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OBJECTIVE This study aimed to compare lipid and blood pressure (BP) control before and after implementing a certified pharmacy technician (CPhT) protocol that optimized electronic health record (EHR) capabilities and shifted work from clinical pharmacy specialists (CPSs) to CPhT. SETTING Kaiser Permanente Colorado's pharmacist-managed cardiac risk reduction service (which manages dyslipidemia, hypertension, and diabetes for all patients with atherosclerotic cardiovascular disease). PRACTICE DESCRIPTION In 2019, a protocol that optimized EHR capabilities and allowed work to be offloaded from CPS to CPhT was implemented. Filtered views within the EHR were created that bucketed patients with specific lipid results criteria. The CPhT protocol provided guidance to CPhT on determining whether patients were at low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein (non-HDL) goals, on appropriate statin intensity, adherent to medications, and whether the most recent BP was controlled. The CPhT notified CPS of uncontrolled patients who would assess and manage these patients, as necessary. The CPhT notified controlled patients of their results. PRACTICE INNOVATION Data on the outcomes of incorporating pharmacy technicians to support CPS clinical activities in ambulatory clinical pharmacy are limited. EVALUATION METHODS This retrospective study compared a "Pharmacist-Driven" (index date: January 1, 2016) with a "Tech-Enhanced" (index date: January 1, 2019) group. The primary outcome was the proportion of patients at all goals defined as LDL-C < 70 mg/dL, non-HDL

Checkpoint inhibitor-based immunotherapy is increasingly used in the treatment of gynecologic cancers, and most often targets the PD-1/PD-L1 axis. Pathologists should be familiar with the biomarkers required to determine candidacy for these treatments based on existing FDA approvals, including mismatch repair protein immunohistochemistry, microsatellite instability testing, tumor mutation burden testing, and PD-L1 immunohistochemistry. This review summarizes the rationale behind these treatments and their associated biomarkers and delivers guidance on how to utilize and readout these tests. It also introduces additional biomarkers which may provide information regarding immunotherapeutic vulnerability in the future such as neoantigen load; POLE mutation status; and immunohistochemical expression of immunosuppressive checkpoints like LAG-3, TIM-3, TIGIT, and VISTA; immune-activating checkpoints such as CD27, CD40, CD134, and CD137; enzymes such as IDO-1 and adenosine-related compounds; and MHC class I.

Cardiogenic shock (CS) represents a spectrum of hemodynamic deficits in which the cardiac output is insufficient to provide adequate tissue perfusion. The Impella (Abiomed Inc, Danvers, MA) device, a contemporary percutaneous ventricular support, is most often indicated for classic, deteriorating, and extremis Society for Coronary Angiography and Intervention stages of CS, which describe CS that is not responsive to optimal medical management and conventional treatment measures. Impella devices are an evolving field of mechanical support that is used with increasing frequency. Critical care transport medicine crews are required to transport patient support by the Impella device with increasing frequency. It is important that critical care transport medicine crews are familiar with the Impella device and are able to troubleshoot complications that may arise in the transport environment. This article reviews many aspects of the Impella device critical to the transport of this complex patient population.

Phenylketonuria (PKU) is the most common inborn error of metabolism of the liver, and results from mutations of both alleles of the phenylalanine hydroxylase gene (PAH). As such, it is a suitable target for gene therapy via gene delivery with a recombinant adeno-associated virus (AAV) vector. Here we use the synthetic AAV vector Anc80 via systemic administration to deliver a functional copy of a codon-optimized human PAH gene, with or without an intron spacer, to the Pahenu2 mouse model of PKU. Dose-dependent transduction of the liver and expression of PAH mRNA were present with both vectors, resulting in significant and durable reduction of circulating phenylalanine, reaching near control levels in males. Coat color of treated Pahenu2 mice reflected an increase in pigmentation from brown to the black color of control animals, further indicating functional restoration of phenylalanine metabolism and its byproduct melanin. There were no adverse effects associated with administration of AAV up to 5 × 1012 VG/kg, the highest dose tested. Only minor and/or transient variations in some liver enzymes were observed in some of the AAV-dosed animals which were not associated with pathology findings in the liver. Finally, there was no impact on cell turnover or apoptosis as evaluated by Ki-67 and TUNEL staining, further supporting the safety of this approach. This study demonstrates the therapeutic potential of AAV Anc80 to safely and durably cure PKU in a mouse model, supporting development for clinical consideration.

Surgical options for advanced Kienböck’s disease include proximal row carpectomy or lunate reconstruction with a medial femoral trochlea osteochondral flap. This study compares morphology of the proximal capitate and the medial femoral trochlear surfaces to the proximal lunate using three-dimensional geometric morphometric analysis. Virtual articular surfaces were extracted from MRI studies of ten healthy volunteers. Distances between corresponding points on the proximal lunate and proximal capitate or medial femoral trochlear surfaces were measured. In seven subjects, mean inter-surface distance for the medial femoral trochlea–proximal lunate pair was significantly lower than the proximal capitate–proximal lunate pairing. In three subjects, mean proximal capitate–proximal lunate distance was significantly lower. We conclude that the medial femoral trochlear flap was anatomically closer to the shape of the proximal lunate in the majority of the examined subjects. However, we found that in three out of ten cases, the proximal capitate was a better match.

Background: Postoperative atrial fibrillation (POAF) commonly occurs after coronary artery bypass graft (CABG) surgery. Patients with POAF are at higher risk of stroke and mortality. The use of oral anticoagulation (OAC) in POAF remains inconsistent, and the care gap is unknown. Objective: We sought to evaluate rate of adherence and factors associated with OAC use in POAF patients after isolated CABG. Methods: In this study, all patients who had an isolated CABG between April 1, 2019 and March 30, 2020, at Health Sciences North, Sudbury retrospectively were evaluated. We identified all patients who developed POAF and captured the use of OAC. Multivariable logistic regression models were used to identify predictors of OAC prescription. Results: In total, 339 CABG patients between April 1, 2019 and March 30, 2020, were identified; 86 patients developed POAF. No patients had major perioperative bleeding. All POAF patients had an indication for OAC therapies based on CHADS 65 score. However, only 17 (19.8%) patients with POAF had OAC prescription at the time of hospital discharge. Baseline characteristics were similar between those with or without OAC. In multivariable analysis, the use of dual antiplatelet therapy was associated with a decreased use of OAC therapy in POAF (OR 0.037 (95% CI 0.005, 0.29), P = .002). Moreover, in comparison to surgeon A, surgeon B was associated with a decreased use of OAC therapy, whereas surgeon C was associated with an increased use of OAC therapy in POAF (OR 0.15 (95% CI 0.03, 0.83), P = .03 and OR 6.49 (95% CI 1.21, 34.82), P = .03, respectively). None of the CHADS 65 elements, including age, hypertension, stroke, diabetes mellitus or congestive heart failure, correlated with the use of OAC. Key findings: Eighty percent of patients who developed POAF after isolated CABG failed to receive stroke prevention therapies. The use of dual antiplatelet therapy and individual surgeons’ preference were associated with the use of OAC therapy among POAF. Conclusions: This data set suggests that approximately only 1 in 5 patients with POAF after isolated CABG got prescribed OAC.

