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Hindawi publishes peer-reviewed, Open Access journals across many areas of science, technology, and medicine, as well as several areas of social science. This collection hosts U of T publications automatically transferred from Hindawi journals.

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Exploring the Landscape of Eco-Mapping in Health Services Research: A Comprehensive Review
(2024-03-27) Saragosa, Marianne; Singh, Hardeep; Steele Gray, Carolyn; Tang, Terence; Orchanian-Cheff, Ani; Nelson, Michelle L. A.
Health services research is important in improving health systems’ and providers’ efficiency and effectiveness. This may require health services to intervene at an individual and community level to address people’s complex social issues. An important issue is social connections, which have been identified as a social determinant of health and can help buffer stressful life events. Social support networks can be visualized using eco-maps, a tool that originated in child welfare practices and has been adopted widely by clinicians and researchers. This paper aims to understand where and how eco-maps have been used in health services research. To answer the research questions, this scoping review used the Joanna Briggs Institute guidelines for scoping reviews. In total, 70 studies were included in the scoping review. The authors found that social support denoted in an eco-map does not guarantee the provision of support; however, the dialogue needed to create an eco-map could facilitate conversations about care expectations, identification of vulnerable points or risk factors, and actions to improve family and individual functioning. A significant gap remains in the knowledge and use of eco-maps in identifying population service and resource gaps and how to bridge the knowledge-to-action chasm better. Further exploration is needed to examine how to optimize the application of eco-mapping in the health services context, including generating guidelines, templates, or instructions for implementation. Therefore, addressing this gap is vital for ensuring eco-mapping informs future service design and policy changes.
Analysis of Physical and Mechanical Properties of Universal Composites under Different Types of Polishing before and after Acid Challenge
(2024-02-29) de Matos, José Roberto Vergínio; Antunes, Letícia Barbero; Catanoze, Isabela Araguê; de Souza, Isabela Saturnino; dos Santos, Paulo Henrique; Guiotti, Aimée Maria
This study aimed to evaluate in vitro the degree of surface smoothness provided by two different polishing techniques and the effect of acid challenge on the alteration of surface roughness (Ra), microhardness (Knoop), and color (ΔE00) of three nanoparticulate composites, simulating 1 year of exposure to hydrochloric acid (HCl). Eighty specimens for each composite were divided into four groups (n = 240), being control without polishing, control with wear, WPC (wear + polishing with Cosmedent Kit), and WPB (wear + BisCover LV liquid polish). Repeated measures ANOVA was applied for Ra and Knoop Microhardness. For the color (ΔE) three-way ANOVA was applied. In cases of statistically significant the Tukey posttest was applied (α = 0.05). Both types of polishing tested resulted in a surface smoothness below the critical value established by the studies (Ra ≥ 0.2 μm), even after immersion. The microhardness of all composite resins decreased after the challenges. The specimens immersed in HCl showed a lower microhardness (42.2 Kgf/mm2) when compared to the specimens immersed in artificial saliva (44.7 Kgf/mm2). Regarding the color change, the composites presented values compatible with clinical acceptability, with a statistically significant difference only between the control group and the other types of polishing for the Z350 XT resin (ΔE00 = 3.78). It was concluded that both mechanical and chemical polishing produced a satisfactory surface smoothness, even after immersions in artificial saliva and HCl. The microhardness of the composites was affected by the challenges and the composites tested were within clinical acceptability with regard to color change.
Intraoperative Ultrasound for Removal of a Fishbone Foreign Body Embedded in the Tongue
(2024-02-14) Daniel, Ryan C.; Hamour, Amr F.; Cottrell, Justin; Le, Trung; Higgins, Kevin M.
Background. Ultrasound (U/S) is a dynamic imaging modality with many applications in medicine. In Otolaryngology, U/S is used routinely in the clinic with several evolving applications intraoperatively. Case Report. A 53-year-old male presented to the emergency department with dysphagia, odynophagia, hoarseness, and sensation of foreign body after ingesting fish. A CT scan identified an approximately 2 cm horizontally-oriented foreign body consistent with a fishbone embedded in the left posterolateral tongue. Intraoperative U/S was used to localize and remove the fishbone without complications. Results. The patient recovered well after surgery and was discharged home on postoperative day 2. No residual foreign body was found on the repeat CT scan. Conclusion. Our case demonstrates the effectiveness of intraoperative U/S for removal of fishbone foreign bodies from the tongue and serves to inspire future applications of this modality in Otolaryngology.
Stressful Life Events and Reward Processing in Adults: Moderation by Depression and Anhedonia
(2024-02-03) Min, Sung; Mazurka, Raegan; Pizzagalli, Diego A.; Whitton, Alexis E.; Milev, Roumen V.; Bagby, R. Michael; Kennedy, Sidney H.; Harkness, Kate L.
