Mis-implementation of evidence-based behavioural health practices in primary care: lessons from randomised trials in Federally Qualified Health Centers.

Background: Implementing evidence-based practices (EBPs) within service systems is critical to population-level health improvements - but also challenging, especially for complex behavioral health interventions in low-resource settings. "Mis-implementation" refers to poor outcomes from an EBP implementation effort; mis-implementation outcomes are an important, but largely untapped, source of information about how to improve knowledge exchange. Aims and objectives: We present mis-implementation cases from three pragmatic trials of behavioral health EBPs in U.S. Federally Qualified Health Centers (FQHCs). Methods: We adapted the Consolidated Framework for Implementation Research and its Outcomes Addendum into a framework for mis-implementation and used it to structure the case summaries with information about the EBP and trial, mis-implementation outcomes, and associated determinants (barriers and facilitators). We compared the three cases to identify shared and unique mis-implementation factors. Findings: Across cases, there was limited adoption and fidelity to the interventions, which led to eventual discontinuation. Barriers contributing to mis-implementation included intervention complexity, low buy-in from overburdened providers, lack of alignment between providers and leadership, and COVID-19-related stressors. Mis-implementation occurred earlier in cases that experienced both patient- and provider-level barriers, and that were conducted during the COVID-19 pandemic. Discussion and conclusion: Multi-level determinants contributed to EBP mis-implementation in FQHCs, limiting the ability of these health systems to benefit from knowledge exchange. To minimize mis-implementation, knowledge exchange strategies should be designed around common, core barriers but also flexible enough to address a variety of site-specific contextual factors and should be tailored to relevant audiences such as providers, patients, and/or leadership.

Exploring Which Patients Use Their Closest Emergency Departments Using Geocoded Data.

BACKGROUND: Each year, roughly 20% of U.S. adults visit an emergency department (ED), but little is known about patients' choice of ED. OBJECTIVES: Examine the discretion patients have to choose among EDs, characteristics associated with ED choice, and relationship between ED choice and self-reported care experiences of ED patients. METHODS: We surveyed adult patients discharged to the community (DTC) in January-March 2018 from 16 geographically dispersed hospital-based EDs, geocoded patient and hospital-based ED addresses within 100 miles of patient addresses, and calculated travel distances. We examined the likelihood of visiting the closest ED based on patient and ED characteristics. Linear regression models examined the association of choosing the closest ED with seven measures of patient experience of care (scaled 0-100), adjusting for patient characteristics. RESULTS: 43.6% of 4647 responding patients visited the ED nearest their home (on average, 5.7 miles away). Patients who chose a farther ED had more urgent conditions, were more educated, and were less likely to be non-Hispanic White. They were significantly more likely to have visited an ED in a higher-rated, metropolitan, network hospital with major teaching status, a cardiac intensive care unit, and a certified trauma center. Patients who chose a farther ED were more likely to recommend that ED, with "medium-to-large" differences in scores (+4.3% more selected "definitely yes", p < 0.05). CONCLUSIONS: Fewer than half of patients visited the closest ED. Patients who chose a farther ED tended to seek higher-rated hospitals and report more favorable experiences.

National travel distances for emergency care.

