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Identification of Alzheimer's disease (AD) onset risk can facilitate interventions before irreversible disease progression. We demonstrate that electronic health records from the University of California, San Francisco, followed by knowledge networks (for example, SPOKE) allow for (1) prediction of AD onset and (2) prioritization of biological hypotheses, and (3) contextualization of sex dimorphism. We trained random forest models and predicted AD onset on a cohort of 749 individuals with AD and 250,545 controls with a mean area under the receiver operating characteristic of 0.72 (7 years prior) to 0.81 (1 day prior). We further harnessed matched cohort models to identify conditions with predictive power before AD onset. Knowledge networks highlight shared genes between multiple top predictors and AD (for example, APOE, ACTB, IL6 and INS). Genetic colocalization analysis supports AD association with hyperlipidemia at the APOE locus, as well as a stronger female AD association with osteoporosis at a locus near MS4A6A. We therefore show how clinical data can be utilized for early AD prediction and identification of personalized biological hypotheses.

BackgroundSingle photon emission computed tomography (SPECT) has limited ability to identify multivessel and microvascular coronary artery disease. Gamma cameras with cadmium zinc telluride detectors allow the quantification of absolute myocardial blood flow (MBF) and myocardial flow reserve (MFR). However, evidence of its accuracy is limited, and of its reproducibility is lacking. We aimed to validate 99mTc-sestamibi SPECT MBF and MFR using standard and spline-fitted reconstruction algorithms compared with 13N-ammonia positron emission tomography in a cohort of patients with known or suspected coronary artery disease and to evaluate the reproducibility of this technique.MethodsAccuracy was assessed in 34 participants who underwent dynamic 99mTc-sestamibi SPECT and 13N-ammonia positron emission tomography and reproducibility in 14 participants who underwent 2 99mTc-sestamibi SPECT studies, all within 2 weeks. A rest/pharmacological stress single-day SPECT protocol was performed. SPECT images were reconstructed using a standard ordered subset expectation maximization (OSEM) algorithm with (N=21) and without (N=30) application of spline fitting. SPECT MBF was quantified using a net retention kinetic model' and MFR was derived as the stress/rest MBF ratio.ResultsSPECT global MBF with splines showed good correlation with 13N-ammonia positron emission tomography (r=0.81, P0.05 for all).ConclusionsMBF and MFR quantification using 99mTc-sestamibi cadmium zinc telluride SPECT with spatiotemporal spline fitting improved the correlation with 13N-ammonia positron emission tomography flow estimates and test/retest reproducibility. The use of splines may represent an important step toward the standardization of SPECT flow estimation.

Disseminated infection caused by nontuberculous mycobacteria (NTM) is very rare, with an incidence of 1.0 to 1.8 cases per 100,000 persons, and typically only occurs in severely immunocompromised hosts. Burn patients suffer a loss of the natural cutaneous barrier as well as injury-induced immune dysfunction, and as a result, commonly develop infections, especially with multidrug-resistant organisms. However, very few NTM infections in burn patients have been reported in the literature. Disseminated NTM infection, in particular, can be a challenge to diagnose in burn patients due to burn-related physiology such as hyperpyrexia and widespread skin injury. We present a case of disseminated infection leading to bacteremia caused by Mycobacterium abscessus in a critically ill burn patient with a 74% total body surface area burn. M. abscessus belongs to the subgroup of NTM known as rapidly growing mycobacteria, which are notable for their ability to form colonies in a matter of days, rather than weeks, and because they are often highly drug-resistant, which complicates antimicrobial therapy. This is the third reported case of bacteremia caused by NTM in a burn patient and the second case that was successfully transitioned from intravenous antimicrobials to an oral regimen.

