A protocol for stakeholder engagement in head and neck cancer pragmatic trials.

Meaningful engagement with stakeholders in research demands intentional approaches. This paper describes the development of a framework to guide stakeholder engagement as research partners in a pragmatic trial proposed to evaluate behavioral interventions for dysphagia in head and neck cancer patients. We highlight the core principles of stakeholder engagement including representation of all perspectives, meaningful participation, respectful partnership with stakeholders, and accountability to stakeholders; and describe how these principles were operationalized to engage relevant stakeholders throughout the course of a large clinical trial.

Supramolecularly-Cross-Linked Nanogel Assemblies for On-Demand, Ultrasound-Triggered Chemotherapy.

Stimulating the release of small nanoparticles (NPs) from a larger NP via the application of an exogenous stimulus offers the potential to address the different size requirements for circulation versus penetration that hinder chemotherapeutic drug delivery. Herein, we report a size-switching nanoassembly-based drug delivery system comprised of ultrasmall starch nanoparticles (SNPs, ∼20-50 nm major size fraction) encapsulated in a poly(oligo(ethylene glycol) methyl ether methacrylate) nanogel (POEGMA, ∼150 nm major size fraction) cross-linked via supramolecular PEG/α-cyclodextrin (α-CD) interactions. Upon heating the nanogel using a non-invasive, high-intensity focused ultrasound (HIFU) trigger, the thermoresponsive POEGMA-CD nanoassemblies are locally de-cross-linked, inducing in situ release of the highly penetrative drug-loaded SNPs. HIFU triggering increased the release of nanoassembly-loaded DOX from 17 to 37% after 3 h, a result correlated with significantly more effective tumor killing relative to nanoassemblies in the absence of HIFU or drug alone. Furthermore, 1.5× more total fluorescence was observed inside a tumor spheroid when nanoassemblies prepared with fluorophore-labeled SNPs were triggered with HIFU relative to the absence of HIFU. We anticipate this strategy holds promise for delivering tunable doses of chemotherapeutic drugs both at and within a tumor site using a non-invasive triggering approach.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

Modelling growth of Bacillus cereus in paneer by one-step parameter estimation.

Bacillus cereus phylogenetic group III and IV strains are commonly associated with food products and cause toxin mediated foodborne diseases. These pathogenic strains have been identified from milk and dairy products, such as reconstituted infant formula and several cheeses. Paneer is a fresh, soft cheese originating from India that is prone to foodborne pathogen contamination, such as by Bacillus cereus. However, there are no reported studies of B. cereus toxin formation in paneer or predictive models quantifying growth of the pathogen in paneer under different environmental conditions. This study assessed enterotoxin-producing potential of B. cereus group III and IV strains, isolated from dairy farm environments, in fresh paneer. Growth of a four-strain cocktail of toxin-producing B. cereus strains was measured in freshly prepared paneer incubated at 5-55 °C and modelled using a one-step parameter estimation combined with bootstrap re-sampling to generate confidence intervals for model parameters. The pathogen grew in paneer between 10 and 50 °C and the developed model fit the observed data well (R2 = 0.972, RMSE = 0.321 log10 CFU/g). The cardinal parameters for B. cereus growth in paneer along with the 95% confidence intervals were: µopt 0.812 log10 CFU/g/h (0.742, 0.917); Topt is 44.177 °C (43.16, 45.49); Tmin is 4.405 °C (3.973, 4.829); Tmax is 50.676 °C (50.367, 51.144). The model developed can be used in food safety management plans and risk assessments to improve safety of paneer while also adding to limited information on B. cereus growth kinetics in dairy products.

An Implementation Assessment of the Virtual Acute Care for Elders Program From the Perspective of Key Stakeholders.

OBJECTIVE: The aim of this study was to obtain feedback from key stakeholders and end users to identify program strengths and weaknesses to plan for wider dissemination and implementation of the Virtual Acute Care for Elders (Virtual ACE) program, a novel intervention that improves outcomes for older surgical patients. BACKGROUND: Virtual ACE was developed to deliver evidence-based geriatric care without requiring daily presence of a geriatrician. Previous work demonstrated that Virtual ACE increased mobility and decreased delirium rates for surgical patients. METHODS: We conducted semi-structured interviews with 30 key stakeholders (physicians, nurses, hospital leadership, nurse managers, information technology staff, and physical/occupational therapists) involved in the implementation and use of the program. RESULTS: Our stakeholders indicated that Virtual ACE was extremely empowering for bedside nurses. The program helped nurses identify older patients who were at risk for a difficult postoperative recovery. Virtual ACE also gave them skills to manage complex older patients and more effectively communicate their needs to surgeons and other providers. Nurse managers felt that Virtual ACE helped them allocate limited resources and plan their unit staffing assignments to better manage the needs of older patients. The main criticism was that the Virtual ACE Tracker that displayed patient status was difficult to interpret and could be improved by a better design interface. Stakeholders also felt that program training needed to be improved to accommodate staff turnover. CONCLUSIONS: Although respondents identified areas for improvement, our stakeholders felt that Virtual ACE empowered them and provided effective tools to improve outcomes for older surgical patients.

