Left Ventricular Dysfunction Associated With Brain Death: Results From the Donor Heart Study.

BACKGROUND: Left ventricular dysfunction in potential donors meeting brain death criteria often results in nonuse of donor hearts for transplantation, yet little is known about its incidence or pathophysiology. Resolving these unknowns was a primary aim of the DHS (Donor Heart Study), a multisite prospective cohort study. METHODS: The DHS enrolled potential donors by neurologic determination of death (n=4333) at 8 organ procurement organizations across the United States between February 2015 and May 2020. Data included medications administered, serial diagnostic tests, and transthoracic echocardiograms (TTEs) performed: (1) within 48 hours after brain death was formally diagnosed; and (2) 24±6 hours later if left ventricular (LV) dysfunction was initially present. LV dysfunction was defined as an LV ejection fraction <50% and was considered reversible if LV ejection fraction was >50% on the second TTE. TTEs were also examined for presence of LV regional wall motion abnormalities and their reversibility. We assessed associations between LV dysfunction, donor heart acceptance for transplantation, and recipient 1-year survival. RESULTS: An initial TTE was interpreted for 3794 of the 4333 potential donors by neurologic determination of death. A total of 493 (13%) of these TTEs showed LV dysfunction. Among those donors with an initial TTE, LV dysfunction was associated with younger age, underweight, and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and troponin levels. A second TTE was performed within 24±6 hours for a subset of donors (n=224) with initial LV dysfunction; within this subset, 130 (58%) demonstrated reversibility. Sixty percent of donor hearts with normal LV function were accepted for transplant compared with 56% of hearts with reversible LV dysfunction and 24% of hearts with nonreversible LV dysfunction. Donor LV dysfunction, whether reversible or not, was not associated with recipient 1-year survival. CONCLUSIONS: LV dysfunction associated with brain death occurs in many potential heart donors and is sometimes reversible. These findings can inform decisions made during donor evaluation and help guide donor heart acceptance for transplantation.

Lipid Testing among Youth in Medicaid: The Role of Social Determinants of Health and Providers.

OBJECTIVE: To assess recent temporal trends in guideline-compliant pediatric lipid testing, and to examine the influence of social determinants of health (SDoH) and provider characteristics on the likelihood of testing in youth. STUDY DESIGN: In this observational, multiyear cross-sectional study, we calculated lipid testing prevalence by year among 268 627 12-year olds from 2015 through 2019 who were enrolled in Florida Medicaid and eligible for universal lipid screening during age 9 to 11, and 11 437 22-year olds (2017-2019) who were eligible for screening during age 17-21. We compared trends in testing prevalence by SDoH and health risk factors at two recommended ages and modeled the associations between patient characteristics and provider type on lipid testing using generalized estimating equations. RESULTS: Testing among 12-year olds remained low between 2015 through 2019 with the highest prevalence in 2015 (8.0%) and lowest in 2017 (6.7%). Screening compliance among 22-year olds was highest in 2017 (21.1%) and fell to 17.8% in 2019. Hispanics and non-Hispanic Blacks in both age groups had about 2%-3% lower testing prevalence than non-Hispanic Whites. Testing in 12-year olds was 12.3% vs 7.7% with and without obesity, and 14.4% vs 7.6% with and without antipsychotic use. Participants who saw providers who were more likely to prescribe lipid testing were more likely to receive testing (OR = 2.3, 95% CI 2.0-2.8, P < .001). CONCLUSIONS: Although lipid testing prevalence was greatest among high-risk children, overall prevalence of lipid testing in youth remains very low. Provider specialty and choices by individual providers play important roles in improving guideline-compliant pediatric lipid testing.

Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity Matched Retrospective Cohort Study.

