Examining provider perceptions and practices for comprehensive geriatric assessment among cancer survivors: a qualitative study with an implementation science focus

Introduction: Cancer rates increase with age, and older cancer survivors have unique medical care needs, making assessment of health status and identification of appropriate supportive resources key to delivery of optimal cancer care. Comprehensive geriatric assessments (CGAs) help determine an older person’s functional capabilities as cancer care providers plan treatment and follow-up care. Despite its proven utility, research on implementation of CGA is lacking.Methods: Guided by a qualitative description approach and through interviews with primary care providers and oncologists, our goal was to better understand barriers and facilitators of CGA use and identify training and support needs for implementation. Participants were identified through Cancer Prevention and Control Research Network partner listservs and a national cancer and aging organization. Potential interviewees, contacted via email, were provided with a description of the study purpose. Eight semi-structured interviews were conducted via Zoom, recorded, and transcribed verbatim by a professional transcription service. The interview guide explored providers’ knowledge and use of CGAs. For codebook development, three representative transcripts were independently reviewed and coded by four team members. The interpretive process involved reflecting, transcribing, coding, and searching for and identifying themes.Results: Providers shared that, while it would be ideal to administer CGAs with all new patients, they were not always able to do this. Instead, they used brief screening tools or portions of CGAs, or both. There was variability in how CGA domains were assessed; however, all considered CGAs useful and they communicated with patients about their benefits. Identified facilitators of implementation included having clinic champions, an interdisciplinary care team to assist with implementation and referrals for intervention, and institutional resources and buy-in. Barriers noted included limited staff capacity and competing demands on time, provider inexperience, and misaligned institutional priorities.Discussion: Findings can guide solutions for improving the broader and more systematic use of CGAs in the care of older cancer patients. Uptake of processes like CGA to better identify those at risk of poor outcomes and intervening early to modify treatments are critical to maximize the health of the growing population of older cancer survivors living through and beyond their disease

Chemoinformatic-Guided Engineering of Polyketide Synthases.

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge is re-engineering a partially reductive PKS module to produce a saturated β-carbon through a reductive loop (RL) exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, offers a viable strategy for RL exchanges. We first introduced a set of donor RLs of diverse genetic origin and chemical substrates  into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with chemical structure similarity between the substrate of the donor RLs and recipient LipPKS1, reaching a titer of 165 mg/L of short-chain fatty acids produced by the host Streptomyces albus J1074. Expanding this method to larger intermediates that require bimodular communication, we introduced RLs of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products

Considerations for Adapting Evidence-Based Health Behavior Interventions for Older, Rural Cancer Survivors

BACKGROUND: Older cancer survivors living in rural areas are more likely to experienceaccelerated aging, difficulty with physical functionality, and chronic pain or fatigue. One likely contributor to poor health outcomes in this population of survivors is low adherence to lifestyle recommendations, such as a healthy diet and increased physical activity. Rural cancer survivors face several challenges to engaging in healthy lifestyle behavior change programming such as access to care, transportation, and health literacy. Though telehealth has been a promising avenue for engaging rural living individuals with health care and lifestyle programming, older cancer survivors may have additional challenges to accessing digital devices and tools that have not yet been described. Survivors at the intersection of older age and rurality face several challenges to behavior change that must be addressed to improve long-term health outcomes. OBJECTIVES: This dissertation is composed of three studies that aim to address the gaps in knowledge about lifestyle behavior adherence among older, rural cancer survivors by: (1) synthesizing the literature related to lifestyle behavior change interventions conducted with rural survivor populations, (2) examining the prevalence of digital technology use for health-related activities among older cancer survivors in both rural and urban settings, and (3) exploring the acceptability of digital technology as a tool for lifestyle behavior change in this population. METHODS: To address aim 1, a systematic review of five databases identified randomized controlled trials and controlled clinical trials that targeted diet, physical activity, alcohol consumption, or tobacco use change in adult cancer survivors living in rural areas of the world. Narrative synthesis was completed to describe eligible studies. A cross-sectional analysis of the Health Information National Trends Survey was completed for aim 2 to examine the prevalence of digital technology use among older cancer survivors. Logistic regression models were used to assess the association between rurality and digital health tool use. A mixed-methods approach was utilized for aim 3 to explore the acceptability of using digital technology for lifestyle behavior change. Phase 1 included a quantitative online survey, followed by semi-structured interviews in phase 2 to explore the findings. RESULTS: Eight studies met inclusion criteria for aim 1. Most studies were conducted in either Australia or the United States, included survivors at least 6-weeks post-treatment, and half included only breast cancer survivors. No articles addressed changes in alcohol or tobacco behavior, and none were prospectively aimed at implementation for older, rural-dwelling survivors. Seven utilized a fully remote or hybrid delivery model. For aim 2, there were few differences in digital technology use among older cancer survivors by rural-urban status and prevalence of use for health-related activities was high overall. Findings from the mixed-methods study completed for aim 3 showed both quantitatively and qualitatively that acceptability of digital technology as a tool for lifestyle behavior change is high. Survivors identified five key features they would like to see incorporated in future digital technology-delivered lifestyle behavior change intervention including accountability, feedback, gamification, socialization, and tracking. CONCLUSION: Few studies have been conducted to implement and evaluate the effectiveness of lifestyle behavior change interventions among older, rural survivors of cancer. The findings from this dissertation provide the critical preliminary proof-of-concept information necessary to adapt evidence-based lifestyle interventions for older cancer survivors living in rural areas using a digital technology-based approach.Release after 05/01/202

