Charting a New Course: Practical Considerations for Implementing an Electronic Health Records System

What is true for many aspects of life is also true for HIT-timing is everything. When a practice is ready to move forward with an EHR system, the potential benefits are numerous, from capturing potential clinical and billing mistakes to lessening the need for additional personnel and the prompt sharing of information with other providers. Attempting to install an EHR system before a practice, or any provider, is ready, however, can lead to disaster, as was discovered at Cedars-Sinai Medical Center when it was forced to shelve its three-month-old, thirtyfour million dollar computer system. This Article explores the legal issues and practical considerations that a practice should be aware of before making the leap to an EHR system

Exploring the Effectiveness of a Prevocational Seminar on Self-Efficacy and Work Motivation among Adults Residing in an Inpatient Mental Health Facility

Objective: This study examined a work-related intervention designed to assist people with serious mental illness (SMI) in overcoming employment barriers. Methods: A pre- post-test experimental design was used to investigate the effects of a 10-session, prevocational seminar on self-efficacy and work motivation among adults with SMI residing in an inpatient psychiatric facility. Three one-way ANCOVAs were applied to analyze post-test results for the dependent measures. Findings: Although significant findings were not found regarding the effectiveness of the prevocational seminar on self-efficacy, other interesting discoveries were made. One noteworthy outcome was persons with SMI wanted to work but experienced barriers, including discrimination, decreased motivation, and work disincentives that impeded their return to employment. Conclusions and Implications for Practice: Vocational rehabilitation (VR) counselors continue to face challenges in their efforts to increase employment among persons with SMI. The results from the present study underscore the need for skills training and innovative VR strategies to mitigate barriers to employment among persons with SMI

Rapid Pathogen-Induced Apoptosis: A Mechanism Used by Dendritic Cells to Limit Intracellular Replication of Legionella pneumophila

Dendritic cells (DCs) are specialized phagocytes that internalize exogenous antigens and microbes at peripheral sites, and then migrate to lymphatic organs to display foreign peptides to naïve T cells. There are several examples where DCs have been shown to be more efficient at restricting the intracellular replication of pathogens compared to macrophages, a property that could prevent DCs from enhancing pathogen dissemination. To understand DC responses to pathogens, we investigated the mechanisms by which mouse DCs are able to restrict replication of the intracellular pathogen Legionella pneumophila. We show that both DCs and macrophages have the ability to interfere with L. pneumophila replication through a cell death pathway mediated by caspase-1 and Naip5. L. pneumophila that avoided Naip5-dependent responses, however, showed robust replication in macrophages but remained unable to replicate in DCs. Apoptotic cell death mediated by caspase-3 was found to occur much earlier in DCs following infection by L. pneumophila compared to macrophages infected similarly. Eliminating the pro-apoptotic proteins Bax and Bak or overproducing the anti-apoptotic protein Bcl-2 were both found to restore L. pneumophila replication in DCs. Thus, DCs have a microbial response pathway that rapidly activates apoptosis to limit pathogen replication

The time delay of the quadruple quasar RX J0911.4+0551

We present optical lightcurves of the gravitationally lensed components A (=A1+A2+A3) and B of the quadruple quasar RX J0911.4+0551 (z = 2.80). The observations were primarily obtained at the Nordic Optical Telescope between 1997 March and 2001 April and consist of 74 I-band data points for each component. The data allow the measurement of a time delay of 146 +- 8 days (2 sigma) between A and B, with B as the leading component. This value is significantly shorter than that predicted from simple models and indicates a very large external shear. Mass models including the main lens galaxy and the surrounding massive cluster of galaxies at z = 0.77, responsible for the external shear, yield H_0 = 71 +- 4 (random, 2 sigma) +- 8 (systematic) km/s/Mpc. The systematic model uncertainty is governed by the surface-mass density (convergence) at the location of the multiple images.Comment: 12 pages, 3 figures, ApJL, in press (June 20, 2002

Poverty-Related Adversity and Emotion Regulation Predict Internalizing Behavior Problems among Low-Income Children Ages 8–11