BACKGROUND: Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial. We compared average intraoperative isoflurane/sevoflurane minimum alveolar concentration equivalents between older adults with and without cannabis use. METHODS: The electronic health records of 22,476 surgical patients ≥65 years old at the University of Florida Health System between 2018-2020 were reviewed. The primary exposure was cannabis use within 60 days of surgery, determined via i) a previously published natural language processing algorithm applied to unstructured notes and ii) structured data, including International Classification of Disease codes for cannabis use disorders and poisoning by cannabis, laboratory cannabinoids screening results, and RxNorm codes. The primary outcome was the intraoperative time-weighted average of isoflurane/sevoflurane minimum alveolar concentration equivalents at one-minute resolution. No a priori minimally clinically important difference was established. Patients demonstrating cannabis use were matched 4:1 to non-cannabis use controls using a propensity score. RESULTS: Among 5,118 meeting inclusion criteria, 1,340 patients (268 cannabis users and 1,072 nonusers) remained after propensity score matching. The median and interquartile range (IQR) age was 69 (67, 73) years; 872 (65.0%) were male, and 1,143 (85.3%) were non-Hispanic White. The median (IQR) anesthesia duration was 175 (118, 268) minutes. After matching, all baseline characteristics were well-balanced by exposure. Cannabis users had statistically significantly higher average minimum alveolar concentrations than nonusers [mean±SD: 0.58±0.23 versus 0.54±0.22, respectively; mean difference=0.04; 95% confidence limits, 0.01 to 0.06; p=0.020]. CONCLUSION: Cannabis use was associated with administering statistically significantly higher inhalational anesthetic minimum alveolar concentration equivalents in older adults, but the clinical significance of this difference is unclear. These data do not support the hypothesis that cannabis users require clinically meaningfully higher inhalational anesthetics doses.

Culturally and linguistically diverse men's experiences of support following perinatal death: A qualitative study.

AIMS AND OBJECTIVES: To explore culturally and linguistically diverse men's experiences of support after perinatal death, including barriers and facilitators to support and how healthcare providers, systems and policies can best support families. BACKGROUND: Many groups of culturally and linguistically diverse families in Australia are at higher risk of experiencing perinatal death. Culturally sensitive bereavement services are essential; however, there has been no previous research specifically examining culturally and linguistically diverse men's experiences of support following perinatal death. DESIGN: Individual semi-structured interviews were completed with healthcare providers, community leaders and culturally and linguistically diverse men who had experienced a perinatal death in Australia (n = 16). Data were analysed using Thematic Analysis and COREQ guidelines were followed. RESULTS: Men's need for support following perinatal death was associated with stigma, and shaped by culturally-relevant religion and ritual, and connection to community and family. Significant barriers to men seeking and gaining support included challenges with self-advocacy and navigating the woman-centred nature of perinatal care in Australia. CONCLUSIONS: Culturally and linguistically diverse men's specific needs should be included in the development of policy and practice surrounding perinatal death. While perinatal bereavement care guidelines acknowledge the importance of culturally informed care following perinatal death, there remains a lack of culturally specific supports available, particularly for culturally and linguistically diverse men. RELEVANCE TO CLINICAL PRACTICE: Specific recommendations from this research include increasing community liaison officers or cultural consultants in hospitals and support organisations; providing culturally and linguistically diverse support groups; adopting family-centred and father-inclusive language in all perinatal death support services and ensuring clear communication and targeted assistance for culturally and linguistically diverse men to self-advocate for their baby and access to support. PATIENT OR PUBLIC CONTRIBUTION: This study came out of consultation with community members and member checking of results was conducted to ensure adequate representation of participants' views.

Culturally and Linguistically Diverse Men's Grief Experiences Following Perinatal Death in Australia.

To explore the grief experiences of men from culturally and linguistically diverse (CALD) backgrounds following perinatal death in Australia. Qualitative analysis of interview data using thematic analysis. Participants were health service providers (n = 6), and CALD community members (n = 10) who were either community leaders with experience working with CALD men following perinatal death in Australia (n = 6), or were CALD men who had lived experience of perinatal death (n = 4). Thematic analysis identified four themes related to CALD men's grief. These included the role of religion and rituals, grief as stoic, the partner- and family-centred nature of men's grief, and finally grief as ensuring and changeable over time. This research points to the strong need for CALD men's specific needs to be included in the development of policy and practice surrounding perinatal death.

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

Effect of contrast administration on the renal function of predialysis patients undergoing fistuloplasty.