BACKGROUND: Most emergency department (ED) patients arrive by their own transport and, for various reasons, may not choose the nearest ED. How far patients travel for ED treatment may reflect both patients' access to care and severity of illness. In this study, we aimed to examine the travel distance and travel time between a patient's home and ED they visited and investigate how these distances/times vary by patient and hospital characteristics. METHODS: We randomly sampled and collected data from 14,812 patients discharged to the community (DTC) between January and March 2016 from 50 hospital-based EDs nationwide. We geocoded and calculated the distance and travel time between patient and hospital-based ED addresses, examined the travel distances/ times between patients' home and the ED they visited, and used mixed-effects regression models to investigate how these distances/times vary by patient and hospital characteristics. RESULTS: Patients travelled an average of 8.0 (SD = 10.9) miles and 17.3 (SD = 18.0) driving minutes to the ED. Patients travelled significantly farther to avoid EDs in lower performing hospitals (p < 0.01) and in the West (p < 0.05) and Midwest (p < 0.05). Patients travelled farther when visiting EDs in rural areas. Younger patients travelled farther than older patients. CONCLUSIONS: Understanding how far patients are willing to travel is indicative of whether patient populations have adequate access to ED services. By showing that patients travel farther to avoid a low-performing hospital, we provide evidence that DTC patients likely do exercise some choice among EDs, indicating some market incentives for higher-quality care, even for some ED admissions. Understanding these issues will help policymakers better define access to ED care and assist in directing quality improvement efforts. To our knowledge, our study is the most comprehensive nationwide characterization of patient travel for ED treatment to date.

Fast myocardial T1 mapping using cardiac motion correction.

PURPOSE: To improve the efficiency of native and postcontrast high-resolution cardiac T1 mapping by utilizing cardiac motion correction. METHODS: Common cardiac T1 mapping techniques only acquire data in a small part of the cardiac cycle, leading to inefficient data sampling. Here, we present an approach in which 80% of each cardiac cycle is used for T1 mapping by integration of cardiac motion correction. Golden angle radial data was acquired continuously for 8 s with in-plane resolution of 1.3 × 1.3 mm2 . Cine images were reconstructed for nonrigid cardiac motion estimation. Images at different TIs were reconstructed from the same data, and motion correction was performed prior to T1 mapping. Native T1 mapping was evaluated in healthy subjects. Furthermore, the technique was applied for postcontrast T1 mapping in 5 patients with suspected fibrosis. RESULTS: Cine images with high contrast were obtained, leading to robust cardiac motion estimation. Motion-corrected T1 maps showed myocardial T1 times similar to cardiac-triggered T1 maps obtained from the same data (1288 ± 49 ms and 1259 ± 55 ms, respectively) but with a 34% improved precision (spatial variation: 57.0 ± 12.5 ms and 94.8 ± 15.4 ms, respectively, P < 0.0001) due to the increased amount of data. In postcontrast T1 maps, focal fibrosis could be confirmed with late contrast-enhancement images. CONCLUSION: The proposed approach provides high-resolution T1 maps within 8 s. Data acquisition efficiency for T1 mapping was improved by a factor of 5 by integration of cardiac motion correction, resulting in precise T1 maps.

Simultaneous high-resolution cardiac T1 mapping and cine imaging using model-based iterative image reconstruction.

PURPOSE: To provide high-resolution cardiac T1 mapping of various cardiac phases and cine imaging within a single breath-hold using continuous golden ratio-based radial acquisition and model-based iterative image reconstruction. METHODS: Data acquisition was performed continuously using golden ratio-based radial sampling and multiple inversion pulses were applied independent of the heart rate. Native T1 maps of diastole and systole were reconstructed with in-plane resolution of 1.3 × 1.3 mm2 using model-based iterative image reconstruction. Cine images with 30 cardiac phases were reconstructed from the same data using kt-SENSE. The method was evaluated in a commercially available T1 phantom and 10 healthy subjects. In vivo T1 assessment was carried out segment-wise. RESULTS: Evaluation in the phantom demonstrated accurate T1 times (R2 > 0.99) and insensitivity to the heart rate. In vivo T1 values did not differ between systole and diastole, and T1 times assessed by the proposed approach were longer than measured with a modified Look-Locker inversion recovery (MOLLI) sequence, except for lateral segments. Cine images had a consistent dark-blood contrast and functional assessment was in agreement with assessment based on Cartesian cine scans (difference in ejection fraction: 0.26 ± 2.65%, P = 0.65). CONCLUSION: The proposed approach provides native T1 maps of diastole and systole with high spatial resolution and cine images simultaneously within 16 s, which could strongly improve the scan efficiency.

