Real-world experience with clinical management of talquetamab in relapsed/refractory multiple myeloma: a qualitative study of US healthcare providers.

OBJECTIVE: Talquetamab is the first-in-class GPRC5DxCD3 bispecific antibody for relapsed/refractory multiple myeloma. Given limited real-world data, this study was conducted with US healthcare providers (HCPs) to understand real-world talquetamab dosing and symptom management. METHODS: In February/March 2024, individual in-depth interviews (IDIs; n = 10) were conducted with HCPs administering talquetamab in real-world settings. A subsequent expert panel (n = 6) further discussed current practices. RESULTS: The IDIs reported a variety of settings for step-up dosing (SUD), including inpatient (n = 5), outpatient (n = 3), and hybrid models (n = 2), with a trend toward shorter SUD length to reduce healthcare resource utilization. Most HCPs used a biweekly (Q2W) schedule in SUD (n = 7) and treatment phases (n = 8). Eight participants explored reducing dose frequency to every 4 weeks (Q4W) in patients following positive disease response to treatment, considering patient convenience and relieving GPRC5D-related symptoms. Panelists recommended symptom management and prophylactic strategies, such as dexamethasone and nystatin mouthwash or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. CONCLUSION: This study outlines current real-world practices for talquetamab. Findings indicate variation in the SUD care setting. The 0.8 mg/kg Q2W dosing schedule was most common, although switching to Q4W is a real-world symptom management strategy for some patients with responses to therapy. GPRC5D-related symptom management approaches are evolving; prophylactic use of dexamethasone and nystatin mouthwash or zinc and vitamin B complex may be effective strategies to alleviate oral symptoms. Further real-world evidence is needed to inform optimal dosing schedules while mitigating symptom impact.

Talquetamab is a new treatment that was approved in the United States in 2023 for a type of blood cancer called multiple myeloma. This drug is administered at one of two doses, each of which includes a defined step-up dosing schedule where patients first receive smaller amounts of the drug to help avoid serious side effects. Because talquetamab is new and associated with treatment-related symptoms not normally seen with other multiple myeloma treatments, doctors and patients need more guidance on drug administration and symptom management. In this study, we describe findings from interviews and an expert panel discussion with healthcare professionals who have experience using talquetamab. This study found that most healthcare professionals administered step-up dosing with patients staying overnight in the hospital, while other providers administered these doses during outpatient visits. Most providers administered talquetamab once every 2 weeks after utilizing the associated step-up dosing schedule. Additionally, healthcare providers described transitioning some patients, who had responded positively to treatment, to a less frequent dosing schedule of once per month to help reduce the effect of treatment-related symptoms. Participants in the expert panel described approaches for managing or preventing these symptoms, such as dexamethasone and nystatin mouthwashes or zinc and vitamin B complex for oral symptoms, and topical steroids and cosmetic products for skin and nail symptoms. In summary, this study provides valuable real-world information from healthcare providers who have experience treating patients with multiple myeloma with talquetamab.

Analgesia for emergency laparotomy: a systematic review.

Aims/Background Poorly controlled pain is common after emergency laparotomy. It causes distress, hinders rehabilitation, and predisposes to complications: prolonged hospitalisation, persistent pain, and reduced quality of life. The aim of this systematic review was to compare the relative efficacies of pre-emptive analgesia for emergency laparotomy to inform practice. Methods We performed a search of MEDLINE, MEDLINE In-Process, Embase, PubMed, Web of Science and SCOPUS for comparator studies of preoperative/intraoperative interventions to control/reduce postoperative pain in adults undergoing emergency laparotomy (EL) for general surgical pathologies. Exclusion criteria: surgery including non-abdominal sites; postoperative sedation and/or intubation; non-formal assessment of pain; non-English manuscripts. All manuscripts were screened by two investigators. Results We identified 2389 papers. Following handsearching and removal of duplicates, 1147 were screened. None were eligible for inclusion, with many looking at elective and/or laparoscopic surgeries. Conclusion Our findings indicate there is no evidence base for pre-emptive analgesic strategies in emergency laparotomy. This contrasts substantially with elective cohorts. Potential reasons include variation in practice, management of physiological derangement taking priority, and perceived contraindications to neuraxial techniques. We urge a review of contemporary practice, with analysis of clinical data, to generate expert consensus.

