Nurse Standing Orders for Buprenorphine Follow-Up Care in a Community Health Center Network.

BACKGROUND: Less than 20% of individuals with opioid use disorder (OUD) are receiving a medication treatment for OUD in the United States. Though nurses can assume critical roles in outpatient models of OUD care, there are no published reports of buprenorphine standing orders for nurses that guide a nuanced response for patients returning as expected versus those re-engaging after a treatment lapse, without requiring real-time prescriber consultation. METHODS: Standing orders for buprenorphine were created with multiple stakeholders within an urban community health center that includes traditional clinics as well as non-traditional homeless care sites. After more than two years of use, an anonymous survey assessed staff perception of usability and safety of the standing orders using the validated system usability scale (SUS) and a 5-item Likert scale. Patient retention rates at 12 and 18 months were compared for sites that were early- and late-adopters of the standing orders. RESULTS: Of 24 clinicians and 7 nurses who responded to the survey, 46% had used the standing orders. More than 85% reported a perception that the standing orders improved team-based care and increased access to buprenorphine refills. None reported any safety concerns. The median SUS score was 75.0 (SD 15.4), rated as "excellent". There was no statistically significant difference in 12- or 18-month retention rates between early- and late-adopter sites of the standing orders. CONCLUSIONS: Nurse standing orders for buprenorphine follow-up and re-engagement care are feasible, usable and perceived as safe in varied community health center settings.

Theranostic Copolymers Neutralize Reactive Oxygen Species and Lipid Peroxidation Products for the Combined Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) results in the generation of reactive oxygen species (ROS) and lipid peroxidation product (LPOx), including acrolein and 4-hydroxynonenal (4HNE). The presence of these biochemical derangements results in neurodegeneration during the secondary phase of the injury. The ability to rapidly neutralize multiple species could significantly improve outcomes for TBI patients. However, the difficulty in creating therapies that target multiple biochemical derangements simultaneously has greatly limited therapeutic efficacy. Therefore, our goal was to design a material that could rapidly bind and neutralize both ROS and LPOx following TBI. To do this, a series of thiol-functionalized biocompatible copolymers based on lipoic acid methacrylate and polyethylene glycol monomethyl ether methacrylate (FW ∼ 950 Da) (O950) were prepared. A polymerizable gadolinium-DOTA methacrylate monomer (Gd-MA) was also synthesized starting from cyclen to facilitate direct magnetic resonance imaging and in vivo tracking of accumulation. These neuroprotective copolymers (NPCs) were shown to rapidly and effectively neutralize both ROS and LPOx. Horseradish peroxidase absorbance assays showed that the NPCs efficiently neutralized H2O2, while R-phycoerythrin protection assays demonstrated their ability to protect the fluorescent protein from oxidative damage. 1H NMR studies indicated that the thiol-functional NPCs rapidly form covalent bonds with acrolein, efficiently removing it from solution. In vitro cell studies with SH-SY5Y-differentiated neurons showed that NPCs provide unique protection against toxic concentrations of both H2O2 and acrolein. NPCs rapidly accumulate and are retained in the injured brain in controlled cortical impact mice and reduce post-traumatic oxidative stress. Therefore, these materials show promise for improved target engagement of multiple biochemical derangements in hopes of improving TBI therapeutic outcomes.

C-reactive protein levels associated with COVID-19 outcomes in the United States.

