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INTRODUCTION: Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. METHODS: We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. RESULTS: Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P <0.002), none of which achieved an AUC >0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. CONCLUSIONS: Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. TRIAL REGISTRATION: ClinicalTrials.gov number NCT01209169.

BACKGROUND: Combination therapy with angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) decreases proteinuria; however, its safety and effect on the progression of kidney disease are uncertain. Methods We provided losartan (at a dose of 100 mg per day) to patients with type 2 diabetes, a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 300, and an estimated glomerular filtration rate (GFR) of 30.0 to 89.9 ml per minute per 1.73 m(2) of body-surface area and then randomly assigned them to receive lisinopril (at a dose of 10 to 40 mg per day) or placebo. The primary end point was the first occurrence of a change in the estimated GFR (a decline of ≥ 30 ml per minute per 1.73 m(2) if the initial estimated GFR was ≥ 60 ml per minute per 1.73 m(2) or a decline of ≥ 50% if the initial estimated GFR was <60 ml per minute per 1.73 m(2)), end-stage renal disease (ESRD), or death. The secondary renal end point was the first occurrence of a decline in the estimated GFR or ESRD. Safety outcomes included mortality, hyperkalemia, and acute kidney injury. Results The study was stopped early owing to safety concerns. Among 1448 randomly assigned patients with a median follow-up of 2.2 years, there were 152 primary end-point events in the monotherapy group and 132 in the combination-therapy group (hazard ratio with combination therapy, 0.88; 95% confidence interval [CI], 0.70 to 1.12; P=0.30). A trend toward a benefit from combination therapy with respect to the secondary end point (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P=0.10) decreased with time (P=0.02 for nonproportionality). There was no benefit with respect to mortality (hazard ratio for death, 1.04; 95% CI, 0.73 to 1.49; P=0.75) or cardiovascular events. Combination therapy increased the risk of hyperkalemia (6.3 events per 100 person-years, vs. 2.6 events per 100 person-years with monotherapy; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years, P<0.001). Conclusions Combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. (Funded by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; VA NEPHRON-D ClinicalTrials.gov number, NCT00555217.).

BACKGROUND: The National Cardiogenic Shock Initiative is a single-arm, prospective, multicenter study to assess outcomes associated with early mechanical circulatory support (MCS) in patients presenting with acute myocardial infarction and cardiogenic shock (AMICS) treated with percutaneous coronary intervention (PCI). METHODS: Between July 2016 and February 2019, 35 sites participated and enrolled into the study. All centers agreed to treat patients with AMICS using a standard protocol emphasizing invasive hemodynamic monitoring and rapid initiation of MCS. Inclusion and exclusion criteria mimicked those of the "SHOCK" trial with an additional exclusion criteria of intra-aortic balloon pump counter-pulsation prior to MCS. RESULTS: A total of 171 consecutive patients were enrolled. Patients had an average age of 63 years, 77% were male, and 68% were admitted with AMICS. About 83% of patients were on vasopressors or inotropes, 20% had a witnessed out of hospital cardiac arrest, 29% had in-hospital cardiac arrest, and 10% were under active cardiopulmonary resuscitation during MCS implantation. In accordance with the protocol, 74% of patients had MCS implanted prior to PCI. Right heart catheterization was performed in 92%. About 78% of patients presented with ST-elevation myocardial infarction with average door to support times of 85 ± 63 min and door to balloon times of 87 ± 58 min. Survival to discharge was 72%. Creatinine ≥2, lactate >4, cardiac power output (CPO) <0.6 W, and age ≥ 70 years were predictors of mortality. Lactate and CPO measurements at 12-24 hr reliably predicted overall mortality postindex procedure. CONCLUSION: In contemporary practice, use of a shock protocol emphasizing best practices is associated with improved outcomes.

Previously published guidelines provide comprehensive recommendations for detecting and preventing healthcare-associated infections (HAIs). The intent of this document is to highlight practical recommendations in a concise format designed to assist acute-care hospitals in implementing and prioritizing their central line-associated bloodstream infection (CLABSI) prevention efforts. This document updates the Strategies to Prevent Central Line-Associated Bloodstream Infections in Acute-Care Hospitals published in 2014. 1 This expert guidance document is sponsored by the Society for Healthcare Epidemiology of America (SHEA). It is the product of a collaborative effort led by SHEA, the Infectious Diseases Society of America (IDSA), the Association for Professionals in Infection Control and Epidemiology (APIC), the American Hospital Association (AHA), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise.

