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The hypothalamic-pituitary-adrenal axis (HPA) is highly relevant in depressive disorders. Some investigations suggest that the HPA axis is altered in depressive disorders as indicated by higher awakening cortisol levels. There are also some results that show relations between cortisol level, psychopathology and neuropsychological performance. However, a systematic investigation of this relationship with a large and matched sample of patients and controls is missing. We tested 59 patients with depressive disorders and 75 healthy controls with tasks from the neuropsychological CANTAB and NEUROBAT battery. Before and after these tests we collected salivary samples. The study ended followed with an extensive measurement of psychopathology (e. g. BDI, HAM-D) and mood (visual analog scales).
The study revealed a significant relationship between salivary cortisol and results in tasks to executive function in the neuropsychological assessment in the control group but not in the patient group. There was no relationship between salivary cortisol and other cognitive performances. While patients with higher salivary cortisol levels reported worse mood, higher salivary levels in healthy controls were associated with better mood. These results could be related to different stress levels and different expectations regarding the examination of the groups.
Neuropsychological impairment in depression is less concise compared to schizophrenia, dementia or other brain disorders. It is varying between patients and over time in the natural course of depression. Furthermore it depends on various co-variables. These characteristics make the detection of depressive patterns in neuropsychological performance very difficult for conventional statistics.
Artificial neural networks are highly parallel nonlinear teachable systems of information processing. They are used for pattern recognition and classification tasks in different fields and can be superior to conventional linear statistics in the analysis of complex data.
The results of 1100 neuropsychological examinations of psychiatric patients with varying diagnoses and healthy controls were used to train different kinds of neural networks. The neuropsychological battery (NEUROBAT) consists of usual test paradigms as optical reaction time, a go-nogo task, recognition and free memory recall, sensorimotor interference and a continuous performance task.
Trained multilayer perceptrons and radial basis function networks allowed a significant recognition of depressive patterns. Patients were classified correctly in up to 71% of cases, whereas up to 64% of depressive disorders were recognized correctly by linear artificial neural networks.
Recognition of depressive neuropsychological patterns seems to be possible by artificial neural networks. But sensitivity and specificity are too low for a possible support of clinical diagnostics. The superiority to linear classification models could not shown clearly. More complex hierarchical neural networks, as they are commonly used in picture recognition, should be tested in future studies in order to improve classification results.
Negative computer attitude has been shown to be a possible co-variable in computerized examinations of psychiatric patients, affecting patient-computer interaction as well as reliability and validity of assessment (Weber et al. 2002, Acta Psychiatr.Scand., 105, 126-130).
It remains still uncertain if the psychological construct of computer attitude can be dependably measured in acute psychiatric inpatients or whether it is impeded by the effects of mental illness. For that reason a German translation of the Groningen Computer Attitude Scale (GCAS) was evaluated in 160 acute psychiatric inpatients under naturalistic conditions.
General test criteria (internal structure, item analysis, internal consistency, split half reliability) to a large extent corresponded to those formerly found in healthy subjects and psychiatric outpatients. The mean GCAS score was calculated as 56.2 ± 10.8 points and a significantly better computer attitude was found in male, better educated and younger patients. Some diverging correlation patterns were found in diagnostic subgroups, indicating a possible minor impact of mental disorder on computer attitude.
Overall, the GCAS was found to be a suitable instrument for measuring computer attitude in acute psychiatric inpatients. It should be used in identifying patients with a negative attitude to computers in order to ensure reliability and validity of computerized assessment.
Impairment of memory function in depressive patients is discussed controversially. At least memory impairment might be expected in more complex and effortful memory tasks.
80 patients with recurrent depressive disorder (ICD-10: F33) were compared to healthy controls in two computerized memory tasks (NEUROBAT verbal recognition and nonverbal free recall). Psychopathology (HDRS, BDI, mood scales) and computer attitude as well as computer experience were controlled as possible co-variables. A correlation between performance in computerized neuropsychological assessment and computer attitude had been found in former studies (Weber et al. 2002, Acta Psychiatr.Scand., 105, 126-130).
Unexpectedly in older patients poorer memory performance could be shown in the simple recognition task and not in the more effortful free recall. No correlations were found to depressive psychopathology. Significant correlations between computer experience and recognition task performance indicate that computer operation might be regarded as a relevant additional executive demand. The additional executive demand seems to cause a relevant inhibition of memory function in patients with lower degree of automation in computer operation.