Background. Exposure to acute stress is associated with reduced reward processing in laboratory studies in animals and humans. However, less clear is the association between reward processing and exposure to naturalistic stressful life events. The goal of the current study was to provide a novel investigation of the relation between past 6-month stressful life events and reward processing, and the extent to which this relation was moderated by depression diagnostic status and state symptoms of anhedonia. Methods. The current study included a secondary analysis of data from 107 adults (37 current-depressed, 25 past-depressed, 45 never-depressed; 75% women) drawn from two previous community studies. Past 6-month stressful life events were assessed with a rigorous contextual interview with independent ratings. Response to monetary reward was assessed with a probabilistic reward task. Results. Among current-depressed participants, and among both current- and past-depressed participants with high levels of anhedonia, greater exposure to independent life events outside of individuals’ control was significantly associated with poorer reward learning. In direct contrast, among those with low levels of anhedonia, greater exposure to independent life events was significantly associated with a greater overall bias toward the more frequently rewarded stimulus. Conclusions. Results suggest that depression and anhedonia are uniquely associated with vulnerability to blunted reward learning in the face of uncontrollable stressors. In contrast, in the absence of anhedonia symptoms, heightened reward processing during or following independent stressful life event exposure may represent an adaptive response.
Minimally Invasive Mitral Valve Repair with Artificial Chordae: Insights from a 6-Year Single-Center Study
(2023-12-06) Bui, Vinh Duc An; Nguyen, Dang; Pizano, Alejandro; Rutledge-Jukes, Heath; Iheagwaram, Chibuikem S.; Bajaj, Simar S.; Van, Dung Hung; Nguyen, Nam Hoai; Theologou, Thomas; Akbar, Armaan F.; Vervoort, Dominique; Harky, Amer; Nguyen, Dinh Hoang
Purpose. Minimally invasive mitral valve repair (MIMVR) has been demonstrated to be safe and effective, but technical difficulty, outcome variation, and lack of standardized protocols undermine the utility of artificial chordae. This study aims to analyze the midterm outcomes of repair using artificial chordae through right minithoracotomy. Methods. A retrospective cohort study was conducted on consecutive patients who underwent MIMVR using artificial chordae at a single center in Vietnam between April 2016 and April 2022. Valve repairs were separated into two groups based on a previously validated complexity score: simple repair (Group 1) and intermediate-to-complex repair (Group 2). Demographic variables, comorbidities, operative characteristics, surgical outcomes, and follow-up data on survival and mitral regurgitation (MR) grade were analyzed. The learning curve was assessed by comparing the number of procedures with operation time and aorta cross-clamp time. Primary endpoints included survival and freedom from recurrent MR at four years. Results. Ninety patients were identified, including 41 simple and 49 intermediate-to-complex repairs. The mean age was 50.5 ± 12.9 years. Both groups had similar preoperative characteristics. The perioperative and postoperative outcomes were favorable, with no cases requiring mitral valve replacement. The median follow-up time was 30.3 months (18.2–40.4), and there were two (2.2%) cardiac deaths, with one in each group. The Kaplan–Meier survival estimates for Groups 1 and 2 at 12 and 24 months were 97% vs. 100% and 97% vs. 96%, respectively (95% CI = 0.05–12.2, ), and estimates for freedom from recurrent MR were 97% vs. 92% and 97% vs. 88%, respectively (95% CI = 0.49–12.0, ). There was a negative association between the volume of operations and the duration of operation and aortic cross-clamp time, leading to shorter durations. Conclusion. Based on our single-center experience, MIMVR using artificial chordae via right mini-thoracotomy can be safely and effectively performed in resource-limited countries for patients with MR. This approach has been shown to be applicable for a range of MR complexities, from simple to intermediate-to-complex MV repairs, and has demonstrated promising results in terms of midterm freedom from MR recurrence.
Human Umbilical Cord Perivascular Cells Prevent Tumor Growth in a Melanoma Tumor-Bearing Mouse Model and Modulate Breast Cancer and Melanoma Cells in a Cell Line-Dependent Manner In Vitro
(2023-11-30) Lopez, Lianet; Shuster-Hyman, Hannah; Marco, Eden; Khan, Hasna; Gasner, Avishai; Uzelac, Aleksandra; Wyse, Brandon; Mander, Poonam; Sangaralingam, Mugundhine; Fish, Joseph; Gorodensky, Ariel; Mouazz, Samar; Kauffman, Amanda; Gallagher, Denis; Gauthier-Fisher, Andrée; Librach, Clifford L.