CONTEXT: COVID-19 caused a worldwide pandemic, and there are still many uncertainties about the disease. C-reactive protein (CRP) levels could be utilized as a prognosticator for disease severity in COVID-19 patients. OBJECTIVES: This study aims to determine whether CRP levels are correlated with COVID-19 patient outcomes and length of stay (LoS). METHODS: A retrospective cohort study was conducted utilizing data obtained between March and May 2020. Data were collected by abstracting past medical records through electronic medical records at 10 hospitals within CommonSpirit Health. Patients were included if they had a positive COVID-19 test from a nasopharyngeal swab sample, and if they were admitted and then discharged alive or had in-hospital mortality and were ≥18 years. A total of 541 patients had CRP levels measured and were included in this report. Patient outcome and LoS were the endpoints measured. RESULTS: The 541 patients had their CRP levels measured, as well as the demographic and clinical data required for analysis. While controlling for body mass index (BMI), number of comorbidities, and age, the first CRP was significantly predictive of mortality (p<0.001). The odds ratio for first CRP indicates that for each one-unit increase in CRP, the odds of death increased by 0.007. For LoS, the first CRP was a significant predictor (p<0.001), along with age (p=0.002). The number of comorbidities also predicted LoS (p=0.007), but BMI did not. The coefficient for the first CRP indicates that, for each one-unit increase in CRP, LoS increased 0.003 days. CONCLUSIONS: The results indicate that there is a positive correlation between the CRP levels of COVID-19 patients and their respective outcomes with regard to death and LoS.

Clinical pathways for primary care: current use, interest and perceived usability.

Objective: Translating clinical evidence to daily practice remains a challenge and may improve with clinical pathways. We assessed interest in and usability of clinical pathways by primary care professionals. Methods: An online survey was created. Interest in pathways for patient care and learning was assessed at start and finish. Participants completed baseline questions then pathway-associated question sets related to management of 2 chronic diseases. Perceived pathway usability was assessed using the system usability scale. Accuracy and confidence of answers was compared for baseline and pathway-assisted questions. Results: Of 115 participants, 17.4% had used clinical pathways, the lowest of decision support tool types surveyed. Accuracy and confidence in answers significantly improved for all pathways. Interest in using pathways daily or weekly was above 75% for the respondents. Conclusion: There is low utilization of, but high interest in, clinical pathways by primary care clinicians. Pathways improve accuracy and confidence in answering written clinical questions.

A Countercultural Heritage: Rediscovering the Relationship-Centered and Social Justice Roots of Family Medicine-A Perspective from the Keystone IV Conference.

The 2015 G. Gayle Stephens Keystone conference convened a cohort of primary care professionals to discuss what promises personal physicians will make to their patients going forward. New physicians were prompted to rediscover the foundational values of and historic context for family medicine. At the heart of this rediscovery was learning of the writings and teachings of Dr. G. Gayle Stephens, a founder of family medicine who emphasized the essentiality of relationship-centered care and social justice to the new specialty. Dr. Stephens viewed family medicine as being in a countercultural relationship to mainstream medicine, as family medicine fought for justice and equity in an inequitable and fragmented health care system. Here we argue that by reaffirming and renewing this countercultural heritage the new generation of family physicians will have better clarity in approaching the many challenges in health care today. Particularly for trainees and new physicians, the historic lens offered by Dr. Stephens's writing and other foundational documents allows us to better see ourselves in a trajectory of ongoing health care reform.

Residency Curricula on Physician-Pharmaceutical Industry Interaction: A CERA Study.

BACKGROUND AND OBJECTIVES: Physician interaction with pharmaceutical representatives results in less evidence-based prescribing and increased costs. Many organizations have called for strong conflict of interest policies in academic institutions. Implementing policy without educational interventions may not adequately address the influence of industry on physician prescribing patterns. The objective of this study is to assess the implementation and content of family medicine residency curricula on the physician-pharmaceutical industry relationship. METHODS: We surveyed US family medicine program directors using the Council of Academic Family Medicine Educational Research Alliance (CERA) platform. The presence of a formal curriculum on the physician-industry interaction and specific curricular elements (ethics of interaction, understanding detailing sessions and advertisements, use of unbiased pharmaceutical information) were the outcome measures of interest. RESULTS: Fifty-two percent (212 of 406) of program directors responded. Forty percent (95% confidence interval [CI]: 33%--46%) reported having a formal curriculum on physician-pharmaceutical industry interactions. The presence of a formal curriculum was more likely in residencies permitting interaction with industry (52% [48/92] versus 30% [36/120]) or with a university affiliation (43% [75/173] versus 19% [7/36]). The use of unbiased sources of information relating to pharmaceutical products and the ethics of the physician-pharmaceutical industry relationship were the most common curricular elements (59% and 55%, respectively). CONCLUSIONS: This study shows that less than half of US family medicine programs have a curriculum addressing physician-industry interactions. Further research on the efficacy of and barriers to curriculum creation and implementation is warranted.

