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Biliary dyskinesia (BD) is a well-established gallbladder pathology in adult patients and rates of cholecystectomy for BD continue to rise in the United States. Many pediatric patients with vague abdominal pain of variable duration are evaluated for biliary dyskinesia. It remains unknown which cohort of pediatric patients diagnosed with BD are most likely to have sustained improvement in symptoms following laparoscopic cholecystectomy. We aimed to determine whether cholecystectomy resulted in symptom relief and led to a reduction in the number of medical visits related to gastrointestinal (GI) symptoms after surgery. We performed a multi-institution retrospective review of all children

Background: Several reports have observed that cancer patients who recently underwent chemotherapy or surgery had a higher risk of severe events compared with patients without cancer. Limited data is available on outcomes in specific cancer types, as well as the impact of non-cytotoxic systemic treatment, such as targeted therapy and hormonal therapy on severe outcomes. We aim to identify whether active treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in breast cancer patients. Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, in both tertiary and non-tertiary centers. Patients must carry a diagnosis of breast cancer, and have a completed SARS-CoV-2 test between March 1st and April 30th, 2020. Chi-squared and Fisher’s exact tests were performed to compare the proportion of patients experiencing severe outcomes between treatment groups. Results: As of April 30, 2020, a total of 70 patients with breast cancer who had a positive SARS-COV-2 test were identified. Median age 64.5, median BMI 30.8, 62.9% (n=44) black, 27.1% (n=19) current/former smokers, HTN (n=52) and DM2 (n=22) were the most common comorbidities, and 12.9% (n=9) of patients had stage IV disease. Of these patients, 58.6% (n=41) were on hormonal treatment, and another 12.9% (n=9) were receiving other forms of systemic therapy (cytotoxic chemotherapy or targeted therapy). In terms of severe outcomes, 32.9% (n=23) of patients required hospitalization, 8.6% (n=6) required ICU admission with 7.1% (n=5) patients requiring intubation, 11.4% (n=8) of patients died. There was not a statistical difference in rate of severe outcomes (rate of hospitalization, ICU admission, intubation, and death) among breast cancer patients receiving active treatment (chemotherapy, targeted therapy, or hormonal therapy) vs those receiving no active treatment. There was also no difference in terms of severe outcomes by race. Conclusion: With an ongoing global COVID-19 pandemic, it is important to identify how the treatment and management of cancer impacts COVID-19 outcomes. This small cohort does not identify active treatment as a risk factor for increased rate of severe outcomes in patients with breast cancer. Further analyses describing impact of specific hormonal and chemotherapy regimens on risk of hospitalization and death will be completed by time of presentation. Citation Format: Karine Tawagi, Jeff Burton, Michael Lunski, Diana Maslov, John Cole. Breast cancer and COVID-19: Impact of active treatment on severe outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-47.

The updated VCOG‐CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG‐CTCAE v1.0 and v1.1 were consulted for input, and additional co‐authors sought for expansion and refinement of the adverse event (AE) categories. VCOG‐CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural‐specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision‐making process applied to determination of dose‐limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

Tumour stage has been demonstrated to have prognostic significance in canine oral malignant melanoma (OMM). Various evaluation techniques of positron emission tomography/computed tomography (PET/CT) have been reported for staging of head-and-neck tumours in people, but canine-specific data are limited, and reports for CT accuracy have been variable. In this prospective study, the head/neck of client-owned dogs with cytologically or histologically diagnosed OMM were imaged with 18 Fluorine-fluorodeoxyglucose (18 F-FDG) PET/ CT. Bilateral mandibular lymphadenectomy was performed for histopathologic assessment. Two evaluation techniques for CT and PET were applied by four independent observers. CT evaluation utilized both a standardized grading scheme and a subjective clinical interpretation. PET evaluation was first performed solely on 18 F-FDG-uptake in lymph nodes compared to background on a truncated scan excluding the oral cavity. Subsequently, the entire head/neck scan and standardized uptake value (SUV) measurements were available. Receiver operating characteristic analysis was performed with histopathology as gold standard. Twelve dogs completed the study and metastatic OMM was identified in six mandibular lymph nodes from five dogs. Of the CT-interpretation techniques, use of clinical grading performed best (sensitivity = 83% and specificity = 94%). Both PET techniques resulted in 100% sensitivity, but primary tumour site evaluation and use of SUV increased specificity from 78% to 94%. The SUVmax cut-point, 3.3, led to 100% sensitivity and 83% specificity. In this population of dogs, PET appeared to be highly sensitive but at risk of being less specific without use of appropriate parameters and thresholds.

Summary Objective Iron is emerging as a key player in aging-associated diseases due to its propensity for driving free radical formation. Studies examining the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. Our objective was to establish a direct relationship between excess iron and OA by administering iron dextran to a guinea pig strain with decreased propensity for developing this disease. Design Twenty, 12-week-old Strain 13 guinea pigs received either iron dextran or dextran control intraperitoneally once weekly for 4 weeks; termination occurred at 16 weeks of age. Iron levels were determined systemically (serum and liver) and within diarthrodial joints [femoral head articular cartilage and infrapatellar fat pads (IFPs) of knee joints]. One knee was collected to score structural changes associated with OA via microcomputed tomography (microCT) and histology using published grading schemes. Articular cartilage and IFPs were harvested from contralateral knees for gene expression analyses. Results Iron overload was confirmed systemically via increased serum iron and liver iron concentration. Articular cartilage and IFPs in the iron dextran group also had higher levels of iron. Excess iron worsened knee OA using both microCT and histologic scoring systems. Gene analyses revealed that exogenous iron altered the expression of iron trafficking proteins, select cytokines, and structural components of cartilage. Conclusion These results demonstrate that systemic iron overload caused cellular iron accumulation in the knee joint. This excess iron is associated with increased expression of local inflammatory mediators and early onset and progression of knee joint OA in Strain 13 animals.

Long working hours have been shown to negatively impact adverse events in health care. In this study, a retrospective correlational design was used to evaluate the relationship between working hours and near-miss medication error alerts. During a two-year period, 5372 nurses triggered 420,706 near-miss alerts on 9, 285, 786 medication administrations. Nurses who worked 60 h or more in a week yielded an average near-miss rate of 4.0% compared to 3.0% (

Purpose This study aimed to compare the proinsulin to C-peptide (PI:C) ratio in those with recent-onset type 1 diabetes versus those with no diabetes and to explore the effect of age on PI:C ratio. Methods Nineteen participants (n=9 with type 1 diabetes and n=10 with no diabetes) between 10 and 19 years of age were enrolled in a single-visit cross-sectional study and underwent blood collection after 10 hours fasting to measure proinsulin and C-peptide levels as well as other glycemic parameters. Results The median PI:C ratio was significantly different between type 1 diabetes and nondiabetes groups (6.24% vs. 1.46%, Pl0.01). A significant negative correlation was seen between PI:C ratio and patient age after adjustment for duration of diabetes (r2=0.61, P=0.02) in the type 1 diabetes group. Conclusion Even in this narrow age window, a higher degree of β-cell dysfunction indicated by a higher PI:C ratio was seen in younger children.