National Testing of the Emergency Department Patient Experience of Care Discharged to Community Survey and Implications for Adjustment in Scoring.

BACKGROUND: The emergency department (ED) setting is unique and measuring quality of care in the ED requires the development of ED-specific tools. The Emergency Department Patient Experience of Care Discharged to Community Survey was designed to measure patient experience in the ED setting. OBJECTIVES: Describe results from the Emergency Department Patient Experience of Care Discharged to Community Survey including respondent characteristics and reported patient experience, and examine factors, including mode of survey administration, associated with response propensity and response patterns. RESEARCH DESIGN: In total, 16,006 discharges were sampled from 50 hospitals nationwide to receive the survey using a mode experiment design. Logistic regression modeled response propensity; linear regression examined associations between response patterns and patient characteristics and mode. SUBJECTS: In total, 3122 survey respondents. MEASURES: Measures of patient experience. RESULTS: Patients reported that hospitals consistently informed them of the purpose of any new medications (84% yes, definitely), but did not consistently explain their possible side effects (53%). Age, education, health, and arrival by ambulance were significantly associated with response patterns. There were significant differences in response rate by mode: 29% mixed mode, 22% telephone only and 14% mail only. Mode of administration was significantly associated with response patterns whereby patients surveyed using telephone-only or mixed mode tended to respond more positively than those surveyed using mail only. CONCLUSIONS: There is room for improvement in terms of patient experience in the ED setting. Effects of patient characteristics and survey mode on responses were large enough to necessitate appropriate adjustments if hospitals are to be compared in the future.

Assessing and improving organizational readiness to implement substance use disorder treatment in primary care: findings from the SUMMIT study.

BACKGROUND: Millions of people with substance use disorders (SUDs) need, but do not receive, treatment. Delivering SUD treatment in primary care settings could increase access to treatment because most people visit their primary care doctors at least once a year, but evidence-based SUD treatments are underutilized in primary care settings. We used an organizational readiness intervention comprised of a cluster of implementation strategies to prepare a federally qualified health center to deliver SUD screening and evidence-based treatments (extended-release injectable naltrexone (XR-NTX) for alcohol use disorders, buprenorphine/naloxone (BUP/NX) for opioid use disorders and a brief motivational interviewing/cognitive behavioral -based psychotherapy for both disorders). This article reports the effects of the intervention on key implementation outcomes. METHODS: To assess changes in organizational readiness we conducted pre- and post-intervention surveys with prescribing medical providers, behavioral health providers and general clinic staff (N = 69). We report on changes in implementation outcomes: acceptability, perceptions of appropriateness and feasibility, and intention to adopt the evidence-based treatments. We used Wilcoxon signed rank tests to analyze pre- to post-intervention changes. RESULTS: After 18 months, prescribing medical providers agreed more that XR-NTX was easier to use for patients with alcohol use disorders than before the intervention, but their opinions about the effectiveness and ease of use of BUP/NX for patients with opioid use disorders did not improve. Prescribing medical providers also felt more strongly after the intervention that XR-NTX for alcohol use disorders was compatible with current practices. Opinions of general clinic staff about the appropriateness of SUD treatment in primary care improved significantly. CONCLUSIONS: Consistent with implementation theory, we found that an organizational readiness implementation intervention enhanced perceptions in some domains of practice acceptability and appropriateness. Further research will assess whether these factors, which focus on individual staff readiness, change over time and ultimately predict adoption of SUD treatments in primary care.

Renal cortical pyruvate depletion during AKI.

Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15-60 minutes; 0-18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury.

It takes a village: A pilot study of a group telehealth intervention for support persons affected by opioid use disorder.