Time Heals Most Wounds - Perceptions of Thyroidectomy Scars in Patients With Thyroid Cancer.

BACKGROUND: Patients understandably have concerns about thyroidectomy scars. This study aimed to characterize patients' perceptions of their thyroidectomy scar before and up to 1-y after surgery. METHODS: Patients with papillary thyroid cancer (n = 83) completed semi-structured interviews before and at 2-wks, 6-Wk, 6-mo, and 1-y post-thyroidectomy. Interviews probed about scar concerns and appearance. Content analysis was used to identify themes. RESULTS: The majority of participants did not express concerns about scar appearance. When expressed, preoperative concerns often stemmed from previous surgery experiences or unease with neck incisions. Postoperatively, concerns about scar appearance decreased over time throughout the healing period with most patients being satisfied with their scar appearance by 6-mo after surgery. CONCLUSIONS: Patients with papillary thyroid cancer express few concerns about scar thyroidectomy appearance. Surgeons can reassure patients who have preoperative concerns that most patients are satisfied with their scar appearance by 6-mo after surgery.

Comparing thermal stress reduction strategies that influence MDSC accumulation in tumor bearing mice.

Myeloid derived suppressor cells (MDSCs) are a diverse collection of immune cells that suppress anti-tumor immune responses. Decreasing MDSCs accumulation in the tumor microenvironment could improve the anti-tumor immune response and improve immunotherapy. Here, we examine the impact of physiologically relevant thermal treatments on the accumulation of MDSCs in tumors in mice. We found that different temperature-based protocols, including 1) weekly whole-body hyperthermia, 2) housing mice at their thermoneutral temperature (TT, ~30 °C), and 3) housing mice at a subthermoneutral temperature (ST,~22 °C) while providing a localized heat source, each resulted in a reduction in MDSC accumulation and improved tumor growth control compared to control mice housed at ST, which is the standard, mandated housing temperature for laboratory mice. Additionally, we found that low dose ß-adrenergic receptor blocker (propranolol) therapy reduced MDSC accumulation and improved tumor growth control to a similar degree as the models that relieved cold stress. These results show that thermal treatments can decrease MDSC accumulation and tumor growth comparable to propranolol therapy.

Evaluating the relationship between citation set size, team size and screening methods used in systematic reviews: a cross-sectional study.

BACKGROUND: Standard practice for conducting systematic reviews (SRs) is time consuming and involves the study team screening hundreds or thousands of citations. As the volume of medical literature grows, the citation set sizes and corresponding screening efforts increase. While larger team size and alternate screening methods have the potential to reduce workload and decrease SR completion times, it is unknown whether investigators adapt team size or methods in response to citation set sizes. Using a cross-sectional design, we sought to understand how citation set size impacts (1) the total number of authors or individuals contributing to screening and (2) screening methods. METHODS: MEDLINE was searched in April 2019 for SRs on any health topic. A total of 1880 unique publications were identified and sorted into five citation set size categories (after deduplication): < 1,000, 1,001-2,500, 2,501-5,000, 5,001-10,000, and > 10,000. A random sample of 259 SRs were selected (~ 50 per category) for data extraction and analysis. RESULTS: With the exception of the pairwise t test comparing the under 1000 and over 10,000 categories (median 5 vs. 6, p = 0.049) no statistically significant relationship was evident between author number and citation set size. While visual inspection was suggestive, statistical testing did not consistently identify a relationship between citation set size and number of screeners (title-abstract, full text) or data extractors. However, logistic regression identified investigators were significantly more likely to deviate from gold-standard screening methods (i.e. independent duplicate screening) with larger citation sets. For every doubling of citation size, the odds of using gold-standard screening decreased by 15 and 20% at title-abstract and full text review, respectively. Finally, few SRs reported using crowdsourcing (n = 2) or computer-assisted screening (n = 1). CONCLUSIONS: Large citation set sizes present a challenge to SR teams, especially when faced with time-sensitive health policy questions. Our study suggests that with increasing citation set size, authors are less likely to adhere to gold-standard screening methods. It is possible that adjunct screening methods, such as crowdsourcing (large team) and computer-assisted technologies, may provide a viable solution for authors to complete their SRs in a timely manner.