OBJECTIVE To evaluate the use of transrectal ultrasonography (TRUS) for the assessment of prostatic tumors in dogs and to compare results for TRUS with results for other imaging modalities. ANIMALS 10 client-owned male dogs. PROCEDURES Client-owned dogs identified with prostatic carcinoma were enrolled. Fluoroscopy, transabdominal ultrasonography (TAUS), TRUS, and MRI were performed on all dogs. Tumor measurements, urethral penetration (identification of abnormal tissue within the urethral lumen), and tumor extension into the urinary tract were recorded for all imaging modalities. Agreement between results for MRI (considered the criterion-referenced standard) and results for other modalities were compared. RESULTS Median body weight of the 10 dogs was 26.3 kg (range, 9.4 to 49.5 kg). No complications were encountered during or after TRUS. Significant moderate to good agreements (intraclass correlation coefficients, 0.60 to 0.86) among TAUS, TRUS, fluoroscopy, and MRI were identified for tumor length and height. Assessments of urethral penetration and tumor extension into the bladder with TRUS did not differ significantly from those made with MRI and were superior in terms of absolute agreement with MRI when compared with those for TAUS. CONCLUSIONS AND CLINICAL RELEVANCE TRUS was successfully and safely used to evaluate prostatic carcinoma in dogs. There was moderate to good agreement with MRI results for tumor height and length measurements, and TRUS was found to be superior to TAUS for some assessments. Transrectal ultrasonography can be considered an adjunctive imaging modality for the performance of prostatic interventional procedures or assessment of response to treatment.

OBJECTIVE To describe the procedure of prostatic artery embolization (PAE) in dogs with prostatic carcinoma and to evaluate the short-term outcome for treated dogs. ANIMALS 20 client-owned dogs with prostatic carcinomas between May 2014 and July 2017. PROCEDURES In this prospective cohort study, dogs with carcinoma of the prostate underwent PAE with fluoroscopic guidance. Before and after PAE, dogs underwent CT and ultrasonographic examinations of the prostate, and each owner completed a questionnaire about the dog's clinical signs. Results for before versus after PAE were compared. RESULTS Prostatic artery embolization was successfully performed in all 20 dogs. Tenesmus, stranguria, and lethargy were significantly less common 30 days after PAE (n = 2, 1, and 0 dogs, respectively), compared with before PAE (9, 10, and 6 dogs, respectively). Median prostatic volume was significantly less 30 days after PAE (14.8 cm3; range, 0.4 to 48.1 cm3; interquartile [25th to 75th percentile] range, 6.7 to 19.5 cm3), compared with before PAE (21.7 cm3; range, 2.9 to 77.7 cm3; interquartile range, 11.0 to 35.1 cm3). All dogs had a reduction in prostatic volume after PAE, with a median prostatic volume loss of 39.4% (95% CI, 20.3% to 59.3%). CONCLUSIONS AND CLINICAL RELEVANCE Prostatic artery embolization was associated with decreased prostate volume and improved clinical signs in this cohort. The short-term response to PAE appears promising, and evaluation of the long-term impact on survival time is needed.

CASE DESCRIPTION 3 dogs with retroperitoneal masses (2 renal and 1 located near the diaphragm) were treated by percutaneous microwave ablation (MWA). CLINICAL FINDINGS Dogs between 11 and 13 years of age weighing between 13.7 and 43.8 kg had either a renal mass (n = 2) or a mass located in the caudodorsal aspect of the retroperitoneal space near the right side of the diaphragm (1). Cytology revealed that one of the renal masses and the mass located near the diaphragm were malignant neoplasias. Findings on cytologic evaluation of a sample of the other renal mass was nondiagnostic. Maximum mass diameters ranged between 1.4 and 2.5 cm. TREATMENT AND OUTCOME All dogs were treated by percutaneous MWA. Probes were directed into tumors by use of ultrasound and CT guidance, and microwave energy was applied to each mass. Findings on imaging of each mass following MWA was consistent with successful treatment. No intraprocedural or major postprocedural complications occurred, and all dogs were discharged from the hospital within 3 days of treatment. Two dogs died at 3 and 21 months after MWA with no known local recurrence; 1 dog was still alive 64 months after treatment. CLINICAL RELEVANCE Although the indications for MWA in the treatment of neoplasia in companion animals are limited, the outcomes of dogs in the present report provided preliminary evidence that percutaneous MWA can be safely used to effectively treat retroperitoneal neoplasia. This procedure was successfully performed with image guidance in all 3 dogs.

Introduction Exercise usually results in less weight loss than expected. This suggests increased energy intake and/or deceased expenditure counteract the energy deficit induced by exercise. The aim of this study was to evaluate changes in components of daily energy expenditure (doubly labeled water and room calorimetry) after 24 wk of exercise training with two doses of aerobic exercise. Methods This was an ancillary study in 42 (29 women, 13 men) sedentary, middle-age (47.8 ± 12.5 yr) individuals with obesity (35 ± 3.7 kg·m-2) enrolled in the Examination of Mechanisms of Exercise-induced Weight Compensation study. Subjects were randomized to three groups: healthy living control group (n = 13), aerobic exercise that expended 8 kcal·kg-1 of body weight per week (8 KKW, n = 14), or aerobic exercise that expended 20 kcal per kilogram of weight per week (20 KKW, n = 15). Total daily energy expenditure (TDEE) was measured in free-living condition by doubly labeled water and in sedentary conditions in a metabolic chamber over 24 h (24EE). Energy intake was calculated over 14 d from TDEE before and after the intervention using the intake-balance method. Results Significant weight loss occurred with 20 KKW (-2.1 ± 0.7 kg, P = 0.04) but was only half of expected. In the 20 KKW group free-living TDEE increased by ~4% (P = 0.03), which is attributed to the increased exercise energy expenditure (P = 0.001), while 24EE in the chamber decreased by ~4% (P = 0.04). Aerobic exercise at 8 KKW did not induce weight change, and there was no significant change in any component of EE. There was no significant change in energy intake for any group (P = 0.53). Conclusions Structured aerobic exercise at a dose of 20 KKW produced less weight loss than expected possibly due to behavioral adaptations leading to reduced 24EE in a metabolic chamber without any change in energy intake.