Estimating the Rates of Undiagnosed Prediabetes and Diabetes Among People Experiencing Homelessness.

OBJECTIVES: The rising prevalence of type 2 diabetes in Canada poses a significant health challenge. Despite the convenience of screening for diabetes with glycated hemoglobin (A1C) concentration, people experiencing homelessness (PEH) often face barriers to accessing diabetes screening, potentially leading to underdiagnosis. In this study, we aim to assess the prevalence of undiagnosed diabetes among PEH in Calgary, Alberta, and contribute insights for planning health-care services and public health initiatives. METHODS: Four screening clinics were held, and participants were recruited through posters and word of mouth. Participants underwent point-of-care A1C testing using the Siemens DCA Vantage point-of-care analyzer. Descriptive statistics were used to identify the proportions of prediabetes and diabetes, whereas CANRISK survey scores were used to identify the pre-test probability of diabetes. RESULTS: The mean age of participants (n=102) was 47.6 years, and the self-reported causes of homelessness among the participants were diverse, including housing and financial issues (n=53), interpersonal and family issues (n=35), and health- or corrections-related factors (n=27). The average A1C was 5.60% (standard deviation 0.57%), with 5 values in the diabetes range and 12 in the prediabetes range, for a total of 17 participants found to have previously undiagnosed dysglycemia. CONCLUSIONS: The high rate of undiagnosed prediabetes and diabetes among PEH reflects at least what is already seen in the general population in Canada. More resources are required to reduce the barriers to screening for diabetes among this population.

Utilizing Nurse Practitioners and Physician Assistants in Academic Emergency Departments Does Not Reduce Residents' Exposure to More Complex Patients.

BACKGROUND: Whether integration of nurse practitioners (NPs) and physician assistants (PAs) into academic emergency departments (EDs) affects emergency medicine (EM) resident clinical learning opportunities is unclear. OBJECTIVE: We sought to compare EM resident exposure to more-complex patients, as well as patients undergoing Accreditation Council for Graduate Medical Education (ACGME)-required procedures, at nonpediatric academic EDs with lower, moderate, and higher levels of NP/PA utilization. METHODS: In this cross-sectional study of National Hospital Ambulatory Medical Care Survey (NHAMCS) data for 2016-2020, nonpediatric academic EDs were classified into the following three groups based on the percentage of patients seen by an NP or PA: lower (≤ 10%), moderate (10.1-30%), and higher (> 30%) NP/PA utilization. The proportion of EM resident-seen patients meeting previously established complex patient criteria was then determined for EDs at each level of NP/PA utilization. The proportion of EM resident-seen patients receiving certain ACGME-required procedures was also determined. Survey analytic procedures and weighting as recommended by NHAMCS were used to calculate and compare proportions using 95% CIs. RESULTS: The weighted 2016-2020 NHAMCS data sets represent 44,130,996 adult resident-seen patients presenting to nonpediatric academic EDs. The proportion of resident-seen patients meeting complex patient criteria did not significantly differ for lower (43.2%; 95% CI 30.6-56.8%), moderate (41.7%; 95% CI 33.0-50.9%), or higher (38.9%; 95% CI 29.3-49.4%) NP/PA utilization EDs. The proportion of patients undergoing an ACGME-required procedure also did not significantly differ across level of NP/PA utilization. CONCLUSIONS: Higher levels of NP/PA utilization in nonpediatric academic EDs do not appear to reduce EM resident exposure to more-complex patients or ACGME-required procedures.

Patient Perspectives on a Tailored Self-Management Education and Support Intervention for Low-Income Seniors With Chronic Health Conditions.