A cost-effectiveness analysis of alternative HIV retesting strategies in sub-saharan Africa.

BACKGROUND: Guidelines in sub-Saharan Africa on when HIV-seronegative persons should retest range from never to annually for lower-risk populations and from annually to every 3 months for high-risk populations. METHODS: We designed a mathematical model to compare the cost-effectiveness of alternative HIV retesting frequencies. Cost of HIV counseling and testing, linkage to care, treatment costs, disease progression, and mortality, and HIV transmission are modeled for three hypothetical cohorts with posited annual HIV incidence of 0.8%, 1.3%, and 4.0%, respectively. The model compared costs, quality-adjusted life-years gained, and secondary infections averted from testing intervals ranging from 3 months to 30 years. Input parameters from sub-Saharan Africa were used and explored in sensitivity analyses. RESULTS: Accounting for secondary infections averted, the most cost-effective testing frequency was every 7.5 years for 0.8% incidence, every 5 years for 1.3% incidence, and every 2 years for 4.0% incidence. Optimal testing strategies and their relative cost-effectiveness were most sensitive to assumptions about HIV counseling and testing and treatment costs, rates of CD4 decline, rates of HIV transmission, and whether tertiary infections averted were taken into account. CONCLUSIONS: While higher risk populations merit more frequent HIV testing than low risk populations, regular retesting is beneficial even in low-risk populations. Our data demonstrate benefits of tailoring testing intervals to resource constraints and local HIV incidence rates.

The FliK protein and flagellar hook-length control.

The bacterial flagellum is a highly complex prokaryotic organelle. It is the motor that drives bacterial motility, and despite the large amount of energy required to make and operate flagella, motile organisms have a strong adaptive advantage. Flagellar biogenesis is both complex and highly coordinated and it typically involves at least three two-component systems. Part of the flagellum is a type III secretion system, and it is via this structure that flagellar components are exported. The assembly of a flagellum occurs in a number of stages, and the "checkpoint control" protein FliK functions in this process by detecting when the flagellar hook substructure has reached its optimal length. FliK then terminates hook export and assembly and transmits a signal to begin filament export, the final stage in flagellar biosynthesis. As yet the exact mechanism of how FliK achieves this is not known. Here we review what is known of the FliK protein and discuss the evidence for and against the various hypotheses that have been proposed in recent years to explain how FliK controls hook length, FliK as a molecular ruler, the measuring cup theory, the role of the FliK N terminus, the infrequent molecular ruler theory, and the molecular clock theory.

Oxidative phenotype protects myofibers from pathological insults induced by chronic heart failure in mice.

The fiber specificity of skeletal muscle abnormalities in chronic heart failure (CHF) has not been defined. We show here that transgenic mice (8 weeks old) with cardiac-specific overexpression of calsequestrin developed CHF (50.9% decrease in fractional shortening and 56.4% increase in lung weight, P<0.001), cachexia (37.8% decrease in body weight, P<0.001), and exercise intolerance (69.3% decrease in running distance to exhaustion, P<0.001) without a significant change in muscle fiber-type composition. Slow oxidative soleus muscle maintained muscle mass, whereas fast glycolytic tibialis anterior and plantaris muscles underwent atrophy (11.6 and 13.3%, respectively; P<0.05). In plantaris muscle, glycolytic type IId/x and IIb, but not oxidative type I and IIa, fibers displayed significant decreases in cross-sectional area (20.3%, P<0.05). Fast glycolytic white vastus lateralis muscle showed sarcomere degeneration and decreased cytochrome c oxidase IV (39.5%, P<0.01) and peroxisome proliferator-activated receptor gamma co-activator 1alpha protein expression (30.3%, P<0.01) along with a dramatic induction of the MAFbx/Atrogin-1 mRNA. These findings suggest that exercise intolerance can occur in CHF without fiber type switching in skeletal muscle and that oxidative phenotype renders myofibers resistant to pathological insults induced by CHF.