Acceptability of Hormonal Contraceptives as a Smoking Cessation Aid for Women of Reproductive Age: A Web-Based Cross-Sectional Survey

Introduction: Cigarette smoking is the most common cause of preventable cancers and other premature morbidity and mortality. Modifying hormonal patterns using hormonal contraceptives (HCs) may lead to improved smoking cessation outcomes in women, though the acceptability of this is unknown. Therefore, we explored the willingness of reproductive-age women who smoke to use HC for cessation. Methods: A cross-sectional online survey was conducted with a convenience sample of reproductive-age women living in the United States who self-reported smoking combustible cigarettes. Questions covered smoking history, previous HC use, and willingness to use various HC methods (i.e., injectable, oral, patch, vaginal insert) for cessation. Chi-squared tests and logistic regression were conducted using StataBE 17.1. Results: Of 358 eligible respondents, n?=?312 (86.9%) reported previous HC use. Average age of those with HC use history was 32.1???6.1 years compared with 27.8???6.7 years for those without history of HC use (p?=?0.001). Of respondents who reported previous HC use, 75.6% reported willingness to use HCs, compared with 60.9% of those without a history of HC use. Overall, willingness to use various types of HC ranged from 22.6% for the vaginal insert to 59.2% willing to use an oral contraceptive. Discussion: These observations indicate that most women who smoke cigarettes are willing to use HC for a smoking cessation aid, especially if they have a history of HC use and with an oral form of HC. To improve the rate of smoking cessation for women of reproductive age, future interventions should explore how to incorporate HC for cessation

Qualitative assessment of COVID-19 vaccination acceptance among healthcare workers in Pima County

In the Spring of 2021, the COVID-19 vaccination was authorized for emergency use by the Food and Drug Administration. Healthcare workers (HCWs) are one of the most trusted sources of information for vaccination choices. However, HCWs at this time appeared to continue to have lower rates of COVID-19 vaccination uptake than expected in Arizona. The objective of this study was to examine factors that play a role in the vaccination decision-making process among Arizona HCWs. Between January and April 2021, 18 semi-structured interviews were conducted among physicians, emergency medical technicians and long-term care nurses in Pima County. The informed consent process was completed for each participant. The interview guide was informed by the Increasing Vaccination model to collect information on vaccination decision-making. A codebook was developed using an inductive approach. Coding and analysis was conducted using the software MAXQDA. Participants were primarily male (11/18, 61%) and white (11/18, 61%). Three participants identified as Hispanic. Initial themes that emerged included: mixed opinions concerning the innovations in COVID-19 vaccine development, access-related barriers, issues related to distribution inequities, concerns about misinformation and conspiracy theories, and dialogue concerning the benefits of requiring mandatory vaccination. The results gathered from this study indicate that there continues to be hesitancy among some healthcare professionals in Pima County. These results will be used to help Arizonan Health Departments promote rollout of novel vaccines more effectively through targeting relevant vaccination decision-making factors among HCWs

