Designing an automated clinical decision support system to match clinical practice guidelines for opioid therapy for chronic pain

Abstract Background Opioid prescribing for chronic pain is common and controversial, but recommended clinical practices are followed inconsistently in many clinical settings. Strategies for increasing adherence to clinical practice guideline recommendations are needed to increase effectiveness and reduce negative consequences of opioid prescribing in chronic pain patients. Methods Here we describe the process and outcomes of a project to operationalize the 2003 VA/DOD Clinical Practice Guideline for Opioid Therapy for Chronic Non-Cancer Pain into a computerized decision support system (DSS) to encourage good opioid prescribing practices during primary care visits. We based the DSS on the existing ATHENA-DSS. We used an iterative process of design, testing, and revision of the DSS by a diverse team including guideline authors, medical informatics experts, clinical content experts, and end-users to convert the written clinical practice guideline into a computable algorithm to generate patient-specific recommendations for care based upon existing information in the electronic medical record (EMR), and a set of clinical tools. Results The iterative revision process identified numerous and varied problems with the initially designed system despite diverse expert participation in the design process. The process of operationalizing the guideline identified areas in which the guideline was vague, left decisions to clinical judgment, or required clarification of detail to insure safe clinical implementation. The revisions led to workable solutions to problems, defined the limits of the DSS and its utility in clinical practice, improved integration into clinical workflow, and improved the clarity and accuracy of system recommendations and tools. Conclusions Use of this iterative process led to development of a multifunctional DSS that met the approval of the clinical practice guideline authors, content experts, and clinicians involved in testing. The process and experiences described provide a model for development of other DSSs that translate written guidelines into actionable, real-time clinical recommendations.http://deepblue.lib.umich.edu/bitstream/2027.42/78267/1/1748-5908-5-26.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/2/1748-5908-5-26.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/3/1748-5908-5-26-S3.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/4/1748-5908-5-26-S2.TIFFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78267/5/1748-5908-5-26-S1.TIFFPeer Reviewe

Improved Resolution Haplogroup G Phylogeny in the Y Chromosome, Revealed by a Set of Newly Characterized SNPs

Background: Y-SNP haplogroup G (hgG), defined by Y-SNP marker M201, is relatively uncommon in the United States general population, with only 8 additional sub-markers characterized. Many of the previously described eight sub-markers are either very rare (2–4%) or do not distinguish between major populations within this hg. In fact, prior to the current study, only 2 % of our reference Caucasian population belonged to hgG and all of these individuals were in sub-haplogroup G2a, defined by P15. Additional Y-SNPs are needed in order to differentiate between individuals within this haplogroup. Principal Findings: In this work we have investigated whether we could differentiate between a population of 63 hgG individuals using previously uncharacterized Y-SNPs. We have designed assays to test these individuals using all known hgG SNPs (n = 9) and an additional 16 unreported/undefined Y-SNPS. Using a combination of DNA sequence and genetic genealogy databases, we have uncovered a total of 15 new hgG SNPs that had been previously reported but not phylogenetically characterized. Ten of the new Y-SNPs are phylogenetically equivalent to M201, one is equivalent to P15 and, interestingly, four create new, separate haplogroups. Three of the latter are more common than many of the previously defined Y-SNPs. Y-STR data from these individuals show that DYS385*12 is present in (70%) of G2a3b1-U13 individuals while only 4 % of non-G2a3b1-U13 individuals posses the DYS385*12 allele. Conclusions: This study uncovered several previously undefined Y-SNPs by using data from several database sources. Th

Cardiovascular comorbidities among public health clinic patients with diabetes: the Urban Diabetics Study