First trimester (FTM) and term human umbilical cord perivascular cells are promising mesenchymal stromal cell candidates to mitigate side effects of oncotherapy, but their safety for cancer patients remains to be determined. This study was designed to determine if human umbilical cord perivascular cells modulate tumor growth when injected systemically in a tumor-bearing mouse model. Immunodeficient mice-bearing palpable subcutaneous SK-MEL-28 human melanoma tumors were randomized to receive a tail vein injection of three human umbilical cord perivascular cell lines resuspended in hank’s buffer saline solution (vehicle) or vehicle only, as a control. Fibroblast cells were included as a cell control in some experiments. Tumor size was monitored weekly and weighed at 3-weeks postinjection. Cell fate and tumor cell proliferation, apoptosis, vascularization as well as tumor-associated immune cells were assessed using immunostaining and flow cytometry. Serum tumor necrosis factor alpha and C-reactive protein levels were measured using enzyme-linked immunosorbent assays. Transwell coculture models were used to study the paracrine effects of multiple lines of human umbilical cord cells on human melanoma cell lines as well as breast cancer cell lines. Systemic administration of FTM and term human umbilical cord perivascular cells, but not fibroblast cells, prevented melanoma tumor growth in a tumor-bearing animal model by modulating tumor cell proliferation and systemic inflammatory mechanisms. Cancer cell- and donor-dependent paracrine effects on cancer cell growth were observed in vitro. Our preclinical studies thus suggest that, with regards to its effects on tumor growth, systemic administration of FTM and term human umbilical cord perivascular cells may be a safe cell therapy to address the side effects of cancer.
Parental Involvement in the Transition from Paediatric to Adult Care for Youth with Chronic Illness: A Scoping Review of the North American Literature
(2023-11-24) Badour, Bryn; Bull, Amanda; Gupta, Abha A.; Mirza, Raza M.; Klinger, Christopher A.
With medical advancements and improvements in medical technology, an increasing number of children with chronic conditions survive into adulthood. There is accordant growing interest toward supporting adolescents throughout the transition from paediatric to adult care. However, there is currently a paucity of research focusing on the role that these patients’ parents should play during and after the transition to adult care and if maintained parental involvement is beneficial during this transition within a North American context. Accordingly, this scoping review utilized Arksey and O’Malley’s five-step framework to consider parental roles during chronically ill children’s transition to adult care. APA PsycInfo, CINAHL, EMBASE, MEDLINE, ProQuest, and Scopus were searched alongside advanced Google searches. Thematic content analysis was conducted on 30 articles meeting the following inclusion criteria: (1) published in English between 2010 and 2022, (2) conducted in Canada or the United States, (3) considered adolescents with chronic conditions transitioning to adult care, (4) family being noted in the title or abstract, and (5) patient populations of study not being defined by delays in cognitive development, nor mental illness. Three themes emerged from the literature: the impacts of maintaining parental involvement during transition to adult care for patients, parents experiencing feeling loss of stability and support surrounding the transition of their child’s care, and significant nonmedical life events occurring for youths at the time of transition of care. Parents assuming supportive roles which change alongside their maturing child’s needs were reported as being beneficial to young peoples’ transition processes, while parents who hover over or micromanage their children during this time were found to hinder successful transitions. Ultimately, the majority of reviewed articles emphasized maintained parental involvement as having a net positive impact on adolescents’ transitions to adult care. As such, practice and policies should be structured to engage parents throughout the transition process to best support their chronically ill children during this time of change.
Examining the Director of Nursing Role in Long-Term Care: An Integrative Review
(2023-11-06) Fineczko, Julia; Chu, Charlene H.; Cranley, Lisa; Wills, Aria; McGilton, Katherine S.
Aim. To identify and examine the structures and processes that support the director of nursing role in long-term care homes. Background. The director of nursing in long-term care homes is central to overseeing and supporting the workforce and delivery of safe, quality resident care. With ongoing health human resource challenges and an aging population requiring care from long-term care homes, it is important to understand what individual and organizational factors support the director of nursing leadership in these settings. Evaluation. This review was guided by Cooper’s five stages of the integrative review process. Donabedian’s structure-process-outcome framework was applied to synthesize the literature. Key Issue(s). Five individual-level structures (years of experience, level of education, demonstrated leadership capabilities, completed certification and/or established linkages with a professional association, and completed continuing education); three organizational-level structures (physical presence of leadership across the organization, a clear job description, and salary); and four processes (nursing home administrators and the director of nursing relationship, availability of onsite continuing education opportunities targeting directors of nursing and support for continuing education, cultivating relationships and enhancing networks beyond the long-term care home, and orientation to the role) were identified across 11 articles to support the director of nursing role in long-term care homes. Conclusion(s). The findings indicate that there are individual characteristics that support the director of nursing in their role. Notably, there are organizational structures and processes that can be modified at the practice and policy level to better recruit, retain, and support the performance of directors of nursing. Implications for Nursing Management. There are actionable steps that leaders and decision-makers can take to support nursing leadership across long-term care homes and directly address health human resource challenges.