In Brief Objective: To evaluate the comparative effectiveness of sleeve gastrectomy (SG), laparoscopic gastric bypass (RYGB), and laparoscopic adjustable gastric banding (LAGB) procedures. Background: Citing limitations of published studies, payers have been reluctant to provide routine coverage for SG for the treatment of morbid obesity. Methods: Using data from an externally audited, statewide clinical registry, we matched 2949 SG patients with equal numbers of RYGB and LAGB patients on 23 baseline characteristics. Outcomes assessed included complications occurring within 30 days, and weight loss, quality of life, and comorbidity remission at 1, 2, and 3 years after bariatric surgery. Results: Matching resulted in cohorts of SG, RYGB, and LAGB patients that were well balanced on baseline characteristics. Overall complication rates among patients undergoing SG (6.3%) were significantly lower than for RYGB (10.0%, P < 0.0001) but higher than for LAGB (2.4%, P < 0.0001). Serious complication rates were similar for SG (2.4%) and RYGB (2.5%, P = 0.736) but higher than for LAGB (1.0%, P < 0.0001). Excess body weight loss at 1 year was 13% lower for SG (60%) than for RYGB (69%, P < 0.0001), but was 77% higher for SG than for LAGB (34%, P < 0.0001). SG was similarly closer to RYGB than LAGB with regard to remission of obesity-related comorbidities. Conclusions: With better weight loss than LAGB and lower complication rates than RYGB, SG is a reasonable choice for the treatment of morbid obesity and should be covered by both public and private payers. Citing limitations of published studies, payers have been reluctant to provide routine coverage for sleeve gastrectomy for the treatment of morbid obesity. Using data from a statewide, externally audited clinical registry, our study compares rates of complications, and weight loss, comorbidity remission, quality of life, and satisfaction for 3 years after bariatric surgery among nearly 9000 morbidly obese patients. We find that with better weight loss than adjustable gastric band and lower complication rates than gastric bypass, sleeve gastrectomy is a reasonable choice for the treatment of morbid obesity and should be covered by both public and private payers.

IMPORTANCE: While current reports suggest that a disproportionate share of US coronavirus disease 2019 (COVID-19) cases and deaths are among Black residents, little information is available regarding how race is associated with in-hospital mortality. OBJECTIVE: To evaluate the association of race, adjusting for sociodemographic and clinical factors, on all-cause, in-hospital mortality for patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included 11 210 adult patients (age ≥18 years) hospitalized with confirmed severe acute respiratory coronavirus 2 (SARS-CoV-2) between February 19, 2020, and May 31, 2020, in 92 hospitals in 12 states: Alabama (6 hospitals), Maryland (1 hospital), Florida (5 hospitals), Illinois (8 hospitals), Indiana (14 hospitals), Kansas (4 hospitals), Michigan (13 hospitals), New York (2 hospitals), Oklahoma (6 hospitals), Tennessee (4 hospitals), Texas (11 hospitals), and Wisconsin (18 hospitals). EXPOSURES: Confirmed SARS-CoV-2 infection by positive result on polymerase chain reaction testing of a nasopharyngeal sample. MAIN OUTCOMES AND MEASURES: Death during hospitalization was examined overall and by race. Race was self-reported and categorized as Black, White, and other or missing. Cox proportional hazards regression with mixed effects was used to evaluate associations between all-cause in-hospital mortality and patient characteristics while accounting for the random effects of hospital on the outcome. RESULTS: Of 11 210 patients with confirmed COVID-19 presenting to hospitals, 4180 (37.3%) were Black patients and 5583 (49.8%) were men. The median (interquartile range) age was 61 (46 to 74) years. Compared with White patients, Black patients were younger (median [interquartile range] age, 66 [50 to 80] years vs 61 [46 to 72] years), were more likely to be women (2259 [49.0%] vs 2293 [54.9%]), were more likely to have Medicaid insurance (611 [13.3%] vs 1031 [24.7%]), and had higher median (interquartile range) scores on the Neighborhood Deprivation Index (-0.11 [-0.70 to 0.56] vs 0.82 [0.08 to 1.76]) and the Elixhauser Comorbidity Index (21 [0 to 44] vs 22 [0 to 46]). All-cause in-hospital mortality among hospitalized White and Black patients was 23.1% (724 of 3218) and 19.2% (540 of 2812), respectively. After adjustment for age, sex, insurance, comorbidities, neighborhood deprivation, and site of care, there was no statistically significant difference in risk of mortality between Black and White patients (hazard ratio, 0.93; 95% CI, 0.80 to 1.09). CONCLUSIONS AND RELEVANCE: Although current reports suggest that Black patients represent a disproportionate share of COVID-19 infections and death in the United States, in this study, mortality for those able to access hospital care did not differ between Black and White patients after adjusting for sociodemographic factors and comorbidities.

