"Breaking Bread" With Respondents: Strategies to Increase Response Rates and Create Long-Term Cooperation With Health Clinic Administrators.

BACKGROUND AND OBJECTIVES: To fully understand the impact of unintended pregnancy, as well as to evaluate the implementation and outcomes of programs targeted at reducing unintended pregnancy, it is critical that researchers be able to collect comprehensive data from health clinics that provide these services in vulnerable communities. METHODS: Our paper details recruitment and incentive strategies, as well as the theories that guided them, which allowed us to achieve a high survey response rate among health clinic administrators in public health clinics in 2 Southeastern states-South Carolina and Alabama-both of which have high rates of unintended pregnancy. RESULTS: Grounded in organizational theory, and utilizing the Tailored Design Method, we achieved a 68% response rate utilizing paper and web survey administration with multiple contact modes. Our incentive structure comprised both traditional cash-based and food-based incentives. CONCLUSIONS: Findings indicate high response rates are achievable despite high survey burden (ie, detailed information, length of survey). We found that sample screening was critical and that food-based incentives made an impression on respondents that positively impacted the researcher-respondent relationship. Providing detailed methodology and additional literature will assist researchers working with similar populations-a gap in the applied methodological literature that was problematic at the project's onset.

Novel Peripheral Intravenous Catheter Securement for Children and Catheter Failure Reduction: A Randomized Clinical Trial.

Importance: Peripheral intravenous catheters (PIVCs) facilitate essential treatment. Failure of these essential devices is frequent and new securement strategies may reduce failure and improve patient outcomes. Objective: To evaluate clinical effectiveness of novel PIVC securement technologies for children to reduce catheter failure. Design, Setting, and Participants: A 3-arm, parallel group, superiority randomized clinical trial was conducted at 2 regional Australian hospitals from February 5, 2020, to January 14, 2022. Children aged 6 months to 8 years who were anticipated to require admission with a PIVC for at least 24 hours of in hospital treatment were eligible. Data were analyzed from May 25, 2022, to February 20, 2024. Interventions: Participants were randomly allocated in a 1:1:1 ratio to standard care, bordered polyurethane (Tegaderm [3M]), integrated securement dressing (SorbaView SHIELD [Medline]), and integrated securement dressing with tissue adhesive (Secureport IV). One catheter was studied per patient. Main Outcomes and Measures: Primary outcome was PIVC failure, defined as premature cessation of PIVC function for any reason prior to completion of planned treatment. Secondary outcomes were PIVC complications (any time dislodgement, occlusion, infiltration, partial dislodgement, extravasation, device leaking, phlebitis, pain), PIVC longevity, intervention acceptability (clinicians, participants, caregivers; 0-10 scale), and pain on removal (participants and caregivers; 0-10 scale relevant to age), adverse events, and health care costs. Results: A total of 383 patients (51% female; median age 36 [25th-75th percentiles, 22-72] months) were randomized 134 to standard care, 118 to integrated securement dressing, and 131 to integrated securement dressing with tissue adhesive. PIVC failure was lowest in integrated securement dressing with tissue adhesive (15 [12%]; adjusted hazard ratio [aHR], 0.47; 95% CI, 0.26-0.84) compared with integrated securement dressing (24 [21%]; aHR, 0.78; 95% CI, 0.47-1.28) and standard care (43 [34%]). Direct costs were significantly lower for integrated securement dressing with tissue adhesive (median, Australian dollars [A$], 312 [A$1 is equal to $0.65 US dollars]; IQR, A$302-A$380) and integrated securement dressing (median, A$303; IQR, A$294-A$465) compared with standard care (median, A$341; IQR, A$297-A$592; P ≤ .002) when considering the economic burden related to failure of devices. PIVC longevity and intervention acceptability were similar across all groups. Conclusions and Relevance: In this study, PIVCs secured with integrated securement dressings and tissue adhesive, in comparison with standard care, bordered polyurethane dressings, were associated with significantly reduced PIVC failure, for children admitted to hospital via the emergency department. Further research should focus on implementation in inpatient units where prolonged dwell and reliable intravenous access is most needed. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12619001026112.

Clinically Silent, Metastatic Renal Cell Carcinoma Detected on Routine Screening Mammogram: A Report of a Rare Case and Review of Literature.

