Outcomes with inpatient use of midodrine in patients with heart failure and kidney failure on maintenance dialysis.

BACKGROUND: Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF. METHODS: The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities. RESULTS: Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality. CONCLUSION: This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.

A framework for future national pediatric pandemic respiratory disease severity triage: The HHS pediatric COVID-19 data challenge.

Introduction: With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist. Methods: HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions? Results: This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected. Conclusion: This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.

The Role of Informatics in Implementing Guidelines for Chronic Opioid Therapy Risk Assessment in Primary Care: A Narrative Review Informed by the Socio-Technical Model.

Approximately 2 million Americans live with opioid use disorder (OUD), most of whom also have chronic pain. The economic burden of chronic pain and prescription opioid misuse runs into billions of dollars. Patients on prescription opioids for chronic non-cancer pain (CNCP) are at increased risk for OUD and overdose. By adhering to the Center for Disease Control and Prevention (CDC) opioid prescribing guidelines, primary care providers (PCPs) have the potential to improve patient outcomes. But numerous provider, patient, and practice-specific factors challenge adherence to guidelines in primary care. Many of the barriers may be mediated by informatics interventions, but gaps in knowledge and unmet needs exist. This narrative review examines the risk assessment and harm reduction process in a socio-technical context to highlight the gaps in knowledge and unmet needs that can be mediated through informatics intervention.

Constitutive expression and discovery of antimicrobial peptides in Zygogramma bicolorata (Coleoptera: Chrysomelidae).

The expression, identification, and discovery of less toxic antimicrobial peptides (AMPs) are significant in managing infectious pathogens. AMPs triggered in response to the immune system have evolved to defend against pathogens and wounding. The protein composition of Zygogramma bicolorata hemolymph is of diagnostic importance as the open circulatory systems of the insects involve signaling through hemolymph. They have conserved many ancestral vertebrate genes that may help better understand the evolution of innate immunity. The present work describes the isolation, purification, identification, and bioinformatics analysis of AMPs from the immunized hemolymph of Z. bicolorata. Thirty-nine peptides were isolated from reverse-phase high-performance liquid chromatography and sequenced via mass spectrometry analysis. The immunization process recorded a threefold higher protein concentration in immunized hemolymph when compared with nonimmunized one. For the first time, the proteomic study on Z. bicolorata hemolymph unveils the three novel proteins in the family Chrysomelidae with no homology in the database, indicating its novelty and the expression of the rest of 36 well-known proteins, including heat-shock, immune, structural, signaling proteins, and others speak for its method validity. Combining the expression of novel AMPs, detoxifying enzymes, hemolytic, and cytotoxic assays, and this work can elucidate new pathways to immune response mechanisms. Its molecular basis also holds the potential applicability in the future drug development process against pathogenic fungi such as Aspergillus niger and Candida albicans.

Priorities of Hybrid Clinician-Managers: A Qualitative Study of How Managers Balance Clinical Quality Among Competing Responsibilities.

OBJECTIVE: Oversight of clinical quality is only one of physical therapy managers' multiple responsibilities. With the move to value-based care, organizations need sound management to navigate this evolving reimbursement landscape. Previous research has not explored how competing priorities affect physical therapy managers' oversight of clinical quality. The purpose of this study was to create a preliminary model of the competing priorities, motivations, and responsibilities of managers while overseeing clinical quality. METHODS: This qualitative study used the Rapid Qualitative Inquiry method. A purposive sample of 40 physical therapy managers and corporate leaders was recruited. A research team performed semi-structured interviews and observations in outpatient practices. The team used a grounded theory-based immersion/crystallization analysis approach. Identified themes delineated the competing priorities and workflows these managers use in their administrative duties. RESULTS: Six primary themes were identified that illustrate how managers: (1) balance managerial and professional priorities; (2) are susceptible to stakeholder influences; (3) experience internal conflict; (4) struggle to measure and define quality objectively; (5) are influenced by the culture and structure of their respective organizations; and (6) have professional needs apart from the needs of their clinics. CONCLUSION: Generally, managers' focus on clinical quality is notably less comprehensive than their focus on clinical operations. Additionally, the complex role of hybrid clinician-manager leaves limited time beyond direct patient care for administrative duties. Managers in organizations that hold them accountable to quality-based metrics have more systematic clinical quality oversight processes. IMPACT: This study gives physical therapy organizations a framework of factors that can be influenced to better facilitate managers' effective oversight of clinical quality. Organizations offering support for those managerial responsibilities will be well positioned to thrive in the new fee-for-value care structure.