BackgroundThe older adult population continues to rapidly expand in number, with a projection by the United States (US) Census Bureau that there will be more individuals older than > 65 years (77.0 million) than those younger than < 18 years (76.5 million) by 2034. This review provides an overview of aging as it relates to wound healing and burn injuries in older adult patients, summarizes current treatment practices, and addresses the key challenges and considerations for treating severe burn injuries in this specific patient population.Materials and methodsA narrative literature search was conducted, focusing on recent primary literature on burns and wound healing in elderly patients.ResultsStudies showed that the aging process results in both physiologic (eg, nutritional and metabolic status) and anatomic changes (eg, thinning dermis) that contribute to a reduced capacity to recover from burn-injury trauma compared with younger patients. Owing to impaired vision, decreased coordination, comorbidities, and medication-induced side effects, older adults (ie, > 65 years) are susceptible to severe burn injury (deep-partial thickness and full-thickness), which is associated with significant morbidity and mortality.ConclusionA better understanding of the effects of age-related changes regarding wound healing in older adult patients who incur severe burn injuries may provide insight into clinical strategies to improve outcomes among this population.

For medical and social reasons, it is important that burn patients attend follow-up appointments (FUAs). Our goal was to examine the factors leading to missed FUAs in burn patients. A retrospective chart review was conducted of adult patients admitted to the burn center from 2016 to 2018. Data collected included burn characteristics, social history, and zip code. Data analysis was conducted using chi-square, Wilcoxon Rank-Sum tests, and multivariate regression models. A total of 878 patients were analyzed, with 224 (25.5%) failing to attend any FUAs and 492 (56.0%) missing at least one appointment (MA). Patients who did not attend any FUAs had smaller burns (4.5 [8]% vs 6.5 [11]% median [inter quartile range]), traveled farther (70.2 [111.8] vs 52.5 [76.7] miles), and were more likely to be homeless (22.8% vs 6.9%) and have drug dependence (47.3% vs 27.2%). Patients who had at least one MA were younger (42 [26] vs 46 [28] years) and more likely to be homeless (17.5% vs 2.6%) and have drug dependence (42.5% vs 19.4%). On multivariate analysis, factors associated with never attending an FUA were distance from hospital (odds ratio [OR] 1.004), burn size (OR 0.96), and homelessness (OR 0.33). Factors associated with missing at least one FUA: age (OR 0.99), drug dependence (OR 0.46), homelessness (OR 0.22), and Emergency Department visits (OR 0.56). A high percentage of patients fail to make any appointment following their injury and/or have at least one MA. Both FUAs and MAs are influenced by social determinants of health.

Blood transfusions following major burn injury are common due to operative losses, blood sampling, and burn physiology. While massive transfusion improves outcomes in adult trauma patients, literature examining its effect in critically ill children is limited. The study purpose was to prospectively compare outcomes of major pediatric burns receiving a 1:1 vs. 4:1 packed red blood cell to fresh frozen plasma transfusion strategy during massive burn excision. Children with >20% total body surface area burns were randomized to a 1:1 or 4:1 packed red blood cell/fresh frozen plasma transfusion ratio during burn excision. Parameters examined include patient demographics, burn size, pediatric risk of mortality (PRISM) scores, pediatric logistic organ dysfunction scores, laboratory values, total blood products transfused, and the presence of blood stream infections or pneumonia. A total of 68 children who met inclusion criteria were randomized into two groups (n = 34). Mean age, PRISM scores, estimated blood loss (600 ml (400-1175 ml) vs. 600 ml (300-1150 ml), P = 0.68), ventilator days (5 vs. 9, P = 0.47), and length of stay (57 vs. 60 days, P = 0.24) had no difference. No differences in frequency of blood stream infection (20 vs. 18, P = 0.46) or pneumonia events (68 vs. 116, P = 0.08) were noted. On multivariate analysis, only total body surface area burn size, inhalation injury, and PRISM scores (P < 0.05) were significantly associated with infections.

Current treatment options for patients with unresectable locally advanced pancreatic cancer (LAPC) include chemotherapy alone or followed by chemoradiation or stereotactic body radiotherapy. However, the prognosis for these patients remains poor, with a median overall survival

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the "One World One Guideline" initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.