Background: The Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study (ACCESS) was a 2 x 2 factorial randomized trial that tested the impact of a tailored self-management education support (SMES) program, which demonstrated a 22% reduction in adverse clinical events. We sought to qualitatively explore participants' perspectives on the SMES intervention, and the ways in which it may have improved self-management skills. Methods: We used a qualitative descriptive approach and conducted individual semistructured interviews. We conducted inductive and deductive thematic analysis using NVivo 12 (QSR International, Burlington, MA). Results: We interviewed 20 participants who had recently completed the 3-year SMES intervention. The following 3 main themes emerged from the data: (i) empowerment; (ii) intervention acceptability; and (iii) suggestions for improvement. Regarding empowerment, we identified subthemes of health literacy, self-efficacy, self-management, and active role in health. Several participants reported that empowerment promoted health behaviour change or improved confidence in self-management. Regarding acceptability, we identified subthemes of ease of use and presentation style. Most participants expressed positive feelings toward the intervention and felt that it was easy to understand. Finally, we identified subthemes of learning style, content, and engagement strategies, within the theme of suggestions for improvement. Some participants said that the messages were too general and did not fully address the complex health concerns they had. Conclusions: Our results highlighted key strategies to promote patient engagement and self-management behaviours and demonstrated how they may have been used to improve clinical endpoints. Additionally, we demonstrated the novel use of marketing principles in SMES interventions.

Contexte: L'étude ACCESS (pour Assessing Outcomes of Enhanced Chronic Disease Care Through Patient Education and a Value-based Formulary Study) était un essai à répartition aléatoire avec un plan factoriel 2 x 2 qui a mesuré l'effet d'un programme personnalisé de soutien à la formation sur l'autogestion dans laquelle une réduction de 22 % des événements cliniques défavorables a été observée. Notre objectif était de réaliser une exploration qualitative du point de vue des patients au sujet de l'intervention et des façons dont elle a permis d'améliorer leurs habiletés d'autogestion. Méthodologie: Nous avons utilisé une approche descriptive et qualitative et nous avons mené des entretiens individuels semi-structurés auprès des participants. Des analyses thématiques inductive et déductive ont été réalisées avec NVivo 12 (QSR International, Burlington MA). Résultats: Des entretiens ont été menés auprès de 20 personnes ayant récemment terminé l'intervention de 3 ans. Les données recueillies ont permis de cerner 3 thèmes principaux : (i) l'autonomisation; (ii) l'acceptabilité de l'intervention; et (iii) les suggestions pour l'amélioration du programme. En ce qui concerne l'autonomisation des patients, nous avons relevé les sous-thèmes de la littératie dans le domaine de la santé, de l'auto-efficacité, de l'autogestion et de la participation active dans le domaine de la santé. Plusieurs participants ont mentionné que l'autonomisation avait favorisé des changements de comportements liés à la santé ou avait amélioré leur niveau de confiance quant à leur autogestion. Pour ce qui est de l'acceptabilité, nous avons noté les sous-thèmes de la facilité d'utilisation et du style des présentations. La plupart des participants ont exprimé une opinion favorable au sujet de l'intervention et la trouvaient facile à comprendre. En dernier lieu, nous avons relevé les thèmes des styles d'apprentissage, du contenu et des stratégies de mobilisation, que nous avons regroupés sous le thème des suggestions d'amélioration. Certains participants ont mentionné que les messages étaient trop généraux et n'abordaient pas leurs préoccupations complexes liées à la santé. Conclusions: Les résultats que nous avons obtenus ont mis en évidence des stratégies clés pour favoriser la participation des patients et leurs comportements d'autogestion et la façon dont elles ont pu améliorer les résultats cliniques de patients. De plus, nous avons démontré une nouvelle utilisation de principes tirés du domaine du marketing dans des interventions de soutien à la formation sur l'autogestion.

Critically examining health complexity experienced by urban Indigenous peoples in Canada by exploring the factors that allow health complexity to persist: a qualitative study of Indigenous patients in Calgary, Alberta.

OBJECTIVES: This study aims to identify and critically examine the components of health complexity, and explore the factors that allow it to exist, among urban Indigenous peoples in Canada. DESIGN: Qualitative exploration with relational conversations. SETTING: Calgary, Alberta, Canada. PARTICIPANTS: A total of nine urban Indigenous patients were recruited from a multidisciplinary primary healthcare clinic that serves First Nations, Métis and Inuit peoples. Recruitment and data collection took place between September and November 2021. RESULTS: Thematic analysis revealed three main themes, namely: sources of health complexity, psychological responses to adversity, and resilience, strengths, and protective factors. Key sources of health complexity arose from material resource disparities and adverse interpersonal interactions within the healthcare environment, which manifest into psychological distress while strengths and resilience emerged as protective factors. CONCLUSION: The healthcare system remains inapt to address complexity among urban Indigenous peoples in Canada. Healthcare violence experienced by Indigenous peoples only further perpetuates health complexity. Future clinical tools to collect information about health complexity among urban Indigenous patients should include questions about the factors defined in this study.