Superior gluteal artery rupture is a rare complication of trauma but a significant one with potential for substantial morbidity and mortality. This case demonstrates the importance of early diagnosis and treatment of this injury pattern. Endovascular embolisation has become the most effective treatment for pelvic haemorrhage. Acknowledgement of this rare injury as a differential diagnosis is vital to facilitate rapid diagnosis and appropriate treatment.

Zoledronic acid (ZOL) is an intravenous bisphosphonate indicated for the use of hypercalcemia of malignancy and management of bony metastases. Its therapeutic effect lies in the targeting of malignant osteoclasts; however, administration can be associated with renal toxicity. The objective of this retrospective study was to evaluate the frequency and severity of acute kidney injury (AKI) following ZOL administration in a cohort of cancer-bearing dogs. A pharmacy search was conducted to identify dogs that received a dose of ZOL between June 2016 and July 2019. Inclusion criteria included baseline and post-treatment chemistry panels. Medical records were reviewed to obtain clinical data including signalment, dose, dosage, number of treatments administered, and changes in renal function. Forty-four dogs met the inclusion criteria. Median number of doses administered was three [interquartile range (IQR), 2–5]. The median highest creatinine value occurred after a median of one dose (IQR, 1–2 doses) compared with the median highest value of blood urea nitrogen, phosphorus, and potassium, which occurred after a median of two doses (IQR, 1–3). Six (13.6%) dogs developed an AKI, and one dog (2.3%) had progression of an existing azotemia after treatment with ZOL was initiated. Two dogs (4.5%) had ZOL treatment discontinued secondary to development of azotemia. Use of concurrent administration of non-steroidal anti-inflammatory drugs or anesthesia did not significantly increase the risk of AKI in this cohort of dogs. Acute kidney injury is observed infrequently in cancer-bearing dogs treated with ZOL and is generally mild to moderate in severity; discontinuation of ZOL due to AKI is uncommon.

Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. Patients and Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively. Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

We update an evidence-based clinical practice guideline for the administration of propofol for emergency department procedural sedation. Both the unique considerations of using this drug in the pediatric population and the substantial new research warrant revision of the 2007 advisory. We discuss the indications, contraindications, personnel requirements, monitoring, dosing, coadministered medications, and adverse events for propofol sedation.

BACKGROUND: An ability to switch between primarily oxidizing fat in the fasted state to carbohydrate in the fed state, termed metabolic flexibility, is associated with insulin sensitivity. Metabolic flexibility has been explored previously in women with polycystic ovary syndrome (PCOS), yet the independent or synergistic contributions of androgen excess and/or insulin resistance is not yet known. Therefore, the purpose of this article was to characterize metabolic flexibility in women with PCOS compared to women of normal BMI, obesity, or type 2 diabetes (T2DM). METHODS: Eighty-six weight-stable women; thirty with either PCOS (n = 30), or fifty-six with obesity (n = 12), T2DM (n = 27), or normal BMI (n = 17) underwent a hyperinsulinemic euglycemic clamp and indirect calorimetry to measure insulin sensitivity and substrate oxidation via indirect calorimetry, respectively. RESULTS: All analyses were adjusted for differences in age, ethnicity, and BMI between groups. Women with PCOS were less metabolically flexible compared to healthy women with obesity (p

ObjectivesInforming research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results.DesignIn the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019.SettingUK stroke services.Participants3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond.ResultsOf those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email.ConclusionIt is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future.Trial registration numberISRCTN83290762; Post-results.

BACKGROUND: This is the largest and only multivariate study evaluating the difference in mortality from coronavirus disease 2019 (COVID-19) between patients with cancer and patients without cancer in the United States. The objective was to assess COVID-19 mortality rates in patients with cancer versus patients without cancer and uncover possible statistically significant characteristics contributing to mortality. METHODS: This retrospective study analyzed patients with cancer and patients without cancer who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 1 through April 30, 2020. This was a multicenter study in the state of Louisiana throughout the Ochsner Health System in both tertiary and nontertiary centers. Patients older than 18 years were eligible. Three hundred twelve patients with cancer were compared with 4833 patients without cancer. RESULTS: Mortality was found to be higher in the cancer group. Patients of advanced age with cancer had a significant increase in mortality (odds ratio [OR], 5.96; P < .001). Other significant risk factors for increased mortality were male sex (OR, 2.15), a history of chronic kidney disease (OR, 3.84), and obesity (OR, 1.30). In hospitalized patients with cancer, adverse vital signs on admission, decreased absolute lymphocyte counts, thrombocytopenia, elevated creatinine, lactic acidosis, and elevated procalcitonin all seemed to increase the risk of death. Among patients with cancer, active or progressive disease (P < .001) and recent therapy (OR, 2.34; 95% confidence interval, 1.08-5.08) were shown to increase mortality. CONCLUSIONS: Patients with cancer have increased mortality in the setting of infection with SARS-CoV-2 in comparison with patients without cancer. Patients with cancer who are 65 years of age or older and those with certain comorbidities have the greatest risk of death. Recent cancer-directed therapy and disease status also seem to play roles in mortality. LAY SUMMARY: This is the largest study of patients with cancer versus patients without cancer to date and is the first multivariate analysis study comparing these 2 patient populations. This study confirms the hypothesis that patients with cancer are at increased risk for mortality and that there are multiple characteristics posing the potential to risk-stratify these patients in the setting of a future outbreak.

Objective While many seroprevalence studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed, few are demographically representative. This investigation focused on defining the nature and frequency of symptomatic and asymptomatic SARS-CoV-2 infection in a representative, cross-sectional sample of communities in Louisiana, USA. Methods A sample of 4,778 adults from New Orleans and Baton Rouge, Louisiana were given a survey of symptoms and comorbidities, nasopharyngeal swab to test for an active infection (PCR), and blood draw to test for a past infection (immunoglobulin G). Odds ratios, cluster analysis, quantification of virus and antibody, and linear modeling were used to understand whether certain symptoms were associated with a positive test, how symptoms grouped together, whether virus or antibody varied by symptom status, and whether being symptomatic was different across the age span. Results Reported anosmia/ageusia was strongly associated with a positive test; 40.6% (93/229) tested positive versus 4.8% (218/4,549) positivity in those who did not report anosmia/ageusia (Common OR: 13.6; CI 10.1, 18.3). Of the people who tested positive, 47.3% (147/311) were completely asymptomatic. Symptom presentation clustered into three groups; low/no symptoms (0.4±0.9 average ±SD), highly symptomatic (7.5±1.9) or moderately symptomatic (4.0±1.5). Quantity of virus was lower in the asymptomatic versus symptomatic group (cycle number 23.3±8.3 versus 17.3±9.0, average ±SD; p, Graphical abstract Image 1