At a crucial time with rapid spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant globally, the United States Food and Drug Administration has issued an emergency use authorization for 2 oral antivirals, molnupiravir (in persons aged ≥18 years) and nirmatrelvir-ritonavir (Paxlovid) (in persons aged ≥12 years weighing ≥40 kg), for the outpatient treatment of patients with mild to moderate coronavirus disease 2019 (COVID-19) who are at risk for progression. Molnupiravir is a nucleoside analogue, whereas nirmatrelvir is a SARS-CoV-2 main protease inhibitor, and ritonavir is a human immunodeficiency virus type 1 protease inhibitor. Drug interactions are a major concern for nirmatrelvir-ritonavir. Nirmatrelvir-ritonavir demonstrated a greater risk reduction in hospitalization and death than molnupiravir compared to placebo. Both drugs need to be started within 5 days of symptoms onset and given for 5 days' duration. This article reviews the 2 oral COVID-19 antiviral drugs including the mechanisms of action, antiviral activity, pharmacokinetics, drug interactions, clinical experience including trials, adverse events, recommended indications, and formulary considerations.

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6% to 15% of myocardial infarctions (MIs) and disproportionately affects women. Scientific statements recommend multimodality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) imaging to assess mechanisms of MINOCA. Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of myocardial infarction. If invasive coronary angiography revealed &lt;50% stenosis in all major arteries, multivessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and nonischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible. Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intraplaque cavity, or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% (62/116) of participants undergoing CMR. A nonischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome, or nonischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% (98/116) of the women with multimodality imaging, higher than with OCT alone ( P &lt;0.001) or CMR alone ( P =0.001). An ischemic cause was identified in 63.8% of women with MINOCA (74/116), a nonischemic cause was identified in 20.7% (24/116) of the women, and no mechanism was identified in 15.5% (18/116). Conclusions: Multimodality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, 75.5% of which were ischemic and 24.5% of which were nonischemic, alternate diagnoses to myocardial infarction. Identification of the cause of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02905357.

BACKGROUND: The Joint Commission on Accreditation of Healthcare Organizations is proposing that hospitals measure culture beginning in 2007. However, a reliable and widely used measurement tool for the operating room (OR) setting does not currently exist. METHODS: OR personnel in 60 US hospitals were surveyed using the Safety Attitudes Questionnaire. The teamwork climate domain of the survey uses six items about difficulty speaking up, conflict resolution, physician-nurse collaboration, feeling supported by others, asking questions, and heeding nurse input. To justify grouping individual-level responses to a single score at each hospital OR level, the authors used a multilevel confirmatory factor analysis, intraclass correlations, within-group interrater reliability, and Cronbach's alpha. To detect differences at the hospital OR level and by caregiver type, the authors used multivariate analysis of variance (items) and analysis of variance (scale). RESULTS: The response rate was 77.1%. There was robust evidence for grouping individual-level respondents to the hospital OR level using the diverse set of statistical tests, e.g., Comparative Fit Index = 0.99, root mean squared error of approximation = 0.05, and acceptable intraclasss correlations, within-group interrater reliability values, and Cronbach's alpha = 0.79. Teamwork climate differed significantly by hospital (F59, 1,911 = 4.06, P < 0.001) and OR caregiver type (F4, 1,911 = 9.96, P < 0.001). CONCLUSIONS: Rigorous assessment of teamwork climate is possible using this psychometrically sound teamwork climate scale. This tool and initial benchmarks allow others to compare their teamwork climate to national means, in an effort to focus more on what excellent surgical teams do well.