The results of the present study confirm the well known difficulties in interpretation of neuropsychological test results in depression. The impairment by computer operation demands predominantly concerns female and older patients. Computer experience and computer attitude should be measured routinely concomitant to computerized neuropsychological assessment. Non-computerized tests should be used additionally in order to confirm results if necessary.
Furthermore the inhibition of distinct cognitive functions by additional executive demands might be regarded as a neuropsychological dimension of depressive psychopathology.
The present open study investigates the feasibility of Mindfulness-based cognitive therapy (MBCT) in groups solely composed of bipolar patients of various subtypes. MBCT has been mostly evaluated with remitted unipolar depressed patients and little is known about this treatment in bipolar disorder.
Bipolar outpatients (type I, II and NOS) were included and evaluated for depressive and hypomanic symptoms, as well as mindfulness skills before and after MBCT. Patients’ expectations before the program, perceived benefit after completion and frequency of mindfulness practice were also recorded.
Of 23 included patients, 15 attended at least four MBCT sessions. Most participants reported having durably, moderately to very much benefited from the program, although mindfulness practice decreased over time. Whereas no significant increase of mindfulness skills was detected during the trial, change of mindfulness skills was significantly associated with change of depressive symptoms between pre- and post-MBCT assessments.
MBCT is feasible and well perceived among bipolar patients. Larger and randomized controlled studies are required to further evaluate its efficacy, in particular regarding depressive and (hypo)manic relapse prevention. The mediating role of mindfulness on clinical outcome needs further examination and efforts should be provided to enhance the persistence of meditation practice with time.
Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions – particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost–benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.
To measure the association between statewide adoption of the Centers for Disease Control and Prevention’s (CDC’s) Core Elements for Hospital Antimicrobial Stewardship Programs (Core Elements) and hospital-associated methicillin-resistant Staphylococcus aureus bacteremia (MRSA) and Clostridioides difficile infection (CDI) rates in the United States. We hypothesized that states with a higher percentage of reported compliance with the Core Elements have significantly lower MRSA and CDI rates.
All US states.
Observational longitudinal study.
We used 2014–2016 data from Hospital Compare, Provider of Service files, Medicare cost reports, and the CDC’s Patient Safety Atlas website. Outcomes were MRSA standardized infection ratio (SIR) and CDI SIR. The key explanatory variable was the percentage of hospitals that meet the Core Elements in each state. We estimated state and time fixed-effects models with time-variant controls, and we weighted our analyses for the number of hospitals in the state.
The percentage of hospitals reporting compliance with the Core Elements between 2014 and 2016 increased in all states. A 1% increase in reported ASP compliance was associated with a 0.3% decrease (P < .01) in CDIs in 2016 relative to 2014. We did not find an association for MRSA infections.
Increasing documentation of the Core Elements may be associated with decreases in the CDI SIR. We did not find evidence of such an association for the MRSA SIR, probably due to the short length of the study and variety of stewardship strategies that ASPs may encompass.
Clonal Mycobacterium mucogenicum isolates (determined by molecular typing) were recovered from 19 bronchoscopic specimens from 15 patients. None of these patients had evidence of mycobacterial infection. Laboratory culture materials and bronchoscopes were negative for Mycobacteria. This pseudo-outbreak was caused by contaminated ice used to provide bronchoscopic lavage. Control was achieved by transitioning to sterile ice.
Environmental scientists and managers increasingly recognize that socio-cultural evaluations expand the understanding of human–nature relationships. Here, user groups’ perceptions of the benefits from and threats to nature were analysed in Tierra del Fuego National Park, Argentina. We hypothesized that the different relationships of users to this place would lead to significantly different valuations among local Ushuaia residents (n = 122), Argentine nationals (n = 147) and international tourists (n = 294). All users perceived a broad spectrum of benefits. The three groups assessed intrinsic and relational values more highly than instrumental benefits, and significant differences included a higher mean valuation of benefits by Argentine visitors. Overall, threats were less perceived than benefits, and significant differences included a higher mean threat assessment by Ushuaia residents. To explain these relationships, we found that mean valuations of benefits and threats were weakly related to increased biodiversity knowledge for residents and international tourists, but not for Argentine visitors. These findings can orient environmental management in Patagonia and elsewhere by identifying areas where information can improve user experiences and by contributing a more pluralistic understanding of nature from multiple stakeholders.