Even though current prescribing trends reveal that high-dose opioid prescribing and opioid prescribing in general has decreased, sustained efforts are needed to help providers adopt and maintain safe prescribing behaviors. The purpose of this four-year type 2 effectiveness-implementation hybrid stepped wedge cluster randomized trial is to: (1) compare the clinical and cost effectiveness of electronic medical record-based clinical decision support [EMR-CDS] versus additional integrated, collaborative behavioral health [EMR-CDS + BHI-CCM] for opioid management of patients with co-morbid chronic non-cancer pain with depression or anxiety; and (2) examine facilitators and barriers to implementing these interventions within 35 primary care clinics in a integrated delivery health system. The EMR-CDS alerts providers to employ opioid risk mitigation and safe prescribing practices at the point of care. The BHI-CCM consists of primary care embedded community health workers for case management; licensed clinical social workers for cognitive behavioral therapy, and a clinical pharmacist for medication management who provide care management via telemedicine (virtual video or audio only visits) under the guidance of a consulting psychiatrist. The primary outcome is reduction in the percentage of patients with average daily opioid dose ≥50 mg morphine equivalent. Secondary outcomes include changes in service utilization, patient reported outcomes and processes of care. The investigators anticipate that study results will elucidate the role of technology versus care team optimization in changing opioid prescribing behaviors. The investigators further anticipate that integrated mental/behavioral health care will increase value-based care and the efficiency with which guideline concordant care is delivered.

Background: Doxorubicin (DOX) is one of the most effective chemotherapeutics for canine high-grade lymphoma. In addition to dose-dependent chronic cardiotoxicity, DOX can trigger acute cardiac arrhythmias during drug infusion. Diphenhydramine premedication is commonly used, as histamine release is a proposed mechanism for DOX-associated arrhythmogenesis. Hypothesis/Objectives: The study objectives were to evaluate the incidence and severity of DOX infusion-related cardiac arrhythmias in dogs with high-grade lymphoma and evaluate the effect of diphenhydramine premedication on arrhythmia frequency and severity during and after DOX infusion. Animals: Twenty-two client-owned dogs with cytologically/histopathologically confirmed high-grade lymphoma were recruited, of which 19 were enrolled and 9 completed the study. Methods: Dogs were screened by echocardiogram and concurrent electrocardiogram for this randomized prospective crossover study. Group A received no premedication for DOX #1 and was premedicated with diphenhydramine for DOX #2; Group B received diphenhydramine with DOX #1 and no premedication for DOX #2. For both visits, Holter monitor data were collected for 1 h pre-DOX and 3 h post-DOX administration. Results: Nineteen dogs were enrolled and 9 dogs [Group A (5), Group B (4)] completed the protocol. There was no statistical difference between the DOX alone and DOX + diphenhydramine when evaluating the total number of ventricular premature complexes (VPCs, P = 0.34), change in VPCs/hour (P = 0.25), total number of atrial premature complexes (APCs, P = 0.5), change in APCs/hour (P = 0.06), or ventricular arrhythmia severity score (P > 0.99). Conclusions and clinical importance: This study demonstrates that in these dogs with rigorous pretreatment cardiovascular screening, DOX infusion did not induce significant arrhythmias. Furthermore, these data suggest that, with this screening approach, diphenhydramine may not alter the arrhythmia number or severity in canine DOX recipients.

Background Obesity affects nearly half of adults in the United States and is contributing substantially to a pandemic of obesity-associated chronic conditions such as type 2 diabetes, hypertension, and arthritis. The obesity-associated chronic condition pandemic is particularly severe in low-income, medically underserved, predominantly African-American areas in the southern United States. Little is known regarding the impact of geographic, income, and racial disparities in continuity of care on major health outcomes for patients with obesity-associated chronic conditions. Objective The aim of this study is to assess, among patients with obesity-associated chronic conditions, and within this group, patients with type 2 diabetes, (1) whether continuity of care is associated with lower overall and potentially preventable emergency department and hospital utilization, (2) the effect of geographic, income, and racial disparities on continuity of care and on health care utilization, (3) whether continuity of care particularly protects individuals at risk for disparities from adverse health outcomes, and (4) whether characteristics of health systems are associated with higher continuity of care and better outcomes. Methods Using 2015-2018 data from 4 practice-based research networks participating in the Southern Obesity and Diabetes Coalition, we will conduct a retrospective cohort analysis and distributed meta-analysis. Patients with obesity-associated chronic conditions and with type 2 diabetes will be assessed within each health system, following a standardized study protocol. The primary study outcomes are overall and preventable emergency department visits and hospitalizations. Continuity of care will be calculated at the facility level using a modified version of the Bice-Boxerman continuity of care index. Race will be assessed using electronic medical record data. Residence in a low-income area or a health professional shortage area respectively will be assessed by linking patient residence ZIP codes to the Centers for Medicare & Medicaid Services database. Results In 4 regional health systems across Tennessee, Mississippi, Louisiana, and Arkansas, a total of 53 adult hospitals were included in the study. A total of 147,889 patients with obesity-associated chronic conditions who met study criteria were identified in these health systems, of which 45,453 patients met the type 2 diabetes criteria for inclusion. Results are expected by the end of 2020. Conclusions This study should reveal whether health system efforts to increase continuity of care for patients with obesity and diabetes have potential to improve outcomes and reduce costs. Analyzing disparities in continuity of care and their effect on major health outcomes can help demonstrate how to improve care and use of health care resources for vulnerable patients with obesity-associated chronic conditions, and within this group, patients with type 2 diabetes. Better understanding of the association between continuity and health care utilization for these vulnerable populations will contribute to the development of higher-value health systems in the southern United States. International Registered Report Identifier (IRRID) DERR1-10.2196/20788

Background Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. Methods In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. Results A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). Conclusions In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.