The current study examines the additive and joint roles of chronic poverty-related adversity and three candidate neurocognitive processes of emotion regulation (ER)—including: (i) attention bias to threat (ABT); (ii) accuracy of facial emotion appraisal (FEA); and (iii) negative affect (NA)—for low-income, ethnic minority children’s internalizing problems (N = 338). Children were enrolled in the current study from publicly funded preschools, with poverty-related adversity assessed at multiple time points from early to middle childhood. Field-based administration of neurocognitively-informed assessments of ABT, FEA and NA as well as parental report of internalizing symptoms were collected when children were ages 8–11, 6 years after baseline. Results suggest that chronic exposure to poverty-related adversity from early to middle childhood predicted higher levels of internalizing symptomatology when children are ages 8–11, even after controlling for initial poverty status and early internalizing symptoms in preschool. Moreover, each of the 3 hypothesized components of ER played an independent and statistically significant role in predicting children’s parent-reported internalizing symptoms at the 6-year follow-up, even after controlling for early and chronic poverty-related adversit

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol

Background: The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients' current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. Methods: We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants' medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant's clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial's primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/- 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy

MeerKLASS: MeerKAT Large Area Synoptic Survey

We discuss the ground-breaking science that will be possible with a wide area survey, using the MeerKAT telescope, known as MeerKLASS (MeerKAT Large Area Synoptic Survey). The current specifications of MeerKAT make it a great fit for science applications that require large survey speeds but not necessarily high angular resolutions. In particular, for cosmology, a large survey over $\sim 4,000 \, {\rm deg}^2$ for $\sim 4,000$ hours will potentially provide the first ever measurements of the baryon acoustic oscillations using the 21cm intensity mapping technique, with enough accuracy to impose constraints on the nature of dark energy. The combination with multi-wavelength data will give unique additional information, such as exquisite constraints on primordial non-Gaussianity using the multi-tracer technique, as well as a better handle on foregrounds and systematics. Such a wide survey with MeerKAT is also a great match for HI galaxy studies, providing unrivalled statistics in the pre-SKA era for galaxies resolved in the HI emission line beyond local structures at z > 0.01. It will also produce a large continuum galaxy sample down to a depth of about 5\,$\mu$Jy in L-band, which is quite unique over such large areas and will allow studies of the large-scale structure of the Universe out to high redshifts, complementing the galaxy HI survey to form a transformational multi-wavelength approach to study galaxy dynamics and evolution. Finally, the same survey will supply unique information for a range of other science applications, including a large statistical investigation of galaxy clusters as well as produce a rotation measure map across a huge swathe of the sky. The MeerKLASS survey will be a crucial step on the road to using SKA1-MID for cosmological applications and other commensal surveys, as described in the top priority SKA key science projects (abridged).Comment: Larger version of the paper submitted to the Proceedings of Science, "MeerKAT Science: On the Pathway to the SKA", Stellenbosch, 25-27 May 201

SD-brane gravity fields and rolling tachyons

S(pacelike)D-branes are objects arising naturally in string theory when Dirichlet boundary conditions are imposed on the time direction. SD-brane physics is inherently time-dependent. Previous investigations of gravity fields of SD-branes have yielded undesirable naked spacelike singularities. We set up the problem of coupling the most relevant open-string tachyonic mode to massless closed-string modes in the bulk, with backreaction and Ramond-Ramond fields included. We find solutions numerically in a self-consistent approximation; our solutions are naturally asymptotically flat and time-reversal asymmetric. We find completely nonsingular evolution; in particular, the dilaton and curvature are well-behaved for all time. The essential mechanism for spacetime singularity resolution is the inclusion of full backreaction between the bulk fields and the rolling tachyon. Our analysis is not the final word on the story, because we have to make some significant approximations, most notably homogeneity of the tachyon on the unstable branes. Nonetheless, we provide significant progress in plugging a gaping hole in prior understanding of the gravity fields of SD-branes.Comment: References added. Analysis for much broader range of solutions presented. Conclusions unchanged. Time-reversal symmetric examples ruled out, new examples are provide

Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex

Ciclopirox (CPX) is an FDA-approved topical antifungal agent that has demonstrated preclinical anticancer activity in a number of solid and hematologic malignancies. Its clinical utility as an oral anticancer agent, however, is limited by poor oral bioavailability and gastrointestinal toxicity. Fosciclopirox, the phosphoryloxymethyl ester of CPX (Ciclopirox Prodrug, CPX-POM), selectively delivers the active metabolite, CPX, to the entire urinary tract following parenteral administration. We characterized the activity of CPX-POM and its major metabolites in in vitro and in vivo preclinical models of high-grade urothelial cancer. CPX inhibited cell proliferation, clonogenicity and spheroid formation, and increased cell cycle arrest at S and G0/G1 phases. Mechanistically, CPX suppressed activation of Notch signaling. Molecular modeling and cellular thermal shift assays demonstrated CPX binding to γ-secretase complex proteins Presenilin 1 and Nicastrin, which are essential for Notch activation. To establish in vivo preclinical proof of principle, we tested fosciclopirox in the validated N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) mouse bladder cancer model. Once-daily intraperitoneal administration of CPX-POM for four weeks at doses of 235 mg/kg and 470 mg/kg significantly decreased bladder weight, a surrogate for tumor volume, and resulted in a migration to lower stage tumors in CPX-POM treated animals. This was coupled with a reduction in the proliferation index. Additionally, there was a reduction in Presenilin 1 and Hes-1 expression in the bladder tissues of CPX-POM treated animals. Following the completion of the first-in-human Phase 1 trial (NCT03348514), the pharmacologic activity of fosciclopirox is currently being characterized in a Phase 1 expansion cohort study of muscle-invasive bladder cancer patients scheduled for cystectomy (NCT04608045) as well as a Phase 2 trial of newly diagnosed and recurrent urothelial cancer patients scheduled for transurethral resection of bladder tumors (NCT04525131)

Incident adverse drug reactions in geriatric inpatients : a multicentred observational study

Background: Adverse drug reactions (ADRs) are common in older adults and frequently have serious clinical and economic consequences. This study was conducted as a feasibility study for a randomized control trial (RCT) that will investigate the efficacy of a software engine to optimize medications and reduce incident (in-hospital) ADRs. This study's objectives were to (i) establish current incident ADR rates across the six sites participating in the forthcoming RCT and (ii) assess whether incident ADRs are predictable. Methods: This was a multicentre, prospective observational study involving six European hospitals. Adults aged 65 years, hospitalized with an acute illness and on pharmacological treatment for three or more conditions were eligible for inclusion. Adverse events (AEs) were captured using a trigger list of 12 common ADRs. An AE was deemed an ADR when its association with an administered drug was adjudicated as being probable/certain, according to the World Health Organization Uppsala Monitoring Centre causality assessment. The proportion of patients experiencing at least one, probable/certain, incident ADR within 14 days of enrolment/discharge was recorded. Results: A total of 644 patients were recruited, evenly split by sex and overwhelmingly of White ethnicity. Over 80% of admissions were medical. The median number of chronic conditions was five (interquartile range 4-6), with eight or more conditions present in approximately 10%. The mean number of prescribed medications was 9.9 (standard deviation 3.8), which correlated strongly with the number of conditions (r = 0.54, p < 0.0001). A total of 732 AEs were recorded in 382 patients, of which 363 were incident. The majority of events were classified as probably or possibly drug related, with heterogeneity across sites (chi(2) = 88.567, df = 20, p value < 0.001). Out of 644 patients, 139 (21.6%; 95% confidence interval 18.5-25.0%) experienced an ADR. Serum electrolyte abnormalities were the most common ADR. The ADRROP (ADR Risk in Older People) and GerontoNet ADR risk scales correctly predicted ADR occurrence in 61% and 60% of patients, respectively. Conclusion: This feasibility study established the rates of incident ADRs across the six study sites. The ADR predictive power of ADRROP and GerontoNet ADR risk scales were limited in this population