Renal cell carcinoma (RCC) is the most common and the most lethal urogenital malignancy, and can metastasize rapidly via hematogenous spread. Even so, RCC metastasis within the breast is extremely rare and may appear deceptively benign on screening mammograms. In this article, we present a rare case of RCC that remained undiagnosed until an intra-mammary metastasis was detected on a routine screening mammogram. Further imaging workup and core needle biopsy of the mass ultimately confirmed a new diagnosis of metastatic clear cell RCC. Given that the presence of an RCC breast metastasis indicated advanced-stage RCC, the patient in this case underwent treatment with systemic immunotherapy. This case report describes key imaging features of metastatic RCC on common breast imaging modalities. It underscores the vital role that screening mammography can play in the initial detection of clinically silent, extra-mammary malignancies, including RCC. Thorough imaging workup and tissue biopsy are essential to distinguish a primary breast lesion from intra-mammary metastatic disease, to inform the management plan, and to prevent lumpectomy or mastectomy when it does not benefit the patient.

Preclinical characterization and IND-enabling safety studies for PNT001, an antibody that recognizes cis-pT231 tau.

BACKGROUND: The cis-conformer of tau phosphorylated at threonine-231 (cis-pT231 tau) is hypothesized to contribute to tauopathies. PNT001 is a humanized, monoclonal antibody that recognizes cis-pT231 tau. PNT001 was characterized to assess clinical development readiness. METHODS: Affinity and selectivity were assessed by surface plasmon resonance and enzyme-linked immunosorbent assay. Immunohistochemistry (IHC) was performed with brain sections from human tauopathy patients and controls. Real-time quaking-induced conversion (RT-QuIC) was used to assess whether PNT001 reduced tau seeds from Tg4510 transgenic mouse brain. Murine PNT001 was evaluated in vivo in the Tg4510 mouse. RESULTS: The affinity of PNT001 for a cis-pT231 peptide was 0.3 to 3 nM. IHC revealed neurofibrillary tangle-like structures in tauopathy patients with no detectable staining in controls. Incubation of Tg4510 brain homogenates with PNT001 lowered seeding in RT-QuIC. Multiple endpoints were improved in the Tg4510 mouse. No adverse findings attributable to PNT001 were detected in Good Laboratory Practice safety studies. DISCUSSION: The data support clinical development of PNT001 in human tauopathies.

Motives for nonmedical use of prescription stimulants in community college students.

Objective: The present study identified common motives for nonmedical use of prescription stimulants (NMUS) among community college (CC) students and examined behavioral and demographic correlates of certain motives. Participants: The survey was completed by 3,113 CC students (72.4% female; 81.7% White). Methods: Survey results from 10 CCs were evaluated. Results: NMUS was reported by 9% (n = 269) participants. The most common motive for NMUS was to "focus on studies or to improve academic performance" (67.5%) followed by to "have more energy" (52.4%). Females were more likely to report NMUS for weight loss, and males were more likely to report NMUS to experiment. The motive "to feel good or get high" was linked to polysubstance use. Conclusions: CC students report similar motives for NMUS to those commonly endorsed by 4-year university students. These findings may help identify CC students susceptible to risky substance use.

Phase I study of novel SYK inhibitor TAK-659 (mivavotinib) in combination with R-CHOP for front-line treatment of high-risk diffuse large B-cell lymphoma.

Background: TAK-659, a novel oral SYK inhibitor, has demonstrated efficacy in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We report results of a phase I single-institution escalation study of front-line treatment with R-CHOP and TAK-659 in treatment-naïve high-risk DLBCL. Methods: Patients with high-risk DLBCL were treated with R-CHOP for 1 cycle, followed by combined R-CHOP and TAK-659 for an additional five cycles, with TAK-659 dosing escalated from 60 mg, to 80 mg, to 100 mg daily, based on a 3 + 3 design. The primary objective was to determine the safety and establish the maximum tolerated dose (MTD) of TAK-659 in this setting. Results: Twelve patients were enrolled. Dose level 3 (100 mg) was established as the MTD. Dose level 1 (60 mg) maintained a similar area under the curve (AUC) to the MTD. With a median follow-up of 21 months, 92% of patients achieved complete response (CR). The most common treatment-emergent adverse events were lymphopenia (100%), infection (50%, n = 3 opportunistic), aspartate aminotransferase elevation (100%), and alanine aminotransferase elevation (83%). Conclusion: A TAK-659 dose of 60 mg was well tolerated, did not require dose modifications, and maintained a similar AUC to the MTD. The combination of R-CHOP and TAK-659 in patients with newly diagnosed high-risk DLBCL produces promising CR rates.