INTRODUCTION: Opioid use disorder (OUD) has devastating effects on individuals, families, and communities. The Community Reinforcement and Family Training (CRAFT) is a Support Person (SP)-focused intervention that aims to increase SPs' communication strategies, positive reinforcement/rewards, and social support. This pilot study, called eINSPIRE (INtegrating Support Persons Into REcovery), adapted CRAFT for delivery via group telehealth. The aims were to evaluate the feasibility, acceptability, and preliminary effectiveness of this intervention on patient buprenorphine retention and SP mental health. METHODS: The study recruited patients receiving buprenorphine treatment in a primary care setting across five community health centers with their SP (N = 100 dyads). SP participants were randomly assigned to receive usual care (UC) or the eINSPIRE intervention. We interviewed Patients and SPs at baseline and three months later. The study collected patient buprenorphine retention data from the electronic medical record three months post-baseline. RESULTS: About 88 % (656/742) of potentially eligible patients were able to nominate a SP and 69 % (100/145) of nominated SPs were eligible and consented to the study. eINSPIRE groups had low reach (25 % of SPs attended), but high exposure (M = 7 of 10 sessions attended) and acceptability (classes helped them with their patient's OUD). The proportion of eINSPIRE patients (68 %) and UC patients (53 %) retained on buprenorphine at follow-up were similar (p = 0.203). SPs in both conditions reported similar reductions in their depression, anxiety, and impairment symptoms. CONCLUSIONS: Preliminary data suggest that eINSPIRE groups may not be feasible in primary care without further adaptations for this population. A future study with a larger sample size is needed to elucidate the observed distribution differences in buprenorphine retention. Future research should also explore methods to reduce barriers to SP session attendance to improve the reach of this evidence-based intervention.

Progressive endothelin-1 gene activation initiates chronic/end-stage renal disease following experimental ischemic/reperfusion injury.

This study assessed whether endothelin-1 (ET-1) helps mediate postischemic acute kidney injury (AKI) progression to chronic kidney disease (CKD). The impact(s) of potent ETA or ETB receptor-specific antagonists (Atrasentan and BQ-788, respectively) on disease progression were assessed 24 h or 2 weeks following 30 min of unilateral ischemia in CD-1 mice. Unilateral ischemia caused progressive renal ET-1 protein/mRNA increases with concomitant ETA, but not ETB, mRNA elevations. Extensive histone remodeling consistent with gene activation and increased RNA polymerase II (Pol II) binding occurred at the ET-1 gene. Unilateral ischemia produced progressive renal injury as indicated by severe histologic injury and a 40% loss of renal mass. Pre- and post-ischemia or just postischemic treatment with Atrasentan conferred dramatic protective effects such as decreased tubule/microvascular injury, normalized tissue lactate, and total preservation of renal mass. Nuclear KI-67 staining was not increased by Atrasentan, implying that increased tubule proliferation was not involved. Conversely, ETB blockade had no protective effect. Thus, our findings provide the first evidence that ET-1 operating through ETA can have a critical role in ischemic AKI progression to CKD. Blockade of ETA provided dramatic protection, indicating the functional significance of these results.

Post-ischemic azotemia as a partial 'brake', slowing progressive kidney disease.

BACKGROUND: Recent experimental work suggests a paradox: although uremia evokes systemic toxicities, in the setting of AKI, it can induce intrarenal cytoprotective and anti-inflammatory effects. Whether these influences can attenuate post-ischemic kidney disease progression remains unknown. METHODS: To explore this possibility, male CD-1 mice were subjected to a 30-min unilateral (left) kidney ischemia model, previously shown to reduce renal mass by ∼50% over 2-3 weeks. Stepwise azotemia/acute uremia was superimposed by inducing different lengths of contralateral (right) kidney ischemia (0, 15, 18, 20 min). Subsequent loss of left renal mass (kidney weight) was assessed 2 weeks later and contrasted with the degree of initial azotemia 24-h BUN. RESULTS: A striking correlation between 24-h BUNs and 2-week left renal mass was observed (r, 0.77; P < 0.001). With 20 min of right kidney ischemia, left kidney size was completely preserved. This preservation did not result from increased tubular cell proliferation or decreased microvascular loss, as gauged by KI-67 and CD-34 immunohistochemistry, respectively. Rather, an early reduction in proximal tubule cell dropout (as judged by renal cortical N-acetyl-glucosaminidase content), with a subsequent preservation of tubule mass, was observed. CONCLUSIONS: In summary, these findings advance a novel concept: acute uremia can confer early post-ischemic cytoprotection resulting in a slowed progression of post-ischemic kidney disease.