OBJECTIVE: The aim of this study was to investigate if administration of iodinated contrast during endovascular interventions in arteriovenous fistula (AVF) in patients not requiring dialysis (predialysis patients) (1) negatively affects their renal function and (2) if oral hydration has a protective effect. METHODS: All pre-dialysis patients who underwent endovascular interventions in AVF between August 2010 and April 2019 were included in the study. During the procedures, 35 to 50 mL of Iodixanol were administered. A pre-hydration protocol was introduced in March 2015. Data were grouped before and after this date. The difference between pre- and post-contrast estimated glomerular filtration rate (eGFR) and the difference between the eGFR of hydrated and non-hydrated groups were calculated. RESULTS: Eighty-four patients who underwent 151 procedures were included in the study. In 60.3% of procedures, a mean decrease of 1.35 mL/min/1.73 m2 in eGFR was noted (95% confidence interval [CI], 1.02-1.69 mL/min/1.73 m2), whereas in 35.1% of procedures, there was a mean increase of 1.06 mL/min/1.73 m2 (95% CI, 0.84-1.28 mL/min/1.73 m2). The mean difference between pre- and post-procedure eGFR was -0.44 mL/min/1.73 m2 (95% CI, -0.72 to -0.16 mL/min/1.73 m2; P = .002). Oral hydration was associated with a smaller mean change in eGFR of -0.32 mL/min/1.73 m2 (95% CI, -0.62 to -0.03 mL/min/1.73 m2) compared with the non-hydrated group, with mean change of -0.47 mL/min/1.73 m2 (95% CI, -0.91 to -0.03 mL/min/1.73 m2), but this was not statistically significant (P = .586). CONCLUSIONS: This study demonstrates that administration of up to 50 mL of iodinated contrast for endovascular interventions in AVF in predialysis patients has minimal adverse effect on the eGFR with questionable clinical significance. In addition, oral hydration before and after the procedure has only a mild protective effect against a decrease in eGFR.

Temporal trends and current use of de novo belatacept in kidney transplant recipients in the United States.

The adoption of de novo belatacept in kidney transplant (kTx) recipients was hampered by an increased risk of acute cellular rejection (ACR) with variation in adopted belatacept based immunosuppressive therapies across centers. We used data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate the temporal trends in belatacept use and describe the associated induction and maintenance regimens in US adult kTx recipients transplanted between June 2011 and December 2018. The number of patients receiving de novo-belatacept based immunosuppressive therapy increased from .74% in 2011 to 3.11% in 2016. In 2016, 66/207 centers used de novo belatacept-based regimen with 3.03% using it in over 50% of their patients. The use of T-cell depleting agents increased with time. Since 2012, the rate of calcineurin inhibitor (CNI) use in combination with belatacept remained stable around 50% and ∼30% remained under belatacept/CNI combination at 1-year post-transplantation. The adoption of belatacept as de novo immunosuppressive regimen has been slow and its use remains low in the United States. Various regimens have been used to modulate the risk of ACR. Further studies evaluating the long-term outcomes of these regimens and assessing their safety especially with regard to the risk of infection are needed.

Perineal Injury via Personal Watercraft Hydrostatic Jet: A Case Report.

BACKGROUND: Traumatic injuries resulting from personal watercraft hydrostatic jets are expected to increase as personal watercrafts are affordable, portable, and used in an increasingly wide range of locales. CASE PRESENTATION: This case study presents an unusual severe perineal injury in a 17-year-old adolescent girl resulting from a fall from a personal watercraft and contact with the vehicle's hydrostatic jet. This case report provides an overview of the mechanism, treatment, and prevention of personal watercraft injuries. CONCLUSION: Knowledge of this mechanism's potential for serious morbidity and mortality, patient assessment and management principles, and injury prevention strategies are essential to providing effective trauma center care.

CMV high-risk status and posttransplant outcomes in kidney transplant recipients treated with belatacept.

INTRODUCTION: Cytomegalovirus (CMV) remains associated with poor outcomes after kidney transplantation (kTx). The impact of belatacept on CMV infection remains understudied. In this study, we assessed the impact of belatacept on patient and graft survivals. METHODS: CMV seronegative kTx recipients were included. Patient and graft survival were studied using Kaplan-Meier method, log-rank test. Cox models were used to compare outcomes by CMV risk and immunosuppressive regimen. Incidence and persistence of CMV viremia under belatacept vs tacrolimus were compared. RESULTS: Among 308 CMV seronegative recipients, 168 CMV high-risk and 203 belatacept-treated patients were included. High-risk CMV status was associated with lower patient survival and graft survival. Among the CMV high-risk group, patients treated with belatacept presented a higher incidence of CMV viremia, a higher rate of first-line treatment failure and a longer time to virus clearance. They had a nonsignificant trend toward a lower graft survival. CONCLUSION: Belatacept-based maintenance immunosuppression is associated with an increased risk of CMV primary-infection and a prolonged course of viral replication in CMV high-risk patients. Further studies are needed to confirm the nonsignificant trend towards a lower graft survival in CMV high-risk patients treated with belatacept and whether it is explained by the higher risk of CMV reactivation and infection.

