IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors.

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αß-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that CD27+ Ly6C- cells convert into CD27+Ly6C+ cells, and these CD27+Ly6C+ cells control cancer progression in mice, while the CD27+Ly6C- cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27+Ly6C+ cells and human Vδ2+ cells, while IL-27 is dispensable for mouse CD27+Ly6C- cell and human Vδ1+ cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.

The Radiation Therapy Technology Evidence Matrix: a framework to visualize evidence development for innovations in radiation therapy.

Clinical evidence is crucial in enabling the judicious adoption of technological innovations in radiation therapy (RT). Pharmaceutical evidence development frameworks are not useful for understanding how technical advances are maturing. In this paper, we introduce a new framework, the Radiation Therapy Technology Evidence Matrix (rtTEM), that helps visualize how the clinical evidence supporting new technologies is developing. The matrix is a unique 2D model based on the R-IDEAL clinical evaluation framework. It can be applied to clinical hypothesis testing trials, as well as publications reporting clinical treatment. We present the rtTEM and illustrate its application, using emerging and mature RT technologies as examples. The model breaks down the type of claim along the vertical axis and the strength of the evidence for that claim on the horizontal axis, both of which are inherent in clinical hypothesis testing. This simplified view allows for stakeholders to understand where the evidence is and where it is heading. Ultimately, the value of an innovation is typically demonstrated through superiority studies, which we have divided into three key categories - administrative, toxicity and control, to enable more detailed visibility of evidence development in that claim area. We propose the rtTEM can be used to track evidence development for new interventions in RT. We believe it will enable researchers and sponsors to identify gaps in evidence and to further direct evidence development. Thus, by highlighting evidence looked for by key policy decision makers, the rtTEM will support wider, timely patient access to high value technological advances.

Hepatitis C (HCV) prevalence in citizens of the Métis Nation of Ontario.

BACKGROUND: Hepatitis C virus (HCV) infection is a major global concern, with Indigenous Peoples bearing the highest burden. Previous studies exploring HCV prevalence within Indigenous populations have predominantly used a pan-Indigenous approach, consequently resulting in limited availability of Métis-specific HCV data. The Métis are one of the three recognized groups of Indigenous Peoples in Canada with a distinct history and language. The Métis Nation of Ontario (MNO) is the only recognized Métis government in Ontario. This study aims to examine the prevalence of self-reported HCV testing and positive results among citizens of the MNO, as well as to explore the association between sociodemographic variables and HCV testing and positive results. METHODS: A population-based online survey was implemented by the MNO using their citizenship registry between May 6 and June 13, 2022. The survey included questions about hepatitis C testing and results, socio-demographics, and other health related outcomes. Census sampling was used, and 3,206 MNO citizens responded to the hepatitis C-related questions. Descriptive statistics and bivariate analysis were used to analyze the survey data. RESULTS: Among the respondents, 827 (25.8%, CI: 24.3-27.3) reported having undergone HCV testing and 58 indicated testing positive, resulting in a prevalence of 1.8% (CI: 1.3-2.3). Respondents with a strong sense of community belonging, higher education levels, and lower household income were more likely to report having undergone HCV testing. Among those who had undergone testing, older age groups, individuals with lower education levels, and retired individuals were more likely to test positive for HCV. CONCLUSION: This study is the first Métis-led and Métis-specific study to report on HCV prevalence among Métis citizens. This research contributes to the knowledge base for Métis health and will support the MNO's health promotion program and resources for HCV. Future research will examine the actual HCV incidence and prevalence among MNO citizens.

Landscape of Métis health and wellness: protocol for a scoping review.