Glucagon-Like Peptide-1 Receptor Agonists for Chronic Weight Management
(2023-09-20) Wojtara, Magda; Mazumder, Ashmita; Syeda, Yusra; Mozgała, Nikodem
Rates of obesity have risen over the past few decades. Subsequently, the popularity of the pharmaceutical weight-loss drug market has grown over the past few years to meet growing demand. Among the most commonly prescribed drugs for weight management, many are glucagon-like peptide-1 receptor agonists (GLP-1 agonists) which are also utilized for the management of type 2 diabetes. There is a substantial and growing body of research comparing the efficacy of different clinical trials and examining long-term safety. This literature review examines the rise of off-label prescribing practices in the management of weight, with a focus on GLP-1 agonists. Physicians and patients should be aware of the unique aspects of existing treatment options, the impacts of off-label prescribing, and the effects of these medications. This review emphasizes the importance of informed decision-making, as well as the need for further research to guide future clinical practice.
Academic and Clinical Nurses’ Perceptions and Experiences on Academic-Practice Partnership in Evidence-Based Practice: An Interpretive Description
(2023-09-19) Chen, Qirong; Halili, Xirongguli; Chen, Wenjun; Zhao, Junqiang; Castro, Aimee R.; Tang, Siyuan; Wang, Honghong; Xia, Yuting; Wang, Guiyun; Huang, Chongmei
Aim. To explore academic and clinical nurses’ perceptions and experiences on academic-practice partnership in evidence-based practice. Background. Academic-practice partnership could promote evidence-based practice which is crucial for high-quality care. Academic and clinical nurses are the foundation of the partnerships; however, there is little knowledge of their perceptions and experiences on academic-practice partnership in evidence-based practice. Methods. This is an interpretive description study. Twenty-two eligible participants were interviewed through face-to-face or online videoconferencing meetings. Guiding questions for the interviews focused on the perceptions and experiences of academic-practice partnership in the context of evidence-based practice. Interviews were recorded, transcribed, and checked verbatim. We used constant comparative analysis to analyze the qualitative data. Results. Four themes with fifteen subthemes were generated: necessities, modes, challenges, and benefits of the academic-practice partnership in evidence-based practice. Participants believed that academic-practice partnership was a necessary strategy to promote evidence-based practice and could be built through different modes. Nevertheless, most academic-practice partnerships were superficial because of specific types of challenges. However, a good academic-practice partnership could create a win-win situation for both nursing academia and clinical practice. Conclusion. Academic-practice partnership is a win-win strategy for both the academic side and clinical side to promote evidence-based practice. Different modes of academic-practice partnership provide academic and clinical nurses with more opportunities to promote evidence-based practice with a higher likelihood of successful implementation. However, related challenges require multilevel measures to provide better environments to initiate, build, and maintain intensive collaborations between academic and clinical nurses. Implications for Nursing Management. Academic and clinical organizations, leaders, and individuals should take multilevel measures to initiate, build, and maintain a close academic-practice partnership to promote evidence-based practice, which is crucial for high-quality nursing care, patient safety, and nursing discipline development.
A Likelihood Ratio Approach for Utilizing Case-Control Data in the Clinical Classification of Rare Sequence Variants: Application to BRCA1 and BRCA2
(2023-09-14) Zanti, Maria; O'Mahony, Denise G.; Parsons, Michael T.; Li, Hongyan; Dennis, Joe; Aittomäkkiki, Kristiina; Andrulis, Irene L.; Anton-Culver, Hoda; Aronson, Kristan J.; Augustinsson, Annelie; Becher, Heiko; Bojesen, Stig E.; Bolla, Manjeet K.; Brenner, Hermann; Brown, Melissa A.; Buys, Saundra S.; Canzian, Federico; Caputo, Sandrine M.; Castelao, Jose E.; Chang-Claude, Jenny; GC-HBOC study Collaborators,; Czene, Kamila; Daly, Mary B.; De Nicolo, Arcangela; Devilee, Peter; Dörk, Thilo; Dunning, Alison M.; Dwek, Miriam; Eccles, Diana M.; Engel, Christoph; Evans, D. Gareth; Fasching, Peter A.; Gago-Dominguez, Manuela; García-Closas, Montserrat; García-Sáenz, José A.; Gentry-Maharaj, Aleksandra; Geurts - Giele, Willemina R. R.; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; Gómez Garcia, Encarna B.; Güendert, Melanie; Guénel, Pascal; Hahnen, Eric; Haiman, Christopher A.; Hall, Per; Hamann, Ute; Harkness, Elaine F.; Hogervorst, Frans B. L.; Hollestelle, Antoinette; Hoppe, Reiner; Hopper, John L.; Houdayer, Claude; Houlston, Richard S.; Howell, Anthony; ABCTB