Background: Decreasing selection and consumption of sodium and added sugars in the school cafeteria setting is important to provide optimal nutrition to children. Objective: To determine if Louisiana (LA) Health, a school-based obesity prevention intervention, could successfully reduce children’s selection and consumption of sodium and added sugars during school lunches vs. the control group. Design: Food selection, consumption, and plate waste from student lunches (3 consecutive days) in 33 public schools in rural Louisiana were collected and analyzed using the digital photography of foods method at baseline and after a 28-month obesity prevention intervention (LA Health) beginning in 4th-6th grade (87% of children received free or reduced cost lunch). Selection and consumption of energy, added sugar, and sodium was objectively measured using digital photography of foods. Mixed models, including Race and BMI, were used to determine if change in selection and consumption differed by group. Results: Sodium decreased for selection (−233.1±89.4 mg/lunch, p=0.04) and consumption (−206.3±65.9, mg/lunch) in the intervention (vs. control) by month 18, and in consumption by month 28 (−153.5±66.9 mg/lunch, p=0.03). Change in added sugar consumption decreased in the intervention (vs. control) at month 18 (−3.7±1.6, p=0.05) and at month 28 (−3.5±1.6 tsp/lunch, p=0.05). Conclusions: LA Health decreased the amount of added sugar and sodium selected and consumed, but not plate waste, by month 28. Results highlight the importance of long-term interventions and policies targeting provision and selection to improve dietary patterns in children, with less focus on plate waste. Trial Registration: clinicaltrials.gov NCT00289315 https://clinicaltrials.gov/ct2/show/NCT00289315?term=LA+Health&rank=1

BACKGROUND: U.S. health systems, incentivized by financial penalties, are designing programs such as case management to reduce service utilization among high-cost, high-need populations. The major challenge is identifying patients for whom targeted programs are most effective for achieving desired outcomes. OBJECTIVE: To evaluate a health system’s outpatient complex case management (OPCM) for Medicare beneficiaries for patients overall and for high-risk patients using system-tailored taxonomy, and examine whether OPCM lowers service utilization and healthcare costs. DESIGN: Retrospective case-control study using Medicare data collected between 2012 and 2016 for Ochsner Health System. PARTICIPANTS: Super-utilizers defined as Medicare patients with at least two hospital/ED encounters within 180 days of the index date including the index event. INTERVENTION: Outpatient complex case management. MAIN MEASURES: Propensity score-adjusted multivariable logistic regression analysis was conducted for primary outcomes (90-day hospital readmission; 90-day ED re-visit). A difference-in-difference analysis was conducted to examine changes in per membership per month (PMPM) costs based on OPCM exposure. KEY RESULTS: Among 18,882 patients, 1197 (6.3%) were identified as “high-risk” and 470 (2.5%) were OPCM participants with median enrollment of 49 days. High-risk OPCM cases compared to high-risk controls had lower odds of 90-day hospital readmissions (0.81 [0.40–1.61], non-significant) and lower odds of 90-day ED re-visits (0.50 [0.32–0.79]). Non-high-risk OPCM cases compared to non-high-risk controls had lower odds of 90-day hospital readmissions (0.20 [0.11–0.36]) and 90-day ED re-visits (0.66 [0.47–0.94]). Among OPCM cases, high-risk patients compared to non-high-risk patients had greater odds of 90-day hospital readmissions (4.44 [1.87–10.54]); however, there was no difference in 90-day ED re-visits (0.99 [0.58–1.68]). Overall, OPCM cases had lower total cost of care compared to controls (PMPM mean [SD]: − $1037.71 [188.18]). CONCLUSIONS: Use of risk stratification taxonomy for super-utilizers can identify patients most likely to benefit from case management. Future studies must further examine which OPCM components drive improvements in select outcome for specific populations.

This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing.Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use.Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P.001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change.EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed.

Objective Determine whether an individual is at greater risk of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection because of their community or their individual risk factors. Study design and setting 4,752 records from two large prevalence studies in New Orleans and Baton Rouge, Louisiana were used to assess whether zip code tabulation areas (ZCTA)-level area deprivation index (ADI) or individual factors accounted for risk of infection. Logistic regression models assessed associations of individual-level demographic and socioeconomic factors and the zip code-level ADI with SARS-CoV-2 infection. Results In the unadjusted model, there were increased odds of infection among participants residing in high versus low ADI (both cities) and high versus mid-level ADI (Baton Rouge only) zip codes. When individual-level covariates were included, the odds of infection remained higher only among Baton Rouge participants who resided in high versus mid-level ADI ZCTAs. Several individual factors contributed to infection risk. After adjustment for ADI, race and age (Baton Rouge) and race, marital status, household size, and comorbidities (New Orleans) were significant. Conclusions While higher ADI was associated with higher risk of SARS-CoV-2 infection, individual-level participant characteristics accounted for a significant proportion of this association. Additionally, stage of the pandemic may affect individual risk factors for infection.

Background: Prepregnancy maternal obesity and excessive weight gain during pregnancy lead to significant morbidities in mothers and their children. Mothers who never return to their prepregnancy weight begin subsequent pregnancies at a greater weight and have a larger propensity for excess gestational weight gain and postpartum weight retention. Methods: In this pilot study, 40 postpartum women credentialed to receive postpartum women, infants, and children (WIC) service were randomized to usual care (“WIC Moms”) or a personalized health intervention delivered via a SmartPhone (“E-Moms”). Assessments, including body weight, vital signs, circumferences, and body composition, were completed at week 0 (6–8 weeks postpartum), week 8, and week 16. Results: Results are presented as change from week 0 at 16. As per the completers analysis, body weight change was not different between the groups (WIC Moms vs. E-Moms; 1.8 ± 0.9 vs. −0.1 ± 0.9 kg; p = 0.10), neither was the change in percent body fat (1.7 ...

The goals of this retrospective study were to determine the patient characteristics of dogs with high-grade primary mediastinal lymphoma and to determine outcome and associated prognostic factors. A total of 42 dogs were identified, in which 36 received treatment and had follow-up information available. The most common clinical signs included lethargy, anorexia and polyuria/polydipsia. Hypercalcemia and pleural effusion were common findings at diagnosis. The phenotype was almost exclusively T-cell, most often in association with lymphoblastic cytomorphology as defined by the World Health Organization (WHO) lymphoma classification scheme. The overall progression-free survival (PFS) and overall survival (OS) were 133 and 183 days, respectively. Treatment with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) protocol was associated with an improved PFS (144 days) and OS (194 days) when compared with dogs that received other medical therapies (P = .005 and P = .002, respectively); the absence of pleural effusion at diagnosis was associated with an increased OS but not PFS. These results suggest that while the prognosis for dogs with mediastinal lymphoma is poor, survival may be improved with treatment using a CHOP-based protocol.

Background: Calorie restriction (CR) influences aging processes and extends average and maximal life spans. The CALERIE 2 (Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy Phase 2) study was the first randomized clinical trial to examine the metabolic and psychological effects of CR in nonobese humans.Objective: We conducted a 2-y follow-up study of adults who underwent 2 y of CR or ad libitum (control) consumption and determined whether weight loss and acquired behaviors persisted after the study ended when participants determined their own lifestyle behaviors.Design: In this prospective, longitudinal study, we assessed differences in weight, body composition, psychological function, and energy expenditure in 39 nonobese [body mass index (in kg/m2): 22-28] men and women (25% CR: n = 24; control: n = 15) 12 and 24 mo after they completed the CALERIE 2 study at Pennington Biomedical.Results: Of 39 participants who were in the follow-up study, 29 subjects (CR: n = 18; control: n = 11) completed all visits at follow-up months 12 and 24. After the CR intervention, a mean ± SEM weight loss of 9.0 ± 0.6 kg was observed in the CR group, in which only 54% of the weight was regained 2 y later. Despite such a regain, weight, the percentage of body fat, and fat mass remained significantly reduced from baseline throughout follow-up and remained significantly less than in the control group (P < 0.05). At follow-up, the CR group retained higher degrees of dietary restraint and avoidance of certain foods.Conclusion: After a 2-y intensive CR intervention, ∼50% of CR-induced weight loss was maintained 2 y later, which was probably the result of lasting effects on acquired behaviors and dietary restraint. This trial was registered at clinicaltrials.gov as NCT00943215.