INTRODUCTION: In Canada, Métis people are one of three distinct Indigenous peoples whose rights are recognised and affirmed in Section 35 of the federal Constitution Act, 1982. In line with Métis people having a unique culture, history, language and way of life, a distinctions-based approach is critical to understand the current landscape of Métis-specific health. In this paper, we present a scoping review protocol to describe this research landscape in Canada led by the Métis Nation of Ontario (MNO). METHODS AND ANALYSIS: This scoping review protocol is reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews reporting guidelines and follows Arksey and O'Malley's scoping review methodology. We will search electronic databases (Scopus, MEDLINE, Embase, Web of Science, CINAHL, APA PsycINFO, Anthropology Plus, Bibliography of Indigenous Peoples of North America, Canadian Business and Current Affairs, Indigenous Studies Portal, Informit Indigenous Collection, Collaborative Indigenous Garden, PubMed, ProQuest), grey literature sources and reference lists from selected papers. Two reviewers (HMB and SK) will double-blind screen all titles/abstracts and full-text studies for inclusion. Any health-related study or health report that includes a Métis-specific health, well-being or Métis social determinant of health outcome will be included. Relevant variables will be extracted following an iterative process whereby the data charting will be reviewed and updated. ETHICS AND DISSEMINATION: Findings from this scoping review will be shared back through the MNO's existing community-based communication channels. Traditional academic dissemination will also be pursued. Research ethics board approval is not required, since data are from peer-reviewed publications or publicly shared health reports and knowledge translation products.

Public Health Dashboards in Overdose Prevention: The Rhode Island Approach to Public Health Data Literacy, Partnerships, and Action.

As the field of public health rises to the demands of real-time surveillance and rapid data-sharing needs in a postpandemic world, it is time to examine our approaches to the dissemination and accessibility of such data. Distinct challenges exist when working to develop a shared public health language and narratives based on data. It requires that we assess our understanding of public health data literacy, revisit our approach to communication and engagement, and continuously evaluate our impact and relevance. Key stakeholders and cocreators are critical to this process and include people with lived experience, community organizations, governmental partners, and research institutions. In this viewpoint paper, we offer an instructive approach to the tools we used, assessed, and adapted across 3 unique overdose data dashboard projects in Rhode Island, United States. We are calling this model the "Rhode Island Approach to Public Health Data Literacy, Partnerships, and Action." This approach reflects the iterative lessons learned about the improvement of data dashboards through collaboration and strong partnerships across community members, state agencies, and an academic research team. We will highlight key tools and approaches that are accessible and engaging and allow developers and stakeholders to self-assess their goals for their data dashboards and evaluate engagement with these tools by their desired audiences and users.

COVID-19 vaccination intention and vaccine hesitancy among citizens of the Métis Nation of Ontario.

OBJECTIVE: The study objective is to measure the influence of psychological antecedents of vaccination on COVID-19 vaccine intention among citizens of the Métis Nation of Ontario (MNO). METHODS: A population-based online survey was implemented by the MNO when COVID-19 vaccines were approved in Canada. Questions included vaccine intention, the short version of the "5C" psychological antecedents of vaccination scale (confidence, complacency, constraint, calculation, collective responsibility), and socio-demographics. Census sampling via the MNO Registry was used achieving a 39% response rate. Descriptive statistics, bivariate analyses, and multinomial logistic regression models (adjusted for sociodemographic variables) were used to analyze the survey data. RESULTS: The majority of MNO citizens (70.2%) planned to be vaccinated. As compared with vaccine-hesitant individuals, respondents with vaccine intention were more confident in the safety of COVID-19 vaccines, believed that COVID-19 is severe, were willing to protect others from getting COVID-19, and would research the vaccines (Confident OR = 19.4, 95% CI 15.5-24.2; Complacency OR = 6.21, 95% CI 5.38-7.18; Collective responsibility OR = 9.83, 95% CI 8.24-11.72; Calculation OR = 1.43, 95% CI 1.28-1.59). Finally, respondents with vaccine intention were less likely to let everyday stress prevent them from getting COVID-19 vaccines (OR = 0.47, 95% CI 0.42-0.53) compared to vaccine-hesitant individuals. CONCLUSION: This research contributes to the knowledge base for Métis health and supported the MNO's information sharing and educational activities during the COVID-19 vaccines rollout. Future research will examine the relationship between the 5Cs and actual uptake of COVID-19 vaccines among MNO citizens.