Prostate Cancer Screening Patient Decision Aids: A Systematic Review and Meta-analysis.

CONTEXT: Although screening recommendations for prostate cancer using prostate-specific antigen testing often include shared decision making, the effect of patient decision aids on patients' intention and uptake is unclear. This study aimed to review the effect of decision aids on men's screening intention, screening utilization, and the congruence between intentions and uptake. EVIDENCE ACQUISITION: Data sources were searched through April 6, 2018, and included MEDLINE, Scopus, CENTRAL, CT.gov, Cochrane report, PsycARTICLES, PsycINFO, and reference lists. This study included RCTs and observational studies of decision aids that measured prostate screening intention or behavior. The analysis was completed in April 2018. EVIDENCE SYNTHESIS: Eighteen studies (13 RCTs, four before-after studies, and one non-RCT) reported data on screening intention for ≅8,400 men and screening uptake for 2,385 men. Compared with usual care, the use of decision aids in any format results in fewer men (aged ≥40 years) planning to undergo prostate-specific antigen testing (risk ratio=0.88, 95% CI=0.81, 0.95, p=0.006, I2=66%, p<0.001, n=8). Many men did not follow their screening intentions during the first year after using a decision aid; however, most men who were planning to undergo screening did so (probability that men who wanted to be screened would receive screening was 95%). CONCLUSIONS: Integration of decision aids in clinical practice may result in a decrease in the number of men who elect prostate-specific antigen testing, which may in turn reduce screening uptake. To ensure high congruence between intention and screening utilization, providers should not delay the shared decision-making discussion after patients use a decision aid.

Pacemaker pocket infection due to environmental mycobacteria: Successful management of an outbreak and steps for prevention in future.

BACKGROUND: An outbreak of surgical site infection (SSI) due to environmental mycobacteria (EMB) occurred in a hospital in Eastern India. METHOD: A quality improvement project (QIP) was undertaken to analyze the causes and prevent further outbreak. Step (1) Proof of the need: Four patients who had undergone pacemaker implantation consecutively during a 10-day period developed SSI. Step (2) Diagnostic journey: Since all patients developed SSI within 2 months of implantation, a common source of infection was likely. Atypical mycobacteria (AMB) were grown from surgical sites as well as from the surface of operation table, image intensifier, and lead aprons. It was a rapid growing variety that lacked pigment, a characteristic of EMB with pathogenic potential. The EMB was finally traced to its source, the overhead water tank. Step (3) Remedial journey: By thorough cleaning of the water tank and enriching its chlorine content, the EMB was eliminated from its source. Step (4) Holding the gains: Protocol for cleaning the water tank once in 3 months was made. A checklist was prepared to ensure compliance to asepsis protocol in the operation theater. In the ensuing 5 years, the infection did not recur. RESULT: The bacteria that caused SSI were identified as EMB that grew in the water tank and contaminated the operation room. It could be eliminated by appropriate measures. INTERPRETATION: Water is a potential reservoir for EMB. Use of the term 'environmental mycobacteria' instead of 'atypical mycobacteria' will generate awareness about contamination as the cause of SSI.

Hypokalemic quadriparesis in dengue.

Dengue infection is the leading cause of illness and death in tropical and subtropical regions of the world. The common complications associated with dengue fever are usual hematological abnormalities, shock, and organ failure. The neurological complications of dengue are uncommon. However, evidence of dengue virus neurotropism and complications has been slowly but surely rising as seen from increased literature on this subject over the last decade. We report an uncommon case of hypokalemic quadriparesis with dengue that had a favorable outcome.

Computational prediction of toxicity.

With increasing number of chemicals produced each year, it still remains a daunting task to keep up with the toxicity profile of each chemical. In this paper, we attempt to predict toxicity of compounds using computational techniques, where results from certain in vitro assays applied on 309 chemicals, along with computed properties of chemicals are used to predict the toxicity caused by them at a particular endpoint. We show that both Random Forest (RF) and Naïve Bayes (NB) have a good performance. We also show that using small and related trees in RF helps to further improve the performance.

Text categorization of biomedical data sets using graph kernels and a controlled vocabulary.