Primary care physicians' opioid-related prevention behaviors and intentions: A descriptive analysis.

OBJECTIVE: Primary care physicians (PCPs) are positioned to mitigate opioid morbidity and mortality, but their engagement in primary, secondary, and tertiary opioid-related prevention behaviors is unclear. The objective of this study was to evaluate Tennessee PCPs' engagement in and intention to engage in multiple opioid-related prevention behaviors. METHODS: A survey instrument was developed, pretested, and pilot tested with practicing PCPs. Thereafter, a census of eligible Tennessee PCPs was conducted using a modified, four-wave tailored design method approach. Three patient scenarios were employed to assess physician intention to engage in 10 primary, secondary, and tertiary prevention behaviors. Respondents were asked to report, given 10 similar scenarios, the number of times (0-10) they would engage in prevention behaviors. Descriptive statistics were calculated using SPSS version 25. RESULTS: A total of 296 usable responses were received. Physician intention to engage in prevention behaviors varied across the 10 behaviors studied. Physicians reported frequently communicating risks associated with prescription opioids to patients (8.9 ± 2.8 out of 10 patients), infrequently utilizing brief questionnaires to assess for risk of opioid misuse (1.7 ± 3.3 out of 10 patients), and screening for current opioid misuse (3.1 ± 4.3 out of 10 patients). Physicians reported seldomly co-prescribing naloxone for overdose reversal and frequently discharging from practice patients presenting with an opioid use disorder. CONCLUSIONS: This study noted strengths and opportunities to increase engagement in prevention behaviors. Understanding PCPs' engagement in opioid-related prevention behaviors is important to effectively target and implement morbidity and mortality reducing interventions.

Bolus Versus Continuous Nasogastric Feeds for Infants With Bronchiolitis: A Randomized Trial.

BACKGROUND AND OBJECTIVES: Infants hospitalized with bronchiolitis are commenced on nasogastric feeding to maintain hydration. Feeding strategies vary according to physician or institution preference. The current study hypothesized that continuous nasogastric feeding would prolong length of stay (LOS) when compared to bolus feeding. METHODS: A randomized, parallel-group, superiority clinical trial was performed within an Australian children's hospital throughout 2 bronchiolitis seasons from May 2018 to October 2019. Infants <12 months hospitalized with bronchiolitis and requiring supplemental nasogastric feeding were randomly assigned to continuous or bolus nasogastric regimens. LOS was the primary outcome. Secondary outcome measures included pulmonary aspirations and admissions to intensive care. RESULTS: The intention-to-treat analysis included 189 patients: 98 in the bolus nasogastric feeding group and 91 in the continuous group. There was no significant difference in LOS (median LOS of the bolus group was 54.25 hours [interquartile range 40.25-82] and 56 hours [interquartile range 38-78.75] in the continuous group). A higher proportion of admissions to intensive care was detected in the continuous group (28.57% [26 of 91] of the continuous group vs 11.22% [11 of 98] of the bolus group [P value 0.004]). There were no clinically significant pulmonary aspirations or statistically significant differences in vital signs between the groups within 6 hours of feed initiation. CONCLUSIONS: No significant difference in LOS was found between bolus and continuous nasogastric feeding strategies for infants hospitalized with bronchiolitis. The continuous feeding group had a higher proportion of intensive care admissions, and there were no aspiration events.

Variation in CT use for paediatric head injuries across different types of emergency departments in Australia and New Zealand.

