Vaccine-induced ErbB (EGFR/HER2)-specific immunity in spontaneous canine cancer.

Epidermal Growth Factor Receptor (EGFR) is overexpressed on a number of human cancers, and often is indicative of a poor outcome. Treatment of EGFR/HER2 overexpressing cancers includes monoclonal antibody therapy (cetuximab/trastuzumab) either alone or in conjunction with other standard cancer therapies. While monoclonal antibody therapy has been proven to be efficacious in the treatment of EGFR/HER2 overexpressing tumors, drawbacks include the lack of long-lasting immunity and acquired resistance to monoclonal therapy. An alternative approach is to induce a polyclonal anti-EGFR/HER2 tumor antigen response by vaccine therapy. In this phase I/II open-label study, we examined anti-tumor immunity in companion dogs with spontaneous EGFR expressing tumors. Canine cancers represent an outbred population in which the initiation, progression of disease, mutations and growth factors closely resemble that of human cancers. Dogs with EGFR expressing tumors were immunized with a short peptide of the EGFR extracellular domain with sequence homology to HER2. Serial serum analyses demonstrated high titers of EGFR/HER2 binding antibodies with biological activity similar to that of cetuximab and trastuzumab. Canine antibodies bound both canine and human EGFR on tumor cell lines and tumor tissue. CD8 T cells and IgG deposition were evident in tumors from immunized dogs. The antibodies inhibited EGFR intracellular signaling and inhibited tumor growth in vitro. Additionally, we illustrate objective responses in reducing tumors at metastatic sites in host animals. The data support the approach of amplifying anti-tumor immunity that may be relevant in combination with other immune modifying therapies such as checkpoint inhibitors.

Perceptions on Diversity in Cardiology: A Survey of Cardiology Fellowship Training Program Directors.

Background The lack of diversity in the cardiovascular physician workforce is thought to be an important driver of racial and sex disparities in cardiac care. Cardiology fellowship program directors play a critical role in shaping the cardiology workforce. Methods and Results To assess program directors' perceptions about diversity and barriers to enhancing diversity, the authors conducted a survey of 513 fellowship program directors or associate directors from 193 unique adult cardiology fellowship training programs. The response rate was 21% of all individuals (110/513) representing 57% of US general adult cardiology training programs (110/193). While 69% of respondents endorsed the belief that diversity is a driver of excellence in health care, only 26% could quote 1 to 2 references to support this statement. Sixty-three percent of respondents agreed that "our program is diverse already so diversity does not need to be increased." Only 6% of respondents listed diversity as a top 3 priority when creating the cardiovascular fellowship rank list. Conclusions These findings suggest that while program directors generally believe that diversity enhances quality, they are less familiar with the literature that supports that contention and they may not share a unified definition of "diversity." This may result in diversity enhancement having a low priority. The authors propose several strategies to engage fellowship training program directors in efforts to diversify cardiology fellowship training programs.

Reirradiation of canine nasal carcinomas treated with coarsely fractionated radiation protocols: 37 cases.

Data from 37 dogs with nasal carcinomas treated with two or more coarsely fractionated courses of radiation therapy (RT) were retrospectively reviewed. The median radiation dose for the first course of RT was 24 Gray (Gy). All dogs clinically responded, and 11 had complete resolution of signs for a median of 114 days. Dogs were retreated at relapse, with a median dose of 20 Gy, and 26 of 37 dogs (70%) had clinical responses. The second course of RT was initiated at a median of 150 days following completion of the first course. Side effects were mild: four dogs had chronic ocular conditions necessitating medication, one of which required enucleation. Median survival time (ST) from the first dose of RT was 453 days and 180 days from the first dose of the second course of RT. The following factors were examined but were not significant for survival: total RT dose, dose of the first course of RT, complete resolution of clinical signs, use of either chemotherapy or nonsteroidal anti-inflammatory drugs (NSAIDs), and stage (T1/T2 versus T3/T4). Dogs responded well to reirradiation with a subset experiencing chronic ocular side effects.

Evaluation of fixation time using Diff-Quik for staining of canine mast cell tumor aspirates.

BACKGROUND: Mast cell tumors are the most common cutaneous tumor in the dog and are often diagnosed via fine-needle aspiration and cytology. Many veterinary practices use Diff-Quik stain for these cases because it is easy to use and provides rapid results. Anecdotal reports suggest that Diff-Quik does not stain mast cell tumor granules well and that increased duration of fixation time can improve staining quality; however, this has not been prospectively evaluated. OBJECTIVES: The aim of this study was to determine if varying fixation time would affect the staining quality of mast cell granules using the Diff-Quik stain. The null hypothesis was that there would be no difference in the staining of the granules based on duration of time in the fixation solution. METHODS: Fine-needle aspirates of cutaneous mast cell tumors were obtained from 21 dogs and distributed on multiple slides. These slides were then stained in Diff-Quik at varying fixation times (ie, 5 seconds, 30 seconds, 1 minute, 2 minutes). One slide was stained with modified Wright stain as a control. Mast cell staining quality was evaluated either by blinded clinicopathologic review (n = 12) or by computer analysis of photomicrographs (n = 6). Results were compared with histopathologic grade. RESULTS: There was no difference in staining quality among groups. CONCLUSIONS: Alteration in fixation time using Diff-Quik does not improve staining characteristics of mast cell tumors.