Context Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Objective Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Design Cross-sectional study. Setting Academic research center. Participants Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Main Outcome Total daily energy expenditure (TDEE) determined by DLW. Results TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Conclusions Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation.

Background Oral chemotherapy agents are frequently compounded in veterinary medicine however, the potency of some formulations have been shown to vary from that of Food and Drug Administration (FDA)-approved products. Aims The objective of this study was to evaluate the potency and stability of three compounded oral chemotherapeutics commonly prescribed to be administered over time. Materials & Methods Compounded chlorambucil 1 mg, cyclophosphamide 5 mg and melphalan 1 mg were obtained and for potency tested upon receipt and 6 weeks later. Results Potency ranged from 71 to 104% for chlorambucil and 58 to 109% for melphalan; 1/4 and 2/4 samples were

Recent news stories have explicitly stated that patients with symptoms of COVID‐19 were “turned away” from emergency departments. This commentary addresses these serious allegations, with an attempt to provide the perspective of academic emergency departments (EDs) around the Nation. The overarching point we wish to make is that academic EDs never deny emergency care to any person.

Our lack of understanding of the immune microenvironment in canine osteosarcoma (cOSA) has limited the identification of potential immunotherapeutic targets. In particular, our ability to utilize readily available tissue from a dog's primary tumour to predict the type and extent of immune response in their pulmonary metastatic lesions is unknown. We, therefore, collected 21 matched pairs of primary tumours and pulmonary metastatic lesions from dogs with OSA and performed immunohistochemistry to quantify T-lymphocyte (CD3), FOXP3+ cell, B-lymphocyte (Pax-5), and CD204+ macrophage infiltration. We found that T-lymphocytes and FOXP3+ infiltrates in primary tumours positively correlated with that of metastatic lesions (ρ = 0.512, P = 0.038 and ρ = 0.698, P = 0.007, respectively), while a strong trend existed for CD204+ infiltrates (ρ = 0.404, P = 0.087). We also observed T- and B-lymphocytes, and CD204+ macrophages to be significantly higher in a dog's pulmonary metastasis compared to their primary tumour (P = 0.018, P = 0.018, P = 0.016, respectively), while FOXP3+ cells were only significantly higher in metastases when all primary tumour and metastasis lesions were compared without pairing (P = 0.036). Together, these findings suggest that the metastatic immune microenvironment may be influenced by that of the primary cOSA, and that primary tumour immune biomarkers could potentially be applied to predict immunotherapeutic responses in gross metastatic disease. We, therefore, provide a rationale for the treatment of cOSA pulmonary metastases with immunotherapeutics that enhance the anti-tumour activity of these immune cells, particularly in dogs with moderate to high immune cell infiltration in their primary tumours.

Background: Inadequate pain management and undertreatment remain a serious clinical issue among hospitalized adults, contributing to chronic pain syndromes and opioid dependency. Implementation of individual pain care interventions has been insufficient to improve pain care quality. The purpose of this interprofessional, patient-centered project was to implement a 6-component bundle of evidence-based pain management strategies to improve patients’ perception of pain care quality and 24-hour pain experience outcomes. Methods: A quasi-experimental design was used to test the effect of a bundled pain management intervention on 3 medical surgical units. Baseline outcomes using the Pain Care Quality-Interdisciplinary (PainCQ-I(©)) and Pain Care Quality-Nursing (PainCQ-N(©)) surveys were measured monthly for 4 months preintervention and 30 months postintervention. Results: A convenience sample of 846 patients was analyzed. The effect of the intervention on pain outcomes could not be tested because unit-based adherence did not meet the goal of 80%. A subsample of 70.2% (594/846) of participants was sufficient to complete a 3-group analysis of preintervention and postintervention participants with confirmed intervention adherence. Participants in the postintervention group who received all 6 components (n=65) had significantly higher odds of higher PainCQ(©) scores than those in the preintervention group (n=141) (PainCQ-I(©): odds ratio [OR] 2.61, 95% confidence interval [CI] 1.54-4.42; PainCQ-N(©): OR 3.82, 95% CI 2.06-7.09) or those in the postintervention group receiving ≤5 components (n=388) (PainCQ-I(©): OR 2.52, 95% CI 1.57-4.03; PainCQ-N(©): OR 3.84, 95% CI 2.17-6.80). Conclusion: Medical surgical patients participating in this study who received the bundled 6-component intervention reported significantly higher levels of perceived pain care quality, suggesting that a bundled approach may be more beneficial than unstandardized strategies.

Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by inactivation of ADAMTS13. It is characterized by thrombocytopenia and microangiopathic hemolytic anemia. Previous studies have produced conflicting data regarding seasonal association of TTP diagnoses. This study evaluated the seasonal distribution of acute TTP in southern Louisiana. Additionally, this study timeline overlapped with the initiation of a new screening protocol for ADAMTS13 testing. Study Design and Methods: A retrospective analysis of patients receiving ADAMTS13 testing at Ochsner Medical Center from January 2010 to December 2017 was performed. TTP patient episodes were defined by ADAMTS13 activity

As part of community-engaged educational partnerships, students are paired with community members in instructor-focused activities linked to an academic curriculum. Scholars widely agree that this type of approach can significantly improve the learning experience for students while simultaneously having a positive impact on the community. As faculty in higher education implement this pedagogical tool, it is a natural progression for it to expand into online classrooms. In particular, while there is a growing body of research related to community engagement in online healthcare and science-related fields, less research exists on the incorporation of community engagement in other types of online pre-professional courses. This paper explores student perceptions in online pre-professional undergraduate courses in the legal studies and human resources fields in which community engagement projects were utilized. These experiences should lead to a deeper understanding of the benefits and challenges of community-engaged online classrooms and give guidance for developing future projects.