OBJECTIVES: CT of the brain (CTB) for paediatric head injury is used less frequently at tertiary paediatric emergency departments (EDs) in Australia and New Zealand than in North America. In preparation for release of a national head injury guideline and given the high variation in CTB use found in North America, we aimed to assess variation in CTB use for paediatric head injury across hospitals types. METHODS: Multicentre retrospective review of presentations to tertiary, urban/suburban and regional/rural EDs in Australia and New Zealand in 2016. Children aged <16 years, with a primary ED diagnosis of head injury were included and data extracted from 100 eligible cases per site. Primary outcome was CTB use adjusted for severity (Glasgow Coma Scale) with 95% CIs; secondary outcomes included hospital length of stay and admission rate. RESULTS: There were 3072 head injury presentations at 31 EDs: 9 tertiary (n=900), 11 urban/suburban (n=1072) and 11 regional/rural EDs (n=1100). The proportion of children with Glasgow Coma Score ≤13 was 1.3% in each type of hospital. Among all presentations, CTB was performed for 8.2% (95% CI 6.4 to 10.0) in tertiary hospitals, 6.6% (95% CI 5.1 to 8.1) in urban/suburban hospitals and 6.1% (95% CI 4.7 to 7.5) in regional/rural. Intragroup variation of CTB use ranged from 0% to 14%. The regional/rural hospitals admitted fewer patients (14.6%, 95% CI 12.6% to 16.9%, p<0.001) than tertiary and urban/suburban hospitals (28.1%, 95% CI 25.2% to 31.2%; 27.3%, 95% CI 24.7% to 30.1%). CONCLUSIONS: In Australia and New Zealand, there was no difference in CTB use for paediatric patients with head injuries across tertiary, urban/suburban and regional/rural EDs with similar intragroup variation. This information can inform a binational head injury guideline.

Community pharmacist engagement in opioid use disorder prevention and treatment behaviors: A descriptive analysis.

OBJECTIVES: This study describes community pharmacists' opioid analgesic and medication for opioid use disorder (MOUD) practice behaviors and behavioral intentions in the context of primary, secondary, and tertiary prevention of opioid use disorder (OUD). METHODS: The study sampling frame consisted of 2302 Tennessee community-practice pharmacists who were asked to complete a mailed, paper questionnaire. Behavioral intentions were elicited by asking pharmacists to indicate the number of times (0 to 10) they engage in a behavior, given 10 patients in 3 distinct vignettes. Perceptions of evidence-based MOUD and pain management patient care practices were also elicited. RESULTS: A response rate of 19.7% was achieved. Pharmacists reported using a brief questionnaire to evaluate risk of opioid misuse with 2.1 ± 3.7 (mean ± SD) out of 10 patients, screening 2.1 ± 3.7 patients for current opioid misuse, discussing co-dispensing of naloxone with 2.9 ± 3.4 to 3.3 ± 4 out of 10 patients at a risk of overdose, and dispensing buprenorphine/naloxone to a mean of 4.6 ± 4.2 patients when they presented a prescription. Respondents perceived 38% of pain management and 30% of MOUD prescribers in their area to practice evidenced-based care. CONCLUSION: Pharmacists have an opportunity to improve the outcomes for patients prescribed opioids by increasing engagement across OUD prevention levels.

ACR Appropriateness Criteria® Pancreatic Cyst.

Incidental pancreatic cysts are increasingly detected on imaging studies performed for unrelated indications and may be incompletely characterized on these studies. Adequate morphological characterization is critical due to the small risk of malignant degeneration associated with neoplastic pancreatic cysts, as well as the risk of associated pancreatic adenocarcinoma. For all pancreatic cysts, both size and morphology determine management. Specifically, imaging detection of features, such as pancreatic ductal communication and presence or absence of worrisome features or high-risk stigmata, have important management implications. The recommendations in this publication determine the appropriate initial imaging study to further evaluate a pancreatic cyst that was incidentally detected on a nondedicated imaging study. The recommendations are designed to maximize the yield of diagnostic information in order to better risk-stratify pancreatic cysts and assist in guiding future management. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

"It's Took Over This Region": Patient Perspectives of Prescription Drug Abuse in Appalachia.

Background: Prescription drug abuse is a public health problem in the United States and the region of Appalachia, specifically. Primary care and addiction medicine-as possible points of access for prescription drugs with abuse potential and points of intervention for prescription drug abuse-are among the medical fields at its forefront. Little is known, however, about perceptions of prescription drug abuse across the two patient populations. Objectives: The objective of this qualitative analysis was to explore perceptions of the scale and context of prescription drug abuse among primary care and addiction medicine patients in Appalachia. Methods: As part of a mixed methods study, semi-structured interviews were conducted with 20 patients from primary care and addiction medicine in Central and South Central Appalachia from 2014 to 2015. The interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify themes. Results: Three themes were identified: (1) pervasiveness of prescription drug abuse, describing perceptions of its high prevalence and negative consequences; (2) routes and routine practices for prescription drug acquisition and distribution, describing perceptions of routes of access to prescription drugs and behaviors exhibited to acquire and distribute prescription drugs; and (3) rationales for prescription drug acquisition and distribution, describing perceptions of the two underlying reasons for these processes-tolerance/addiction and revenue source. Conclusions/Importance: Perceptions of prescription drug abuse among primary care and addiction medicine patients in Appalachia are multifaceted, especially regarding prescription drug acquisition and distribution. Clinical practice implications for mitigating prescription drug abuse are discussed.