Previous research on burn patients who test positive for methamphetamines (meth) has yielded mixed results regarding whether meth-positive status leads to worse outcomes and longer hospitalizations. We hypothesized that meth-positive patients at our regional burn center would have worse outcomes. We reviewed burn admissions from January 2014 to December 2017 and compared total patients versus meth-positive, and matched meth-negative versus meth-positive for total BSA burn, length of stay (LOS), intensive care unit (ICU) days, days on ventilator, discharge status (lived/died), number of operating room (OR) visits, number of procedures, socioeconomic status, comorbidities, and discharge disposition. Of 1363 total patients, 264 (19.4%) were meth-positive on toxicology screen. We matched 193 meth-positive patients with meth-negative controls based on TBSA burn, age, and inhalation injury. In the total population comparison, meth-positive patients had larger burns (15.6% vs 12.2%; P = .004), longer LOS (17.8 vs 14.3 days; P = .041), and fewer operations/TBSA (0.12 vs 0.2; P = .04), and lower socioeconomic status. Meth-positive patients were less likely to be discharged to a skilled nursing facility, and more likely to leave against medical advice. In the matched patients, we found no significant differences in LOS or OR visits/TBSA burn. Meth-positive patients have lower socioeconomic status, larger burns, and longer LOS compared to the total burn population. Methamphetamine use, by itself, does not appear to change outcomes. Methamphetamine use leads to larger burns in a population with fewer resources than the general population.

IN BRIEF Treatment of lower-extremity burn injuries in adults with diabetes can be complex, and some diabetes-related factors can lead to impaired healing of such wounds, putting patients at risk of amputation. In this retrospective review of adult patients with lower-extremity burns, patients with pre-injury neuropathy and higher A1C levels were more likely to require amputations after their burn injury. The authors conclude that lower-extremity burn injuries in patients with diabetes require close follow-up and possibly referral to a burn specialist for interventions and treatment strategies to offset more serious complications.

BackgroundEffective co-management of patients with chronic kidney disease (CKD) between primary care physicians (PCPs) and nephrologists is increasingly recognized as a key strategy to ensure the delivery of efficient and high-quality CKD care. However, the co-management of patients with CKD remains suboptimal.ObjectiveWe aimed to identify PCPs' perceptions of key barriers and facilitators to effective co-management of patients with CKD at the PCP-nephrology interface.Study designQualitative study SETTING AND PARTICIPANTS: Community-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC; and San Francisco, CA APPROACH: We conducted four focus groups of PCPs. Two members of the research team coded transcribed audio-recorded interviews and identified major themes.Key resultsMost of the 32 PCPs (59% internists and 41% family physicians) had been in practice for > 10 years (97%), spent ≥ 80% of their time in clinical care (94%), and practiced in private (69%) or multispecialty group practice (16%) settings. PCPs most commonly identified barriers to effective co-management of patients with CKD focused on difficulty developing working partnerships with nephrologists, including (1) lack of timely adequate information exchange (e.g., consult note not received or CKD care plan unclear); (2) unclear roles and responsibilities between PCPs and nephrologists; and (3) limited access to nephrologists (e.g., unable to obtain timely consultations or easily contact nephrologists with concerns). PCPs expressed a desire for "better communication tools" (e.g., shared electronic medical record) and clear CKD care plans to facilitate improved PCP-nephrology collaboration.ConclusionsInterventions facilitating timely adequate information exchange, clear delineation of roles and responsibilities between PCPs and nephrologists, and greater access to specialist advice may improve the co-management of patients with CKD.