Drug use among gay and bisexual men at weekend dance parties: the role of intentions and perceptions of peers' behaviors.

Substance use is high among gay and bisexual men attending weekend dance events, yet little research has investigated motivations for drug use and contextual factors influencing use in these settings. We hypothesized that beliefs about peer drug use interact with individuals' own drug use intentions to predict use. 489 men attending weekend dance events completed an anonymous assessment asking about their own and their beliefs about other attendants' drug use intentions--47 % completed a follow-up assessment after the event. Forty-four percent reported intending to use ecstasy at the event; intentions to use GHB, marijuana, cocaine, unprescribed erectile dysfunction drugs, and poppers were also high. Perceptions about other attendant's drug use predicted use among those intending and those not intending to use drugs. Normative beliefs are important predictors of drug use at weekend dance events; event-specific prevention strategies should encompass messages that correct misperceptions of drug use among party attendants.

Plasma and urinary heme oxygenase-1 in AKI.

AKI induces upregulation of heme oxygenase 1 (HO-1), which exerts cytoprotective effects and modulates the renal response to injury, suggesting that a biomarker of intrarenal HO-1 activity may be useful. Because HO-1 largely localizes to the endoplasmic reticulum and has no known secretory pathway, it is unclear whether plasma or urinary levels of HO-1 reflect intrarenal HO-1 expression. We measured plasma and urinary levels of HO-1 by ELISA during the induction and/or maintenance phases of four mouse models of AKI: ischemia/reperfusion, glycerol-induced rhabdomyolysis, cisplatin nephrotoxicity, and bilateral ureteral obstruction. In addition, we measured levels of HO-1 mRNA and protein in the renal cortex. Each AKI model increased renal HO-1 gene expression, which corresponded with release of HO-1 into plasma and urine by 4 hours. Over time, the magnitudes of plasma and urinary HO-1 paralleled renal cortical gene expression. AKI and the associated uremia did not seem to affect extrarenal HO-1 gene activity assessed in the liver, lung, and spleen. In iron-challenged, cultured proximal tubule cells, we observed a positive correlation between HO-1 mRNA level and HO-1 release. In humans, 10 patients with AKI demonstrated markedly higher levels of plasma and urine HO-1 levels than 10 critically ill patients without AKI or 20 patients with CKD or ESRD. In summary, these data suggest that plasma and urinary HO-1 levels may serve as biomarkers of AKI and intrarenal HO-1 gene activity.

Screening for opioid use disorder and co-occurring depression and post-traumatic stress disorder in primary care in New Mexico.

BACKGROUND: Identifying patients in primary care services with opioid use disorder and co-occurring mental health disorders is critical to providing treatment. Objectives of this study were to (1) assess the feasibility of recruiting people to screen in-person for opioid use disorder and co-occurring mental health disorders (depression and/or post-traumatic stress disorder) in primary care clinic waiting rooms in preparation for a randomized controlled trial, and (2) compare results of detecting these disorders by universal in-person screening compared to electronic health record (EHR) diagnoses. METHODS: This cross-sectional feasibility and pilot study recruited participants from four primary care clinics, two rural and two urban, from three health care organizations in New Mexico. Inclusion criteria were adults (≥ 18 years), attending one of the four clinics as a patient, and who spoke English or Spanish. Exclusion criteria were people attending the clinic for a non-primary care visit (e.g., dental, prescription pick up, social support). The main outcomes and measures were (1) recruitment feasibility which was assessed by frequencies and proportions of people approached and consented for in-person screening, and (2) relative differences of detecting opioid use disorder and co-occurring mental health disorders in waiting rooms relative to aggregate EHR data from each clinic, measured by prevalence and prevalence ratios. RESULTS: Over two-weeks, 1478 potential participants were approached and 1145 were consented and screened (77.5% of patients approached). Probable opioid use disorder and co-occurring mental health disorders were identified in 2.4% of those screened compared to 0.8% in EHR. Similarly, universal screening relative to EHR identified higher proportions of probable opioid use disorder (4.5% vs. 3.4%), depression (17.5% vs. 12.7%) and post-traumatic stress disorder (19.0% vs. 3.6%). CONCLUSIONS: Universal screening for opioid use disorder, depression, and post-traumatic stress disorder was feasible, and identified three times as many patients with these co-occurring disorders compared to EHR. Higher proportions of each condition were also identified, especially post-traumatic stress disorder. Results support that there are likely gaps in identification of these disorders in primary care services and demonstrate the need to better address the persistent public health problem of these co-occurring disorders.