Communication Experiences of DATA-Waivered Physicians with Community Pharmacists: A Qualitative Study.

Background: Patients engaged in evidence-based opioid use disorder (OUD) treatment can obtain prescriptions for buprenorphine containing products from specially trained physicians that are subsequently dispensed by community pharmacists. Despite the involvement of physicians and community pharmacists in buprenorphine prescribing and dispensing, respectively, our understanding of their interactions in this context is limited. Objective: To qualitatively describe the communication and collaborative experiences between Drug Addiction Treatment Act 2000 (DATA)-waivered physicians and community pharmacists from the perspective of the physician. Methods: Ten key informant interviews were conducted with DATA-waivered physicians practicing in Northeast Tennessee. A semi-structured interview guide was used to explore communication and collaborative experiences between the physicians and community pharmacists. Interviews were audio recorded and transcribed verbatim. A coding frame was developed using concepts from the scientific literature and emerging codes from physician interviews. Interviews were coded using NVivo 11, with the data subsequently organized and evaluated for themes. Results: Four themes were identified: (1) mechanics of communication; (2) role specification and expectations; (3) education and understanding; and (4) climate of clinical practice. Physician-pharmacist communication primarily occurred indirectly through patients or staff and perceived challenges to collaboration included; lack of trust, stigma, and fear of regulatory oversight. Physicians also indicated the two professionals may lack clear roles and responsibilities as well as common expectations for treatment plans. Conclusions: Communication between DATA-waivered physicians and community pharmacists is influenced by multiple factors. Further research is warranted to improve physician-community pharmacist collaboration (PCPC) in the context of OUD pharmacotherapy and addiction treatment.

A Queensland research support network in emergency healthcare.

PURPOSE: The purpose of this paper is to describe the structure and impact of a Queensland Research Support Network (RSN) in emergency medicine (EM). DESIGN/METHODOLOGY/APPROACH: This paper presents a descriptive summary of EM networks, network evaluations and the structure and development of the Emergency Medicine Foundation's (EMF) RSN in Queensland, including an observational pre- and post-study of research metrics. FINDINGS: In two years, the RSN supported 33 Queensland emergency departments (EDs), of which 14 developed research strategies. There was an increase in research active clinicians, from 23 in 2015 to 181 in 2017. Collaborator engagement increased from 9 in 2015 to 276 in 2017 as did the number of research presentations, from 6 in 2015 to 61 in 2017. EMF experienced a growth in new researchers, with new investigators submitting approximately 60 per cent of grant applications in 2016 and 2017. EMF also received new applications from a further three HHS (taking EMF-funded research activity from 8 to 11 HHS). RESEARCH LIMITATIONS/IMPLICATIONS: This paper describes changes in KPIs and research metrics, which the authors attribute to the establishment of the RSN. However, it is possible that attribution bias plays a role in the KPI improvements. SOCIAL IMPLICATIONS: This network has actively boosted and expanded EM research capacity and capability in Queensland. It provides services, in the form of on-the-ground managers, to develop novice clinician-researchers, new projects and engage entire EDs. This model may be replicated nationwide but requires funding commitment. ORIGINALITY/VALUE: The RSN improves front-line clinician research capacity and capability and increases research activity and collaborations with clear community outcomes. Collaborations were extended to community, primary health networks, non-government organisations, national and international researchers and academic institutions. Evaluating and measuring a network's benefits are difficult, but it is likely that evaluations will help networks obtain funding.

Palliative Care Usage in Young Adult Oncology Population.