Qualitative Analysis of Single-Site Headache Surgery: Is It Different From Multiple-Site Surgery?

BACKGROUND: Migraine surgery has been shown to be efficacious, but nuanced effects of surgery on pain and individuals' lives remain incompletely understood. Surgery may be performed at a single or multiple "primary" sites. The aims of this study were to investigate patient perceptions following single-site surgery and compare themes in patients undergoing single-site surgery with those from a previously published conceptual framework generated with patients undergoing multisite surgery. METHODS: Patients who underwent single-site headache surgery participated in open-ended interviews at least 1 year after surgery. Participants (n = 14) had undergone either occipital, temporal, or nasoseptal site surgery. A multidisciplinary team analyzed transcripts. Recurring themes were identified and compared and contrasted to those observed in patients who underwent multiple-site surgery (n = 15) in a previous study (Plast Reconstr Surg 2019;144(4):956-964). RESULTS: Similar recurring themes emerged from the single-site cohort, and the conceptual framework was applicable to all participants. Two new themes emerged from the single-site analysis. First, 5 of 14 participants described being "migraine-free" postoperatively, a finding not observed in the multisite group. Second, several individuals described financial benefits after surgery, via decreased prescription medication requirements, raises at work, and improved productivity. CONCLUSIONS: Single-site headache surgery appears to positively impact patients' lives in ways that support and expand upon previously published outcomes. Patients undergoing surgery at a single site may be more likely to experience a "pain-free" state, which may relate to the underlying pathophysiology of chronic headache. The effect of surgery on finances appears to be an outcome of interest to patients, which should be explored further.

A Novel Surgical Patient Engagement Model: A Qualitative Study of Postoperative Patients.

BACKGROUND: Strong patient engagement is often associated with better postoperative outcomes and reduced risk of dangerous and expensive complications for the patient. Our goal with this project is to define a new model specifically for surgical patient engagement to guide future work to improve patient outcomes. METHODS: Open-ended qualitative interviews were conducted with 38 postoperative patients, analyzed using the conventional content analysis method, and coded with NVivo 11. Patients from either a safety net or private hospital in the Houston area between the ages of 18 and 70 y were recruited after surgery for either thyroid, parathyroid, colon, or rectal cancer, inflammatory bowel disease, and diverticulitis. Pregnant and incarcerated patients in addition to those with postoperative complications or interview time frames greater than 4 wk postoperatively were excluded. RESULTS: Of patients completing the Patient Activation Measure, 98% obtained a score of 3 or 4, indicating optimal levels of activation despite differences in socio-economic status. Upon analysis of coded transcripts, four main themes of "self-efficacy," "resilience," "transitional agency," and "enabling agency," in addition to a fifth emergency rescue activator, "family and social support," were discovered as "drivers" of patient engagement. CONCLUSIONS: A novel model of patient engagement specific to surgical patients is necessary because of the unique recovery track they endure. Our new model can be used to develop interventions for these patients to improve their engagement and thereby their outcomes.

The Biokinetic Spectrum for Temperature and optimal Darwinian fitness.