Significance Statement Kidney involvement may occur in coronavirus disease 2019 (COVID-19), and can be severe among Black individuals. In this study of collapsing glomerulopathy in six Black patients with COVID-19, the authors found that all six had variants in the gene encoding apo L1 (APOL1) that are more common among those of African descent and linked by past research to susceptibility to collapsing glomerulopathy in non–COVID-19 patients. They found no evidence of direct kidney viral infection but observed changes in gene expression in kidney biopsy samples suggesting that the mechanism is likely driven by a host response. These findings suggest that Black individuals with an APOL1 high-risk genotype and severe acute respiratory syndrome coronavirus 2 infection are at increased risk for experiencing an aggressive form of kidney disease associated with high rates of kidney failure. Background Kidney involvement is a feature of COVID-19 and it can be severe in Black patients. Previous research linked increased susceptibility to collapsing glomerulopathy, including in patients with HIV-associated nephropathy, to apo L1 ( APOL1 ) variants that are more common in those of African descent. Methods To investigate genetic, histopathologic, and molecular features in six Black patients with COVID-19 presenting with AKI and de novo nephrotic-range proteinuria, we obtained biopsied kidney tissue, which was examined by in situ hybridization for viral detection and by NanoString for COVID-19 and acute tubular injury–associated genes. We also collected peripheral blood for APOL1 genotyping. Results This case series included six Black patients with COVID-19 (four men, two women), mean age 55 years. At biopsy day, mean serum creatinine was 6.5 mg/dl and mean urine protein-creatinine ratio was 11.5 g. Kidney biopsy specimens showed collapsing glomerulopathy, extensive foot process effacement, and focal/diffuse acute tubular injury. Three patients had endothelial reticular aggregates. We found no evidence of viral particles or SARS-CoV-2 RNA. NanoString showed elevated chemokine gene expression and changes in expression of genes associated with acute tubular injury compared with controls. All six patients had an APOL1 high-risk genotype. Five patients needed dialysis (two of whom died); one partially recovered without dialysis. Conclusions Collapsing glomerulopathy in Black patients with COVID-19 was associated with high-risk APOL1 variants. We found no direct viral infection in the kidneys, suggesting a possible alternative mechanism: a “two-hit” combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection. Given this entity’s resemblance with HIV-associated nephropathy, we propose the term COVID-19–associated nephropathy to describe it.

Acute kidney injury (AKI) commonly occurs in hospitalized patients and is independently and strongly associates with morbidity and mortality. The clinical benefits of a timely and definitive diagnosis of AKI have not been fully realized due to limitations imposed by the use of serum creatinine and urine output to fulfill diagnostic criteria. These restrictions often lead to diagnostic delays, potential misclassification of actual injury status, and provide little information regarding underlying cause. Novel biomarkers of damage have shown ability to reflect ongoing kidney injury and help further refine existing Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN) diagnostic criteria. A comprehensive review of the published literature to date was performed using previously published methodology of the Acute Dialysis Quality Initiative (ADQI) working group to establish consensus statements regarding (i) the overall implementation of injury biomarkers in the concept of AKI diagnosis, (ii) their clinical use, and (iii) future research. On the basis of published data on the ability of novel damage biomarkers to provide diagnostic and prognostic information on AKI, we recommend that novel damage biomarkers may, in the appropriate clinical setting and context (situation consistent with AKI), be used to diagnose AKI even in the absence of changes in serum creatinine or the presence of oliguria as described in the existing RIFLE/AKIN criteria for diagnosis of AKI. Adding injury biomarkers as a criterion for AKI will complement the ability of RIFLE/AKIN to define AKI. Promising diagnostic injury markers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18) and liver-type fatty acid binding protein (L-FABP). However, there are currently insufficient data on damage biomarkers to support their use for AKI staging. Rigorous validation studies measuring the association between the novel damage biomarker(s) and clinically relevant outcomes are needed.

Patients with fibromyalgia (FM) experience increased lifetime levels of psychosocial adversity, trauma, and emotional conflict. To address these risk factors, we developed emotion awareness and expression therapy (EAET) and tested its benefits against an active control condition, FM education, and the field's gold standard intervention for FM, cognitive behavioral therapy (CBT) for symptom management. Adults with FM (N = 230) formed 40 treatment groups, which were randomized to EAET, CBT, or education and given 8, 90-minute sessions. Patient-reported outcomes were assessed at baseline, posttreatment, and 6-month follow-up (primary end point). Retention of patients to follow-up was excellent (90.4%). Intent-to-treat analyses indicated that although EAET did not differ from FM education on pain severity (primary outcome), EAET had significantly better outcomes than FM education on overall symptoms, widespread pain, physical functioning, cognitive dysfunction, anxiety, depression, positive affect, and life satisfaction (between-condition d's ranging from 0.29-0.45 SD) and the percentage of patients reporting being "very much/much" improved (34.8% vs 15.4%). Emotional awareness and expression therapy did not differ from CBT on the primary or most secondary outcomes, but compared to CBT, EAET led to significantly lower FM symptoms (d = 0.35) and widespread pain (d = 0.37) and a higher percentage of patients achieving 50% pain reduction (22.5% vs 8.3%). In summary, an intervention targeting emotional awareness and expression related to psychosocial adversity and conflict was well received, more effective than a basic educational intervention, and had some advantages over CBT on pain. We conclude that EAET should be considered as an additional treatment option for FM.