Background The Blastomyces antigen concentration in urine (BACU) test is used to diagnose blastomycosis and monitor treatment in dogs. It is unknown if a higher BACU is associated with shorter survival. Objectives To determine if the magnitude of BACU before treatment is associated with survival in dogs with blastomycosis. Animals Fifty‐two dogs with blastomycosis. Methods Retrospective case review. BACU, radiographic lung severity (RLS) score (0‐4 scale), and survival time up to 1 year after diagnosis were obtained through medical record review of dogs with Blastomyces dermatitidis. Results The overall survival was: discharge, 87%; 1 week, 85%; 2 months, 74%; and 6 months, 69%. BACU correlated with RLS score (r s = 0.33, P = .02). BACU and RLS scores were lower in survivors to 2 months than nonsurvivors (average BACU difference of 2.5 ng/mL, 95% confidence interval [CI]: 0.2‐4.8 ng/mL, P = .04; median RLS difference of 2; range, 0‐4, P = .02). Dogs with BACU 5 ng/mL (P = .03) and dogs with severe (3‐4) RLS scores (P = .04). All dogs with a BACU

BACKGROUND: Homologous recombination deficiency (HRD) score is related to chemotherapy response in some cancers, but its role in endometrial cancer in not known. We determined frequency and clinical significance of alterations in the HR pathway in endometrial cancer. METHODS: 253 endometrioid endometrial adenocarcinoma (EEA) samples from two independent cohorts (discovery and replication) were tested for HRD score using the Myriad HRD assay, microsatellite instability (MSI) and tumor mutation burden (TMB) using a next generation sequencing assay. HRD scores were also generated on endometrial cancer cell lines and in vivo response to olaparib was assessed. RESULTS: ROC curves were employed to determine optimal cutoffs of HRD in relation to survival impact in endometrial cancer and a cutoff of HRD ≥ 4 was suggested for DFS using discovery cohort. Patients from two independent cohorts with HRD score ≥ 4 trended toward worse survival as compared to those with HRD score

Major histocompatibility complex (MHC) class I is a membrane-bound protein complex expressed on nucleated human cells. MHC class I presents intracellular protein fragments to cytotoxic T cells and triggers an activation cascade upon neoantigen detection by these cells. MHC class I loss by tumor cells decreases tumor neoantigen presentation to the immune system and therefore represents a possible mechanism of immunotherapeutic resistance even among cancers that otherwise appear to be good candidates for checkpoint inhibition, such as mismatch repair (MMR)-deficient and PD-L1-positive malignancies. We herein assess MHC class I expression in a range of endometrial carcinomas, including MMR-deficient and PD-L1-positive cancers. Immunohistochemical staining for combined MHC class I A-, B-, and C-heavy chains was performed on 76 cases of endometrial carcinoma and was classified as present, subclonally lost, or diffusely lost. Tumoral PD-L1 expression, PD-L1 combined positive score, and CD3-positive T lymphocytes were also quantified. Forty-two percent of tumors showed loss of MHC class I expression, either in a subclonal (26%) or diffuse (16%) pattern. This included 46% of MMR-deficient and 25% of PD-L1-positive cancers. These findings suggest that tumoral MHC class I status may be an important factor to consider when selecting endometrial cancer patients for checkpoint inhibition.

MLH1/PMS2 loss due to epigenetic hypermethylation of the MLH1 promoter is the most common cause of mismatch repair deficiency in endometrial carcinoma, and typically provides reassurance against an associated germline mutation. To further characterize the genetic features of MLH1/PMS2-deficient endometrial cancers, the departmental database was searched for cases with dual MLH1/PMS2 loss and retained MSH2/6 expression which underwent MLH1 hypermethylation testing. Genetic testing results were obtained when available. One hundred seventeen endometrial cancers met inclusion criteria: 100 (85%) were MLH1-hypermethylated, 3 (3%) were low-level/borderline, 7 (6%) were nonmethylated, and 7 (6%) were insufficient for testing. Sixteen cases (12 MLH1-hypermethylated, 3 nonmethylated, and 1 insufficient for testing) underwent germline testing, 6 of which (37.5%) demonstrated germline variants of unknown significance (VUS) (MSH6, PMS2, POLD1, BRIP1, RAD51D, CHEK2) but no known deleterious mutations. Notably, however, the patients harboring the MSH6 and PMS2 germline VUS had clinical features concerning for Lynch syndrome. One nonmethylated, germline-normal case underwent somatic tumor testing, and demonstrated a somatic MLH1 mutation. In summary, MLH1-hypermethylation accounts for the vast majority of MLH1/PMS2-deficient cancers in a universally screened population, although MLH1 somatic and germline mutations can occur. Occasionally, patients with MLH1-hypermethlated tumors also bear germline VUS in other mismatch repair genes as well as genes implicated in other hereditary cancer syndromes, but their clinical relevance is unclear. Family and personal cancer histories must always be evaluated to determine the need for germline testing in women with loss of MLH1/PMS2, even in the setting of hypermethylation.

PURPOSE: Fertility is a quality of life outcome adversely affected by cancer therapy. Many childhood cancer patients, however, are not offered options to preserve their fertility. Providers acknowledge difficulty discussing impaired fertility to patients due to lack of knowledge of available options. Our objective was to review the impact of a pediatric multidisciplinary fertility preservation program on providers’ fertility preservation counseling and discussion of options. METHODS: A retrospective medical chart review was conducted for pediatric cancer patients prior to and following program establishment. Fertility preservation discussions, consults, and incidence were noted. Following filtering and stratification, 198 and 237 patients were seen prior to and following program establishment, respectively. RESULTS: Following program establishment, provider–patient discussions of impaired fertility (p = 0.007), fertility preservation consults (p = 0.01), and incidence of fertility preservation procedures (p < 0.001) increased among patients. Furthermore, the number of patients who received fertility preservation consults after receiving gonadotoxic treatment decreased (p < 0.001). This trend was particularly noted in pre-pubertal and female patients, for whom fertility preservation options are limited without an established program. CONCLUSION: The establishment of a formal program greatly improved access to fertility preservation consults and procedures in children with cancer.