Context: Early integration of palliative care (PC) into adult oncology practice has been shown to improve quality of life and health care utilization; however, little is known about PC in young adults with cancer. Objectives: Our primary objective was to determine rates and timing of PC consultation in young adult patients with advanced solid tumor cancer at a single institution. Methods: We conducted a retrospective analysis of young adults of age 18-39 years with advanced solid tumor malignancy at an urban academic medical center between June 1, 2014 and June 30, 2015. Results: Of 129 patients identified, 70 of 129 (54%) had a PC consult and 34 of 70 were inpatient-only consults. PC consults occurred for a median of 104 days before death, and for those with inpatient-only consults, PC consults occurred for a median of 18 days. Patients with worse recent Eastern Cooperative Oncology Group (ECOG) performance status were more likely to have had a PC consult (p < 0.001). Of the patients who died during the study period, patients with PC consults were more likely to have been hospitalized (72% vs. 47%), in the intensive care unit (21% vs. 0%), in the emergency room (ER) (72% vs. 47%), and have received chemotherapy (17% vs. 0%) within 30 days of death compared with those who did not have a consult; however, these differences were not statistically significant. Conclusion: In this analysis, over half of young adults with advanced solid tumors received PC consults. PC consult typically occurred for one year after diagnosis and about three months before death. Additional research is needed to identify how to better integrate PC early in this patient population and assess the resulting impact.

Transnasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergent intubation (Kids THRIVE): a protocol for a randomised controlled trial.

INTRODUCTION: Emergency intubation of children with abnormal respiratory or cardiac physiology is a high-risk procedure and associated with a high incidence of adverse events including hypoxemia. Successful emergency intubation is dependent on inter-related patient and operator factors. Preoxygenation has been used to maximise oxygen reserves in the patient and to prolong the safe apnoeic time during the intubation phase. Transnasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE) prolongs the safe apnoeic window for a safe intubation during elective intubation. We designed a clinical trial to test the hypothesis that THRIVE reduces the frequency of adverse and hypoxemic events during emergency intubation in children and to test the hypothesis that this treatment is cost-effective compared with standard care. METHODS AND ANALYSIS: The Kids THRIVE trial is a multicentre randomised controlled trial performed in participating emergency departments and paediatric intensive care units. 960 infants and children aged 0-16 years requiring emergency intubation for all reasons will be enrolled and allocated to THRIVE or control in a 1:1 allocation with stratification by site, age (<1, 1-7 and >7 years) and operator (junior and senior). Children allocated to THRIVE will receive weight appropriate transnasal flow rates with 100% oxygen, whereas children in the control arm will not receive any transnasal oxygen insufflation. The primary outcomes are defined as follows: (1) hypoxemic event during the intubation phase defined as SpO2 <90% (patient-dependent variable) and (2) first intubation attempt success without hypoxemia (operator-dependent variable). Analyses will be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: Ethics approval for the protocol and consent process has been obtained (HREC/16/QRCH/81). The trial has been actively recruiting since May 2017. The study findings will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ACTRN12617000147381.

Effectiveness of a hydrogel dressing as an analgesic adjunct to first aid for the treatment of acute paediatric thermal burn injuries: study protocol for a randomised controlled trial.

BACKGROUND: Burns are a painful and traumatic experience, particularly in children. Reduced pain and anxiety positively influences re-epithelialisation rates in paediatric burn patients, however current literature fails to fully explain the effects of pain and anxiety and their links with wound healing. This study will determine if Burnaid® hydrogel dressing is an effective treatment for reducing pain in the acute period of a burn injury. It is hypothesised that a reduction in pain will then improve re-epithelialisation time in comparison to plastic wrap, which is standard practice at our institution - a metropolitan tertiary paediatric hospital located in Brisbane, Australia. METHODS/DESIGN: A randomised controlled trial will be conducted to assess the effectiveness of Burnaid® as an analgesic adjunct to cold running water first aid for the treatment of paediatric burns. Participants will include children aged between 0 and 16 years with an acute thermal burn injury (total burn surface area < 20%) presenting to the Department of Emergency within 24 h of the burn occurring. Participants will be randomised into one of two groups: (1) Burnaid® hydrogel (intervention arm) or (2) plastic wrap (control arm). Participants will also be stratified into one of two groups based on factors that influence pain intensity: (1) high pain risk or (2) low pain risk. High pain risk factors include foot burns, hot coal/ash/fire pit burns, burn area greater than 5%, and circumferential burns. The primary outcome is the intervention's effect on reducing acute pain. Secondary outcomes include days to re-epithelialisation, pulse rate, temperature, salivary cortisol and α-amylase, anxiety, and cost-effectiveness. Sample size calculations have shown that 36 participants will be recruited into each group. DISCUSSION: This study will provide comprehensive data on the analgesic properties of Burnaid® as an adjunct to first aid for the treatment of acute paediatric thermal burns. If the intervention is effective in reducing pain, Burnaid® will be integrated as standard practice within the hospital's Department of Emergency. This study replicates a real-world scenario in order to identify clinically significant analgesic and wound-healing effects. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617001274369 . Prospectively registered on 5 Sept 2017.