COVID-19 has become a pandemic in the United States and worldwide. COVID-19-induced coagulopathy (CIC) is commonly encountered at presentation manifested by considerable elevation of D-dimer and fibrin split products but with modest or no change in activated partial thromboplastin time and prothrombin time. CIC is a complex process that is distinctly different from conventional sepsis-induced coagulopathy. The cytokine storm induced by COVID-19 infection appears to be more severe in COVID-19, resulting in development of extensive micro- and macrovascular thrombosis and organ failure. Unlike conventional sepsis, anticoagulation plays a key role in the treatment of COVID-19, however without practice guidelines tailored to these patients. We propose a scoring system for COVID-19-coagulopathy (CIC Scoring) and stratification of patients for the purpose of anticoagulation therapy based on risk categories. The proposed scoring system and therapeutic guidelines are likely to undergo revisions in the future as new data become available in this evolving field.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a considerable impact on US hospitalizations, affecting processes and patient population. OBJECTIVE: To evaluate the impact of COVID-19 pandemic on central-line-associated bloodstream infections (CLABSIs) and catheter associated urinary tract infections (CAUTIs) in hospitals. METHODS: We performed a retrospective study of CLABSIs and CAUTIs in 78 US 12 months before COVID-19 and 6 months during COVID-19 pandemic. RESULTS: During the 2 study periods, there were 795,022 central-line days and 817,267 urinary catheter days. Compared to the period before the COVID-19 pandemic, CLABSI rates increased by 51.0% during the pandemic period from 0.56 to 0.85 per 1,000 line days (P < .001) and by 62.9% from 1.00 to 1.64 per 10,000 patient days (P < .001). Hospitals with monthly COVID-19 patients representing >10% of admissions had a National Health Safety Network (NHSN) device standardized infection ratio for CLABSI that was 2.38 times higher than hospitals with <5% prevalence during the pandemic period (P = .004). Coagulase-negative Staphylococcus CLABSIs increased by 130% from 0.07 to 0.17 events per 1,000 line days (P < .001), and Candida spp by 56.9% from 0.14 to 0.21 per 1,000 line days (P = .01). In contrast, no significant changes were identified for CAUTI (0.86 vs 0.77 per 1,000 catheter days; P = .19). CONCLUSIONS: The COVID-19 pandemic was associated with substantial increases in CLABSIs but not CAUTIs. Our findings underscore the importance of hardwiring processes for optimal line care and regular feedback on performance to maintain a safe environment.

Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. We randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. We found that the reminder texts that we tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was "waiting for you." Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy.

BACKGROUND: Improving patient safety is an increasing priority for surgeons and hospitals since sentinel events can be catastrophic for patients, caregivers, and institutions. Patient safety initiatives aimed at creating a safe operating room (OR) culture are increasingly being adopted, but a reliable means of measuring their impact on front-line providers does not exist. METHODS: We developed a surgery-specific safety questionnaire (SAQ) and administered it to 2769 eligible caregivers at 60 hospitals. Survey questions included the appropriateness of handling medical errors, knowledge of reporting systems, and perceptions of safety in the operating room. MANOVA and ANOVA were performed to compare safety results by hospital and by an individual's position in the OR using a composite score. Multilevel confirmatory factor analysis was performed to validate the structure of the scale at the operating room level of analysis. RESULTS: The overall response rate was 77.1% (2135 of 2769), with a range of 57% to 100%. Factor analysis of the survey items demonstrated high face validity and internal consistency (alpha = 0.76). The safety climate scale was robust and internally consistent overall and across positions. Scores varied widely by hospital [MANOVA omnibus F (59, 1910) = 3.85, P < 0.001], but not position [ANOVA F (4, 1910) = 1.64, P = 0.16], surgeon (mean = 73.91), technician (mean = 70.26), anesthesiologist (mean = 71.57), CRNA (mean = 71.03), and nurse (mean = 70.40). The percent of respondents reporting good safety climate in each hospital ranged from 16.3% to 100%. CONCLUSIONS: Safety climate in surgical departments can be validly measured and varies widely among hospitals, providing the opportunity to benchmark performance. Scores on the SAQ can serve to evaluate interventions to improve patient safety.