Aromatherapy is defined as the use of essential oils, through inhalation or direct application to the skin, to achieve physical, psychological, and spiritual well-being. It has become an increasingly popular trend in modern-day holistic approaches to health care. Essential oils are thought to be natural and pure products, some of the most common being lavender, tea tree, peppermint, and ylang-ylang. In recent years, however, the composition of these oils has been found to be more complex than previously thought. Increased use has led to increasing reports of allergic contact dermatitis (ACD), a delayed-type hypersensitivity reaction to allergens in sensitized individuals. Inquiring about essential oil use is important when conducting clinical evaluations of suspected ACD. Herein, the authors seek to highlight the possibility that natural products may not be necessarily as safe as once thought and in particular seek to highlight ACD caused by essential oils.

The effectiveness of cell-based therapies to treat liver failure is often limited by the diseased liver environment. Here, we provide preclinical proof of concept for hepatocyte transplantation into lymph nodes as a cure for liver failure in a large-animal model with hereditary tyrosinemia type 1 (HT1), a metabolic liver disease caused by deficiency of fumarylacetoacetate hydrolase (FAH) enzyme. Autologous porcine hepatocytes were transduced ex vivo with a lentiviral vector carrying the pig Fah gene and transplanted into mesenteric lymph nodes. Hepatocytes showed early (6 h) and durable (8 months) engraftment in lymph nodes, with reproduction of vascular and hepatic microarchitecture. Subsequently, hepatocytes migrated to and repopulated the native diseased liver. The corrected cells generated sufficient liver mass to clinically ameliorate the acute liver failure and HT1 disease as early as 97 days post-transplantation. Integration site analysis defined the corrected hepatocytes in the liver as a subpopulation of hepatocytes from lymph nodes, indicating that the lymph nodes served as a source for healthy hepatocytes to repopulate a diseased liver. Therefore, ectopic transplantation of healthy hepatocytes cures this pig model of liver failure and presents a promising approach for the development of cures for liver disease in patients., Graphical Abstract, Lillegard and colleagues demonstrate that ectopic hepatocyte transplantation into lymph nodes cures liver failure in a large-animal model of metabolic disease, hereditary tyrosinemia type-1 (HT1). Autologous hepatocytes were transduced ex vivo with a lentiviral vector carrying the Fah gene, missing in HT1. Transplanted hepatocytes generated sufficient liver mass to cure the disease.

Women with heart disease are at increased risk for maternal and fetal complications in pregnancy. Therefore, all women with heart disease should undergo evaluation and counseling, ideally before conception, or as early in pregnancy as possible. In this article we will review the role of risk assessment, the history of development of the cardiac risk prediction tools, and the role of current cardiac risk prediction tools.

Pediatric allergic contact dermatitis (Ped-ACD) is an increasingly recognized highly prevalent skin disease that has a significant impact on the quality of life of patients and their families. Accurate and appropriate patch testing is vital to diagnosing Ped-ACD. This requires knowledge of the most common allergens in the pediatric population, consideration of concurrent diseases that can complicate the clinical picture, and potential modification of techniques to lessen exposure to irritants and sensitizers while obtaining true positive results. This article reviews the most common pediatric allergens and discusses considerations when performing pediatric patch testing.

Activation of lipid-burning pathways in the fat-storing white adipose tissue (WAT) is a promising strategy to improve metabolic health and reduce obesity, insulin resistance, and type II diabetes. For unknown reasons, bilirubin levels are negatively associated with obesity and diabetes. Here, using mice and an array of approaches, including MRI to assess body composition, biochemical assays to measure bilirubin and fatty acids, MitoTracker-based mitochondrial analysis, immunofluorescence, and high-throughput coregulator analysis, we show that bilirubin functions as a molecular switch for the nuclear receptor transcription factor peroxisome proliferator–activated receptor α (PPARα). Bilirubin exerted its effects by recruiting and dissociating specific coregulators in WAT, driving the expression of PPARα target genes such as uncoupling protein 1 (Ucp1) and adrenoreceptor β 3 (Adrb3). We also found that bilirubin is a selective ligand for PPARα and does not affect the activities of the related proteins PPARγ and PPARδ. We further found that diet-induced obese mice with mild hyperbilirubinemia have reduced WAT size and an increased number of mitochondria, associated with a restructuring of PPARα-binding coregulators. We conclude that bilirubin strongly affects organismal body weight by reshaping the PPARα coregulator profile, remodeling WAT to improve metabolic function, and reducing fat accumulation.

LAG-3 is an immunosuppressive checkpoint molecule expressed on T cells. One of its ligands, GAL-3, can promote the progression of malignancy and has been identified on tumor cells. Both LAG-3 and GAL-3 are the targets of emerging immunotherapies, but have not been well-studied in endometrial carcinomas. LAG-3, CD3, and GAL-3 immunohistochemistry was performed on 75 endometrial cancers (25 nonmethylated mismatch repair-deficient, 25 MLH1-hypermethylated mismatch repair-deficient, and 25 mismatch repair-intact). LAG-3 and CD3 lymphocytes were averaged per high-power field. Tumoral GAL-3 expression was semiquantitatively scored. Tumor-infiltrating lymphocyte expression of LAG-3 and CD3 were positively correlated (Spearman ρ=0.521, P

OBJECTIVES: Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. METHODS: We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. RESULTS: Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. DISCUSSION: MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.

BACKGROUND Data on primary hypothyroidism and its long-term impact on the health, cognition, and quality of life (QOL) of childhood cancer survivors are limited. This study examined the prevalence of and risk factors for primary hypothyroidism and its associations with physical, neurocognitive, and psychosocial outcomes. METHODS This was a retrospective study with a cross-sectional health outcome analysis of an established cohort comprising 2965 survivors of childhood cancer (52.8% male; median current age, 30.9 years, median time since cancer diagnosis, 22.3 years). Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between primary hypothyroidism and cancer-related risk factors, cardiovascular disease risk factors, frailty, neurocognitive and QOL outcomes, social attainment, and subsequent thyroid carcinoma. Associations between serum free thyroxine and thyrotropin levels at assessment and health outcomes were explored. RESULTS The prevalence of primary hypothyroidism was 14.7% (95% CI, 13.5%-16.0%). It was more likely in females (OR, 1.06; 95% CI, 1.03-1.08), was less likely in non-Whites (OR, 0.96; 95% CI, 0.93-0.99), was associated with thyroid radiotherapy (higher risk at higher doses), and was more common if cancer was diagnosed at an age ≥ 15.0 years versus an age

Posterior medial meniscus root tears (PMMRTs) make up a relatively notable proportion of all meniscus pathology and have been definitively linked to the progression of osteoarthritis (OA). While known risk factors for development of OA in the knee include abnormal tibial coronal alignment, obesity and female gender, PMMRTs have emerged in recent years as another significant driver of degenerative disease. These injuries lead to an increase in average contact pressure in the medial compartment, along with increases in peak contact pressure and a decrease in contact area relative to the intact state. Loss of the root attachment impairs the function of the entire meniscus and leads to meniscal extrusion, thus impairing the force-dissipating role of the meniscus. Anatomic meniscus root repairs with a transtibial pullout technique have been shown biomechanically to restore mean and peak contact pressures in the medial compartment. However, nonanatomic root repairs have been reported to be ineffective at restoring joint pressures back to normal. Meniscal extrusion is often a consequence of nonanatomic repair and is correlated with progression of OA. In this study, the authors will describe the biomechanical basis of the natural history of medial meniscal root tears and will support the biomechanical studies with a case series including patients that either underwent non-operative treatment (5 patients) or non-anatomic repair of their medial meniscal root tears (6 patients). Using measurements derived from axial MRI, the authors will detail the distance from native root attachment center of the non-anatomic tunnels and discuss the ongoing symptoms of those patients. Imaging and OA progression among patients who were treated nonoperatively before presentation to the authors will be discussed as well. The case series thus presented will illustrate the natural history of meniscal root tears, the consequences of non-anatomic repair, and the findings of symptomatic meniscal extrusion associated with a non-anatomic repair position of the meniscus.