Cervical spine injuries (CIs) carry significant morbidity and mortality; hence, cervical spine immobilization is used liberally in trauma patients, including burns. The incidence, predictors, and outcomes of CI in burn patients are unknown. A retrospective cohort from the National Trauma Data Bank between 2007 and 2012 included all burned patients with and without CI. Predictors of CI were identified by logistic regression. Outcomes with and without CI were compared with Wilcoxon rank sum test. A total of 94,964 patients were identified with burn injuries. The incidence of CI was 0.79% (n = 745). Mechanism of injury, age, and injury severity score (ISS) were significant predictors of CI. Odds of CI were 109.4 (95% CI: 61.2-195.3, P < .0001) for motor vehicle injury, 87.8 (95% CI: 47.0-164.0, P < .0001) for falls, 1.2 (95% CI: 0.6-2.3, P = .66) for fire/flame, and 2.4 (95% CI: 1.0-5.5, P < .0001) for explosion compared with reference of hot object/substance. For every year increase in age, there were 1.02 higher odds of CI (95% CI: 1.01-1.02, P < .0001). For each point increase in ISS, there were 1.05 higher odds of CI (95% CI: 1.04-1.05, P < .0001). Patients with CI had higher mortality (10.3% vs 2.9%, P < .0001), longer total length of stay (12.0 vs 2.0 days, P < .0001), intensive care unit length of stay (4.0 vs 0.0 days, P < .001), and ventilator days (1.0 vs 0.0 days, P < .0001). The incidence of CI in burn patients is low, especially when due to fire, flame, or scalds; however, CI is associated with higher mortality and worse outcomes.

ObjectivesStudies suggest that a restrictive transfusion strategy is safe in burns, yet the efficacy of a restrictive transfusion policy in massive burn injury is uncertain. Our objective: compare outcomes between massive burn (≥60% total body surface area (TBSA) burn) and major (20-59% TBSA) burn using a restrictive or a liberal blood transfusion strategy.MethodsPatients with burns ≥20% were block randomized by age and TBSA to a restrictive (transfuse hemoglobin 0.05).ConclusionsA restrictive transfusion strategy may be beneficial in massive burns in reducing ventilator days, ICU days and blood utilization, but does not decrease infection, mortality, hospital LOS or wound healing.

Hospital length of stay (LOS) after burn injury is commonly estimated as 1 day per percent burn, but LOS often exceeds that estimate. The purpose of this study is to develop a novel method for estimating burn hospital LOS at any time during hospitalization. The authors used the American Burn Association National Burn Repository from 2000 to 2009 to directly estimate the median residual LOS (MRLOS) of patients hospitalized for burn injuries and who survived to discharge. The MRLOS is the median of how many more days a burn patient will be hospitalized given that the person has been in hospital for a specified time period. The authors also estimated the 25th and 75th percentiles of residual life and quantified the relationship between MRLOS and LOS with ordinary least squares for all burn patients, by burn size and by presence of inhalation injury. MRLOS increased with increasing LOS, confirming that discharge estimates change over time. Patients with inhalation injury had longer MRLOS than patients without inhalation injury in the first 100 hospital days. Patients with large burns (>25%) had large MRLOS consistent with prolonged hospitalization, but patients with small burns (

Increased cardiovascular morbidity and mortality in patients with type 2 diabetes is well established; diabetes is associated with at least a 2-fold increased risk of coronary heart disease. Approximately two-thirds of deaths among persons with diabetes are related to cardiovascular disease. Previously, diabetes was regarded as a "coronary risk equivalent," implying a high 10-year cardiovascular risk for every diabetes patient. Following the original study by Haffner et al., multiple studies from different cohorts provided varying conclusions on the validity of the concept of coronary risk equivalency in patients with diabetes. New guidelines have started to acknowledge the heterogeneity in risk and include different treatment recommendations for diabetic patients without other risk factors who are considered to be at lower risk. Furthermore, guidelines have suggested that further risk stratification in patients with diabetes is warranted before universal treatment. The Imaging Council of the American College of Cardiology systematically reviewed all modalities commonly used for risk stratification in persons with diabetes mellitus and summarized the data and recommendations. This document reviews the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease risk and develops an algorithm for screening based on available data.