The impact of belatacept on third-party HLA alloantibodies in highly sensitized kidney transplant recipients.

Recent evidence suggests that belatacept reduces the durability of preexisting antibodies to class I and class II human leukocyte antigens (HLAs). In this case series of 163 highly sensitized kidney transplant candidates whose calculated panel-reactive antibody (cPRA) activity was ≥98% to 100%, the impact of belatacept on preexisting HLA antibodies was assessed. Of the 163 candidates, 72 underwent transplantation between December 4, 2014 and April 15, 2017; 60 of these transplanted patients remained on belatacept consecutively for at least 6 months. We observed a decrease in the breadth and/or strength of HLA class I antibodies as assessed by FlowPRA in belatacept-treated patients compared to controls who did not receive belatacept. Specifically, significant HLA antibody reduction was evident for class I (P < .0009). Posttransplant belatacept-treated patients also had a clinically significant reduction in their cPRA compared to controls (P < .01). Collectively, these findings suggest belatacept can reduce HLA class I antibodies in a significant proportion of highly sensitized recipients and could be an option to improve pretransplant compatibility with organ donors.

The Type and Amount of Dietary Fat Affect Plasma Factor VIIc, Fibrinogen, and PAI-1 in Healthy Individuals and Individuals at High Cardiovascular Disease Risk: 2 Randomized Controlled Trials.

BACKGROUND: Factor VIIc, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) are cardiovascular disease (CVD) risk factors and are modulated, in part, by fat type and amount. OBJECTIVE: We evaluated fat type and amount on the primary outcomes: factor VIIc, fibrinogen, and PAI-1. METHODS: In the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Trial, 2 controlled crossover feeding studies evaluated substituting carbohydrate or MUFAs for SFAs. Study 1: healthy participants (n = 103) were provided with (8 wk) an average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA], a Step 1 diet (30%E fat, 9% SFA), and a diet low in SFA (Low-Sat; 26%E fat, 5% SFA). Study 2: participants (n = 85) at risk for CVD and metabolic syndrome (MetSyn) were provided with (7 wk) an AAD, a step 1 diet, and a high-MUFA diet (designed to provide 37%E fat, 8% SFA, 22% MUFA). RESULTS: Study 1: compared with AAD, the Step 1 and Low-Sat diets decreased mean factor VIIc by 1.8% and 2.6% (overall P = 0.0001), increased mean fibrinogen by 1.2% and 2.8% (P = 0.0141), and increased mean square root PAI-1 by 0.0% and 6.0% (P = 0.0037), respectively. Study 2: compared with AAD, the Step 1 and high-MUFA diets decreased mean factor VIIc by 4.1% and 3.2% (overall P < 0.0001), increased mean fibrinogen by 3.9% and 1.5% (P = 0.0083), and increased mean square-root PAI-1 by 2.0% and 5.8% (P = 0.1319), respectively. CONCLUSIONS: Replacing SFA with carbohydrate decreased factor VIIc and increased fibrinogen in healthy and metabolically unhealthy individuals and also increased PAI-1 in healthy subjects. Replacing SFA with MUFA decreased factor VIIc and increased fibrinogen but less than carbohydrate. Our results indicate an uncertain effect of replacing SFA with carbohydrate or MUFA on cardiometabolic risk because of small changes in hemostatic factors and directionally different responses to decreasing SFA. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT00000538?term=NCT00000538&rank=1 as NCT00000538.

Design and methodology challenges of environment-wide association studies: A systematic review.

Environment-wide association studies (EWAS) are an untargeted, agnostic, and hypothesis-generating approach to exploring environmental factors associated with health outcomes, akin to genome-wide association studies (GWAS). While design, methodology, and replicability standards for GWAS are established, EWAS pose many challenges. We systematically reviewed published literature on EWAS to categorize scope, impact, types of analytical approaches, and open challenges in designs and methodologies. The Web of Science and PubMed databases were searched through multiple queries to identify EWAS articles between January 2010 and December 2018, and a systematic review was conducted following the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) reporting standard. Twenty-three articles met our inclusion criteria and were included. For each study, we categorized the data sources, the definitions of study outcomes, the sets of environmental variables, and the data engineering/analytical approaches, e.g. neighborhood definition, variable standardization, handling of multiple hypothesis testing, model selection, and validation. We identified limited exploitation of data sources, high heterogeneity in analytical approaches, and lack of replication. Despite of the promising utility of EWAS, further development of EWAS will require improved data sources, standardization of study designs, and rigorous testing of methodologies.

Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. METHODS: ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059. FINDINGS: Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group). INTERPRETATION: The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies. FUNDING: Bayer.

Uncuffed Endotracheal Tubes: Not Appropriate for Pediatric Critical Care Transport.

OBJECTIVE: The effect of using uncuffed endotracheal tubes in children during interfacility critical care transport has not yet been assessed. We hypothesized that many children with uncuffed endotracheal tubes experience complications leading to replacement with a cuffed tube after arrival at a tertiary pediatric care facility. METHODS: We conducted a retrospective case review of all intubated patients transported by our dedicated pediatric critical care transport team to our pediatric intensive care unit over a 3-year period. The incidence of urgent reintubation was studied. RESULTS: A total of 213 children were referred for transport with an endotracheal tube in place, with 55 of those with an uncuffed endotracheal tube (25.8% of all intubated patients). Of those with uncuffed tubes, 24 patients needed their tubes replaced on an urgent basis by the medical team because of issues with ineffective ventilation (43.6% of patients with uncuffed tubes or 11.3% of all intubated patients). No cuffed tubes required replacement. CONCLUSION: Placing an uncuffed endotracheal tube in the critically ill child who is referred to tertiary pediatric care results in a significant number of these patients undergoing a repeat laryngoscopy, with all associated risks, to replace the uncuffed tube with a cuffed tube.

ACC/AHA Special Report: Clinical Practice Guideline Implementation Strategies: A Summary of Systematic Reviews by the NHLBI Implementation Science Work Group: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

BACKGROUND: In 2008, the National Heart, Lung, and Blood Institute convened an Implementation Science Work Group to assess evidence-based strategies for effectively implementing clinical practice guidelines. This was part of a larger effort to update existing clinical practice guidelines on cholesterol, blood pressure, and overweight/obesity. OBJECTIVES: Review evidence from the published implementation science literature and identify effective or promising strategies to enhance the adoption and implementation of clinical practice guidelines. METHODS: This systematic review was conducted on 4 critical questions, each focusing on the adoption and effectiveness of 4 intervention strategies: (1) reminders, (2) educational outreach visits, (3) audit and feedback, and (4) provider incentives. A scoping review of the Rx for Change database of systematic reviews was used to identify promising guideline implementation interventions aimed at providers. Inclusion and exclusion criteria were developed a priori for each question, and the published literature was initially searched up to 2012, and then updated with a supplemental search to 2015. Two independent reviewers screened the returned citations to identify relevant reviews and rated the quality of each included review. RESULTS: Audit and feedback and educational outreach visits were generally effective in improving both process of care (15 of 21 reviews and 12 of 13 reviews, respectively) and clinical outcomes (7 of 12 reviews and 3 of 5 reviews, respectively). Provider incentives showed mixed effectiveness for improving both process of care (3 of 4 reviews) and clinical outcomes (3 reviews equally distributed between generally effective, mixed, and generally ineffective). Reminders showed mixed effectiveness for improving process of care outcomes (27 reviews with 11 mixed and 3 generally ineffective results) and were generally ineffective for clinical outcomes (18 reviews with 6 mixed and 9 generally ineffective results). Educational outreach visits (2 of 2 reviews), reminders (3 of 4 reviews), and provider incentives (1 of 1 review) were generally effective for cost reduction. Educational outreach visits (1 of 1 review) and provider incentives (1 of 1 review) were also generally effective for cost-effectiveness outcomes. Barriers to clinician adoption or adherence to guidelines included time constraints (8 reviews/overviews); limited staffing resources (2 overviews); timing (5 reviews/overviews); clinician skepticism (5 reviews/overviews); clinician knowledge of guidelines (4 reviews/overviews); and higher age of the clinician (1 overview). Facilitating factors included guideline characteristics such as format, resources, and end-user involvement (6 reviews/overviews); involving stakeholders (5 reviews/overviews); leadership support (5 reviews/overviews); scope of implementation (5 reviews/overviews); organizational culture such as multidisciplinary teams and low-baseline adherence (9 reviews/overviews); and electronic guidelines systems (3 reviews). CONCLUSION: The strategies of audit and feedback and educational outreach visits were generally effective in improving both process of care and clinical outcomes. Reminders and provider incentives showed mixed effectiveness, or were generally ineffective. No general conclusion could be reached about cost effectiveness, because of limitations in the evidence. Important gaps exist in the evidence on effectiveness of implementation interventions, especially regarding clinical outcomes, cost effectiveness and contextual issues affecting successful implementation.