OBJECTIVES/SPECIFIC AIMS: Triple-negative breast cancer (TNBC) accounts for one-fifth of the breast cancer patient population. The heterogeneous nature of TNBC and lack of options for targeted therapy make its treatment a constant adventure. The deficiency of tumor suppressors p53 and ARF is one of the known genetic signatures enriched in TNBC. Crucial questions remain about how TNBC is regulated by these genetic alterations. METHODS/STUDY POPULATION: In order to address this issue, we established p53/ARF-defective murine embryonic fibroblast and mammary epithelial cell to study the molecular and phenotypic consequences. Moreover, transgenic mice were generated to investigate the effect of p53/ARF deficiency on mammary tumor development in vivo. RESULTS/ANTICIPATED RESULTS: Increased proliferation and transformation capability were observed in p53/ARF-defective cells, and an aggressive form of mammary tumor was also seen in p53−/−ARF−/− mice. Gene expression profiling and knock-down experiments using shRNAs were conducted to identify inflammatory marker ISG15 and RNA-editing enzyme ADAR1 as potential culprits for the elevated oncogenic potential. Interestingly, we found that the overexpression of ISG15 and ADAR1 is also prevalent in human TNBC cell lines. Reducing ADAR1 expression abrogated the oncogenic potential of human TNBC cell lines, while non-TNBC cells are less susceptible. DISCUSSION/SIGNIFICANCE OF IMPACT: These results indicate critical roles played by the tumor suppressors p53 and ARF in the pathogenesis of TNBC, likely through regulating ADAR1-mediated RNA modifications. Further understanding of this pathway promises to shed light on genetics-driven vulnerabilities of TNBC and inform development of more effective therapeutic strategies.
Introduction: Emergency departments (EDs) are overcrowded and patient acuity and volumes are ever-increasing. While changes to the flow of ED patient input and output are outside the control of frontline ED teams, the efficiency of ED throughput can be optimized. One widely studied intervention is the implementation of a physician liaison role to assist in managing overall ED flow. The Physician Float (PF) acts as a triage liaison, second physician for resuscitations, ED procedural sedation physician, and fields ED referral calls. This is a first-iteration proof-of-concept trial to plan, implement and evaluate if the PF role could decrease ED length of stay (LOS) by a goal of 30 minutes, over a four-week period, without adverse changes to left without being seen (LWBS) and bounce-back rates. Methods: The PF role was implemented as a scheduled emergency physician shift in the fall of 2017. Ongoing iterations of this role implementation are being reviewed for re-implementation. The primary outcome measure was ED LOS; secondary outcomes included time-to-physician initial assessment (PIA), EMS offload rates, and LWBS and 72-hour bounce-back rates. Qualitative data including patient concerns and physician feedback were also collected. Data were collected after the trial from a centralized, de-identified ED information system database with time-stamp quantifiers and compared to the following four-week time period where the shift is a regular ED physician shift at the same time. The ED physician and nursing team planned and implemented the PF role, then results were evaluated and shared with the wider ED staff in departmental grand rounds and quality council presentation formats, and recommendations were gathered from to adjust and strengthen future iterations of PF role implementation. Results: Descriptive statistics and Mann-Whitney and Median tests were calculated. On average there were 185 daily ED visits in the trial and comparison periods. Median ED LOS decreased by 12 minutes in the PF trial period (p<0.05). Furthermore, there was a 12 minute decreased ED LOS for all discharged patients (p<0.05). PIA time decreased by 13 minutes for patients that were admitted. The average percentage of EMS offloads within 60 min improved from 75% to 80.7% for admitted patients. LWBS and 72-hour bounce-back rates were unchanged. No additional patient concerns arose related to or during the trial. Physician feedback on the PF role was mainly positive. Conclusion: The defined role of a PF in an ED can decrease ED LOS, albeit not achieving the desired 30-minute reduction on the first iteration, this trial supported proof-of-concept for implementation of a PF role in a tertiary care centre ED. Further iterations are needed to evaluate the scalability and sustainability of this role.