Introduction Patients undergoing radiotherapy for pelvic cancers will often experience acute and late toxicity which can result in symptoms which have a significant impact on psychosocial functioning and quality of life. Having written information regarding these symptoms enables informed decision-making and ongoing support. Transgender and non-binary communities are a marginalised but steadily growing subsection of the radiotherapy patient population yet their needs differ from those of the general population. This study aimed to evaluate the relevance of the pelvic radiotherapy patient information booklets with regard to this communities. Methods An online survey was distributed via social media to evaluate the perceptions of these communities of four commonly distributed pelvic radiotherapy information booklets. Results There were 19 full responses and most participants expressed discomfort regarding being provided with (11/19) or picking up (10/19) the booklets. Although most (11/19) agreed that the material in the booklets was relevant, the same number felt that the wording was not. Some of the language and assumptions made regarding the transgender and non-binary communities were incorrect and had the potential to cause distress. Conclusion The importance of providing guidance and support to these communities was identified. Implications for practice Further research is required to establish how best to provide inclusive patient information for transgender and non-binary individuals.

Author(s): Jennings, Lee A; Turner, Maurice; Keebler, Chandra; Burton, Carl H; Romero, Tahmineh; Wenger, Neil S; Reuben, David B | Abstract: Background/objectivesAlthough Alzheimer disease and other dementias are life limiting, only a minority of these patients or their proxy decision makers participate in advance care planning. We describe end-of-life care preferences and acute care and hospice use in the last 6 months of life for persons enrolled in a comprehensive dementia care management program.DesignObservational, retrospective cohort.SettingUrban, academic medical center.ParticipantsA total of 322 persons enrolled in dementia care management after July 1, 2012, who died before July 1, 2016.InterventionDementia care comanagement model using nurse practitioners partnered with primary care providers and community organizations to provide comprehensive dementia care, including advance care planning.MeasurementsAdvance care preferences, use of Physician Orders for Life Sustaining Treatment (POLST), hospice enrollment, and hospitalizations and emergency department (ED) visits in the last 6 months of life obtained from electronic health record data.ResultsNearly all decedents (99.7%, N = 321) had a goals-of-care conversation documented (median = 3 conversations; interquartile range = 2-4 conversations), and 64% had advance care preferences recorded. Among those with recorded preferences, 88% indicated do not resuscitate, 48% limited medical interventions, and 35% chose comfort-focused care. Most patients (89%) specified limited artificial nutrition, including withholding feeding tubes. Over half (54%) had no hospitalizations or ED visits in the last 6 months of life, and intensive care unit stays were rare (5% of decedents). Overall, 69% died on hospice. Decedents who had completed a POLST were more likely to die in hospice care (74% vs 62%; P = .03) and die at home (70% vs 59%; P = .04).ConclusionsEnrollees in a comprehensive dementia care comanagement program had high engagement in advance care planning, high rates of hospice use, and low acute care utilization near the end of life. Wider implementation of such programs may improve end-of-life care for persons with dementia. J Am Geriatr Soc 67:443-448, 2019.

Background Intensive lifestyle interventions in pregnancy have shown success in limiting gestational weight gain, but the effects on mood and quality of life in pregnancy and postpartum are less known. The purpose was to quantify changes in mental and physical quality of life and depressive symptoms across pregnancy and the postpartum period, to determine the association between gestational weight gain and change in mood and quality of life, and to assess the effect of a behavioral intervention targeting excess gestational weight gain on these outcomes. Methods A three group parallel-arm randomized controlled pilot trial of 54 pregnant women who were overweight or obese was conducted to test whether the SmartMoms® intervention decreased the proportion of women with excess gestational weight gain. Individuals randomized to Usual Care (n = 17) did not receive any weight management services from interventionists. Individuals randomized to the SmartMoms® intervention (n = 37) were provided with behavioral weight management counseling by interventionists either in clinic (In-Person, n = 18) or remotely through a smartphone application (Phone, n = 19). In a subset of 43 women, mood and mental and physical quality of life were assessed with the Beck Depression Inventory-II and the Rand 12-Item short form, respectively, in early pregnancy, late pregnancy, 1–2 months postpartum, and 12 months postpartum. Results The SmartMoms® intervention and Usual Care groups had higher depressive symptoms (p

Author(s): Griffin, Maureen A; Culp, William TN; Giuffrida, Michelle A; Ellis, Peter; Tuohy, Joanne; Perry, James A; Gedney, Allison; Lux, Cassie N; Milovancev, Milan; Wallace, Mandy L; Hash, Jonathan; Mathews, Kyle; Liptak, Julius M; Selmic, Laura E; Singh, Ameet; Palm, Carrie A; Balsa, Ingrid M; Mayhew, Philipp D; Steffey, Michele A; Rebhun, Robert B; Burton, Jenna H; Kent, Michael S | Abstract: BackgroundLower urinary tract transitional cell carcinoma (TCC) is an important but rarely described disease of cats.ObjectivesTo report the clinical characteristics, treatments, and outcomes in a cohort of cats with lower urinary tract TCC and to test identified variables for prognostic relevance.AnimalsOne-hundred eighteen client-owned cats with lower urinary tract carcinoma.MethodsMedical records were retrospectively reviewed to obtain information regarding clinical characteristics, treatments, and outcomes. Recorded variables were analyzed statistically.ResultsMedian age of affected cats was 15 years (range, 5.0-20.8 years) and median duration of clinical signs was 30 days (range, 0-730 days). The trigone was the most common tumor location (32/118; 27.1%) as assessed by ultrasound examination, cystoscopy, or both. Treatment was carried out in 73 of 118 (61.9%) cats. Metastatic disease was documented in 25 of 118 (21.2%) cats. Median progression-free survival and survival time for all cats were 113 days (95% confidence interval [CI], 69-153) and 155 days (95% CI, 110-222), respectively. Survival increased significantly (P l .001) when comparing cats across the ordered treatment groups: no treatment, treatment without partial cystectomy, and treatment with partial cystectomy. Partial cystectomy (hazard ratio [HR], 0.31; 95% CI, 0.17-0.87) and treatment with nonsteroidal anti-inflammatory drugs (HR, 0.55; 95% CI, 0.33-0.93) were significantly associated with longer survival times.Conclusions and clinical importanceThe results support treatment using partial cystectomy and NSAIDs in cats with TCC.