RéSUMé: OBJECTIF: Nous avons cherché à mesurer l'influence des antécédents psychologiques de vaccination sur l'intention de se faire vacciner contre la COVID-19 chez les citoyennes et citoyens de la Nation métisse de l'Ontario (NMO). MéTHODE: Un sondage populationnel en ligne a été mis en œuvre par la NMO quand des vaccins contre la COVID-19 ont été approuvés au Canada. Les questions posées ont porté sur l'intention de se faire vacciner, la version abrégée du modèle « 5C ¼ de l'échelle de vaccination (Confiance, Contraintes, Complaisance, Calcul et responsabilité Collective) et le profil sociodémographique. Nous avons utilisé l'échantillonnage fondé sur le recensement via le registre de la NMO pour obtenir un taux de réponse de 39 %. Des statistiques descriptives, des analyses bivariées et des modèles de régression logistique multinomiale (ajustés selon les variables sociodémographiques) ont servi à analyser les données du sondage. RéSULTATS: La majorité (70,2 %) des citoyennes et citoyens de la NMO prévoyaient se faire vacciner. Comparativement aux personnes réticentes à l'égard de la vaccination, les personnes ayant l'intention de se faire vacciner avaient plus confiance en l'innocuité des vaccins contre la COVID-19, considéraient la COVID-19 comme une maladie grave, étaient disposées à protéger les autres contre la COVID-19 et cherchaient à se renseigner au sujet des vaccins (Confiance : RC = 19,4, IC95% 15,5­24,2; Complaisance : RC = 6,21, IC95% 5,38­7,18; responsabilité Collective : RC = 9,83, IC95% 8,24­11,72; Calcul : RC = 1,43, IC95% 1,28­1,59). Enfin, les répondantes et les répondants ayant l'intention de se faire vacciner étaient moins susceptibles de laisser le stress quotidien les empêcher de se faire vacciner contre la COVID-19 (RC = 0,47, IC95% 0,42­0,53) comparativement aux personnes réticentes à l'égard de la vaccination. CONCLUSION: Cette étude contribue à la base de connaissances sur la santé des Métis et a appuyé les activités de sensibilisation et d'échange d'informations de la NMO pendant le déploiement des vaccins contre la COVID-19. Une étude future portera sur la relation entre les « 5C ¼ et le recours réel aux vaccins contre la COVID-19 chez les citoyennes et citoyens de la NMO.

SARS-CoV and SARS-CoV-2 display limited neuronal infection and lack the ability to transmit within synaptically connected axons in stem cell-derived human neurons.

Sarbecoviruses such as SARS and SARS-CoV-2 have been responsible for two major outbreaks in humans, the latter resulting in a global pandemic. While sarbecoviruses primarily cause an acute respiratory infection, they have been shown to infect the nervous system. However, mechanisms of sarbecovirus neuroinvasion and neuropathogenesis remain unclear. In this study, we examined the infectivity and trans-synaptic transmission potential of the sarbecoviruses SARS and SARS-CoV-2 in human stem cell-derived neural model systems. We demonstrated limited ability of sarbecoviruses to infect and replicate in human stem cell-derived neurons. Furthermore, we demonstrated an inability of sarbecoviruses to transmit between synaptically connected human stem cell-derived neurons. Finally, we determined an absence of SARS-CoV-2 infection in olfactory neurons in experimentally infected ferrets. Collectively, this study indicates that sarbecoviruses exhibit low potential to infect human stem cell-derived neurons, lack an ability to infect ferret olfactory neurons, and lack an inbuilt molecular mechanism to utilise retrograde axonal trafficking and trans-synaptic transmission to spread within the human nervous system.

Educator's blueprint: A how-to guide for creating analog serious games for learning in medical education.

Serious games are an emerging tool for teaching and learning within medical education. These games can be used to facilitate learning or to demonstrate complex concepts in short bursts of interactive learning. This educator's blueprint will provide 10 strategies for creating a serious game, focusing on card and board games. These strategies include creating a project charter; determining the nature of the game; establishing game mechanics; selecting the best medium; prototyping and playtesting; reviewing sensitivity to equity, diversity, and inclusion; reviewing and refining content; funding game development, manufacture, and distribution; marketing and publicizing the game; and future-proofing the game. This blueprint hopes to help aspiring serious game designers and educators to conceptualize the steps for successfully creating a new serious game for medical education.

Vertebral artery dissection in relation to pregnancy: a case series and literature review.

Cervical artery dissection is an uncommon condition for which pregnancy and postpartum states confer increased risk. Although the majority of patients with this condition fully recover, including resolution of the dissection on imaging, long-term sequelae include a variety of cardiovascular conditions that may be associated with high rates of morbidity and mortality. Here, we review 2 cases of vertebral artery dissection in relation to pregnancy. Our first case will review the management of a pregnant patient with a history of vertebral artery dissection; whereas our second case reviews a presentation of postpartum vertebral artery dissection. Providers should maintain a high suspicion of cervical artery dissection in pregnant and postpartum patients presenting with headache and neck pain.