Novel approaches to the treatment of multiple myeloma.

The treatment landscape for multiple myeloma (MM) has evolved significantly over the last decade with the approval of novel therapies and combinations in the newly diagnosed and relapsed/refractory settings. There has also been a shift toward a risk-adapted approach to induction and maintenance regimens, with the goal of achieving better response rates for those with high-risk disease. The incorporation of anti-CD38 monoclonal antibodies into induction regimens has led to longer progression-free survival and higher rates of measurable residual disease negativity. In the relapsed setting, the emergence of B-cell maturation antigen-directed therapy, including antibody-drug conjugates, chimeric antigen receptor T-cell therapy, and more recently, bispecific antibodies, has produced deep and durable responses in heavily pretreated patients. This review article describes novel approaches to the treatment of MM in both the newly diagnosed and the relapsed/refractory setting.

Incidence of breakthrough fungal infections on isavuconazole prophylaxis compared to posaconazole and voriconazole.

BACKGROUND: Invasive fungal infections (IFIs) are a common infectious complication during the treatment of acute myeloid leukemia (AML), high-risk myelodysplastic syndrome (MDS) or post hematopoietic cell transplantation (HCT). For these patients, the National Comprehensive Cancer Network recommends posaconazole or voriconazole for IFI prophylaxis. In clinical practice, however, there has been increased use of isavuconazole due to favorable pharmacokinetic and pharmacodynamic parameters despite limited data for this indication. The comparative prophylactic efficacy of antifungals in this patient population has not been reported, and an analysis is warranted. METHODS: This retrospective, matched cohort, single-center study, included AML, MDS, or HCT patients who began treatment or underwent transplant between January 1, 2015 and July 31, 2021. Isavuconazole patients were matched 1:2 with patients receiving posaconazole or voriconazole prophylaxis. RESULTS: A total of 126 patients were included, 42 received isavuconazole, 81 received posaconazole, and three received voriconazole. The majority of patients were male receiving secondary IFI prophylaxis while receiving steroids for treatment of GVHD. The incidence of possible, probable or proven IFI was 16.7% in the isavuconazole group compared to 10.7% in the posaconazole and voriconazole group (OR 1.28, 95% CI -0.9-1.4; p = .67). Hepatotoxicity occurred in 16 total patients, 14 receiving posaconazole and two receiving isavuconazole. CONCLUSION: Patients who received isavuconazole prophylaxis during AML induction therapy or post-HCT experienced a similar incidence of breakthrough fungal infections compared to those who received posaconazole or voriconazole. These results suggest no difference in antifungal prophylactic efficacy; however larger prospective comparative studies are needed.

Applying National Diabetic Care Standards for the Management of a Hispanic Population Attending a Free Clinic.

BACKGROUND: National quality measures set goals for diabetes management. Hispanic populations are higher risk for diabetes and associated complications, especially low-income communities. Research suggests free clinics provide suboptimal diabetes management. Our quality improvement project aims to improve diabetes management in the Hispanic free clinic population. METHODS: Clínica Latina's volunteer medical students and physicians serve predominantly uninsured Spanish-speaking patients. Established diabetes patients that attended clinic during the study were included. Data was collected regarding patients' diabetes care for two months, then analyzed compared to quality metrics. We implemented paper checklists and electronic medical record (EMR) smart phrases for volunteers to utilize in managing diabetes. RESULTS: 32 patients were included in the study. At baseline, 78% had an A1C check in the past 3 months, 81% were on a statin. In the past year, 81% had a lipid panel, 19% had an eye exam, 63% had a diabetic foot exam, 53% had a urine microalbumin-creatinine screening. After interventions, 97% had an A1C check, 93% were on a statin, 91% had a lipid panel, 31% had an eye exam, 75% had a foot exam, 63% had a urine microalbumin-creatinine. Patients with an LDL < 100 increased from 62 to 66%. The mean A1C did not statistically significantly change. Volunteer smart phrase utilization increased from 37 to 59.1%. CONCLUSION: We implemented a checklist and EMR smart phrase to optimize diabetes management in a student-run Hispanic free clinic, which improved quality metrics. Low-resource clinics serving Spanish-speaking populations may benefit from similar interventions to improve diabetic care.