Evidence-based burn nursing literature is extremely limited and often nonexistent. As a result, there is a lack of standardization in burn nursing care. Our objective was to evaluate burn nursing knowledge at an academic medical center and to implement innovative educational tools to enhance staff competency and improve the quality of care. A collaboration of practicing clinical nurses developed a 24-question knowledge assessment survey (presurvey) to evaluate fundamental burn nursing knowledge (fluid management, burn pathophysiology, burn-related procedures, wound care, and infection control). Pre-education knowledge surveys were administered to 59 burn nurses electronically. A writing team of new and experienced nurses was established and a 51-page handbook focusing on areas of need identified in the survey developed. This book was disseminated to staff as required for reading. Post-educational surveys were sent to the same nurses who completed the initial survey. Forty-six nurses (46/59, 78.0%) completed the survey, with a mean (SD) of 55.9 (11.0)% of questions being answered correctly. Postsurveys sent to the same 46 nurses who completed the presurvey had a response rate of 78.3% (36/46). We observed a significant increase in correctly answered questions (mean [SD]: 69.6 [8.7]%, P < .001) in the postsurvey intervention. The handbook improved education and significantly improved overall fundamental burn knowledge of practicing nursing staff. The use of electronic surveys to drive development of targeted educational interventions provides evidence-based tools for establishing burn nursing standards and developing quality improvement metrics.

The goal of this study is to quantify the number of medications administered to burn patients and identify potential drugs interfering with laboratory testing. The authors reviewed the medical records of 12 adult (age ≥ 18 years) burn patients with more than 20% TBSA burns from an existing glucose control database at our institution. Dose, interval, and route of medications administered from admission to discontinuation of intensive insulin therapy were recorded. Interfering drugs were identified based on established clinical chemistry literature. The retrospective cohort of adult burn patients exhibited a mean (SD) age of 37.9 (3.0) years. Mean TBSA burn was 51.3 (9.3)%. Disease severity determined by the average multiple organ dysfunction score was 5.4 (0.2). Mean and median medications administered per day were 42.1 (9.5) and 49 (with a daily range of 0-65), respectively. A total of 666 potential laboratory test interferences caused by medications were identified. There were 261 different effects (eg, increased glucose, decreased potassium). Multiple interferences, 71.0% (475/666), were caused by more than one medication. Investigation of the number of medications administered to a burn patient and delineation of potential laboratory test interferences has not been conducted in burn patients. Given the substantial number of medications administered to burn patients, physicians and laboratory personnel should work together to identify potential interferences and define appropriate countermeasures while enhancing the laboratorians understanding of this unique population. This synergistic partnership can lead to intelligent support tools and potentially autocorrecting instruments.

BackgroundEarly detection of acute kidney injury (AKI) in severely burn-injured patients can help alter treatment to prevent progression to acute failure and reduce the need for renal replacement therapy. We hypothesized that whole blood neutrophil gelatinase-associated lipocalin (NGAL) will be increased in severely burn-injured patients who develop AKI during acute resuscitation.Materials and methodsWe performed a prospective observation study of adult burn patients with a 20% total body surface area (TBSA) burned or greater burn injury. Two-hour serial measurements of NGAL, serum creatinine (Cr), and hourly urine output (UO) were collected for 48 h after admission. Our primary goal was to correlate the risk of AKI in the first week after burn injury with serial NGAL levels in the first 48 h after admission. Our secondary goal was to determine if NGAL was an earlier independent predictor of AKI compared with Cr and UO.ResultsWe enrolled 30 adult (age ≥ 18 y) burn patients with the mean ± standard deviation age of 40.9 ± 15.4 and mean TBSA of 46.4 ± 22.4. Fourteen patients developed AKI within the first 7 d after burn injury. There were no differences in age, TBSA, fluid administration, mean arterial pressure, UO, and Cr between AKI and no-AKI patients. NGAL was significantly increased as early as 4 h after injury (182.67 ± 83.3 versus 107.37 ± 46.15) in the AKI group. Controlling for age, TBSA, and inhalation injury, NGAL was a predictor of AKI at 4 h after injury (odds ratio, 1.02) and remained predictive of AKI for the period of more than the first 24 h after admission. UO and Cr were not predictive of AKI in the first 24 h after admission.ConclusionsWhole blood NGAL is markedly increased in burn patients who develop AKI in the first week after injury. In addition, NGAL is an early independent predictor of AKI during acute resuscitation for severe burn injury. UO and Cr are not predictive of AKI during this time period.