Renal cortical hemopexin accumulation in response to acute kidney injury.

Hemopexin (Hpx) is a liver-generated acute phase reactant that binds and neutralizes prooxidant free heme. This study tested whether acute kidney injury (AKI) triggers renal Hpx accumulation, potentially impacting heme Fe-mediated tubular injury. Mice were subjected to glycerol, cisplatin, ischemia-reperfusion (I/R), or endotoxemic [lipopolysaccharide (LPS)] AKI. In each instance, 3- to 30-fold renal cortical and isolated proximal tubule segment (PTS) Hpx increases resulted. Although renal cortex and PTS showed variable Hpx mRNA increases, due, in part, to increased mRNA stability, mRNA levels did not correlate with renal Hpx protein accumulation. Conversely, AKI evoked three- to fourfold increases in hepatic Hpx gene induction, which corresponded with three- to fourfold plasma Hpx increases. Renal immunohistochemistry, and increased urinary Hpx excretion, indicated that circulating Hpx gains tubule luminal/urinary access, followed by proximal tubule endocytic uptake. Paradoxically, in cultured renal cells (HK-2, HEK-293), Fe depletion, and not free heme excess, increased Hpx mRNA. LPS acutely increased HK-2 cell Hpx mRNA. This finding, coupled with observations that LPS evoked ∼30-fold greater renal Hpx mRNA increases than any other AKI model, suggests that inflammation, not heme exposure, activates the renal Hpx gene. Each form of AKI evoked early increases in circulating free heme, which subsequently fell to subnormal levels as plasma Hpx rose. In addition, purified Hpx blunted free Fe-mediated HK-2 cell death. In sum, these data indicated that AKI-associated hepatic stress generates Hpx, which gains renal tubule access. Given its ability to bind free heme and mitigate free Fe toxicity, Hpx loading can potentially confer cytoprotective effects.

Development and validation of a patient experience of care survey for emergency departments.

OBJECTIVES: To (1) develop a survey to assess the patient experience of care in hospital-based emergency departments (ED) and (2) evaluate the reliability and validity of composite measures of patient experience using data collected through the experimental implementation of the newly developed Emergency Department Patient Experience of Care (EDPEC) Discharged to Community (DTC) Survey. DATA SOURCE: 4893 adult patients were treated in the ED of 16 hospitals across the United States in 2018. STUDY DESIGN: The study utilized a cross-sectional survey. DATA COLLECTION: Survey development activities included a literature review, focus groups, and cognitive interviews with recently discharged ED patients, technical expert panels, and multiple field experiments. Survey development resulted in a 34-item instrument; the analysis reported here focuses on 18 items on patient experience of care. Using data from the EDPEC DTC Survey in the 2018 Feasibility Test, we performed confirmatory factor analysis to group 15 evaluative survey items into composite measures. We examined internal consistency reliability, interunit reliability, and associations between each composite measure and patients' overall rating and willingness to recommend the ED. PRINCIPAL FINDINGS: Analyses of 15 evaluative items identified four composite measures: Getting Timely Care, How Well Doctors and Nurses Communicate, Communication about Medications, and Communication about Follow-up. Patient-level internal consistency reliability exceeded 0.75 for two of four composites; ED-level internal consistency reliability exceeded 0.83 for all four composites. Interunit reliability estimates indicated that 450 survey completes per ED results in at least 0.70 reliability for all composites. Higher scores on each composite were associated with higher overall ratings and willingness to recommend the ED. CONCLUSIONS: The composite measures derived from the EDPEC DTC Survey are statistically reliable and valid. These results provide guidance for EDPEC DTC Survey adopters on how to construct meaningful and psychometrically-sound composite measures for monitoring the quality of care they provide.