Receiving threatening or obscene messages from a partner and mental health, self-harm and suicidality: results from the Adult Psychiatric Morbidity Survey.

PURPOSE: Threatening or obscene messaging is repeated, unwanted texts, emails, letters or cards experienced by the recipient as threatening or obscene, and causing fear, alarm or distress. It is rarely examined as an aspect of intimate partner violence. We describe the prevalence of exposure to threatening/obscene messaging from a current or ex-partner; characteristics of victims; and associations with other forms of violence and abuse, mental disorder, self-harm, and suicidality. METHODS: Cross-sectional probability-sample survey of the general population in England aged 16 + . Multivariable regression modelling tested associations between receipt of threatening/obscene messaging and current common mental disorder, past-year self-harm and suicidality. RESULTS: Threatening/obscene messages were received from a current/ex-partner by 6.6% (95%CI: 5.9-7.3) of adults who had been in a relationship; 1.7% received these in the past year. Victims were more likely to be female, under 35, single or divorced, socioeconomically disadvantaged, and to have experienced other forms of sexual and partner violence and abuse. Those who received threatening/obscene messages in the past year were more likely to experience common mental disorder (adjusted odds ratio 1.89; 1.01-3.55), self-harm (2.31; 1.00-5.33), and suicidal thoughts (2.00; 1.06-3.78). CONCLUSION: Threatening/obscene messaging commonly occurs in the context of intimate partner violence. While often occurring alongside sexual and physical violence, messaging has an additional association with mental disorder and suicidality. Routine enquiry in service settings concerning safety, including those working with people who have escaped domestic violence, should ask about ongoing contact from previous as well as current partners. This should include asking about messaging, as well as other forms of potentially technology-enabled abuse which may become increasingly common.

COVID-19 Vaccination Rates and Vaccine Hesitancy Among Spanish-Speaking Free Clinic Patients.

We sought to assess COVID-19 vaccination rates, as well as attitudes and beliefs towards the vaccine, of patients in a Spanish-speaking student-run free clinic in Columbus, Ohio. A cross-sectional study was performed. Surveys were distributed to all individuals over 18 years who presented to La Clínica Latina between July, 2022 and September, 2022. A convenience sample was used: patients in the waiting room and their accompanying family members or friends were invited to participate. Subjects were excluded if under the age of 18 or over the age of 75, or if non-Spanish speaking. Of the 158 individuals who agreed to participate in our study, 146 responded to the question regarding vaccination status, revealing 90.4% of respondents had received a COVID-19 vaccination. Most respondents learned about the vaccine from social media (26.4%) or television (22.7%). The majority of participants sought answers to questions surrounding the vaccine by asking their doctor (49.1%). The most common reason among unvaccinated participants for not undergoing vaccination was fear of an adverse reaction to the vaccine (n = 11). We found that a large proportion (90.4%) of individuals seeking care at a Spanish-speaking free clinic were vaccinated against COVID-19. Our study also provides perspective on the means of health knowledge acquisition and behaviors in this predominantly Latinx patient population in central Ohio. We can utilize our results to optimize and tailor clinic services and initiatives for COVID-19 boosters to meet the needs of this community.

Developing and evaluating a SAFER model to screen for diabetes complications among people experiencing homelessness: a pilot study protocol.