Investigators,; Jakimovska, Milena; Jakubowska, Anna; Jernström, Helena; John, Esther M.; Kaaks, Rudolf; Kitahara, Cari M.; Koutros, Stella; Kraft, Peter; Kristensen, Vessela N.; Lacey, James V.; Lambrechts, Diether; Léoné, Melanie; Lindblom, Annika; Lubiński, Jan; Lush, Michael; Mannermaa, Arto; Manoochehri, Mehdi; Manoukian, Siranoush; Margolin, Sara; Martinez, Maria Elena; Menon, Usha; Milne, Roger L.; Monteiro, Alvaro N.; Murphy, Rachel A.; Neuhausen, Susan L.; Nevanlinna, Heli; Newman, William G.; Offit, Kenneth; Park, Sue K.; James, Paul; Peterlongo, Paolo; Peto, Julian; Plaseska-Karanfilska, Dijana; Punie, Kevin; Radice, Paolo; Rashid, Muhammad U.; Rennert, Gad; Romero, Atocha; Rosenberg, Efraim H.; Saloustros, Emmanouil; Sandler, Dale P.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Shu, Xiao-Ou; Simard, Jacques; Southey, Melissa C.; Stone, Jennifer; Stoppa-Lyonnet, Dominique; Tamimi, Rulla M.; Tapper, William J.; Taylor, Jack A.; Teo, Soo Hwang; Teras, Lauren R.; Terry, Mary Beth; Thomassen, Mads; Troester, Melissa A.; Vachon, Celine M.; Vega, Ana; Vreeswijk, Maaike P. G.; Wang, Qin; Wappenschmidt, Barbara; Weinberg, Clarice R.; Wolk, Alicja; Zheng, Wei; Feng, Bingjian; Couch, Fergus J.; Spurdle, Amanda B.; Easton, Douglas F.; Goldgar, David E.; Michailidou, Kyriaki
A large number of variants identified through clinical genetic testing in disease susceptibility genes are of uncertain significance (VUS). Following the recommendations of the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the frequency in case-control datasets (PS4 criterion) can inform their interpretation. We present a novel case-control likelihood ratio-based method that incorporates gene-specific age-related penetrance. We demonstrate the utility of this method in the analysis of simulated and real datasets. In the analysis of simulated data, the likelihood ratio method was more powerful compared to other methods. Likelihood ratios were calculated for a case-control dataset of BRCA1 and BRCA2 variants from the Breast Cancer Association Consortium (BCAC) and compared with logistic regression results. A larger number of variants reached evidence in favor of pathogenicity, and a substantial number of variants had evidence against pathogenicity—findings that would not have been reached using other case-control analysis methods. Our novel method provides greater power to classify rare variants compared with classical case-control methods. As an initiative from the ENIGMA Analytical Working Group, we provide user-friendly scripts and preformatted Excel calculators for implementation of the method for rare variants in BRCA1, BRCA2, and other high-risk genes with known penetrance.
Spray Encapsulation of Iron in Chitosan Biopolymer for Tea Fortification
(2023-09-11) Siddiqui, Juveria; McGee, Elisa June Teresa; Mhasavade, Deepak; Palagiri, Swathy; Balamurugan, V.; Diosady, Levente László
Aim. Tea was studied as a carrier for iron in a fortification strategy to reduce iron deficiency. Iron forms insoluble coloured complexes with tea polyphenols which lower consumer acceptability. Complexation of iron by polyphenols and quinones derived from tea inhibits iron absorption in the first segment of the small intestine. Spray-dried chitosan-iron microcapsules were prepared to prevent iron-polyphenol interaction before the beverage is consumed. A competing chelating agent (EDTA) or antioxidant (sodium ascorbate) was added to prevent interactions and help improve iron bioavailability. Methods. The effect of concentration of chitosan (0.2–1.5%w/w), iron loading (10–60% w/w FeSO4), addition of secondary coatings on particle morphology, surface iron exposure and release, and bioaccessibility were evaluated. Tea-containing chitosan microcapsules and chelating agents to enable iron absorption were evaluated for sensory acceptability. Results. The iron release profile at pH 1 and pH 7 exhibited reverse enteric behaviour of non-cross-linked chitosan microcapsules. Increasing the iron content leads to more iron exposure on the surface due to a high core to coat ratio. Cross-linked chitosan effectively encapsulated iron, and its release in tea was inhibited, as indicated by lower delta E values in comparison with untreated tea and positive sensory testing scores. The use of maltodextrin as secondary coating slightly improved the spray process and produced larger particles, with less exposed iron on the surface. However, it did not improve the colour performance in milk tea. Conclusions. Tea fortified with encapsulated iron and a chelating agent providing 40% of the daily iron requirement of an adult, prepared in a traditional South Asian manner, i.e., with milk and water, resulted in tea with acceptable colour and taste. However, further research is required to develop an encapsulation formulation for stable iron encapsulation in hot tea and exploration of equivalent plant-based chitosan sources to address concerns of consumers with dietary restrictions.