Background: Individuals with hip osteoarthritis (OA) commonly walk with less hip extension compared to individuals without hip OA. This alteration is often attributed to walking speed, structural limitation, and/or hip pain. It is unclear if individuals who are at increased risk for future OA (i.e., individuals with pre-arthritic hip disease [PAHD]) also walk with decreased hip extension.Objectives: (1) Determine if individuals with PAHD exhibit less hip extension compared to individuals without hip pain during walking, and (2) investigate potential reasons for these motion alterations.Methods: Adolescent and adult individuals with PAHD and healthy controls without hip pain were recruited for the study. Kinematic data were collected while walking on a treadmill at three walking speeds: preferred, fast (25% faster than preferred), and prescribed (1.25 m/s). Peak hip extension, peak hip flexion, and hip excursion were calculated for each speed. Linear regression analyses were used to examine the effects of group, sex, side, and their interactions.Results: Individuals with PAHD had 2.9° less peak hip extension compared to individuals in the Control group (p = 0.014) when walking at their preferred speed. At the prescribed speed, the PAHD group walked with 2.7° less hip extension than the Control group (p = 0.022). Given the persistence of the finding despite walking at the same speed, differences in preferred speed are unlikely the reason for the reduced hip extension. At the fast speed, both groups increased their hip extension, hip flexion, and hip excursion by similar amounts. Hip extension was less in the PAHD group compared to the Control group (p = 0.008) with no significant group-by-task interaction (p = 0.206). Within the PAHD group, hip angles and excursions were similar between individuals reporting pain and individuals reporting no pain.Conclusions: The results of this study indicate that kinematic alterations common in individuals with hip OA exist early in the continuum of hip disease and are present in individuals with PAHD. The reduced hip extension during walking is not explained by speed, structural limitation, or current pain.

Exposure to and consumption of brackish water are associated with an elevated risk of infection, hypernatremia, and hypothermia. Minimal data exist to support the diagnosis and treatment of patients with long-term brackish water exposure. We present a case of a patient who spent 5 to 10 d semisubmerged in the Elizabeth River in coastal Virginia. A 55-y-old male presented via ambulance after 5 to 10 d of being "stuck in the mud." He was hypernatremic, with a sodium of 176 mEq·L-1, hypothermic to 34.5°C (94.1°F), and hypotensive at 88/50 mm Hg, with a sodium concentration of 176 mEq·L-1 and an osmolality of 412 mosm·kg-1. He developed pneumonia, with respiratory cultures growing Vibrio parahemolyticus, Klebsiella oxytoca, and Shewanella algae. He had pustules, which grew Aeromonas hydrophilia and Aeromonas caviae. A nasogastric tube was placed. Using suction, 500 mL of coarse sand and gravel was removed from his stomach. Antibiotics and intravenous fluids were given. The patient fully recovered after 3 wk and was discharged to rehabilitation. Exposure to brackish water can present a unique set of infectious and metabolic complications. Initial care should include treatment of metabolic derangements, such as hypovolemia, hypernatremia, and hypothermia, and treatment of infections with antibiotics based on knowledge of the most likely causative organisms.

Antecedent interventions are often used preventatively to address engagement, but few studies have evaluated their effectiveness with students at risk for disability. This study evaluated the effectiveness of two commonly recommended antecedent interventions that have limited empirical support for use with students at risk: social stories and visual supports. Both interventions were evaluated separately in the context of two single-case alternating treatments designs across five elementary students at risk for emotional and behavioral disorders. Social stories were not effective for improving students’ levels of engagement during targeted activities; visual supports resulted in increases in students’ engagement relative to baseline conditions. Future use of visual supports for students at risk should include evaluations of the feasibility of implementation by teaching staff.

Introduction: Mental distress frequently develops in sufferers of chronic diseases, including cancer. We examined the association between physical activity and mental distress among Veteran cancer survivors with heart disease or diabetes. Methods: Data for American military Veteran cancer survivors ( n = 16,643) were retrieved from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System (BRFSS). Ordinary least squares (OLS) multiple linear regression was used to explore the effect of physical activity on self-reported mental distress among Veteran cancer survivors with coronary heart disease or diabetes. Geographic information system (GIS) software was used to examine the state-level distribution of mental distress among Veteran cancer survivors. Results: Geographic analysis showed that mental distress (in days) in the last month among Veteran cancer survivors was highest in Alabama (M = 3.99), while those in Wyoming reported the lowest number of days (M = 0.76). After controlling for relevant confounding factors, physical activity was associated with fewer days of mental distress days among Veteran cancer survivors with coronary heart disease. Discussion: Results of this study suggest that physical activity may be beneficial in reducing mental distress among Veteran cancer survivors with heart disease.

Objective: Factors associated with maternal functioning in biological mothers whose infants were admitted to a Neonatal Intensive Care Unit (NICU) were identified as measured by a modified...

General safety and toxicology assessments supporting in vivo lentiviral vector-based therapeutic development are sparse. We have previously demonstrated the efficacy of a lentiviral vector expressi...

Measles virus causes a highly infectious disease in NHP. Clinical signs range from asymptomatic to fatal, although measles virus is most well-known for its characteristic generalized maculopapular rash. Along with appropriate quarantine practices, restricted human access, and appropriate personal protective equipment, vaccines are used to combat the risk of infection. The canine distemper–measles vaccine (CDMV), administered at the manufacturer's standard dose (1.0 mL IM), has been shown to be effective against clinical measles disease in rhesus macaques (Macaca mulatta). The goal of the current study was to test whether doses smaller than the manufacturer's recommended dose stimulated adequate antibody production to protect against infection. We hypothesized that either 0.25 or 0.5 mL IM of CDMV would stimulate antibody production comparable to the manufacturer's recommended dose. We found that the 0.25-mL dose was less effective at inducing antibodies than either the standard (1.0 mL) or 0.5-mL dose, which both yielded similar titers. The primary implication of this study informs balancing resource allocation and providing efficacious immunity. By using half the manufacturer-recommended dose, the 50% cost reduction may provide sufficient monetary incentive to implement, maintain, or modify measles vaccination programs at NHP facilities.