Introduction: Survival from cardiac arrest has been linked to the quality of resuscitation care. Unfortunately, healthcare providers frequently underperform in these critical scenarios, with a well-documented deterioration in skills weeks to months following advanced life support courses. Improving initial training and preventing decay in knowledge and skills are a priority in resuscitation education. The spacing effect has repeatedly been shown to have an impact on learning and retention. Despite its potential advantages, the spacing effect has seldom been applied to organized education training or complex motor skill learning where it has the potential to make a significant impact. The purpose of this study was to determine if a resuscitation course taught in a spaced format compared to the usual massed instruction results in improved retention of procedural skills. Methods: EMS providers (Paramedics and Emergency Medical Technicians (EMT)) were block randomized to receive a Pediatric Advanced Life Support (PALS) course in either a spaced format (four 210-minute weekly sessions) or a massed format (two sequential 7-hour days). Blinded observers used expert-developed 4-point global rating scales to assess video recordings of each learner performing various resuscitation skills before, after and 3-months following course completion. Primary outcomes were performance on infant bag-valve-mask ventilation (BVMV), intraosseous (IO) insertion, infant intubation, infant and adult chest compressions. Results: Forty-eight of 50 participants completed the study protocol (26 spaced and 22 massed). There was no significant difference between the two groups on testing before and immediately after the course. 3-months following course completion participants in the spaced cohort scored higher overall for BVMV (2.2 ± 0.13 versus 1.8 ± 0.14, p=0.012) without statistically significant difference in scores for IO insertion (3.0 ± 0.13 versus 2.7± 0.13, p= 0.052), intubation (2.7± 0.13 versus 2.5 ± 0.14, p=0.249), infant compressions (2.5± 0.28 versus 2.5± 0.31, p=0.831) and adult compressions (2.3± 0.24 versus 2.2± 0.26, p=0.728) Conclusion: Procedural skills taught in a spaced format result in at least as good learning as the traditional massed format; more complex skills taught in a spaced format may result in better long term retention when compared to traditional massed training as there was a clear difference in BVMV and trend toward a difference in IO insertion.
Introduction: NSAIDS offer more effective analgesia than opioids, require less rescue medication, and decrease the incidence of nausea and vomiting in renal colic patients. Alpha blockers and Opioids are also prescribed frequently, but doses used and treatment durations are not well described. Our objective was to investigate ED prescribing decisions and medication compliance by patients with acute renal colic. Methods: In this prospective two-city cohort study, we invited patients with a first ED visit for image-confirmed 2-10 mm ureteric stones to consent to a telephone survey 10 days after their ED visit. During follow-up interviews, patients were asked what drugs they were prescribed and how many doses they required. This study was REB approved. Results: A convenience sample of 224 patients, including 152 males (67.9%) and 72 females (median age= 52.4 years) completed 10-day surveys. NSAIDS were prescribed for 48.7%, tamsulosin for 65.2% and opioids for 81.7%. One-third received a tamsulosin-NSAID combination, 40% an opioid-NSAID combination and 28% a tamsulosin-NSAID-opioid combination. Of 109 patients prescribed an NSAID, only 70 (64.2%) took 1 dose/day; however an additional 28 who were not prescribed NSAIDs took 1 NSAID dose/day. Mean (sd) NSAID intake in the overall study group was 1.1 (1.5) doses/day from day 1-5 and 0.6 (1.1) doses/day on days 6-10, with 90%ile values of 3.0 and 2.0 doses/day. NSAID compliance was more common in patients who stated they received high quality discharge instructions (63.8% vs. 32.6%; RR=1.95; 95% CI 1.47-2.60). Mean opioid intake in the overall study group was 1.2 (1.7) doses/day from day 1-5 and 0.5 (1.3) doses/day on days 6-10, with 90%ile values of 4.0 and 2.0 doses/day. Among patients prescribed tamsulosin, the average was 4.0 days of compliance (sd=4.3), with a 90%ile value of 10 days. Conclusion: This study provides estimates for the amount of drug actually used by renal colic patients during the 10-days after their ED visit. Patients used fewer opioid doses than expected, and NSAID and tamsulosin compliance appears relatively poor. NSAID compliance was better in patients who perceived high quality discharge instructions. This study suggests there is room for improvement in medication prescribing and discharge instructions for ED patients with an acute episode of ureteral colic.