First-in-Human PET Imaging of [18F]SDM-4MP3: A Cautionary Tale
(2023-09-08) Desmond, Kimberly L.; Lindberg, Anton; Garcia, Armando; Tong, Junchao; Harkness, Michael B.; Dobrota, Elena; Smart, Kelly; Uribe, Carme; Meyer, Jeffrey H.; Houle, Sylvain; Strafella, Antonio P.; Li, Songye; Huang, Yiyun; Vasdev, Neil
[18F]SynVesT-1 is a PET radiopharmaceutical that binds to the synaptic vesicle protein 2A (SV2A) and serves as a biomarker of synaptic density with widespread clinical research applications in psychiatry and neurodegeneration. The initial goal of this study was to concurrently conduct PET imaging studies with [18F]SynVesT-1 at our laboratories. However, the data in the first two human PET studies had anomalous biodistribution despite the injected product meeting all specifications during the prerelease quality control protocols. Further investigation, including imaging in rats as well as proton and carbon 2D-NMR spectroscopic studies, led to the discovery that a derivative of the precursor had been received from the manufacturer. Hence, we report our investigation and the first-in-human study of [18F]SDM-4MP3, a structural variant of [18F]SynVesT-1, which does not have the requisite characteristics as a PET radiopharmaceutical for imaging SV2A in the central nervous system.
Attitudes and Practices Surrounding Opioid Prescriptions following Open Reduction Internal Fixation of Distal Radius and Ankle Fractures: A Survey of the Canadian Orthopaedic Association Membership
(2023-09-07) Abouali, Jihad A.; Curd, Evan D.; Mei, Xin Y.; Sheth, Ujash; Khan, Moin; de SA, Darren; Tjong, Vehniah K.; Rana, Jesleen
Background. The past two decades have seen a significant increase in consequences associated with nonmedical misuse of prescription opioids, such as addiction and unintentional overdose deaths. This study aimed to use an electronic survey to assess attitudes and opioid-prescribing practices of Canadian orthopaedic surgeons and trainees following open reduction internal fixation (ORIF) of distal radius and ankle fractures. This study was the first to assess these factors following ORIF of distal radius and ankle fractures using a survey design. Methods. A 40-item survey was developed focusing on four themes: respondent demographics, opioid-prescribing practice, patients with substance use disorders, and drug diversion. The survey was distributed among members of the Canadian Orthopaedic Association. Descriptive statistics were used to summarize respondent demographics and outcomes of interest. A Chi-square test was used to determine if proportion of opioid prescriptions between attending surgeons and surgeons in training was equal. Results. 191 surveys were completed. Most respondents prescribed 10–40 tabs of immediate-release opioids, though this number varied considerably. While most respondents believed patients consumed only 40–80% of the prescribed opioids (73.6%), only 28.7% of respondents counselled patients on safe storage/disposal of leftover opioids. 30.5% of respondents felt confident in their knowledge of opioid use and mechanisms of addiction. Most respondents desired further education on topics such as procedure-based opioid-prescribing protocols (74.2%), alternative pain management strategies (69.7%), and mechanisms of opioid addiction (49.0%). Conclusions. The principle finding of this study is the lack of a standardized approach to postoperative prescribing in distal radius and ankle fractures, illustrated by the wide range in number of opioids prescribed by Canadian orthopaedic surgeons. Our data suggest a trend towards overprescription among respondents following distal radius and ankle ORIF. Future studies should aim to rationalize interventions targeted at reducing postoperative opioid prescribing for common orthopaedic trauma procedures.
Gastrointestinal Stromal Tumours (GISTs) with KRAS Mutation: A Rare but Important Subset of GISTs
(2023-08-24) Mullen, Dorinda; Vajpeyi, Rajkumar; Capo-Chichi, Jose-Mario; Nowak, Klaudia; Wong, Newton; Chetty, Runjan
Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the GI tract, usually found in the stomach, jejunum, and ileum. Typically, they are KIT or PDGFR-mutated, allowing for targetable treatments with tyrosine kinase inhibitors such as imatinib. Here, we present two KRAS-mutated wild-type gastrointestinal tumours (GISTs). Both cases occurred in the small bowel of females. Immunohistochemical studies on both tumours showed KIT and DOG-1 positivity, with SDHB retained. Molecular analysis revealed a KRAS G12D mutation and a KRAS G13D mutation, respectively. Wild-type GISTs are extremely uncommon. They typically occur in the stomach or the small bowel. KRAS is one of the genes implicated in this subset of GIST, with KRAS G12D being the most frequently encountered mutation. GIST KRAS mutations can arise alone or in conjunction with KIT, PDFRA, or BRAF mutations. Identification of these rare molecular subtypes is clinically important due to their resistance to imatinib therapy.