Purpose: Only one chemical class of topoisomerase I (TOP1) inhibitors is FDA approved, the camptothecins with irinotecan and topotecan widely used. Because of their limitations (chemical instability, drug efflux-mediated resistance, and diarrhea), novel TOP1 inhibitors are warranted. Indenoisoquinoline non-camptothecin topoisomerase I (TOP1) inhibitors overcome chemical instability and drug resistance that limit camptothecin use. Three indenoisoquinolines, LMP400 (indotecan), LMP776 (indimitecan), and LMP744, were examined in a phase I study for lymphoma-bearing dogs to evaluate differential efficacy, pharmacodynamics, toxicology, and pharmacokinetics. Experimental Design: Eighty-four client-owned dogs with lymphomas were enrolled in dose-escalation cohorts for each indenoisoquinoline, with an expansion phase for LMP744. Efficacy, tolerability, pharmacokinetics, and target engagement were determined. Results: The MTDs were 17.5 mg/m2 for LMP 776 and 100 mg/m2 for LMP744; bone marrow toxicity was dose-limiting; up to 65 mg/m2 LMP400 was well-tolerated and MTD was not reached. None of the drugs induced notable diarrhea. Sustained tumor accumulation was observed for LMP744; γH2AX induction was demonstrated in tumors 2 and 6 hours after treatment; a decrease in TOP1 protein was observed in most lymphoma samples across all compounds and dose levels, which is consistent with the fact that tumor response was also observed at low doses LMP744. Objective responses were documented for all indenoisoquinolines; efficacy (13/19 dogs) was greatest for LMP744. Conclusions: These results demonstrate proof-of-mechanism for indenoisoquinoline TOP1 inhibitors supporting their further clinical development. They also highlight the value of the NCI Comparative Oncology Program (https://ccr.cancer.gov/Comparative-Oncology-Program) for evaluating novel therapies in immunocompetent pets with cancers.

Background A doxorubicin (DOX)-based chemotherapy protocol, CHOP, is the most effective treatment for canine high-grade B-cell lymphoma; however, the cost and time requirements associated with this protocol are not feasible for many pet owners. An alternative treatment option is the use of DOX, the most effective drug, in combination with prednisone. Prior studies with single-agent DOX included dogs with T-cell lymphoma, a known negative prognostic factor, which may have resulted in shorter reported survival times than if dogs with B-cell lymphoma were analyzed separately. The purpose of this study was to evaluate the outcome of dogs with high-grade B-cell lymphoma when treated with DOX and prednisone with or without L-asparaginase (L-ASP). Identification of prognostic factors was of secondary interest. Results Thirty-three dogs were included in the study; 31 dogs were evaluable for response with an overall response rate of 84%. The median progression free survival (PFS) and overall survival (OS) were 147 days and 182 days, respectively. The one-year survival fraction was 23%. No variable other than protocol completion was found to be significant for either PFS or OS including historical prognostic factors such as substage, thrombocytopenia, and body weight. Conclusions Dogs with high-grade B-cell lymphoma treated with DOX and prednisone with or without L-ASP have similar response rates, PFS, and OS to prior studies that did not differentiate between lymphoma immunophenotype. This protocol is not a replacement for CHOP; however, it is an alternative if time and cost are factors, while providing therapeutic benefit greater than prednisone alone.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.

Objective Determine whether prolonged consumption of high- or low-protein diets modifies the thermogenic response to a standard meal. Methods Twenty-four healthy individuals were randomized to overfeeding diets containing low (5%, n = 8), normal (15%, n = 9), or high (25%, n = 7) protein for 56 days while inpatients. The thermic effect of food (TEF) was measured over 4 h by indirect calorimetry following a standard meal (20% of energy, 20% protein) or a meal that matched the study diet (“study meal”). Results As expected, the TEF following the study meal (i.e., either low, normal, or high protein content) was significantly associated with dietary protein (P = 0.007), and the TEF was significantly increased in the high-protein diet (15.4%) versus the normal-protein (5.6%) and low-protein diets (6.4%) (P = 0.05 and P = 0.03, respectively). However, returning to a standard meal (20% protein) after 42 days of overfeeding the study diets, the TEF response did not differ from baseline between groups or within subjects regardless of the prolonged intake of the habitual study diet (high protein: P = 0.32, low protein: P = 0.11, normal protein: P = 0.79). Conclusions TEF is related to acute dietary protein intake but not altered by prolonged intake of high-energy diets with high or low protein content.

Growing demand for palm oil is driving its expansion into the African tropics, potentially leading to significant carbon emissions if tropical forest is converted to palm monoculture. In this first study of a Central African oil palm concession (31,800 ha), we predict that the conversion of 11,500 ha of logged forest to a palm plantation in Gabon will release 1.50 Tg C (95% CI = [1.29, 1.76]). These emissions could be completely offset over 25 years through sequestration in planned forest set-asides given a 2.6:1 ratio of logged to converted forest. Using an agricultural suitability model, we find that careful national land-use planning could largely avoid high carbon emissions while meeting goals for palm oil production. We recommend that Gabon adopts a national carbon threshold for land conversion and requires concession-level set-aside ratios that meet no-net emissions criteria as mechanisms for steering plantations away from high carbon forests.

OBJECTIVE To conduct a secondary analysis designed to test whether gestational weight gain is the result of increased energy intake or adaptive changes in energy expenditures. METHODS In this secondary analysis, energy intake and energy expenditure of 45 pregnant women (body mass index [BMI] 18.5-24.9 [n=33] and BMI 25 or greater [n=12]) were measured preconceptionally and at 22 and 36 weeks of gestation. Energy intake was calculated as the sum of total energy expenditure measured by doubly-labeled water and energy deposition determined by the four-compartment body composition model. Measurements of weight, body composition, and basal metabolic rate were completed preconceptionally and 9, 22, and 36 weeks of gestation. Basal metabolic rate was measured by indirect calorimetry in a room calorimeter and activity energy expenditure by doubly-labeled water. RESULTS Energy intake from 22 to 36 weeks of gestation was significantly higher in high gainers (n=19) (3,437±99 kcal per day) compared with low+ideal gainers (n=26) (2,687±110, P

Objective The goal was to examine lipoprotein subclass responses to regular exercise as measured in 10 exercise interventions derived from six cohorts. Methods Nuclear magnetic resonance spectroscopy was used to quantify average particle size, total and subclass concentrations of very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein particles (VLDL-P, LDL-P, and HDL-P, respectively) before and after an exercise intervention in 1555 adults from six studies, encompassing 10 distinct exercise programs: APOE (N = 106), DREW (N = 385), GERS (N = 79), HERITAGE (N = 715), STRRIDE I (N = 168) and II (N = 102). Random-effects meta-analyses were performed to evaluate the overall estimate of mean change across the unadjusted and adjusted mean change values from each exercise group. Results Meta-analysis of unadjusted data showed that regular exercise induced significant decreases in the concentration of large VLDL-P, small LDL-P, and medium HDL-P and mean VLDL-P size, with significant increases in the concentration of large LDL-P and large HDL-P and mean LDL-P size. These changes remained significant in meta-analysis with adjustment for age, sex, race, baseline body mass index, and baseline trait value. Conclusions Despite differences in exercise programs and study populations, regular exercise produced putatively beneficial changes in the lipoprotein subclass profile across 10 exercise interventions. Further research is needed to examine how exercise-induced changes in lipoprotein subclasses may be associated with (concomitant changes in) cardiovascular disease risk.