The objectives of this study were to determine both surgical and subsequent cancer outcomes for high-risk women from the University of Virginia's High-Risk Breast/Ovarian Cancer clinic undergoing ovarian cancer risk-reducing surgery. Retrospective review identified high risk women who had ovarian risk reducing surgery over the past decade and surgical outcomes, pathology, pre-operative screening results, and pre-/post-operative cancer diagnoses were evaluated. One hundred and eighty-three high-risk women had risk reducing surgery at a mean age of 50.1 years and with a mean BMI of 28.9 kg/m2 at the time of surgery. Most women (103; 56.3%) had a strong family history of cancer concerning for a hereditary syndrome without an identified mutation, 35.5% of women carried a known deleterious mutation and 7.7% of women had a personal history of breast or ovarian cancer. The most common procedure was a risk-reducing bilateral salpingo-oophorectomy with or without hysterectomy (RRBSO, 89.1%). All women underwent the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) pathology protocol which found two (1.1%) invasive ovarian cancers (one ovarian/tubal carcinosarcoma, one granulosa cell ovarian cancer), three (1.6%) serous tubal intraepithelial carcinomas (STIC), and one (1.1%) invasive fallopian tube cancer. Subsequent cancer diagnoses included one (0.5%) primary peritoneal cancer, four (2.2%) DCIS, and seven (3.8%) invasive breast cancers. Ultimately, among all high-risk women undergoing RR surgery, about 3.3% were diagnosed with a STIC or an ovarian cancer none of which were identified on screening. All STIC and tubal cancers were diagnosed in women with BRCA mutations (6.6% rate for this group)., Highlights • Ovarian risk reducing surgery improves outcomes. • Women with BRCA 1 mutations have a higher risk of occult tubal pathology. • Subsequent cancers, particularly breast cancer, occur in these women.

The mental health status of veteran cancer survivors is understudied. Given that studies show that physical activity (PA) may alleviate mental distress in cancer patients, the purpose of this study was to examine the relationship between PA and mental distress in veteran lung and colorectal cancer survivors. Data for the present study were retrieved from the 2016 Behavioral Risk Factor Surveillance System. The relationship between PA and the number of mentally distressful days in the last 30 days was examined among veteran lung cancer survivors and veteran colorectal cancer survivors with survey-weighted multiple linear regression. After adjusting for relevant covariates, results showed that colorectal cancer survivors had significantly more mentally distressful days compared to lung cancer survivors, B = 0.75 (95% confidence interval [CI] = 0.64, 0.86). Furthermore, PA was significantly related to fewer days of mental distress in both lung and colorectal cancer survivors, B = −0.33 (95% CI = −0.4...

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed

Background: Heart failure (HF) exacerbations often relate to poor self-care. Education programs improve outcomes, but are resource-intensive. We developed a video-based educational intervention and evaluated it in patients with HF. Methods: Congestive Heart Failure Outreach Program of Education was a pragmatic multicenter randomized trial. We included subjects with HF if they were hospitalized, seen in the emergency department (ED), or high-risk outpatients, and randomized them to intervention or control. Intervention included a 20-minute video, supplementary booklet, and 3 bimonthly newsletters focusing on salt and fluid restriction, daily weights, and medications. Subjects watched the video and were encouraged to review it at home, along with the booklet/newsletters. Control subjects received the booklet only. The primary outcome was the difference in cardiovascular hospitalizations or ED visits between groups at 6 months. Secondary outcomes included clinical events and in-hospital days. Results: We recruited 539 subjects from 22 centers in Canada and the United States. Baseline characteristics were similar in both groups: 64% were male and had a mean age of 66 (± 13) years, mean ejection fraction 31% (± 13.5), and 65% New York Heart Association Functional Classification III/IV. The primary outcome occurred in 57 subjects (21%) in the intervention group compared with 61 subjects (23%) in the control group (P = 0.66). There were no significant differences in prespecified secondary outcomes; however, death occurred in 18 subjects (7%) in the intervention group and 33 subjects (12%) in the control group (P = 0.03). Conclusion: Video education on self-care did not reduce hospitalizations or ED visits in patients with HF. Of note, mortality was lower in the intervention group. Résumé: Introduction: L’exacerbation de l’insuffisance cardiaque (IC) est souvent liée à une mauvaise prise en charge autonome des soins. Les programmes d’enseignement améliorent les résultats cliniques, mais exigent beaucoup de ressources. Nous avons conçu une intervention éducative par vidéo et l’avons évaluée auprès de patients atteints d’IC. Méthodes: Le Congestive Heart Failure Outreach Program of Education était une étude pragmatique multicentrique à répartition aléatoire. Nous avons sélectionné les sujets atteints d’IC s’ils étaient hospitalisés, vus au service des urgences (SU) ou patients en consultation externe exposés à un risque élevé, et les avons répartis de manière aléatoire au groupe d’intervention ou au groupe témoin. L’intervention a consisté en une vidéo de 20 minutes, un livret supplémentaire et 3 bulletins bimensuels portant sur la restriction du sel et des liquides, les mesures quotidiennes du poids et les médicaments. Après que les sujets eurent regardé la vidéo, nous les avons encouragés à la revoir à la maison, en plus de lire le livret et les bulletins. Les sujets témoins ont reçu seulement le livret. Le critère de jugement principal était la différence dans les hospitalisations en raison d’une maladie cardiovasculaire ou les visites au SU entre les groupes après 6 mois. Les critères de jugement secondaires étaient les événements cliniques et les jours d’hospitalisation. Résultats: Nous avons recruté 539 sujets de 22 centres au Canada et aux États-Unis. Les caractéristiques initiales étaient similaires dans les 2 groupes : 64 % étaient des hommes et avaient un âge moyen de 66 ans (± 13), une fraction d’éjection moyenne de 31 % (± 13,5), et 65 % avaient une classification fonctionnelle III/IV de la New York Heart Association. Le critère de jugement principal est survenu chez 57 sujets (21 %) dans le groupe d’intervention et chez 61 sujets (23 %) dans le groupe témoin (P = 0,66). Il n’y a eu aucune différence significative dans les critères secondaires prédéfinis. Toutefois, 18 sujets (7 %) du groupe d’intervention et 33 sujets (12 %) du groupe témoin sont morts (P = 0,03). Conclusion: L’enseignement sur les autosoins par vidéo n’a pas réduit les hospitalisations ou les visites au SU des patients atteints d’IC. Notamment, la mortalité a été plus faible dans le groupe d’intervention.