Preliminary Assessment of Reference Region Quantification and Reduced Scanning Times for [18F]SynVesT-1 PET in Parkinson’s Disease
(2023-08-11) Smart, Kelly; Uribe, Carme; Desmond, Kimberly L.; Martin, Sarah L.; Vasdev, Neil; Strafella, Antonio P.
Synaptic density in the central nervous system can be measured in vivo using PET with [18F]SynVesT-1. While [18F]SynVesT-1 has been proven to be a powerful radiopharmaceutical for PET imaging of neurodegenerative disorders such as Parkinson’s disease (PD), its currently validated acquisition and quantification protocols are invasive and technically challenging in these populations due to the arterial sampling and relatively long scanning times. The objectives of this work were to evaluate a noninvasive (reference tissue) quantification method for [18F]SynVesT-1 in PD patients and to determine the minimum scan time necessary for accurate quantification. [18F]SynVesT-1 PET scans were acquired in 5 patients with PD and 3 healthy control subjects for 120 min with arterial blood sampling. Quantification was performed using the one-tissue compartment model (1TCM) with arterial input function, as well as with the simplified reference tissue model (SRTM) to estimate binding potential () using centrum semiovale (CS) as a reference region. The SRTM2 method was used with fixed to either a sample average value (0.037 min-1) or a value estimated first through coupled fitting across regions for each participant. Direct SRTM estimation and the Logan reference region graphical method were also evaluated. There were no significant group differences in CS volume, radiotracer uptake, or efflux (). Each fitting method produced estimates in close agreement with those derived from the 1TCM (subject ,), with no difference in bias between the control and PD groups. With SRTM2, estimates from truncated scan data as short as 80 min produced values in excellent agreement with the data from the full 120 min scans (). While these are preliminary results from a small sample of patients with PD (), this work suggests that accurate synaptic density quantification may be performed without blood sampling and with scan time under 90 minutes. If further validated, these simplified procedures for [18F]SynVesT-1 PET quantification can facilitate its application as a clinical research imaging technology and allow for larger study samples and include a broader scope of patients including those with neurodegenerative diseases.
Temporomandibular Disorders among Dental Students in Pakistan: Assessment of Prevalence, Severity, and Associated Factors Based on Questionnaire
(2023-07-18) Nazir, Muhammad Ashraf; Izhar, Faisal; Hassan, Shafia; Tanvir, Maha; Nemat, Faris; Ashraf, Muhammad Waleed; Alamri, Abdulaziz
Objective. To evaluate the prevalence, severity, and associated factors of temporomandibular disorder (TMD) among dental students. Methods. This cross-sectional study was performed on undergraduate dental students from four dental colleges in Punjab, Pakistan. Fonseca’s questionnaire was used to measure the prevalence and severity of the TMD among the study participants. Bivariate and multiple logistic regression analyses were performed. Results. Of 364 dental students, 323 returned the completed questionnaires and the response rate of the study was 88.7%. The study included 52.6% males and 47.4% females. The prevalence of TMD was 66.9% with mild TMD in 40.90%, moderate TMD in 14.6%, and severe TMD in 11.50% of the participants. Psychological stress (29.6%), malocclusion (20%), and hypersensitivity (19.5%) were common among participants. The mean TMD score of the sample was 31.54 ± 24.86 which was significantly higher among participants with no/school-educated mothers () and fathers (). The participants with arthritis (72.81 ± 32.19) and malocclusion (59.46 ± 31.09) and those who received orthodontic treatment (53.21 ± 34.21) demonstrated higher TMD. After controlling for other study variables, the participants with arthritis were 4.71 times more likely to have moderate/severe TMD () than those without arthritis. Similarly, the participants with malocclusion had significantly higher odds (OR = 3.57, ) of having moderate/severe TMD than those without malocclusion. Conclusion. This sample of dental students demonstrated a high prevalence and severity of TMD. The participants with arthritis and malocclusion demonstrated higher TMD. The study findings underscore the importance of prevention, early diagnosis, and management of TMD among the dental students.
Di-(2-Ethylhexyl) Phthalate (DEHP) in House Dust in Canadian Homes: Behaviors and Associations with Housing Characteristics and Consumer Products
(2023-07-25) Zhang, Luyao; Navaranjan, Garthika; Takaro, Tim K.; Bernstein, Sarah; Jantunen, Liisa; Lou, Wendy; Mandhane, Piush J.; Moraes, Theo J.; Scott, James A.; Simons, Elinor; Turvey, Stuart E.; Subbarao, Padmaja; Brook, Jeffrey R.