BACKGROUND: We sought to determine the frequency and distribution of cardiovascular comorbidities in a large cohort of low-income patients with diabetes who had received primary care for diabetes at municipal health clinics. METHODS: Outpatient data from the Philadelphia Health Care Centers was linked with hospital discharge data from all Pennsylvania hospitals and death certificates. RESULTS: Among 10,095 primary care patients with diabetes, with a mean observation period of 4.6 years (2.8 after diabetes diagnosis), 2,693 (14.3%) were diagnosed with heart disease, including 270 (1.4%) with myocardial infarction and 912 (4.8%) with congestive heart failure. Cerebrovascular disease was diagnosed in 588 patients (3.1%). Over 77% of diabetic patients were diagnosed with hypertension. Incidence rates of new complications ranged from 0.6 per 100 person years for myocardial infarction to 26.5 per 100 person years for hypertension. Non-Hispanic whites had higher rates of myocardial infarction, and Hispanics and Asians had fewer comorbid conditions than African Americans and non-Hispanic whites. CONCLUSION: Cardiovascular comorbidities were common both before and after diabetes diagnosis in this low-income cohort, but not substantially different from mixed-income managed care populations, perhaps as a consequence of access to primary care and pharmacy services

A Blue Spectral Shift of the Hemoglobin Soret Band Correlates with the Age (Time Since Deposition) of Dried Bloodstains

The ability to determine the time since deposition of a bloodstain found at a crime scene could prove invaluable to law enforcement investigators, defining the time frame in which the individual depositing the evidence was present. Although various methods of accomplishing this have been proposed, none has gained widespread use due to poor time resolution and weak age correlation. We have developed a method for the estimation of the time since deposition (TSD) of dried bloodstains using UV-VIS spectrophotometric analysis of hemoglobin (Hb) that is based upon its characteristic oxidation chemistry. A detailed study of the Hb Soret band (λmax = 412 nm) in aged bloodstains revealed a blue shift (shift to shorter wavelength) as the age of the stain increases. The extent of this shift permits, for the first time, a distinction to be made between bloodstains that were deposited minutes, hours, days and weeks prior to recovery and analysis. The extent of the blue shift was found to be a function of ambient relative humidity and temperature. The method is extremely sensitive, requiring as little as a 1 µl dried bloodstain for analysis. We demonstrate that it might be possible to perform TSD measurements at the crime scene using a portable low-sample-volume spectrophotometer

X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Temporary reduction in daily global CO2 emissions during the COVID-19 forced confinement

Government policies during the COVID-19 pandemic have drastically altered patterns of energy demand around the world. Many international borders were closed and populations were confined to their homes, which reduced transport and changed consumption patterns. Here we compile government policies and activity data to estimate the decrease in CO2 emissions during forced confinements. Daily global CO2 emissions decreased by –17% (–11 to –25% for ±1σ) by early April 2020 compared with the mean 2019 levels, just under half from changes in surface transport. At their peak, emissions in individual countries decreased by –26% on average. The impact on 2020 annual emissions depends on the duration of the confinement, with a low estimate of –4% (–2 to –7%) if prepandemic conditions return by mid-June, and a high estimate of –7% (–3 to –13%) if some restrictions remain worldwide until the end of 2020. Government actions and economic incentives postcrisis will likely influence the global CO2 emissions path for decades

An Ultra-High Discrimination Y Chromosome Short Tandem Repeat Multiplex DNA Typing System