Progress in overall survival rates for childhood non-Hodgkin lymphoma (NHL) can be largely attributed to effective development and conduct of a number of international treatment studies. Knowledge gained from these studies has shifted the treatment paradigm from a "one-size fits all" strategy to a histologically dependent approach. More specifically, many now adhere to a risk-stratified approach, prescribing cumulative doses and intensities of chemotherapeutic exposures based upon the aggressiveness of disease. Moreover, recognition that high cure rates could be achieved without the use of radiation has eliminated the use of this modality in frontline settings for the majority of newly diagnosed children. These changes have contributed to the emergence of a heterogeneous group of NHL survivors. As the number of NHL survivors continues to increase, providers will encounter a wide spectrum of individuals whose risk for long-term complications are accordingly diverse. The following review summarizes the existing literature surrounding late effects, such as chronic health conditions, functional and neurocognitive performance outcomes, and health-related quality of life, that are unique to NHL survivors, as well as those extrapolated from the broader childhood cancer survivor population.

Historically in cancer genetic counseling, when a pathogenic variant is found which explains the cancers in the family, at risk family members are offered site-specific testing to identify whether or not they have the previously identified pathogenic variant. Factors such as turnaround times, cost, and insurance coverage all made site-specific testing the most appropriate testing option; however, as turnaround times and costs have substantially dropped and the recognition of double heterozygous families and families with nontraditional presentations has increased, the utility of site-specific testing should be questioned. We present four cases where ordering site-specific testing would have missed a clinically relevant pathogenic variant which raises the question of whether or not site-specific testing should be regularly used in cancer genetic testing.

Objective: The purpose of this study was to explore differences in oral health among students by military service status in postsecondary settings. Participants: Secondary data were obtained from the American College Health Association's 2011-2014 National College Health Assessment II. Method: Demographic characteristics of the study sample were explored by calculating frequencies and percentages by military service status. Research questions were explored with maximum likelihood multiple logistic regression. Results: Service member and veteran students are at greater risk for neglecting health behaviors associated with positive oral health, including that they were less likely to get dental exams and that those who deployed in the past were the least likely to be practicing good oral health. Conclusions: The results suggest that improving oral health will contribute to improving health and mental health outcomes in this population, and provide important information for health specialists working with service members and veterans on college campuses.

Background: Childhood cancer survivors are at elevated risk for motor and/or sensory neuropathy. The study aims to evaluate the concordance between self-report peripheral neuropathy compared with clinically ascertained peripheral neuropathy, and to identify factors associated with misclassification of peripheral neuropathy among survivors. Methods: The concordance between self-report and clinically ascertained peripheral neuropathy was evaluated among 2,933 5+ years old childhood cancer survivors (mean age 33.3, SD = 8.9). The sensitivity, specificity, and accuracy of self-report peripheral motor neuropathy (PMN) and peripheral sensory neuropathy (PSN) were calculated with reference to clinically assessed peripheral neuropathy. Results: Female survivors were more likely than male survivors to have clinically ascertained PMN (8.4% vs. 5.6%, P = 0.004). For females, having either PSN or PMN the most sensitive, specific, and accurate self-reported symptom was endorsing ≥2 symptoms on the self-report questionnaire (43.2%, 90.3%, and 85.2%, respectively), with kappa of 0.304. For males, having either PSN or PMN the most sensitive, specific, and accurate self-reported symptom was endorsing ≥2 symptoms on the self-report questionnaire (38.8%, 90.5%, and 86.3%, respectively) with kappa of 0.242. Age at diagnosis, emotional distress, and reporting pain in legs in the past 4 weeks were associated with an increased risk for false-positive reporting of peripheral neuropathy. Race (White), age at assessment, and emotional distress were associated with increased risk for false-negative reporting of peripheral neuropathy. Conclusions: Agreement between self-report and clinically ascertained peripheral neuropathy was poor in survivors. Choosing self-report versus clinical ascertained peripheral neuropathy should be carefully considered. Impact: The current study identifies the need for a self-report questionnaire that accurately assesses symptoms of peripheral neuropathy among cancer survivors.

ObjectivesTo investigate the safety and outcomes of elective para-aortic (PA) nodal irradiation utilizing modern treatment techniques for patients with node positive cervical cancer.MethodsPatients with pelvic lymph node positive cervical cancer who received radiation were included. All patients received radiation therapy (RT) to either a traditional pelvic field or an extended field to electively cover the PA nodes. Factors associated with survival were identified using a Cox proportional hazards model, and toxicities between groups were compared with a chi-square test.Results96 patients were identified with a mean follow up of 40 months. The incidence of acute grade ≥ 2 toxicity was 31% in the elective PA nodal RT group and 15% in the pelvic field group (Chi-square p = 0.067. There was no significant difference in rates of grade ≥ 3 acute or late toxicities between the two groups (p>0.05). The KM estimated 5-year OS was not statistically different for those receiving elective PA nodal irradiation compared to a pelvic only field, 54% vs. 73% respectively (log-rank p = 0.11).ConclusionsElective PA nodal RT can safely be delivered utilizing modern planning techniques without a significant increase in severe (grade ≥ 3) acute or late toxicities, at the cost of a possible small increase in non-severe (grade 2) acute toxicities. In this series there was no survival benefit observed with the receipt of elective PA nodal RT, however, this benefit may have been obscured by the higher risk features of this population. While prospective randomized trials utilizing a risk adapted approach to elective PA nodal coverage are the only way to fully evaluate the benefit of elective PA nodal coverage, these trials are unlikely to be performed and instead we must rely on interpretation of results of risk adapted approaches like those used in ongoing clinical trials and retrospective data.

Broadening participation in computing is a key priority for both the tech industry and academia. However, high rates of attrition from Ph.D. programs represent a tremendous loss of talent, potential, and resources that stifles efforts to diversify computing. The purpose of this study was to understand the extent to which students consider departure and to uncover prominent threats to student persistence. Findings reveal that students primarily consider departure due to a lack of support and inclusion in their department.

Introduction: Coronavirus disease 2019 (COVID-19) has forced health care systems to rethink the optimal delivery of health care services and has dramatically increased demand for general medicine providers (internal medicine, family medicine, emergency medicine), while simultaneously reducing demand for many subspecialty services. At Kaiser Permanente, we implemented a program wherein health care providers drawn from multiple disciplines perform daily telemedicine check-ins on COVID-19 patients, allowing us to both maintain social distancing and make use of providers in specialties who otherwise may have had lower in-clinic volumes. Methods: Kaiser Permanente patients testing positive for COVID-19 between March and October 2020 were referred to our program. Physicians and nurses (RNs) were invited to participate in our program and were trained using Microsoft Teams™ meetings. Patients receive daily phone calls by a physician or RN. Select patients receive portable pulse oximeter devices based on standardized criteria incorporating age and comorbidities. When patients are determined to be clinically stable, they are discharged back to their primary care physician for ongoing management. Results: Descriptive results for the virtual home care program (VHCP) are reported through October 2020, though these results do not represent a planned statistical analysis. Forty-two percent of the patients were male, 43% were black, and 30% were Hispanic. The most common comorbidities of patients in our program were obesity (body mass index >30 kg/m2; 35%), followed by hypertension (32%) and diabetes mellitus (19%). Then, 8.2% of patients ultimately required hospital admission. Mortality rate for patients in our program was 1.33%. Discussion: Our program was able to provide virtual care for thousands of COVID-19 positive Kaiser members in the Washington, DC, and Baltimore Metro regions. We did so by utilizing physicians and RNs from specialties experiencing a decrease in clinic volume attributable to the COVID-19 pandemic. The experiences of our program may be valuable to clinicians wishing to establish similar programs of their own.