Background. Di-(2-ethylhexyl) phthalate (DEHP), which is ubiquitous in indoor environments, was the predominant phthalate measured in house dust in the Canadian CHILD Cohort and was found to be associated with a large increased risk of childhood asthma. Objective. To inform interventions by identifying sources of DEHP in dust and assessing behaviors related to DEHP concentrations in house dust. Methods. DEHP levels were measured in 726 dust samples collected at ~3 months of age in CHILD as well as in ~50 homes at two time points (June and November) in the CHILD pilot study. DEHP metabolites were measured in urine for a subset of the ~3-month-old infants. Housing characteristics were assessed at the time of dust and urine collection. Numerous factors from these surveys were investigated as potential sources of DEHP using univariate analyses and multivariable regressions. Correlations between DEHP in dust and urinary metabolites and between repeat dust samples were examined to study the relationship between dust measurement and DEHP exposure. Results. Overall, DEHP dust concentrations were higher for lower-income families. Homes with vinyl flooring in the kitchen and bathroom showed higher levels of DEHP than those without vinyl flooring. The quantity of vinyl furniture and the presence of mold were associated with higher DEHP concentrations, while the use of mattress covers reduced concentration. No other significant associations were found. DEHP concentrations in dust were consistent over 6 months, although the correlation between dust and DEHP metabolites in urine was low. Conclusion. DEHP in house dust persisted over multiple months, contributed to infant internal exposure, and was associated with specific housing characteristics. These findings may inform the public on their choice of building materials and products, as well as future policies, aimed at reducing the health risk associated with exposures in the indoor environment especially for children.
Management of Mixed Warm/Cold Autoimmune Hemolytic Anemia: A Case Report and Review of Current Literature
(2023-07-24) Smith, Elliot C.; Kahwash, Nabeel; Piran, Siavash
Background. Mixed warm/cold autoimmune hemolytic anemia (AIHA) is a rare diagnostic entity with limited therapeutic options. Previous literature has described the diagnostic difficulty in this pathology and the limited response rates to corticosteroids. Furthermore, there is limited evidence regarding the use of rituximab in this condition. Methods. Alongside our case report, we conducted a scoping review of case reports/case series describing mixed AIHA, their treatment, and clinical outcomes since 2000. Inclusion criteria included a confirmed diagnosis of mixed AIHA (confirmed warm antibodies and cold agglutinins based on DAT). Case Summary/Results. We present a case of mixed AIHA in an 83-year-old female presenting with extensive, bilateral pulmonary embolisms and left renal vein thrombosis. The patient underwent extensive workup with no identifiable provoking etiology. Initial treatment involved prednisone therapy was transitioned to rituximab upon diagnosis of mixed AIHA. The patient demonstrated a mixed response with stable hemoglobin and transfusion independence; however, with persistently elevated hemolytic indices following completion of rituximab treatment. Our literature review identified 16 articles; two were excluded for unavailable clinical details. The most commonly associated conditions included autoimmune conditions (n = 5, 26%) and lymphoproliferative disorders (n = 3, 12%). The most common treatment involved corticosteroids; seven studies involved the use of rituximab. Conclusion. Mixed AIHA represents a complex diagnosis and optimal management is not well established. Consistent with our case, recent literature suggests a promising response to rituximab and a limited response to steroid treatment. Given the limited literature, additional studies are required to elucidate optimal management of this unique pathology.
Functional Characterization of Novel Lunatic Fringe Variants in Spondylocostal Dysostosis Type-III with Scoliosis
(2023-07-11) Wengryn, Parker; Silveira, Karina da Costa; Oborn, Connor; Soltys, Carrie-Lynn; Beke, Alexander; Chacon-Fonseca, Inara; Damseh, Nadirah; Rodriguez, Marco Quesada; Badilla-Porras, Ramses; Kannu, Peter
Scoliosis affects over four million Americans, with most cases having an idiopathic cause. Pathogenic variants in the LUNATIC FRINGE (LFNG) gene can cause spondylocostal dysostosis type-III (SCD3), which is a rare skeletal dysplasia characterized by the absence, fusion, or partial development of vertebrae and ribs. Acute restrictive lung disease and scoliosis may also be present in some cases. The variability in symptoms suggests that there may be other underlying pathological mechanisms that are yet to be discovered. We conducted an analysis of two novel LFNG variants, c.766G>A (p.G256S) and c.521G>A (p.R174H), that were observed in a patient with SCD3 phenotype and scoliosis. Characterizing these variants can help us better understand the relationship between genotype and phenotype. We assessed both variants for impaired glycosyltransferase activity, subcellular mislocalization, and aberrant pre-proprotein processing. Our results indicate that the p.G256S variant is enzymatically nonfunctional, while the p.R174H variant is functionally less effective. Both variants were correctly localized and processed. Our findings suggest that the hypomorphic variant (p.R174H) may have partially improved the patient’s stature, as evidenced by a lower arm span-to-height ratio, increased height, and more vertebrae. However, this variant did not appear to have any effect on the severity of vertebral malformations, including scoliosis. Further research is necessary to determine the extent to which variations in LFNG activity affect the presentation of SCD3.

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