BACKGROUND: Diabetes management combined with housing instability intersects, forcing individuals to triage competing needs and critical stressors, such as safety and shelter, with fundamental diabetes self-management tasks like attending healthcare appointments to screen for the complications of diabetes, leaving individuals overwhelmed and overburdened. We aim to address this disjuncture found within our current healthcare delivery system by providing point-of-care screening opportunities in a more patient-centered approach. METHOD: We describe a pilot study of a novel clinical intervention which provides timely, comprehensive, and accessible screening for diabetes complications to people experiencing homelessness. We will assess the reach, effectiveness, adoption, implementation, and maintenance, as per the RE-AIM framework, of a SAFER model of care (i.e., screening for A1C, feet, eyes, and renal function). A trained nurse will provide this screening within a homeless shelter. During these encounters, eligible participants will be screened for microvascular complications (neuropathy, nephropathy, retinopathy) and have their A1C measured, all at the point of care, using bedside tools and novel technology. Effectiveness, our primary objective, will be evaluated using a pre-post design, by comparing the rate of completion of full microvascular screening during the study period with individuals' own historical screening in the 2-year period prior to enrollment. The other domains of the RE-AIM framework will be assessed using process data, chart reviews, patient surveys, and qualitative semi-structured interviews with service providers and participants. This study will be conducted in a large inner-city homeless shelter within a major urban Canadian city (Calgary, Canada). DISCUSSION: Currently, screening for diabetes complications is often inaccessible for individuals experiencing homelessness, which places heavy burdens on individuals and, ultimately, on already strained emergency and acute care services when complications go undetected at earlier stages. The SAFER intervention will modify the current standard of care for this population in a way that is less fragmented, more person-focused, and timely, with the goal of ultimately improving the rate of screening in an acceptable fashion to identify those requiring specialist referral at earlier stages.

Inpatient primary prophylaxis of cancer-associated thromboembolism (CAT).

PURPOSE: Cancer-associated thrombosis (CAT) increases morbidity and mortality in oncology patients. The risk of CAT is increased with hospitalization for acute medical illness. The goal of this review will be to examine the available evidence for (1) risk assessment and (2) primary thromboprophylaxis, (3) international published guideline recommendations, and (4) future directions to manage oncology patients admitted for an acute medical illness. METHODS: A review was performed for each subject to gather information on the available evidence and recommendations available for oncology patients hospitalized for an acute medical illness. RESULTS: Risk assessments for thrombosis are primarily developed and validated in the general population. There is not a risk assessment that has specifically been developed and validated in oncology patients hospitalized for an acute medical illness. Most evidence for thromboprophylaxis of oncology patients is from sub-group analysis of larger randomized-controlled trials in the general population. Evidence is conflicting and suggests an individualized approach evaluating the risk-benefit of thromboprophylaxis. The strength of recommendations of international guidelines is limited because of the available evidence. Guidelines usually recommend utilizing and/or offering thromboprophylaxis to oncology patients hospitalized for an acute medical illness barring contraindications. Future evidence needs to improve risk assessments and knowledge of the appropriate agent, dose, and duration of thromboprophylaxis if indicated. CONCLUSION: Evidence for risk assessments and primary prophylaxis for oncology patients hospitalized for acute medical illness appears limited, with many research opportunities available to improve understanding on management of this patient population.

Healthy food prescription incentive programme for adults with type 2 diabetes who are experiencing food insecurity: protocol for a randomised controlled trial, modelling and implementation studies.

INTRODUCTION: The high cost of many healthy foods poses a challenge to maintaining optimal blood glucose levels for adults with type 2 diabetes mellitus who are experiencing food insecurity, leading to diabetes complications and excess acute care usage and costs. Healthy food prescription programmes may reduce food insecurity and support patients to improve their diet quality, prevent diabetes complications and avoid acute care use. We will use a type 2 hybrid-effectiveness design to examine the reach, effectiveness, adoption, implementation and maintenance (RE-AIM) of a healthy food prescription incentive programme for adults experiencing food insecurity and persistent hyperglycaemia. A randomised controlled trial (RCT) will investigate programme effectiveness via impact on glycosylated haemoglobin (primary outcome), food insecurity, diet quality and other clinical and patient-reported outcomes. A modelling study will estimate longer-term programme effectiveness in reducing diabetes-related complications, resource use and costs. An implementation study will examine all RE-AIM domains to understand determinants of effective implementation and reasons behind programme successes and failures. METHODS AND ANALYSIS: 594 adults who are experiencing food insecurity and persistent hyperglycaemia will be randomised to a healthy food prescription incentive (n=297) or a healthy food prescription comparison group (n=297). Both groups will receive a healthy food prescription. The incentive group will additionally receive a weekly incentive (CDN$10.50/household member) to purchase healthy foods in supermarkets for 6 months. Outcomes will be assessed at baseline and follow-up (6 months) in the RCT and analysed using mixed-effects regression. Longer-term outcomes will be modelled using the UK Prospective Diabetes Study outcomes simulation model-2. Implementation processes and outcomes will be continuously measured via quantitative and qualitative data. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Calgary and the University of Alberta. Findings will be disseminated through reports, lay summaries, policy briefs, academic publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04725630. PROTOCOL VERSION: Version 1.1; February 2022.