Locally invasive lymphangiosarcoma in a young domestic shorthair.

A 2-year-old, female spayed, domestic shorthair cat presented to the University of Missouri-Veterinary Medical Teaching Hospital (UMC-VMTH) with an approximately 11-month history of fluid-draining pockets along her ventral thorax and axillae. The skin in these regions was erythematous, and multiple areas drained a serous to serosanguinous fluid. Fluid-filled, nodules formed along the ventrum, but these nodules disappeared as fluid drained spontaneously. Histologic assessment of skin biopsies revealed areas of vascular proliferation extending along the deep margin of the section and rare instances of invasion into the superficial dermis. These vascular channels were devoid of cells, lined by variably pleomorphic endothelial cells which had a low mitotic index. Based on the mild to moderate pleomorphism, positive staining with prospero-related homeobox gene-1 (PROX-1), and the locally aggressive nature of the tumor, a final diagnosis of lymphangiosarcoma was made.

Results of a pilot randomized controlled trial of buprenorphine for opioid dependent women in the criminal justice system.

AIMS: Recent studies have demonstrated the efficacy of both methadone and buprenorphine when used with opioid dependent men transitioning from prison to the community, but no studies have been conducted with women in the criminal justice (CJ) system. The aim of this study was to determine the efficacy of buprenorphine for relapse prevention among opioid dependent women in the CJ system transitioning back to the community. METHODS: 36 women under CJ supervision were recruited from an inpatient drug treatment facility that treats CJ individuals returning back to the community. Nine were enrolled in an open label buprenorphine arm then 27 were randomized to buprenorphine (n=15) or placebo (n=12; double-blind). All women completed baseline measures and started study medication prior to release. Participants were followed weekly, provided urine drug screens (UDS), received study medication for 12 weeks, and returned for a 3-month follow-up. Intent-to-treat analyses were performed for all time points through 3 month follow-up. RESULTS: The majority of participants were Caucasian (88.9%), young (M±SD=31.8±8.4 years), divorced/separated (59.2%) women with at least a high school/GED education (M±SD=12±1.7 years). GEE analyses showed that buprenorphine was efficacious in maintaining abstinence across time compared to placebo. At end of treatment, 92% of placebo and 33% of active medication participants were positive for opiates on urine drug screen (Chi-Square=10.9, df=1; p<0.001). However, by the three month follow-up point, no differences were found between the two groups, with 83% of participants at follow-up positive for opiates. CONCLUSIONS: Women in the CJ system who received buprenorphine prior to release from a treatment facility had fewer opiate positive UDS through the 12 weeks of treatment compared to women receiving placebo. Initiating buprenorphine in a controlled environment prior to release appears to be a viable strategy to reduce opiate use when transitioning back to the community.

Factors predicting substance dependence and psychotropic medication use among offenders in community corrections.

Co-occurring substance abuse and mental illness is prevalent among criminal offenders, but little is known about risk factors for these co-occurring disorders (COD) in community corrections population. To identify risk factors for COD in community corrections offenders, we analyzed assessment data from 5,595 offenders maintained under community supervision at a substance use diversion program. Three groups, offenders with substance use disorders who were taking psychotropic medications (SUPM), offenders with a substance use disorder (SUD) only and controls were compared. Logistic regressions were used to identify predictors of SUPM versus SUD only and controls. SUPM status was predicted by being White or Female, having some medical insurance (private or government aided), being unemployed, prior history of abuse/trauma, and prior history of suicidal ideation or behavior. Offenders with substance use disorders and co-occurring psychiatric problems face salient social risk that may need to be targeted through integrated services.

Impact of self-initiated pre-quit smoking reduction on cessation rates: results of a clinical trial of smoking cessation among female prisoners.

OBJECTIVES: This study examined differences in cessation success based on smokers' self-initiated pre-quit reductions in cigarettes per day (cpd). METHODS: The study utilized data from a nicotine replacement+behavioral therapy smoking cessation intervention conducted in a female prison facility with 179 participants who were wait-listed for 6 months prior to intervention. We compared two groups of smokers based on whether they self-selected to reduce smoking prior to their cessation attempt (n=77) or whether they increased smoking or did not reduce (n=102). General Estimating Equations (GEE) were used to model smoking cessation through 12-month follow-up. RESULTS: Examination of pre-cessation cpd showed that those who reduced were heavier smokers at baseline, relative to those who did not reduce (p<0.001). By the week prior to the quit attempt (week 3) heavier smokers at baseline smoked significantly fewer cigarettes (p<0.001) and had lower CO levels (p<0.05) compared to baseline lighter smokers. GEE analyses showed that individuals who reduced prior to their quit attempt had significantly higher quit rates during early treatment but these gains were not sustained by follow-up points. CONCLUSIONS: Participant-initiated pre-cessation smoking reduction may be initially helpful in preparing to quit smoking, or may serve as a marker for participant motivation to quit smoking, but these differences do not sustain over time. More intensive interventions are still needed for successful cessation.