Recently, graph representations of text have been showing improved performance over conventional bag-of-words representations in text categorization applications. In this paper, we present a graph-based representation for biomedical articles and use graph kernels to classify those articles into high-level categories. In our representation, common biomedical concepts and semantic relationships are identified with the help of an existing ontology and are used to build a rich graph structure that provides a consistent feature set and preserves additional semantic information that could improve a classifier's performance. We attempt to classify the graphs using both a set-based graph kernel that is capable of dealing with the disconnected nature of the graphs and a simple linear kernel. Finally, we report the results comparing the classification performance of the kernel classifiers to common text-based classifiers.

A quantitative EEG method for detecting post clamp changes during carotid endarterectomy.

OBJECTIVE: To apply univariate and multivariate analyses of EEG spectral features in order to detect subtle post-clamp changes during carotid endarterectomy, and to devise a data-driven, multivariate classification method for rapid, real-time detection of small post-clamp EEG changes. METHODS: We used intraoperative EEG records of 27 patients who underwent carotid endarterectomy (CEA) and did not undergo a shunt per surgeon's and technologist's visual inspection of the electro-encephalogram (EEG). Furthermore, these records could not be flagged with r-sBSI (revised spatial brain symmetry index) or r-tBSI (revised temporal brain symmetry index) qEEG (quantitative EEG) metrics. Spectral energies of 10 s EEG snippets were recorded at 5 min intervals from 10 min pre-clamp to 20 min post-clamp. Using receiver operating characteristic curves, the power of standard EEG spectral bands in detection of post-clamp changes was determined. Next, we employed Fisher Linear Discriminant Analysis for classifier-guided multivariate feature selection and classification. RESULTS: In univariate analysis, delta waves in non-frontal areas, irrespective of the laterality of the affected hemisphere, were found to be generally more powerful indicators of clamp-induced EEG changes. In multivariate analysis, cross-validation results for Fisher LDA produced subject-independent equal error rates as low as 32% when separating post-clamp signals from pre-clamp controls. Within our subject group, the intricate clamp-induced EEG signatures were predominantly anterior, bilateral, and had a strong delta rhythm presence. The overall post-clamp saliencies, both in univariate and multivariate analyses, were time-dependent. CONCLUSION: By applying automatic data-driven feature extraction and classification to short EEG records, it is possible to construct subject-independent computational models that can detect subtle post clamp changes possibly caused by small perturbations in cerebral blood flow. These subtle changes are missed by visual inspection of the EEG and by other quantitative EEG techniques such as r-sBSI and r-tBSI. Within our subject group, the intricate post-clamp EEG signatures were predominantly anterior, bilateral, and had a strong delta rhythm presence.

A subject specific multibody model of the knee with menisci.

The menisci of the knee play an important role in joint function and our understanding of knee mechanics and tissue interactions can be enhanced through computational models of the tibio-menisco-femoral structure. Several finite element models of the knee that include meniscus-cartilage contact exist, but these models are typically limited to simplified boundary conditions. Movement simulation and musculoskeletal modeling can predict muscle forces, but are typically performed using the multibody method with simplified representation of joint structures. This study develops a subject specific computational model of the knee with menisci that can be incorporated into neuromusculoskeletal models within a multibody framework. Meniscus geometries from a 78-year-old female right cadaver knee were divided into 61 discrete elements (29 medial and 32 lateral) that were connected through 6x6 stiffness matrices. An optimization and design of experiments approach was used to determine parameters for the 6x6 stiffness matrices such that the force-displacement relationship of the meniscus matched that of a linearly elastic transversely isotropic finite element model for the same cadaver knee. Similarly, parameters for compliant contact models of tibio-menisco-femoral articulations were derived from finite element solutions. As a final step, a multibody knee model was developed and placed within a dynamic knee simulator model and the tibio-femoral and patello-femoral kinematics compared to an identically loaded cadaver knee. RMS errors between finite element displacement and multibody displacement after parameter optimization were 0.017 mm for the lateral meniscus and 0.051 mm for the medial meniscus. RMS errors between model predicted and experimental cadaver kinematics during a walk cycle were less than 11 mm translation and less than 7 degrees orientation. A small improvement in kinematics, compared to experimental measurements, was seen when the menisci were included versus a model without the menisci. With the menisci the predicted tibio-femoral contact force was significantly reduced on the lateral side (937 N peak force versus 633 N peak force), but no significant reduction was seen on the medial side.