Conventional therapy for hereditary tyrosinemia type-1 (HT1) with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) delays and in some cases fails to prevent disease progression to liver fibrosis, liver failure, and activation of tumorigenic pathways. Here we demonstrate for the first time a cure of HT1 by direct, in vivo administration of a therapeutic lentiviral vector targeting the expression of a human fumarylacetoacetate hydrolase (FAH) transgene in the porcine model of HT1. This therapy was well tolerated and provided stable long-term expression of FAH in pigs with HT1. Genomic integration displayed a benign profile, with subsequent fibrosis and tumorigenicity gene expression patterns similar to wild-type animals as compared to NTBC-treated or diseased untreated animals. Indeed, the phenotypic and genomic data following in vivo lentiviral vector administration demonstrate comparative superiority over other therapies including ex vivo cell therapy and therefore support clinical application of this approach.

IntroductionPatients with advanced chronic obstructive pulmonary disease (COPD) experience a great symptom burden. Breathlessness is a very frequently reported symptom that negatively affects all aspects of daily life and could lead to fear of dying. Non-invasive ventilation (NIV) could be an important palliative measure to manage breathlessness in patients with advanced COPD. We decided to conduct a scoping review to attain an overview of the existing research and to identify knowledge gaps. This scoping review aims to systematically map published studies on the use of NIV in the palliative care of COPD patients, including the perspectives and experiences of patients, families and healthcare professionals.Methods and analysisThis scoping review will employ the framework of Arksey and O’Malley. The reporting will be guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A comprehensive and systematic search strategy will be developed in cooperation with an experienced librarian. Database searches will be conducted in AMED, PEDro, Embase, CINAHL, PsycInfo and MEDLINE in February 2021. Pairs of authors will independently assess studies’ eligibility and extract data using a standardised data-charting form. The data will be inductively summarised and organised thematically. The results will be discussed with an advisory board consisting of nurses and physicians from respiratory and intensive care units.Ethics and disseminationApproval for the workshop with the advisory board has been attained from the Norwegian Centre for Research Data (480222), and approval will be attained from the Personal Data Protection Officers of the participating hospitals. All advisory board participants will sign an informed written consent before participation. The results could contribute to developing the body of evidence on the use of NIV in the palliative care of COPD patients and serve to identify directions for future research.

Objectives: Sentinel lymph node (SLN) mapping has become the preferred method for surgical staging of endometrial cancer; however, previous studies on SLN mapping have not reported detection rates specifically in terms of obesity class. Our objective was to evaluate the success of SLN detection in endometrial cancer as it relates to body mass index (BMI). Methods: Clinicopathologic data were abstracted for patients who completed surgical staging at a single institution between 2015 and 2020. All patients who completed sentinel lymph node mapping had cervical injection with ICG green and near infrared imaging via the robotic platform. Descriptive statistics were calculated, chi-square tests were used to assess the associations between categorical variables, and independent T tests were used for continuous variables. Results: A total of 337 patients completed surgical staging over the study period. Of these, 226 women completed cervical dye injection with attempted sentinel lymph node mapping. Two hundred and ten women (92.9%) women had at least a unilateral sentinel lymph node detected with 156 women (74.3%) mapping bilaterally. The majority of patients were obese, accounting for 65% of the study population with a mean BMI of 34.4 kg/m2 (range 18.5 - 66.1kg/m2). Mean BMI at the time of surgery was significantly lower for patients with sentinel lymph nodes identified compared to those who did not successfully map correlating with class I versus class II obesity (34.1kg/m2 vs 39.2kg/m2, p=.02). Only two normal weight or overweight patients (2.6%) did not successfully map, while 28.5% of women with super morbid obesity (BMI>50kg/m2) did not map successfully. Of the super morbidly obese patients that mapped, only 3/7 (57.1%) mapped bilaterally. Patients that did not map had significantly longer procedure time by 35 minutes (192 vs 157 minutes, p Download : Download high-res image (147KB) Download : Download full-size image Conclusions: Patients with failed sentinel lymph node identification had a higher mean BMI and longer procedure time, with the highest rates of failed mapping found in super morbidly obese patients. The current results may aide in the selection of surgical staging methods and the preoperative counseling for patients, particularly those with BMI >50kg/m2.

Purpose: This surgical window of opportunity (window) study assessed the short-term effect of medroxyprogesterone acetate (MPA) alone versus MPA plus the histone deacetylase (HDAC) inhibitor entinostat on regulation of progesterone receptor (PR) in women with newly diagnosed endometrioid endometrial adenocarcinoma. Patients and Methods: This multisite, randomized, open-label surgical window study treated women intramuscularly on day 1 with 400 mg MPA. Entinostat given 5 mg by mouth on days 1, 8, and 15 was randomly assigned with equal probability. Surgery followed on days 21–24. Pretreatment and posttreatment tissue was assessed for PR H-scores, Ki-67 levels, and histologic response. Results: Fifty patients were accrued in 4 months; 22 and 20 participants had PR evaluable pretreatment and posttreatment slides in the MPA and MPA/entinostat arms, respectively. Median posttreatment PR H-scores were significantly lower than pretreatment H-scores in both arms but did not differ significantly (MPA: 247 vs. 27, MPA/entinostat 260 vs. 23, respectively, P = 0.87). Decreased Ki-67 was shown in 90% treated with MPA/entinostat compared with 68% treated with MPA alone (P = 0.13). Median PR H-score decreases were larger when Ki-67 was decreased (208) versus not decreased (45). The decrease in PR pretreatment versus posttreatment was associated with loss of Ki-67 nuclear staining, consistent with reduced cellular proliferation (P < 0.008). Conclusions: This surgical window trial rapidly accrued in a multisite setting and evaluated PR as its primary endpoint and Ki-67 as secondary endpoint. Despite no immediate effect of entinostat on PR in this short-term study, lessons learned can inform future window and treatment trials.

Airway management of the critically ill cardiac patient poses unique challenges to the clinician. It requires not only the skills to rapidly manage what may be a difficult airway scenario, but also the ability to anticipate and respond to the complex hemodynamic physiology of patients in varying degrees of cardiogenic shock or cardiac failure. Additionally, special attention must be paid to the pharmacologic management of the cardiac patient requiring advanced airway management. Understanding the hemodynamic derangements that can occur prior to and immediately after intubation of this patient population will set you up for safe and successful airway management.