Acute unilateral ischemic renal injury induces progressive renal inflammation, lipid accumulation, histone modification, and "end-stage" kidney disease.

There is an emerging concept in clinical nephrology that acute kidney injury (AKI) can initiate chronic kidney disease (CKD). However, potential mechanisms by which this may occur remain elusive. Hence, this study tested the hypotheses that 1) AKI triggers progressive activation of selected proinflammatory genes, 2) there is a relative failure of compensatory anti-inflammatory gene expression, 3) proinflammatory lipid accumulation occurs, 4) these changes correspond with "gene-activating" histone acetylation, and 5) in concert, progressive renal disease results. CD-1 mice were subjected to 30 min of unilateral renal ischemia. Assessments were made 1 day, 1 wk, or 3 wk later. Results were contrasted to those observed in uninjured contralateral kidneys or in kidneys from normal mice. Progressive renal injury occurred throughout the 3-wk postischemic period, as denoted by stepwise increases in neutrophil gelatinase-associated lipocalin gene induction and ongoing histologic damage. By 3 wk postischemia, progressive renal disease was observed (massive tubular dropout; 2/3rds reduction in renal weight). These changes corresponded with progressive increases in proinflammatory cytokine/chemokine gene expression (MCP-1, TNF-α, TGF-ß1), a relative failure of anti-inflammatory enzyme/cytokine (heme oxygenase-1; IL-10) upregulation, and progressive renal lipid (cholesterol/triglyceride) loading. Stepwise increases in collagen III mRNA and collagen deposition (Sirius red staining) indicated a progressive profibrotic response. Postischemic dexamethasone treatment significantly preserved renal mass, indicating functional significance of the observed proinflammatory state. Progressive gene-activating H3 acetylation was observed by ELISA, rising from 5% at baseline to 75% at 3 wk. This was confirmed by chromatin immunoprecipitation assay of target genes. In sum, these results provide experimental support for the clinical concept that AKI can trigger CKD, this is partially mediated by progressive postischemic inflammation, ongoing lipid accumulation results (potentially evoking "lipotoxicity"), and increasing histone acetylation at proinflammatory/profibrotic genes may contribute to this self-sustaining injury-promoting state.

Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury.