Darwinian fitness is maximised at a temperature below Topt, but what this temperature is remains unclear. By linking our previous work on the Biokinetic Spectrum for Temperature with a model for temperature-dependent biological growth rate we obtain a plausible value for such a temperature. We find this approach reveals considerable commonalities in how life responds to temperature with implications that follow in evolution, physiology and ecology. We described a data set consisting of 17,021 observations of temperature-dependent population growth rates from 2411 bacterial, archaeal and eukaryal strains. We fitted a thermodynamic model to describe the strains' temperature-dependent growth rate curves that assumed growth was limited by a single rate-limiting enzyme. We defined Umes as an empirical measure of the temperature at which strains grew as fast and also as efficiently as possible. We propose that Darwinian fitness is optimised at Umes by trading-off growth rate and physiological efficiency. Using the full data set we calculated the Biokinetic Spectrum for Temperature (BKST): the distribution of temperature-dependent growth rates for each temperature. We used quantile regression to fit alternative models to the BKST to obtain quantile curves. A quantile is a value that contains a particular proportion of the data. The quantile curves suggested commonalities in temperature-dependencies spanning taxa and ecotype, consistent with the single rate-limiting enzyme concept. We showed that on the log scale, the slopes of the quantile curves were the same as the slopes of the thermodynamic model growth curves at Umes. This was true for Bacteria, Archaea, and Eukarya, and across other conditions (pH, water activity, metabolic type and trophic type). We showed that the quantile curves were the loci of the temperatures and growth rates that optimised Darwinian fitness for each strain at a given temperature-dependence and independently of other conditions. The quantile curves for Archaea and Bacteria shared a number of similarities attributable to the influence of the properties of water on protein folding. Other implications have impact on evolutionary biology, ecology, and physiology. The model predicts the existence of eurythermic strains that grow with about equal efficiency over a broad temperature range. These strains will have higher evolutionary rates with lower mutational costs that are independent of environmental conditions, a factor likely to have been significant during the Precambrian if the early Earth was warmer than today. The model predicts that random mutations are likely to result in shifts along the quantile curves and not across them. It predicts that some psychrophiles will be capable of performing well under climate change, and that selection will favour faster growth rates as the temperature increases. Last, it predicts trade-offs between growth rate and soma production, so that temperature-dependence, and possibly Darwinian fitness, remain constant over a broad temperature range and growth rates.

A Qualitative Analysis of the Preoperative Needs of Patients With Papillary Thyroid Cancer.

BACKGROUND: Thyroid cancer patients report unmet needs after diagnosis. However, little is known about their specific needs. Therefore, we sought to characterize the needs of patients with thyroid cancer before undergoing surgery. MATERIAL AND METHODS: We conducted semistructured interviews with 32 patients with papillary thyroid cancer after their preoperative surgical consultation. Data were analyzed using thematic content analysis. RESULTS: The central need of patients with thyroid cancer was a strong patient-surgeon relationship characterized by informational and emotional support, and respect for the patient as a person. Patients preferred disease- and treatment-related information to be individualized and to take into account aspects of their daily life. They wanted adequate time for asking questions with thoughtful answers tailored to their case. Patients additionally desired emotional support from the surgeon characterized by empathy and validation of their cancer experience. They particularly wanted surgeons to address their fears and anxiety. Patients also highly valued the surgeons' ability to see beyond their disease and acknowledge them as a unique person with respect to their occupation, psychosocial state, and other individual characteristics. When surgeons met patients' needs, they felt reassured, comfortable with their cancer diagnosis, and prepared for treatment. Suboptimal support increased patients' anxiety particularly when they felt the surgeon minimized their concerns. CONCLUSIONS: Preoperatively, patients with thyroid cancer desire a strong patient-surgeon relationship. They rely on the surgeon to provide adequate informational and emotional support and respect them as individuals. In turn, patients feel reassured and prepared for treatment.

Correlates of Early Pharyngeal High-Resolution Manometry Adoption in Expert Speech-Language Pathologists.

Pharyngeal high-resolution manometry (HRM) is at a point of entry into speech-language pathologist (SLP) clinical practice. However, the demographic characteristics of SLPs who are early adopters of HRM are unclear; perspectives of early adopters may shape how the technology is received by the field at large. We hypothesized that younger SLPs, those working in outpatient settings, those with a strong knowledge base in HRM, and those with experience in other types of instrumentation are more likely to have interest in adopting HRM. We surveyed the population of board-certified SLPs (BCS-S; n = 262) with a 33% response rate (n = 78). Firth logistic regression was used to determine differences in those expressing interest in adopting HRM into future practice (n = 28) and those who did not (n = 45) from the analytic sample of 73 respondents. The best fitting model predicted that SLPs: (1) with training in more types of instrumentation; and (2) believing they could explain the HRM procedure to a patient were more likely to plan to adopt pharyngeal HRM into regular clinical practice. Experience with a variety of instrumentation techniques may encourage SLPs to use new forms of technology. Knowledge of early adopter demographics will allow for development of targeted trainings and determination of HRM implementation barriers. Identification of a clinician sub-group more likely to adopt other new technologies in the future may also be possible.

SLP-Perceived Technical and Patient-Centered Factors Associated with Pharyngeal High-Resolution Manometry.

