to be the result of only one event (either tsunami or wind-generated waves). An analogous sand layer, younger than 1390–1530 calyr BP, may record a similar, prior event.
Pollen analysis of a new core from Joe Lake indicates that the late Quaternary vegetation of northwestern Alaska was characterized by four tundra and two forest-tundra types. These vegetation types were differentiated by combining quantitative comparisons of fossil and modern pollen assemblages with traditional, qualitative approaches for inferring past vegetation, such as the use of indicator species. Although imprecisely dated, the core probably spans at least the past 40,000 yr. A graminoid-Salix tundra dominated during the later and early portions of the glacial record. The middle glacial interval and the transition from glacial to interglacial conditions are characterized by a graminoid-Betula-Salix tundra. A Populus forest-Betula shrub tundra existed during the middle potion of this transition, being replaced in the early Holocene by a Betula-Alnus shrub tundra. The modern Picea forest-shrub tundra was established by the middle Holocene. These results suggest that the composition of modem tundra communities in northwestern Alaska developed relatively recently and that throughout much of the late Quaternary, tundra communities were unlike the predominant types found today in northern North America. Although descriptions of vegetation variations within the tundra will always be restricted by the innate taxonomic limitations of their herb-dominated pollen spectra, the application of multiple interpretive approaches improves the ability to reconstruct the historical development of this vegetation type.
Objectives: When incorporating treatment effect estimates derived from a random-effect meta-analysis it is tempting to use the confidence bounds to determine the potential range of treatment effect. However, prediction intervals reflect the potential effect of a technology rather than the more narrowly defined average treatment effect. Using a case study of robot-assisted radical prostatectomy, this study investigates the impact on a cost-utility analysis of using clinical effectiveness derived from random-effects meta-analyses presented as confidence bounds and prediction intervals, respectively.
Methods: To determine the cost-utility of robot-assisted prostatectomy, an economic model was developed. The clinical effectiveness of robot-assisted surgery compared with open and conventional laparoscopic surgery was estimated using meta-analysis of peer-reviewed publications. Assuming treatment effect would vary across studies due to both sampling variability and differences between surgical teams, random-effects meta-analysis was used to pool effect estimates.
Results: Using the confidence bounds approach the mean and median ICER was €24,193 and €26,731/QALY (95%CI: €13,752 to €68,861/QALY), respectively. The prediction interval approach produced an equivalent mean and median ICER of €26,920 and €26,643/QALY (95%CI: -€135,244 to €239,166/QALY), respectively. Using prediction intervals, there is a probability of 0.042 that robot-assisted surgery will result in a net reduction in QALYs.
Conclusions: Using prediction intervals rather than confidence bounds does not affect the point estimate of the treatment effect. In meta-analyses with significant heterogeneity, the use of prediction intervals will produce wider ranges of treatment effect, and hence result in greater uncertainty, but a better reflection of the effect of the technology.