Despite their prooxidant effects, ferric iron compounds are routinely administered to patients with renal disease to correct Fe deficiency. This study assessed relative degrees to which three clinically employed Fe formulations [Fe sucrose (FeS); Fe gluconate (FeG); ferumoxytol (FMX)] impact renal redox- sensitive signaling, cytotoxicity, and responses to superimposed stress [endotoxin; glycerol-induced acute renal failure (ARF)]. Cultured human proximal tubule (HK-2) cells, isolated proximal tubule segments (PTS), or mice were exposed to variable, but equal, amounts of FeS, FeG, or FMX. Oxidant-stimulated signaling was assessed by heme oxygenase-1 (HO-1) or monocyte chemoattractant protein (MCP)-1 mRNA induction. Cell injury was gauged by MTT assay (HK-2 cells), %LDH release (PTS), or renal cortical neutrophil gelatinase-associated lipoprotein (NGAL) protein/mRNA levels. Endotoxin sensitivity and ARF severity were assessed by TNF-alpha and blood urea nitrogen concentrations, respectively. FeS and FeG induced lethal cell injury (in HK-2 cells, PTS), increased HO-1 and MCP-1 mRNAs (HK-2 cells; in vivo), and markedly raised plasma ( approximately 10 times), and renal cortical ( approximately 3 times) NGAL protein levels. Both renal and extrarenal (e.g., hepatic) NGAL production likely contributed to these results, based on assessments of tissue and HK-2 cell NGAL mRNA. FeS pretreatment exacerbated endotoxemia. However, it conferred marked protection against the glycerol model of ARF (halving azotemia). FMX appeared to be "bioneutral," as it exerted none of the above noted FeS/FeG effects. We conclude that 1) parenteral iron formulations that stimulate redox signaling can evoke cyto/nephrotoxicity; 2) secondary adaptive responses to this injury (e.g., HO-1/NGAL induction) can initiate a renal tubular cytoresistant state; this suggests a potential new clinical application for intravenous Fe therapy; and 3) FMX is bioneutral regarding these responses. The clinical implication(s) of the latter, vis a vis the treatment of Fe deficiency in renal disease patients, remains to be defined.

Provider-related barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs) and hospitals.

We examined provider-reported barriers to rapid HIV testing in U.S. urban non-profit community clinics, community-based organizations (CBOs), and hospitals. 12 primary metropolitan statistical areas (PMSAs; three per region) were sampled randomly, with sampling weights proportional to AIDS case reports. Across PMSAs, all 671 hospitals and a random sample of 738 clinics/CBOs were telephoned for a survey on rapid HIV test availability. Of the 671 hospitals, 172 hospitals were randomly selected for barriers questions, for which 158 laboratory and 136 department staff were eligible and interviewed in 2005. Of the 738 clinics/CBOs, 276 were randomly selected for barriers questions, 206 were reached, and 118 were eligible and interviewed in 2005-2006. In multivariate models, barriers regarding translation of administrative/quality assurance policies into practice were significantly associated with rapid HIV testing availability. For greater rapid testing diffusion, policies are needed to reduce administrative barriers and provide quality assurance training to non-laboratory staff.

Study design to evaluate a group-based therapy for support persons of adults on buprenorphine/naloxone.

BACKGROUND: Opioid use disorders (OUDs) have devastating effects on individuals, families, and communities. While medication treatments for OUD save lives and are increasingly utilized, rates of treatment dropout are very high. In addition, most existing medication treatments for OUD may often neglect the impact of untreated OUD on relationships and ignore the potential role support persons (SPs) could have on encouraging long-term recovery, which can also impact patient treatment retention. METHODS/DESIGN: The current study adapts Community Reinforcement and Family Training (CRAFT) for use with SPs (family member, spouse or friend) of patients using buprenorphine/naloxone (buprenorphine) in an outpatient community clinic setting. The study will evaluate whether the adapted intervention, also known as integrating support persons into recovery (INSPIRE), is effective in increasing patient retention on buprenorphine when compared to usual care. We will utilize a two-group randomized design where patients starting or restarting buprenorphine will be screened for support person status and recruited with their support person if eligible. Support persons will be randomly assigned to the INSPIRE intervention, which will consist of 10 rolling group sessions led by two facilitators. Patients and SPs will each be assessed at baseline, 3 months post-baseline, and 12 months post-baseline. Patient electronic medical record data will be collected at six and 12 months post-baseline. We will examine mechanisms of intervention effectiveness and also conduct pre/post-implementation surveys with clinic staff to assess issues that would affect sustainability. DISCUSSION: Incorporating the patient's support system may be an important way to improve treatment retention in medication treatments for OUD. If SPs can serve to support patient retention, this study would significantly advance work to help support the delivery of effective treatments that prevent the devastating consequences associated with OUD. Trial registration This study was registered with ClinicalTrials.gov, NCT04239235. Registered 27 January 2020, https://clinicaltrials.gov/ct2/show/NCT04239235 .