Recently Emerged Novel Henipa-like Viruses: Shining a Spotlight on the Shrew.

Henipaviruses are zoonotic viruses, including some highly pathogenic and capable of serious disease and high fatality rates in both animals and humans. Hendra virus and Nipah virus are the most notable henipaviruses, resulting in significant outbreaks across South Asia, South-East Asia, and Australia. Pteropid fruit bats have been identified as key zoonotic reservoirs; however, the increased discovery of henipaviruses outside the geographic distribution of Pteropid fruit bats and the detection of novel henipa-like viruses in other species such as the shrew, rat, and opossum suggest that Pteropid bats are not the sole reservoir for henipaviruses. In this review, we provide an update on henipavirus spillover events and describe the recent detection of novel unclassified henipaviruses, with a strong focus on the shrew and its emerging role as a key host of henipaviruses.

Research ethics during infectious disease outbreaks: A survey of African research stakeholders using the Ebola virus disease outbreak as a case.

Conducting research during disease outbreaks can be ethically challenging as evidenced in the 2014-2016 Ebola outbreak in West Africa and COVID-19 pandemic. Yet, there has been little empirical research conducted for understanding the views and perspectives of different stakeholders regarding ethical issues in conducting research during disease outbreaks. This preliminary study was conducted to empirically explore African public health research stakeholders' views about research ethics issues during infectious disease outbreaks in Africa. We conducted an online survey of 330 participants attending the International Conference on Re-emerging and Emerging Infectious Disease (ICREID) meeting that took place from 13-15 March 2019 in Addis Ababa, Ethiopia to elicit their views on various research ethics complexities experienced in the 2014 Ebola outbreak. Study results revealed some divergent views on several ethical themes including: ethics of using unregistered interventions in outbreaks; acceptable study design; ethics review processes; risks-benefit assessment; exclusion of pregnant women and children; and biological sample and data sharing. Majority (76.3%) of respondents felt that in the absence of available standard treatments or prevention modalities, the use of investigational interventions can be ethically justifiable if there is a strong scientific rationale and favorable risk-benefit ratio. Regarding conventional placebo-controlled trials during outbreaks with high case fatality rates, respondents that considered this unethical were more than three times those that felt such design were ethically justifiable. We were somewhat surprised that a majority (almost 60%) of respondents were satisfied with the exclusion of pregnant women and children in clinical trials during outbreaks. All respondents concurred with the prioritization of informed consent for research during an outbreak. Based on our findings, research ethics guidance is needed to equip research stakeholders in dealing with ethical complexities arising in the conduct of research during emerging disease outbreaks-especially regarding using experimental interventions; placebo trial design; inclusion or justified exclusion of pregnant women and children; and biological sample/data sharing. The findings will be used in ongoing efforts of developing a consultative and coherent African-centric framework to support ethical conduct of research for future emerging infectious disease outbreaks in Africa.

Prevalence of Parent Mental Health Problems in an Interdisciplinary Feeding Clinic: Short Communication.

Parents of children with pediatric feeding disorder (PFD) often experience high stress and may be at advanced risk for mental health conditions. We conducted a retrospective chart review of 413 parents who completed intake surveys at an interdisciplinary feeding clinic to determine the prevalence and types of mental health conditions among parents; 41.8% of parents reported a mental health diagnosis among the mother and/or father. Of the parents with mental health conditions, the most prevalent conditions reported were anxiety (71.1% for mothers, 50% for fathers) and mood disorders (62.7% for mothers, 40.9% for fathers). For mothers, 21.1% indicated their mental health disorder had a postpartum onset. Parents of children with birth complications were more likely to have a mental health condition (50.9%) than parents of children without a birth complication (38.7%), and parents reporting mental health conditions had children with significantly more co-occurring medical conditions. Since parent stress and mental health can influence parent-child interactions during mealtime, this study suggests the importance of addressing both parent mental health factors and child factors when treating children for PFD. Future studies are needed to develop novel interventions that support the specific mental health needs of parents of children with PFD.