Mechanism of Altered Metformin Distribution in Nonalcoholic Steatohepatitis

Metformin is an antihyperglycemic drug that is widely prescribed for type 2 diabetes mellitus and is currently being investigated for the treatment of nonalcoholic steatohepatitis (NASH). NASH is known to alter hepatic membrane transporter expression and drug disposition similarly in humans and rodent models of NASH. Metformin is almost exclusively eliminated through the kidney primarily through active secretion mediated by Oct1, Oct2, and Mate1. The purpose of this study was to determine how NASH affects kidney transporter expression and metformin pharmacokinetics. A single oral dose of [(14)C]metformin was administered to C57BL/6J (wild type [WT]) and diabetic ob/ob mice fed either a control diet or a methionine- and choline-deficient (MCD) diet. Metformin plasma concentrations were slightly increased in the WT/MCD and ob/control groups, whereas plasma concentrations were 4.8-fold higher in ob/MCD mice compared with WT/control. The MCD diet significantly increased plasma half-life and mean residence time and correspondingly decreased oral clearance in both genotypes. These changes in disposition were caused by ob/ob- and MCD diet-specific decreases in the kidney mRNA expression of Oct2 and Mate1, whereas Oct1 mRNA expression was only decreased in ob/MCD mice. These results indicate that the diabetic ob/ob genotype and the MCD disease model alter kidney transporter expression and alter the pharmacokinetics of metformin, potentially increasing the risk of drug toxicity

A bimodular PKS platform that expands the biological design space.

Traditionally engineered to produce novel bioactive molecules, Type I modular polyketide synthases (PKSs) could be engineered as a new biosynthetic platform for the production of de novo fuels, commodity chemicals, and specialty chemicals. Previously, our investigations manipulated the first module of the lipomycin PKS to produce short chain ketones, 3-hydroxy acids, and saturated, branched carboxylic acids. Building upon this work, we have expanded to multi-modular systems by engineering the first two modules of lipomycin to generate unnatural polyketides as potential biofuels and specialty chemicals in Streptomyces albus. First, we produce 20.6 mg/L of the ethyl ketone, 4,6 dimethylheptanone through a reductive loop exchange in LipPKS1 and a ketoreductase knockouts in LipPKS2. We then show that an AT swap in LipPKS1 and a reductive loop exchange in LipPKS2 can produce the potential fragrance 3-isopropyl-6-methyltetrahydropyranone. Highlighting the challenge of maintaining product fidelity, in both bimodular systems we observed side products from premature hydrolysis in the engineered first module and stalled dehydration in reductive loop exchanges. Collectively, our work expands the biological design space and moves the field closer to the production of "designer" biomolecules

The relationship between sleep and weight change among women diagnosed with breast cancer participating in the Women's Health Initiative

Short and long sleep duration and poor sleep quality are risk factors for weight gain and cancer mortality. The purpose of this study is to investigate the relationship between sleep and weight change among postmenopausal breast cancer survivors. Women participating in the Women's Health Initiative who were diagnosed with incident breast cancer between year one and year three were included. Self-reported sleep duration was categorized as ≤ 5 h (short), 6 h, 7-8 h (optimal), and ≥ 9 h (long). Self-reported sleep quality was categorized as poor, average, and above average. Post-diagnosis weight change was the difference of weight closest to, but preceding diagnosis, and year 3 weight. We used linear regression to evaluate sleep duration and sleep quality associations with post-diagnosis weight change adjusted for potential confounders. Among 1156 participants, 63% were weight stable after diagnosis; average weight gain post cancer diagnosis was 3.2 kg. Six percent of women reported sleeping ≤ 5 h, 26% reported 6 h, 64% reported 7-8 h, and 4% reported ≥ 9 h. There were no differences in adjusted estimates of weight change among participants with short duration (0.37 kg; 95% CI - 0.88, 1.63), or long duration (- 0.56 kg; 95% CI - 2.03, 0.90) compared to optimal duration, nor was there a difference among poor quality (- 0.51 kg; 95% CI - 1.42, 0.41) compared to above average quality. Among postmenopausal breast cancer survivors, sleep duration and quality were not associated with weight change after breast cancer diagnosis. Future studies should consider capturing change in adiposity and to expand beyond self-reported sleep

Chemoinformatic-Guided Engineering of Polyketide Synthases.

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge is re-engineering a partially reductive PKS module to produce a saturated β-carbon through a reductive loop (RL) exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, offers a viable strategy for RL exchanges. We first introduced a set of donor RLs of diverse genetic origin and chemical substrates  into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with chemical structure similarity between the substrate of the donor RLs and recipient LipPKS1, reaching a titer of 165 mg/L of short-chain fatty acids produced by the host Streptomyces albus J1074. Expanding this method to larger intermediates that require bimodular communication, we introduced RLs of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products