Improving the way we die: a coorientation study assessing agreement/disagreement in the organization-public relationship of hospices and physicians.

The movement to reform dying in America promotes hospice as a model for change. Yet terminally ill patients increasingly are closer to death when they enter some 3,300 hospices. Hospice leaders blame physicians for delaying referrals and charge that delays cause hardships for their organizations and patients. Based on symmetrical theory and the coorientation model, a survey of one Southern hospice and its referring physicians was conducted to measure agreement, perceived agreement, and accuracy between the two sides on the issue of timely referral. Results showed that hospice leaders inaccurately perceive a high degree of disagreement when they and physicians generally agree on the issue.

Late thrombosis following treatment of in-stent restenosis with drug-eluting stents after discontinuation of antiplatelet therapy.

Drug-eluting stent usage has become commonplace for the percutaneous treatment of de novo coronary lesions, but the safety and efficacy profile for their evolving usage in restenotic lesions is largely unknown. We report three cases of angiographically confirmed drug-eluting stent thrombosis following treatment of restenotic lesions that occurred late (193, 237, and 535 days) and shortly after interruption of antiplatelet therapy. All three patients suffered ST elevation myocardial infarction, and there was one death. Further studies are necessary to better define the associated risk and ideal duration of antiplatelet therapy necessary in this cohort of patients with restenotic lesions.

Decreases in corporeal vascular endothelial growth factor expression precede vasoreactivity changes in cholesterol fed rabbits.

PURPOSE: We determined temporal changes in vasoreactivity and angiogenic growth factor levels in corporeal tissue at varying time points after the induction of hypercholesterolemia in rabbits. MATERIALS AND METHODS: A total of 42 New Zealand White rabbits were fed a 1% cholesterol (8 per group) or normal (6 per group) diet for 2, 4.5 or 7.5 weeks. Vascular endothelial growth factor (VEGF) mRNA expression in corpus cavernosum was assessed by real-time polymerase chain reaction analyses for the 3 isoforms VEGF121, VEGF165 and VEGF189. Isometric tension studies were performed and dose response curves were generated to evaluate endothelial dependent and endothelial independent vasoreactivity. RESULTS: Real-time polymerase chain reaction analysis showed 2.2 to 2.5 and 1.5 to 2.7-fold decreases in VEGF121 and VEGF165, respectively, in the corporeal tissues of the high cholesterol group vs the normal diet group at the 2 week time point. At 2 weeks VEGF189 was unchanged but it was decreased 1.5 to 2-fold at 4.5 weeks. Acetylcholine isometric tension studies revealed no difference in mean ED50 (-log [M]) +/- SD until 7.5 weeks of high cholesterol diet (5.10 +/- 0.64 vs 3.95 +/- 1.35, p = 0.0269). The response to sodium nitroprusside was not statistically different at any time point. Endothelial cell and smooth muscle content were decreased for the high cholesterol vs normal diet at 4.5 weeks (endothelial only) and 7.5 weeks (each cell). CONCLUSIONS: Alterations in corporeal tissue levels of VEGF occur before abnormalities in vasoreactivity. The results suggest that VEGF has a role in normal vasoreactivity in corporeal tissue and, thereby, in normal erectile function.

Voluntary running induces fiber type-specific angiogenesis in mouse skeletal muscle.

Adult skeletal muscle undergoes adaptation in response to endurance exercise, including fast-to-slow fiber type transformation and enhanced angiogenesis. The purpose of this study was to determine the temporal and spatial changes in fiber type composition and capillary density in a mouse model of endurance training. Long-term voluntary running (4 wk) in C57BL/6 mice resulted in an approximately twofold increase in capillary density and capillary-to-fiber ratio in plantaris muscle as measured by indirect immunofluorescence with an antibody against the endothelial cell marker CD31 (466 +/- 16 capillaries/mm2 and 0.95 +/- 0.04 capillaries/fiber in sedentary control mice vs. 909 +/- 55 capillaries/mm2 and 1.70 +/- 0.04 capillaries/fiber in trained mice, respectively; P < 0.001). A significant increase in capillary-to-fiber ratio was present at day 7 with increased concentration of vascular endothelial growth factor (VEGF) in the muscle, before a significant increase in percentage of type IIa myofibers, suggesting that exercise-induced angiogenesis occurs first, followed by fiber type transformation. Further analysis with simultaneous staining of endothelial cells and isoforms of myosin heavy chains (MHCs) showed that the increase in capillary contact manifested transiently in type IIb + IId/x fibers at the time (day 7) of significant increase in total capillary density. These findings suggest that endurance training induces angiogenesis in a subpopulation of type IIb + IId/x fibers before switching to type IIa fibers.