High-resolution manometry (HRM) objectively measures swallowing-related pressures in the pharynx and esophagus. It has been used in many research applications, but it is unclear how HRM is perceived amongst speech-language pathologists (SLP) as it enters into clinical practice. The purpose of this study was to explore SLP perceptions of clinical HRM use. Based on qualitative data collected at four focus groups held at two national conferences and a survey based on open-ended questions, we found broad consensus among those queried regarding how HRM's objective and targeted data could enhance diagnosis and drive treatments. However, we found less consensus among SLPs regarding which patients may and may not benefit, as well as when in the clinical process HRM would best supplement existing technologies, showing a need for further research. These findings highlight how SLPs can be motivated to adopt new clinical technologies if they see a patient-centered benefit and underscore the need for continued SLP education on pharyngeal HRM.

Use of Game Theory to model patient engagement after surgery: a qualitative analysis.

BACKGROUND: Patient engagement is challenging to define and operationalize. Qualitative analysis allows us to explore patient perspectives on this topic and establish themes. A game theoretic signaling model also provides a framework through which to further explore engagement. METHODS: Over a 6-mo period, thirty-eight interviews were conducted within 6 wk of discharge in patients undergoing thyroid, parathyroid, or colorectal surgery. Interviews were transcribed, anonymized, and analyzed using the NVivo 11 platform. A signaling model was then developed depicting the doctor-patient interaction surrounding the patient's choice to reach out to their physician with postoperative concerns based upon the patient's perspective of the doctor's availability. This was defined as "engagement". We applied the model to the qualitative data to determine possible causations for a patient's engagement or lack thereof. A private hospital's and a safety net hospital's populations were contrasted. RESULTS: The private patient population was more likely to engage than their safety-net counterparts. Using our model in conjunction with patient data, we determined possible etiologies for this engagement to be due to the private patient's perceived probability of dealing with an available doctor and apparent signals from the doctor indicating so. For the safety-net population, decreased access to care caused them to be less willing to engage with a doctor perceived as possibly unavailable. CONCLUSIONS: A physician who understands these Game Theory concepts may be able to alter their interactions with their patients, tailoring responses and demeanor to fit the patient's circumstances and possible barriers to engagement.

An overview of the role of sympathetic regulation of immune responses in infectious disease and autoimmunity.

Stress in patients and pre-clinical research animals plays a critical role in disease progression Activation of the sympathetic nervous system (SNS) by stress results in secretion of the catecholamines epinephrine (Epi) and norepinephrine (NE) from the adrenal gland and sympathetic nerve endings. Adrenergic receptors for catecholamines are present on immune cells and their activity is affected by stress and the accompanying changes in levels of these neurotransmitters. In this short review, we discuss how this adrenergic stress impacts two categories of immune responses, infections and autoimmune diseases. Catecholamines signal primarily through the ß2-adrenergic receptors present on innate and adaptive immune cells which are critical in responding to infections caused by pathogens. In general, this adrenergic input, particularly chronic stimulation, suppresses lymphocytes and allows infections to progress. On the other hand, insufficient adrenergic control of immune responses allows progression of several autoimmune diseases.

In situ-gelling hydrophobized starch nanoparticle-based nanoparticle network hydrogels for the effective delivery of intranasal olanzapine to treat brain disorders.

Intranasal (IN) delivery offers potential to deliver antipsychotic drugs with improved efficacy to the brain. However, the solubilization of such drugs and the frequency of required re-application both represent challenges to its practical implementation in treating various mental illnesses including schizophrenia. Herein, we report a sprayable nanoparticle network hydrogel (NNH) consisting of hydrophobically-modified starch nanoparticles (SNPs) and mucoadhesive chitosan oligosaccharide lactate (COL) that can gel in situ within the nasal cavity and release ultra-small penetrative SNPs over time. Hydrophobization of the SNPs enables enhanced uptake and prolonged release of poorly water soluble drugs such as olanzapine from the NNH depot through mucous and ultimately into the brain via the nose-to-brain (N2B) pathway. The hydrogel shows high in vitro cytocompatibility in mouse striatal neuron and human primary nasal cell lines and in vivo efficacy in an amphetamine-induced pre-clinical rat schizophrenia model, with IN-delivered NNH hydrogels maintaining successful attenuation of locomotor activity for up to 4 h while all other tested treatments (drug-only IN or conventional intraperitoneal delivery) failed to attenuate at any time point past 0.5 h. As such, in situ-gelling NNHs represent a safe excipient for the IN delivery of hydrophobic drugs directly to the brain using customized SNPs that exhibit high penetration and drug complexing properties to maximize effective drug delivery.