Don't Look Back and Spray! Risk of Endoscope Adhesion with Hemospray Application in Retroflexion in a Pediatric Patient.

Although the vast majority of recognized pediatric upper gastrointestinal bleeding (GIB) resolves spontaneously, gastrointestinal hemorrhage is the most common indication for urgent or emergent therapeutic endoscopy in pediatric practice. The application of hemostatic powders, including TC-325 (Hemospray, Cook Medical, Winston-Salem, NC, USA), has shown considerable impact on the control of acute bleeding, with the advantage of potentially covering an extensive area and requiring less technical expertise. We report a case of transient adherence of an esophagogastroduodenoscopy following Hemospray application in a 22-month-old with upper GIB. Our experience does not detract from the significant gains in the management of pediatric GIB from Hemospray; however, it does raise a cautionary note toward the application technique utilized.

Is equipoise a useful concept to justify randomised controlled trials in the cultural context of Pakistan? A survey of clinicians in relation to a trial of talking therapy for young people who self-harm.

BACKGROUND: Clinical equipoise, also defined as the uncertainty principle, is considered essential when recruiting subjects to a clinical trial. However, equipoise is threatened when clinicians are influenced by their own preferences. Little research has investigated equipoise in the context of trial recruitment. METHODS: This cross-sectional survey sought clinicians' views (operationalised as 11 statements relating to treatments offered in a trial of a psychological intervention for young people) about equipoise and individual treatment preferences in the context of moral justification for recruiting young people at risk of self-harm or suicide to a randomised controlled trial (RCT) to evaluate the Youth Culturally Adapted Manual Assisted Psychological Intervention (Y-CMAP) in Pakistan. We compared the views of clinicians involved in Y-CMAP RCT recruitment to those of a sample of clinicians not involved in trial recruitment but treating similar patients, comparing their sociodemographic characteristics and the proportions of those in each group agreeing with each statement. RESULTS: There was a response rate of 96% (75/78). Findings showed that, during trial recruitment and before the RCT results were known, the majority of all responding clinicians (73.3%) considered Y-CMAP to be an effective treatment for young people at risk of self-harm or suicide. Although there was an acknowledgement of individual preferences for the intervention, there was near consensus (90%) on the need to conduct an RCT for reaching an evidence-based decision. However, there were no significant differences in the proportion of recruiting clinicians reporting a treatment preference for Y-CMAP than non-recruiting clinicians (31 (88.6%) versus 36 (90%), p = 0.566). A significantly higher proportion of non-recruiting clinicians (87.5%) as compared to (48.5%) in the trial (p = 0.000) stated that there may be other treatments that may be equally good for the patients, seemingly undermining a preference for the intervention. Those reporting a treatment preference also acknowledged that there was nothing on which this preference was based, however confident they felt about them, thus accepting clinical equipoise as ethical justification for conducting the RCT. There was a significant group difference in views that treatment overall is better as a result of young patients' participation in the Y-CMAP trial (p = 0.015) (i.e. more clinicians not involved in the trial agreed with this statement). Similarly, more clinicians not involved in the trial agreed on the perceived availability of other treatment options that were good for young people at risk of self-harm (p < 0.05). CONCLUSIONS: The paper highlights that clinicians in Pakistan accept the notion of clinical equipoise as an ethical justification for patient participation in RCTs. The need for conducting RCTs to generate evidence base and to reduce bias was considered important by the clinical community.

COVID-19 vaccine behaviour among citizens of the Métis Nation of Ontario: A qualitative study.