In forensic casework, Y chromosome short tandem repeat markers (Y-STRs) are often used to identify a male donor DNA profile in the presence of excess quantities of female DNA, such as is found in many sexual assault investigations. Commercially available Y-STR multiplexes incorporating 12–17 loci are currently used in forensic casework (Promega's PowerPlex® Y and Applied Biosystems' AmpFlSTR® Yfiler®). Despite the robustness of these commercial multiplex Y-STR systems and the ability to discriminate two male individuals in most cases, the coincidence match probabilities between unrelated males are modest compared with the standard set of autosomal STR markers. Hence there is still a need to develop new multiplex systems to supplement these for those cases where additional discriminatory power is desired or where there is a coincidental Y-STR match between potential male participants. Over 400 Y-STR loci have been identified on the Y chromosome. While these have the potential to increase the discrimination potential afforded by the commercially available kits, many have not been well characterized. In the present work, 91 loci were tested for their relative ability to increase the discrimination potential of the commonly used ‘core’ Y-STR loci. The result of this extensive evaluation was the development of an ultra high discrimination (UHD) multiplex DNA typing system that allows for the robust co-amplification of 14 non-core Y-STR loci. Population studies with a mixed African American and American Caucasian sample set (n = 572) indicated that the overall discriminatory potential of the UHD multiplex was superior to all commercial kits tested. The combined use of the UHD multiplex and the Applied Biosystems' AmpFlSTR® Yfiler® kit resulted in 100% discrimination of all individuals within the sample set, which presages its potential to maximally augment currently available forensic casework markers. It could also find applications in human evolutionary genetics and genetic genealogy

The geometry of the infrared and x-ray obscurer in a dusty hyperluminous quasar

We study the geometry of the active galactic nucleus (AGN) obscurer in IRAS 09104+4109, an IR-luminous, radio-intermediate FR-I source at $z$ = 0.442, using infrared data from $\textit{Spitzer}$ and $\textit{Herschel}$, X-ray data from $\textit{NuSTAR}$, $\textit{Swift}$, $\textit{Suzaku}$, and $\textit{Chandra}$, and an optical spectrum from Palomar. The infrared data imply a total rest-frame 1–1000 μm luminosity of 5.5 × 10$^{46}$ erg s$^{−1}$ and require both an AGN torus and a starburst model. The AGN torus has an anisotropy-corrected IR luminosity of 4.9 × 10$^{46}$ erg s$^{−1}$ and a viewing angle and half-opening angle both of approximately 36° from pole-on. The starburst has a star formation rate of (110 ± 34) $M_\odot$ yr$^{−1}$ and an age of <50 Myr. These results are consistent with two epochs of luminous activity in IRAS 09104+4109: one approximately 150 Myr ago, and one ongoing. The X-ray data suggest a photon index of Γ $\simeq$ 1.8 and a line-of-sight column density of $N_\text{H}$ $\simeq$ 5 × 10$^{23}$ cm$^{−2}$. This argues against a reflection-dominated hard X-ray spectrum, which would have implied a much higher $N_\text{H}$ and luminosity. The X-ray and infrared data are consistent with a bolometric AGN luminosity of $L_\text{bol}$ ~ (0.5–2.5) × 10$^{47}$ erg s$^{−1}$. The X-ray and infrared data are further consistent with coaligned AGN obscurers in which the line of sight “skims” the torus. This is also consistent with the optical spectra, which show both coronal iron lines and broad lines in polarized but not direct light. Combining constraints from the X-ray, optical, and infrared data suggest that the AGN obscurer is within a vertical height of 20 pc, and a radius of 125 pc, of the nucleus.ERC (Advanced Grant Feedback 340442

A Directed Molecular Evolution Approach to Improved Immunogenicity of the HIV-1 Envelope Glycoprotein

A prophylactic vaccine is needed to slow the spread of HIV-1 infection. Optimization of the wild-type envelope glycoproteins to create immunogens that can elicit effective neutralizing antibodies is a high priority. Starting with ten genes encoding subtype B HIV-1 gp120 envelope glycoproteins and using in vitro homologous DNA recombination, we created chimeric gp120 variants that were screened for their ability to bind neutralizing monoclonal antibodies. Hundreds of variants were identified with novel antigenic phenotypes that exhibit considerable sequence diversity. Immunization of rabbits with these gp120 variants demonstrated that the majority can induce neutralizing antibodies to HIV-1. One novel variant, called ST-008, induced significantly improved neutralizing antibody responses when assayed against a large panel of primary HIV-1 isolates. Further study of various deletion constructs of ST-008 showed that the enhanced immunogenicity results from a combination of effective DNA priming, an enhanced V3-based response, and an improved response to the constant backbone sequences