Cardiac biomarkers are an important tool for diagnosing cardiac diseases in both human and veterinary patients. Serum concentrations of N-terminal probrain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) have been used to indicate the presence of various cardiac diseases including hypertrophic cardiomyopathy (HCM) in various species including humans. However, these cardiac biomarkers have not been established as a diagnostic tool for detecting cardiac disease in rhesus macaques. In the rhesus macaque colony at the California National Primate Research Center, naturally occurring HCM and various other cardiac diseases have been identified. In this study, commercially available assays were used to measure serum cTnI and NT-proBNP concentrations to evaluate their utility as a diagnostic screening tool for cardiac diseases in rhesus macaques. This study revealed that the serum cTnI concentration was significantly higher in animals with echocardiographically apparent cardiac disease as compared with the animals that had no cardiac structural and functional changes (the control group). However, no significant differences were detected between animals with HCM and non-HCM cardiac disease. Because the area under the receiver operating characteristic curve was 0.81 when the serum cTnI was compared between the control and cardiac disease groups, serum cTnI was considered a moderately accurate test to predict the presence of cardiac disease. The optimal cut-off value of serum cTnI concentration for diagnosis of cardiac disease was 0.0085 ng/mL, with a sensitivity of 0.68 and specificity of 0.94. Significant but weak correlations were noted between the serum cTnI concentration and several echocardiographic parameters. Conversely, no significant differences in NT-proBNP concentrations were detected between animals with and without cardiac diseases. In conclusion, measurement of serum cTnI can be used to aid in diagnosing cardiac diseases in rhesus macaques. However, cTnI measurement does not replace echocardiographic evaluation to diagnose cardiac diseases in rhesus macaques due to the poor sensitivity of the assay and the weak correlation to with more established echocardiographic markers for cardiac disease.

The benefit of continuing medications to prevent or treat illness is often overlooked, since pregnant women tend to overestimate the teratogenic risk of medications. Pharmacists can serve as a resource to prescribers and pregnant women with their knowledge of the appropriate use and management of medications during pregnancy. Little information exists on the value women place on pharmacists' medication management during pregnancy.To assess pregnant women's perceptions of an ambulatory care clinical pharmacist (CP) medication review service during early pregnancy that provided education regarding the risks and benefits of medication use during pregnancy.This was a qualitative study of pregnant women using semistructured telephone interviews performed between December 12, 2018, and January 18, 2019, and conducted in an integrated health care delivery system. Potential participants were identified from CP encounter records. Consented English-speaking women aged ≥ 18 years participated in an up to 30-minute interview within 1 week of the CP encounter. Interviews were professionally transcribed and coded line by line using the constant comparison method with grounded theory used to gain insight into participants' perspectives.62 women were invited to participate in semistructured telephone interviews of whom 24 (39%) completed the interview. Three main themes emerged from the qualitative analysis: satisfaction with the service, comfort with medication use during pregnancy, and connectedness to the health care team. Overall, the CP medication review and education service was perceived positively by the participants. Participants reported satisfaction in the quality, timeliness, and convenience of the service and found it beneficial to have their medications reviewed early during pregnancy to assist in medication use decisions before their first obstetric visit.CP medication review provided a comforting, valuable service for women during early pregnancy when medication-taking decisions can feel exigent.This study was funded by Kaiser Permanente. The authors have nothing to disclose. Preliminary results were presented at the Mountain States Conference for Residents and Preceptors, May 2019, in Salt Lake City, UT.

Purpose: Fertility-related services in pediatric oncology are increasing, but barriers to care remain and few structured programs are described in the literature. Therefore, the study objectives were (1) to characterize fertility-related services in a large pediatric oncology center and (2) to discuss recommendations for fertility-related services across the pediatric cancer continuum. Methods: Medical records of all cases referred to our Fertility Preservation Clinic within a 3-year period were reviewed, which included 292 patients/survivors with malignant disease. Approximately half (n = 152/292, 52.1%) were cancer patients referred prior to treatment (n = 92/152) or while on active therapy (n = 60/152). The other half (n = 140/292; 47.9%) were survivors who had completed treatment. Results: Referrals more than doubled over 3 years. Most patients referred before treatment were offered and opted for FP (72.8% attempted; 58.9% completed). More male than female patients opted for FP (77.6% vs. 22.4%), but completion rates were higher among females (93.3% vs. 76.9%). Rates of FP before treatment did not increase over time (p =.752). Many patients on-treatment were referred for infertility risk counseling, demonstrating information/support needs in this group. Referred survivors questioned their fertility post-treatment and completed fertility assessments, indicating intact fertility among few (~ 15%). Conclusions: This review demonstrated the acceptance and increasing need for fertility-related services in pediatric oncology across the cancer continuum, including FP before treatment, counseling during treatment, and fertility assessment in survivorship. Based on our experiences, current recommendations are discussed and include standardized procedures, streamlined referrals, adequate communication/education (of providers and families), and meeting specific needs of young cancer patients/survivors.

Background: Long-QT syndrome (LQTS) is characterized by a prolonged heart rate–corrected QT interval (QTc). Genome-wide association studies identified common genetic variants that collectively explain ≈8% to 10% of QTc variation in the general population. Methods: Overall, 423 patients with LQT1, LQT2, or LQT3 were genotyped for 61 QTc-associated genetic variants used in a prototype QTc–polygenic risk score (QTc-PRS). A weighted QTc-PRS (range, 0–154.8 ms) was calculated for each patient, and the FHS (Framingham Heart Study) population-based reference cohort (n=853). Results: The average QTc-PRS in LQTS was 88.0±7.2 and explained only ≈2.0% of the QTc variability. The QTc-PRS in LQTS probands (n=137; 89.3±6.8) was significantly greater than both FHS controls (87.2±7.4, difference-in-means±SE: 2.1±0.7, P P P Conclusions: The QTc-PRS explained

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility. Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance ( P −8 ) near NOS1AP , KCNQ1 , and KLF12 , and 1 missense variant in KCNE1 (p.Asp85Asn) at the suggestive threshold ( P −6 ). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation ( h2SNP 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r g =0.40; P =3.2×10 −3 ). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls ( P P Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.

Hip fractures that occur in the elderly population continue to be a growing problem in communities. In this particular population, people 65 years and older, patients often have multiple comorbidities. These comorbidities cause challenges for a patient's optimization preoperatively and throughout the continuum of care. Although unplanned and traumatic, hip fracture patients can benefit from care organized in a comprehensive and standardized way. Having a hip fracture program that is driven by a multidisciplinary team approach has proved to decrease length of stay and promote positive outcomes for patients.