Cardiorenal syndromes (CRS) have been recently classified into five distinct entities, each with different major pathophysiologic mechanisms. CRS type 1 most commonly occurs in the setting of acutely decompensated heart failure where approximately 25% of patients develop a rise in serum creatinine and a reduction of urine output after the first several doses of intravenous diuretics. Altered cardiac and renal hemodynamics are believed to be the most important determinants of CRS type 1. CRS type 2 is the hastened progression of chronic kidney disease (CKD) in the setting of chronic heart failure. Accelerated renal cell apoptosis and replacement fibrosis is considered to be the dominant mechanism. CRS type 3 is acutely decompensated heart failure after acute kidney injury from inflammatory, toxic, or ischemic insults. This syndrome is precipitated by salt and water overload, acute uremic myocyte dysfunction, and neurohormonal dysregulation. CRS type 4 is manifested by the acceleration of the progression of chronic heart failure in the setting of CKD. Cardiac myocyte dysfunction and fibrosis, so-called 'CKD cardiomyopathy', is believed to be the predominant pathophysiologic mechanism. Type 5 CRS is simultaneous acute cardiac and renal injury in the setting of an overwhelming systemic insult such as sepsis. In this scenario, the predominant pathophysiological disturbance is microcirculatory dysfunction as a result of acutely abnormal immune cell signaling, catecholamine cellular toxicity, and enzymatic activation which result in simultaneous organ injury often extending beyond both the heart and the kidneys. This paper will summarize these and other key findings from an international consensus conference on the spectrum of pathophysiologic mechanisms at work in the CRS.

Replacement of functional myocytes with crosslinked collagen as a result of tissue fibrosis is a final common pathway that is central to the progression of heart failure (HF), irrespective of etiology. In response to a variety of mechanical and neurohormonal stimuli, macrophages secrete galectin-3, which works as a paracrine and endocrine factor to stimulate additional macrophages, pericytes, myofibroblasts, and fibroblasts. The response to this signal is cellular proliferation and secretion of procollagen I. This protein is then irreversibly crosslinked to form collagen and result in cardiac fibrosis. With a commercially available assay, galectin-3 can now be measured in blood and has been found to aid in the prognosis of both systolic and nonsystolic HF. Measurement of galectin-3 before hospital discharge, on outpatient evaluation for suspected HF, and approximately twice per year for those with stable symptoms is supported by the evidence available at this time. Levels > 25.9 ng/mL, independent of symptoms, clinical findings, and other laboratory measures, predict a patient who is likely to have rapid progression of HF, resulting in hospitalization and death. In addition, a doubling in galectin-3 level over the course of 6 months, irrespective of baseline value, identifies a high-risk patient in whom additional care management efforts and advanced therapies could be warranted.

External groups requiring measures now include public and private payers, regulators, accreditors and others that certify performance levels for consumers, patients and payers. Although benefits have accrued from the growth in quality measurement, the recent explosion in the number of measures threatens to shift resources from improving quality to cover a plethora of quality-performance metrics that may have a limited impact on the things that patients and payers want and need (ie, better outcomes, better care, and lower per capita costs). Here we propose a policy that quality measurement should be: balanced to meet the need of end users to judge quality and cost performance and the need of providers to continuously improve the quality, outcomes and costs of their services; and parsimonious to measure quality, outcomes and costs with appropriate metrics that are selected based on end-user needs.

Loss of reduction-oxidation (redox) homeostasis and generation of excess free oxygen radicals play an important role in the pathogenesis of diabetes, hypertension, and consequent cardiovascular disease. Reactive oxygen species are integral in routine in physiologic mechanisms. However, loss of redox homeostasis contributes to proinflammatory and profibrotic pathways that promote impairments in insulin metabolic signaling, reduced endothelial-mediated vasorelaxation, and associated cardiovascular and renal structural and functional abnormalities. Redox control of metabolic function is a dynamic process with reversible pro- and anti-free radical processes. Labile iron is necessary for the catalysis of superoxide anion, hydrogen peroxide, and the generation of the damaging hydroxyl radical. Acute hypoxia and cellular damage in cardiovascular tissue liberate larger amounts of cytosolic and extracellular iron that is poorly liganded; thus, large increases in the generation of oxygen free radicals are possible, causing tissue damage. The understanding of iron and the imbalance of redox homeostasis within the vasculature is integral in hypertension and progression of metabolic dysregulation that contributes to insulin resistance, endothelial dysfunction, and cardiovascular and kidney disease.