The impact of quitting smoking on weight among women prisoners participating in a smoking cessation intervention.

OBJECTIVES: We examined the impact of smoking cessation on weight change in a population of women prisoners. METHODS: Women prisoners (n = 360) enrolled in a smoking cessation intervention; 250 received a 10-week group intervention plus transdermal nicotine replacement. RESULTS: Women who quit smoking had significant weight gain at 3- and 6-month follow-ups, with a net difference of 10 pounds between smokers and abstainers at 6 months. By the 12-month follow-up, weight gain decreased among abstainers. CONCLUSIONS: We are the first, to our knowledge, to demonstrate weight gain associated with smoking cessation among women prisoners. Smoking cessation interventions that address postcessation weight gain as a preventative measure may be beneficial in improving health and reducing the high prevalence of smoking in prisoner populations.

Factors related to injection drug use among female prisoners.

Female inmates (N = 655) of a large prison facility in the southeastern United States were surveyed about their substance use, social histories, and demographics. Multinomial logistic regression was used to identify predictors of injection drug use. The sample was primarily young (M = 34 +/- 9 years), and evenly split on race (45.3% White and 44.6% Black). Four predictors were identified as significant risk factors for injection drug use: being White, having a prior history of substance user treatment, having a prior drug-related charge, and being a problem drinker. Implications, limitations, and future directions are discussed.

Smoking characteristics of community corrections clients.

INTRODUCTION: While smoking rates are 3-4 times higher among criminal justice populations than in the general population, no studies have previously examined smoking characteristics in a community corrections population. METHODS: The current study involved descriptive analyses of self-reported survey data from 217 criminal justice supervisees reporting for urine drug screens during a 5-day period at a community corrections facility in the southeastern United States. RESULTS: Most participants were current smokers (72.3%), males (65.9%), and Black (50.2%) who reported smoking three fourths of a pack of cigarettes per day and had been smoking for about 15 years. More than half of smokers reported that they would be interested in receiving cessation assistance if free help were available and of these, 60% were interested in pharmacotherapy. White smokers used more cigarettes per day, were more likely to have already tried medication to help them quit smoking, and were also more interested in pharmacotherapies and less interested in behavioral therapies compared with Black smokers. Female smokers did not differ from male smokers on key smoking characteristics, but male smokers were more likely to have tried or regularly used other tobacco products, such as cigars. Female smokers were significantly more likely to report interest in using a pharmacotherapy agent for future cessation, while male smokers reported more interest in nonpharmacotherapy approaches to quit smoking. DISCUSSION: Results from this study highlight important differences among smoking groups and may indicate the need to test tailored smoking interventions.

The effect of patients' race on provider treatment choices in coronary care: a literature review for model development.

This selective literature review provides insight into the depth and breadth of the problem of unequal medical treatment of Blacks compared with Whites, with particular focus on coronary heart disease. Poor health outcomes among Blacks, when compared with Whites, are well documented, and these disparities are linked to lower quality of and less aggressive medical treatment. It is not clear why these disparities in treatment occur. This review provides theoretical frameworks that attempt to explain the effect of race on treatment and presents an analysis of the quality and strength of existing evidence of racial disparity related to coronary care. Based on the review, implications for policy makers and providers are identified.

Understanding medication errors: discussion of a case involving a urinary catheter implicated in a wrong route error.

Medication errors represent a failure in the medication use process leading to an increase in morbidity and mortality. In an effort to standardize reporting, evaluating, and trending of medication errors, the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) developed and maintains a medication error taxonomy. A case study involving a medication intended for administration via rectal tube and inadvertently given through a Foley catheter is discussed using the NCC MERP medication error taxonomy and critiqued using recent national findings. Awareness of national trends for patient safety, including emerging changes leading to best practices, updates to National Patient Safety Goals, and changes in national policy, can reduce the risk of error involvement.

Health of Indigenous people in Africa.

Our paper is part of a series focusing on Indigenous peoples' health in different world regions. Indigenous peoples worldwide are subject to marginalisation and discrimination, systematically experiencing poorer health than do majority groups. In Africa, poor health in the general population is widely recognised, but the consistently lower health position and social status of Indigenous peoples are rarely noted. Disputed conceptual understandings of indigeneity, a history of discriminatory colonial and post-colonial policies, and non-recognition of Indigenous groups by some governments complicate the situation. We discuss two case studies, of the central African Pygmy peoples and the San of southern Africa, to illustrate recurring issues in Indigenous health in the continent. We make recommendations for the recognition of Indigenous peoples in Africa and improvements needed in the collection of health data and the provision of services. Finally, we argue that wider changes are needed to address the social determinants of Indigenous peoples' health.