Drosophila Model for Gut-Mediated Horizontal Transfer of Narrow- and Broad-Host-Range Plasmids.

Horizontal gene transfer (HGT) is a driving force of microbial evolution. The gut of animals acts as a potent reservoir for the lateral transfer of virulence, fitness, and antimicrobial resistance genes through plasmids. Reduced-complexity models for the examination of host-microbe interactions involved in plasmid transfer are greatly desired. Thus, this study identifies the use of Drosophila melanogaster as a model organism for the conjugation of plasmids of various incompatibility groups in the gut. Enterobacteriaceae conjugation pairs were identified in vitro and used for oral inoculation of the Drosophila gut. Flies were enumerated for the donor, recipient, and transconjugant populations. Each donor-recipient pair was observed to persist in fly guts for the duration of the experiment. Gut concentrations of the donors and recipients were significantly different between male and female flies, with females generally demonstrating increased concentrations. Furthermore, host genetics significantly altered the concentrations of donors and recipients. However, transconjugant concentrations were not affected by host sex or genetics and were detected only in the IncPε and IncI1 plasmid groups. This study demonstrates Drosophila melanogaster as a model for gut-mediated plasmid transfer. IMPORTANCE Microbial evolution in the gut of animals due to horizontal gene transfer (HGT) is of significant interest for microbial evolution as well as within the context of human and animal health. Microbial populations evolve within the host, and factors from the bacteria and host interact to regulate this evolution. However, little is currently known about how host and bacterial factors regulate plasmid-mediated HGT in the gut. This study demonstrates the use of Drosophila and the roles of sexual dimorphism as well as plasmid incompatibility groups in HGT in the gut.

Contributions of elastic fibers, collagen, and extracellular matrix to the multiaxial mechanics of ligament.

Elastin is a biopolymer known to provide resilience to extensible biologic tissues through elastic recoil of its highly crosslinked molecular network. Recent studies have demonstrated that elastic fibers in ligament provide significant resistance to tensile and especially shear stress. We hypothesized that the biomechanics of elastic fibers in ligament could be described as transversely isotropic with both fiber and matrix components in a multi-material mixture. Similarly, we hypothesized that material coefficients derived using the experimental tensile response could be used to predict the experimental shear response. Experimental data for uniaxial and transverse tensile testing of control tissues, and those enzymatically digested to disrupt elastin, were used as inputs to a material coefficient optimization algorithm. An additive decomposition of the strain energy was used to model the total stress as the sum of contributions from collagen fibers, elastic fibers, elastic matrix, and ground substance matrix. Matrices were modeled as isotropic Veronda-Westmann hyperelastic materials, whereas fiber families were modeled as piecewise exponential-linear hyperelastic materials. Optimizations provided excellent fits to the tensile experimental data for each treatment case and material model. Given the disparity in magnitude of stresses between longitudinal and transverse/shear tests and agreement between models and experiments, the hypothesized transversely isotropic material of elastin symmetry was supported. In addition, the coefficients derived from uniaxial and transverse tensile experiments provided reasonable predictions of the experimental behavior during shear deformation. The magnitudes of coefficients representing stress, nonlinearity, and stiffness supported the experimental evidence that elastic fibers dominate the low strain tensile and shear response of ligament. These findings demonstrate that the additive decomposition modeling strategy can represent each discrete fiber and matrix constituent and their relative contribution to the material response of the tissue. These experimental data and the validated constitutive model provide essential inputs and a framework to refine existing computational models of ligament and tendon mechanics by explicitly representing the mechanical contributions of elastic fibers.

Decreasing Blood Culture Contaminants in a Pediatric Emergency Department: An Interrupted Time Series Analysis.