ObjectivesDetermine the relationship between the volume of burn admissions and outcomes for children with burns.DesignRetrospective review of the National Burn Repository from 2000-2009 using mixed effect logistic regression modeling.SettingTertiary burn centers in the United States.PatientsAll children 200 pediatric patients/year) had the lowest mortality when adjusting for age and injury characteristics (p < 0.05).ConclusionsHigher volume pediatric burn centers had lower mortality, particularly at larger burn sizes. The lower mortality of children a high volume centers could reflect greater experience, resource, and specialized expertise in treating pediatric patients.

ImportanceCurrent outcome predictors for illness and injury are measured at a single time point-admission. However, patient prognosis often changes during hospitalization, limiting the usefulness of those predictions. Accurate depiction of the dynamic interaction between competing events during hospitalization may enable real-time outcome assessment.ObjectiveTo determine how the effects of burn outcome predictors (ie, age, total body surface area burn, and inhalation injury) and the outcomes of interest (ie, mortality and length of stay) vary as a function of time throughout hospitalization.Design, setting, and participantsIn this retrospective study, we used the American Burn Association's National Burn Repository, containing outcomes and patient and injury characteristics, to identify 95 579 patients admitted with an acute burn injury to 80 tertiary American Burn Association burn centers from 2000 through 2009. We applied competing risk statistical methods to analyze patient outcomes.Main outcomes and measuresWe estimated the cause-specific hazard rates for death and discharge to assess how the instantaneous risk of these events changed across time. We further evaluated the varying effects of patient age, total body surface area burn, and inhalation injury on the probability of discharge and death across time.ResultsMaximum length of stay among patients who died was 270 days and 731 days among those discharged. Total body surface area, age, and inhalation injury had significant effects on the subdistribution hazard for discharge (P

Traditional burn mortality models are derived using all age groups. We hypothesized that age variably impacts mortality after burn and that age-specific models for children, adults, and seniors will more accurately predict mortality than an all-ages model. We audited data from the American Burn Association (ABA) National Burn Repository (NBR) from 2000 to 2009 and used mixed effect logistic regression models to assess the influence of age, total body surface area (TBSA) burn, and inhalation injury on mortality. Mortality models were constructed for all ages and age-specific models: children (60 years). Model performance was assessed by area under the receiver operating curve (AUC). Main effect and two-way interactions were used to construct age-group specific mortality models. Each age-specific model was compared to the All Ages model. Of 286,293 records 100,051 had complete data. Overall mortality was 4% but varied by age (17% seniors,

Recent disasters highlight the need for predisaster planning, including the need for accurate triage. Data-driven triage tables, such as that generated from the 2002 National Burn Repository, are vital to optimize resource use during a disaster. The study purpose was to generate a burn resource disaster triage table based on current burn-treatment outcomes. Data from the NBR after the year 2000 were audited. Records that missed age, burn size, or survival status were excluded from analysis. Duplicate records, readmissions, transfers, and nonburn injuries were eliminated. Resource use was divided into expectant (predicted mortality >90%), low (mortality 50-90%), medium (mortality 10-50%), high (mortality 70 years began at 50% burn; a 20- to 29-year-old never reached expectant status. Inhalation injury lowered the expectant category to a burn size of 40% in >70-year-olds, and at >90% in 20- to 29-year-olds. The 0- to 1.9-year old group without inhalation injury never reached expectant status; with inhalation injury, expectant status was reached at >80% burn. Changes in the triage tables suggest that burn care has changed in the past 10 years. Inhalation injury significantly alters triage in a burn disaster. Use of these updated tables for triage in a disaster may improve our ability to allocate resources.