Robust Short-Lag Spatial Coherence Imaging of Breast Ultrasound Data: Initial Clinical Results.

Ultrasound is frequently used in conjunction with mammography in order to detect breast cancer as early as possible. However, due largely to the heterogeneity of breast tissue, ultrasound images are plagued with clutter that obstructs important diagnostic features. Short-lag spatial coherence (SLSC) imaging has proven to be effective at clutter reduction in noisy ultrasound images. M -Weighted SLSC and Robust-SLSC (R-SLSC) imaging were recently introduced to further improve image quality at higher lag values, while R-SLSC imaging has the added benefit of enabling the adjustment of tissue texture to produce a tissue signal-to-noise ratio (SNR) that is quantitatively similar to B-mode speckle SNR. This paper investigates the initial application of SLSC, M -Weighted SLSC, and R-SLSC imaging to nine targets in the female breast [two simple cysts, one complicated cyst, two fibroadenomas, one hematoma, one complex cystic and solid mass, one invasive ductal carcinoma (IDC), and one ductal carcinoma in situ (DCIS)]. As expected, R-SLSC beamforming improves cyst and hematoma contrast by up to 6.35 and 1.55 dB, respectively, when compared to the original B-mode image, and similar improvements are achieved with SLSC and M -Weighted SLSC imaging. However, an interesting finding from this initial investigation is that the solid masses (i.e., fibroadenoma, complex cystic and solid mass, IDC, and DCIS), which appear as hypoechoic in the B-mode image, have similarly high coherence to that of surrounding tissue in coherence-based images. This work holds promise for using SLSC, M -Weighted SLSC, and/or R-SLSC imaging to distinguish between fluid-filled and solid hypoechoic breast masses.

LRRC15 Is a Novel Mesenchymal Protein and Stromal Target for Antibody-Drug Conjugates.

Progress in understanding tumor stromal biology has been constrained in part because cancer-associated fibroblasts (CAF) are a heterogeneous population with limited cell-type-specific protein markers. Using RNA expression profiling, we identified the membrane protein leucine-rich repeat containing 15 (LRRC15) as highly expressed in multiple solid tumor indications with limited normal tissue expression. LRRC15 was expressed on stromal fibroblasts in many solid tumors (e.g., breast, head and neck, lung, pancreatic) as well as directly on a subset of cancer cells of mesenchymal origin (e.g., sarcoma, melanoma, glioblastoma). LRRC15 expression was induced by TGFß on activated fibroblasts (αSMA+) and on mesenchymal stem cells. These collective findings suggested LRRC15 as a novel CAF and mesenchymal marker with utility as a therapeutic target for the treatment of cancers with LRRC15-positive stromal desmoplasia or cancers of mesenchymal origin. ABBV-085 is a monomethyl auristatin E (MMAE)-containing antibody-drug conjugate (ADC) directed against LRRC15, and it demonstrated robust preclinical efficacy against LRRC15 stromal-positive/cancer-negative, and LRRC15 cancer-positive models as a monotherapy, or in combination with standard-of-care therapies. ABBV-085's unique mechanism of action relied upon the cell-permeable properties of MMAE to preferentially kill cancer cells over LRRC15-positive CAF while also increasing immune infiltrate (e.g., F4/80+ macrophages) in the tumor microenvironment. In summary, these findings validate LRRC15 as a novel therapeutic target in multiple solid tumor indications and support the ongoing clinical development of the LRRC15-targeted ADC ABBV-085.Significance: These findings identify LRRC15 as a new marker of cancer-associated fibroblasts and cancers of mesenchymal origin and provide preclinical evidence for the efficacy of an antibody-drug conjugate targeting the tumor stroma. Cancer Res; 78(14); 4059-72. ©2018 AACR.