Effect of the iChoose Kidney decision aid in improving knowledge about treatment options among transplant candidates: A randomized controlled trial.

We previously developed a mobile- and web-based decision aid (iChoose Kidney) that displays individualized risk estimates of survival and mortality, for the treatment modalities of dialysis versus kidney transplantation. We examined the effect of iChoose Kidney on change in transplant knowledge and access to transplant in a randomized controlled trial among patients presenting for evaluation in three transplant centers. A total of 470 patients were randomized to standard transplantation education (control) or standard education plus iChoose Kidney (intervention). Change in transplant knowledge (primary outcome) among intervention versus control patients was assessed using nine items in pre- and postevaluation surveys. Access to transplant (secondary outcome) was defined as a composite of waitlisting, living donor inquiries, or transplantation. Among 443 patients (n = 226 intervention; n = 216 control), the mean knowledge scores were 5.1 ± 2.1 pre- and 5.8 ± 1.9 postevaluation. Change in knowledge was greater among intervention (1.1 ± 2.0) versus control (0.4 ± 1.8) patients (P < .0001). Access to transplantation was similar among intervention (n = 168; 74.3%) versus control patients (n = 153; 70.5%; P = .37). The iChoose Kidney decision aid improved patient knowledge at evaluation, but did not impact transplant access. Future studies should examine whether combining iChoose Kidney with other interventions can increase transplantation. (Clinicaltrials.gov NCT02235571).

Differing Effects of Parathyroid Hormone, Alendronate, and Odanacatib on Bone Formation and on the Mineralization Process in Intracortical and Endocortical Bone of Ovariectomized Rabbits.

Bone is formed by deposition of a collagen-containing matrix (osteoid) that hardens over time as mineral crystals accrue and are modified; this continues until bone remodeling renews that site. Pharmacological agents for osteoporosis differ in their effects on bone remodeling, and we hypothesized that they may differently modify bone mineral accrual. We, therefore, assessed newly formed bone in mature ovariectomized rabbits treated with the anti-resorptive bisphosphonate alendronate (ALN-100µ g/kg/2×/week), the anabolic parathyroid hormone (PTH (1-34)-15µ g/kg/5×/week), or the experimental anti-resorptive odanacatib (ODN 7.5 µM/day), which suppresses bone resorption without suppressing bone formation. Treatments were administered for 10 months commencing 6 months after ovariectomy (OVX). Strength testing, histomorphometry, and synchrotron Fourier-transform infrared microspectroscopy were used to measure bone strength, bone formation, and mineral accrual, respectively, in newly formed endocortical and intracortical bone. In Sham and OVX endocortical and intracortical bone, three modifications occurred as the bone matrix aged: mineral accrual (increase in mineral:matrix ratio), carbonate substitution (increase in carbonate:mineral ratio), and collagen molecular compaction (decrease in amide I:II ratio). ALN suppressed bone formation but mineral accrued normally at those sites where bone formation occurred. PTH stimulated bone formation on endocortical, periosteal, and intracortical bone surfaces, but mineral accrual and carbonate substitution were suppressed, particularly in intracortical bone. ODN treatment did not suppress bone formation, but newly deposited endocortical bone matured more slowly with ODN, and ODN-treated intracortical bone had less carbonate substitution than controls. In conclusion, these agents differ in their effects on the bone matrix. While ALN suppresses bone formation, it does not modify bone mineral accrual in endocortical or intracortical bone. While ODN does not suppress bone formation, it slows matrix maturation. PTH stimulates modelling-based bone formation not only on endocortical and trabecular surfaces, but may also do so in intracortical bone; at this site, new bone deposited contains less mineral than normal.

Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic Subarachnoid Hemorrhage and Takotsubo Syndrome.

Takotsubo syndrome is rare in pediatric patients but must be considered in patients with subarachnoid hemorrhage with pulmonary edema and cardiomyopathy. A systematic, collaborative approach is needed to facilitate emergent transfer of patients where extracorporeal cardiopulmonary resuscitation (e-CPR) is used as a lifesaving measure. Extracorporeal membrane oxygenation (ECMO) use in transport requires preplanning, role delineation, resources, and research efforts to be successful. We present an unusual transport case of successful e-CPR/ECMO treatment of Takotsubo syndrome in a 12-year-old boy with an isolated traumatic intracranial injury, cardiomyopathy with pulmonary edema, and multiple cardiac arrests.