BACKGROUND: The burden of the current COVID-19 pandemic is not shared equally in Canadian society, with Indigenous Peoples being disproportionately affected. Moreover, there is a lack of research pertaining to vaccination behaviour in Métis communities. This Métis-specific and Métis-led qualitative study endeavours to understand COVID-19 vaccine behaviour among citizens of the Métis Nation of Ontario (MNO). METHODS: Data was collected via one-on-one interviews. Participants were recruited via the MNO's existing social media channels. Participants filled out a screening survey indicating their intention to vaccinate against COVID-19 as yes, no, or unsure. Sixteen participants (9 yes, 3 unsure, 4 no) were interviewed. Interviews averaged 30 min, and the questions and probes were developed in collaboration with the MNO. The interviewer received Métis-specific cultural safety training. Interviews were transcribed verbatim and uploaded to NVivo 12. RESULTS: A deductive analysis using the Social Ecological Model framework (SEM) for vaccine behaviour and two blinded coders was used to understand the data. An additional factor, COVID-19 public health measures, was added to the framework to better capture the experiences of participants during the COVID-19 pandemic. Overall, the factors with the greatest number of coded references included Vaccine roll-out and availability, Organization of the public into priority groups, Public discourse, Interpersonal influences, Interface with health professionals, Knowledge state, Trust, and Vaccine risk perception. Bandwagoning (following others' behaviour) and Freeloading (perceiving enough people have been vaccinated), both factors of the SEM, were not discussed. Yes, no, and unsure participant groups were compared to understand the influences of each factor based on COVID-19 vaccination intention. CONCLUSIONS: MNO citizens COVID-19 vaccine behaviour was negatively and positively influenced by a number of factors. This information will allow the MNO and public health units to better tailor their messaging for COVID-19 vaccine uptake campaigns and future pandemic emergencies.

Henipavirus-induced neuropathogenesis in mice.

Hendra virus (HeV) and Nipah virus (NiV) are henipaviruses that can cause fatal encephalitis in humans. Many animal models have been used to study henipavirus pathogenesis. In the mouse, HeV infection has previously shown that intranasal challenge can lead to neurological infection, however mice similarly challenged with NiV show no evidence of virus infecting the brain. We generated recombinant HeV (rHeV) and NiV (rNiV) where selected proteins were switched to examine their role in neuroinvasion in the mouse. These viruses displayed similar growth kinetics when compared to wildtype in vitro. In the mouse, infection outcomes with recombinant virus did not differ to infection outcomes of wildtype viruses. Virus was detected in the brain of 5/30 rHeV-challenged mice, but not rNiV-challenged mice. To confirm the permissiveness of mouse neurons to these viruses, primary mouse neurons were successfully infected in vitro, suggesting that other pathobiological factors contribute to the differences in disease outcomes in mice.

Changes and predictors of maternal depressive and anxiety symptoms during the COVID-19 pandemic.

Longitudinal changes in maternal depressive and anxiety symptoms and predictors of symptom variation among a group of middle-to-upper income Canadian women (n = 2152) were examined prior to the pandemic (2017-2019) and at three pandemic timepoints (May-July 2020, March-April 2021, November-December 2021). Mean maternal depression and anxiety scores were elevated throughout the pandemic. Pre-pandemic depressive symptoms were associated with greater increases in depressive symptoms. Coping and relationship quality were protective factors. Supporting the development of coping strategies may mitigate mental health concerns among mothers.

Evaluation of the Safety and Tolerability of Sodium-Glucose Co-transporter 2 Inhibitors in the Older Population: A Systematic Review.

Objective The objective of this systematic review was to evaluate adverse effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors in older people. Data Sources Articles in PubMed and EBSCOhost-Medline databases between January 2011 and 2021 were analyzed. Search terms were SGLT2 inhibitor, SGLT2 inhibitors, geriatric/elderly/older people, and safety/ adverse drug reaction/tolerability. Meta-analyses, systematic reviews, review articles, journal clubs, articles that did not address the research question, excluded patients 65 years of age and older, had an updated article available, did not stratify by age group, or were a commentary on a cohort study were excluded. Data Synthesis The search resulted in 113 articles. There were 62 duplicates removed, and 30 excluded based on the abstract. Of the 32 articles remaining, 19 were removed for not meeting the research question or meeting exclusion criteria. A total of 13 studies, including randomized controlled trials, cohort studies, and case reports, were assessed. Conclusion Current evidence demonstrates that patients taking SGLT2 inhibitors and diuretics were more likely to experience volume depletion. Findings suggest that risk of UTI was highest when the patient's age is 75 years or older. Some studies indicated that risk of genital mycotic infection is prevalent in older people. Use of SGLT2 inhibitors in the older population was not associated with a higher risk of developing diabetic ketoacidosis. Use of SGLT2 inhibitors appears to be relatively safe in older people. The risk of side effects may be decreased by considering concomitant medications. Randomized controlled trials assessing safety of SGLT2 inhibitors in the older population is still warranted.