INTRODUCTION: High peripheral blood culture contamination rates (BCCR) in the emergency department (ED) contribute to overuse and harm. This study describes 2 years of quality improvement (QI) interventions that aimed to decrease a high BCCR in a pediatric ED. METHODS: The QI team created a Key Driver Diagram with multiple Plan-Do-Study-Act (PDSA) cycles. PDSA interventions included a venipuncture sterility checklist (PDSA1), phlebotomist feedback system (PDSA2), and physician ordering guidelines (PDSA3). The specific aim was to decrease the BCCR by 50% within 24 months. The secondary aim was to decrease the peripheral blood culture ordering rate (BCOR) by 10% within 24 months. The balancing measure was the proportion of pathogenic bacteremia cases at ED return visits before and after PDSA3 implementation. A financial measure estimated the savings in charges between the observed and expected contaminants in PDSA3. An interrupted time series design applied statistical process control methodology to detect special cause variations. RESULTS: The BCCR in the baseline, PDSA1, PDSA2, and PDSA3 periods were 3.02%, 2.30%, 1.58%, and 1.17%, respectively. The BCOR in the baseline, PDSA1, PDSA2, and PDSA3 periods was 4.80%, 4.26%, 3.82%, and 3.49%, respectively. Special cause variations occurred after PDSA cycle implementations for both BCCR and BCOR. There was no change in the balancing measure. The interventions were associated with an annual prevention of 95 contaminants and savings of $300,070. CONCLUSIONS: Interventions that focused on improving venipuncture technique and limiting unnecessary blood cultures were associated with fewer contaminants and the achievement of the QI team's project aims.

A systematic review of Federal Drug Administration Docket for community consultation and public disclosure in exception from informed consent trials.

BACKGROUND: Exception from informed consent imposes community consultation and public disclosure requirements on clinical investigation in critically ill and injured patients. In 2011, the Food and Drug Administration instructed sponsors to submit publically disclosed information to the Food and Drug Administration Docket, but to date there has been no comprehensive analysis of available data. We summarized the community consultation and public disclosure practices of exception from informed consent trials published on the Food and Drug Administration Docket in order to better understand the breadth of common practices that exists among acute care clinical research. METHODS: We performed quantitative and qualitative analysis of Docket FDA-1995-S-0036 from its initiation until June 2017 in order to summarize existing practices. We developed a 4-point scoring system to categorize public disclosure and community consultation based on inclusion of key components such as a detailed plan, schedule of events conducted, results, and materials uploaded. RESULTS: The 177 docket submissions represented 34 trials. Material related to public disclosure accounted for 49% of pages, community consultation 45%, and 6% other. The median Docket Review Content Score for public disclosure was 3 (mean: 2.5, range: 0-4) and 2 (mean: 2.1, range: 0-4) for community consultation materials. CONCLUSION: The public information contained in the Docket varies broadly by trial and content. Additionally, as evidenced by the wide range of the Docket Review Content Score, submission guidelines are not followed uniformly. Given the apparent uncertainty about what should be submitted, and the need for best practice recommendations, it is valuable to categorize and summarize existing community consultation and public disclosure content.

Climbing Bloom's taxonomy pyramid: Lessons from a graduate histology course.

Bloom's taxonomy was adopted to create a subject-specific scoring tool for histology multiple-choice questions (MCQs). This Bloom's Taxonomy Histology Tool (BTHT) was used to analyze teacher- and student-generated quiz and examination questions from a graduate level histology course. Multiple-choice questions using histological images were generally assigned a higher BTHT level than simple text questions. The type of microscopy technique (light or electron microscopy) used for these image-based questions did not result in any significant differences in their Bloom's taxonomy scores. The BTHT levels for teacher-generated MCQs correlated positively with higher discrimination indices and inversely with the percent of students answering these questions correctly (difficulty index), suggesting that higher-level Bloom's taxonomy questions differentiate well between higher- and lower-performing students. When examining BTHT scores for MCQs that were written by students in a Multiple-Choice Item Development Assignment (MCIDA) there was no significant correlation between these scores and the students' ability to answer teacher-generated MCQs. This suggests that the ability to answer histology MCQs relies on a different skill set than the aptitude to construct higher-level Bloom's taxonomy questions. However, students significantly improved their average BTHT scores from the midterm to the final MCIDA task, which indicates that practice, experience and feedback increased their MCQ writing proficiency. Anat Sci Educ 10: 456-464. © 2017 American Association of Anatomists.