Rationale and strategies for implementing community-based transfer protocols for primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction.

The focus for the initial approach to the treatment of acute ST-segment elevation myocardial infarction (STEMI) has shifted toward extending the benefits of mechanical reperfusion with primary percutaneous coronary intervention (PCI) to patients who present to community hospitals that have no interventional capabilities. Several randomized clinical trials have shown that transferring STEMI patients to tertiary centers for primary PCI leads to better outcomes than when fibrinolytic therapy is administered at community hospitals. Furthermore, potent pharmacologic reperfusion regimens that enhance early reperfusion of the infarct vessel before primary PCI may enhance the positive result of the transfer approach. Despite these promising findings, several obstacles have hindered the adoption of patient-transfer strategies in the U.S., including greater distances between community and tertiary hospitals, a lack of integrated emergency medical services, and the medical community's limited experience with centralized acute myocardial infarction (AMI) care networks. Nonetheless, the implementation of system-wide changes in the care of STEMI patients analogous to the creation of trauma networks could facilitate the creation and ongoing evaluation of dedicated patient transfer strategies and better early invasive care in the U.S. Within this context, a systematic, stepwise approach to the creation of AMI care networks and to the development of standard nomenclature and performance indicators is necessary to guide quality assurance monitoring and future research efforts as the care of STEMI patients is redefined. Consequently, this current evolution of reperfusion strategies has the potential to further reduce morbidity and mortality for patients presenting with STEMI.

Preclinical models of human peripheral arterial occlusive disease: implications for investigation of therapeutic agents.

Peripheral arterial occlusive disease (PAOD) is now recognized as a combination of clinical syndromes that are associated with significant morbidity and mortality. The primary pathophysiology of PAOD is impaired perfusion to the lower extremity. Effective pharmacotherapy designed to increase perfusion in PAOD is lacking, and revascularization options are suboptimal. New and more efficacious therapies that improve blood flow are definitely needed, and thus designing, describing, and validating these new therapies in preclinical PAOD models will be essential. This study describes the various preclinical PAOD models presently in use, correlates the models to human PAOD, and reviews the available end points that can be used to detect a response to therapy.

Current perspectives on reperfusion therapy for acute ST-segment elevation myocardial infarction: integrating pharmacologic and mechanical reperfusion strategies.

The therapeutic approach to patients with acute ST-segment elevation myocardial infarction (STEMI) has advanced rapidly over the past decade. Intravenous fibrinolytic therapy remains the most common form of reperfusion therapy worldwide, since fibrinolytics are associated with a dramatic reduction in mortality rates. However, primary percutaneous coronary intervention (PCI) is associated with improved outcomes and less bleeding complications compared with fibrinolytic therapy, but it is not widely available. Adjunctive therapies with intracoronary stents, glycoprotein (GP) IIb/IIIa inhibitors, and more potent antithrombin agents have shown great promise for the initial treatment of STEMI and have stimulated further investigation of combined pharmacological/mechanical reperfusion strategies that may be synergistic. Although the optimal combination of fibrinolytics, antiplatelet agents, antithrombins, and mechanical reperfusion at hospitals with and without primary PCI facilities remains elusive, results from recent studies suggest that such a combined approach may facilitate transfer of patients with STEMI from a referral hospital to an invasive hospital for definitive primary PCI after administration of a potent pharmacologic regimen designed to enhance early infarct-related artery reperfusion. Thus, as the reperfusion era continues to evolve, the ideal treatment strategy for patients with STEMI is being redefined to integrate pharmacologic and mechanical approaches to reperfusion.