Exposure to air pollution as a risk factor for anaemia: a global scoping review.

Anaemia is an important global health issue with various factors responsible for its occurrence. Though nutritional deficiency is one of the main causes of the disease, evidence suggests a potential link between long-term exposure to ambient air pollution and an increased risk of developing anaemia. Our scoping review evaluates studies conducted across the world to examine possible associations between anaemia and ambient air pollution. Six databases were searched, 153 sources were identified, and 21 articles were included in the review. Apart from one article which showed no significant effect, studies reported positive associations between anaemia and air pollution. This was true for both indoor and outdoor air pollution, various types of particulate matter exposure, and across demographic groups. The review highlights the importance of recognizing exposure to air pollution as a potential risk factor for anaemia and emphasizes the imperative for focused interventions and policy measures to mitigate air pollution.

Exploring and targeting potential druggable antimicrobial resistance targets ArgS, SecY, and MurA in Staphylococcus sciuri with TCM inhibitors through a subtractive genomics strategy.

Staphylococcus sciuri (also currently Mammaliicoccus sciuri) are anaerobic facultative and non-motile bacteria that cause significant human pathogenesis such as endocarditis, wound infections, peritonitis, UTI, and septic shock. Methicillin-resistant S. sciuri (MRSS) strains also infects animals that include healthy broilers, cattle, dogs, and pigs. The emergence of MRSS strains thereby poses a serious health threat and thrives the scientific community towards novel treatment options. Herein, we investigated the druggable genome of S. sciuri by employing subtractive genomics that resulted in seven genes/proteins where only three of them were predicted as final targets. Further mining the literature showed that the ArgS (WP_058610923), SecY (WP_058611897), and MurA (WP_058612677) are involved in the multi-drug resistance phenomenon. After constructing and verifying the 3D protein homology models, a screening process was carried out using a library of Traditional Chinese Medicine compounds (consisting of 36,043 compounds). The molecular docking and simulation studies revealed the physicochemical stability parameters of the docked TCM inhibitors in the druggable cavities of each protein target by identifying their druggability potential and maximum hydrogen bonding interactions. The simulated receptor-ligand complexes showed the conformational changes and stability index of the secondary structure elements. The root mean square deviation (RMSD) graph showed fluctuations due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points where the pattern of the RMSD and root mean square fluctuation (RMSF) (< 1.0 Å) support any major domain shifts within the structural framework of the protein-ligand complex and placement of ligand was well complemented within the binding site. The ß-factor values demonstrated instability at few points while the radius of gyration for structural compactness as a time function for the 100-ns simulation of protein-ligand complexes showed favorable average values and denoted the stability of all complexes. It is assumed that such findings might facilitate researchers to robustly discover and develop effective therapeutics against S. sciuri alongside other enteric infections.

Genomic landscape of the emerging XDR Salmonella Typhi for mining druggable targets clpP, hisH, folP and gpmI and screening of novel TCM inhibitors, molecular docking and simulation analyses.

Typhoid fever is transmitted by ingestion of polluted water, contaminated food, and stool of typhoid-infected individuals, mostly in developing countries with poor hygienic environments. To find novel therapeutic targets and inhibitors, We employed a subtractive genomics strategy towards Salmonella Typhi and the complete genomes of eight strains were primarily subjected to the EDGAR tool to predict the core genome (n = 3207). Human non-homology (n = 2450) was followed by essential genes identification (n = 37). The STRING database predicted maximum protein-protein interactions, followed by cellular localization. The virulent/immunogenic ability of predicted genes were checked to differentiate drug and vaccine targets. Furthermore, the 3D models of the identified putative proteins encoded by the respective genes were constructed and subjected to druggability analyses where only "highly druggable" proteins were selected for molecular docking and simulation analyses. The putative targets ATP-dependent CLP protease proteolytic subunit, Imidazole glycerol phosphate synthase hisH, 7,8-dihydropteroate synthase folP and 2,3-bisphosphoglycerate-independent phosphoglycerate mutase gpmI were screened against a drug-like library (n = 12,000) and top hits were selected based on H-bonds, RMSD and energy scores. Finally, the ADMET properties for novel inhibitors ZINC19340748, ZINC09319798, ZINC00494142, ZINC32918650 were optimized followed by binding free energy (MM/PBSA) calculation for ligand-receptor complexes. The findings of this work are expected to aid in expediting the identification of novel protein targets and inhibitors in combating typhoid Salmonellosis, in addition to the already existing therapies.

Subtractive sequence analysis aided druggable targets mining in Burkholderia cepacia complex and finding inhibitors through bioinformatics approach.

Burkholderia cepacia complex (BCC) is a group of gram-negative bacteria composed of at least 20 different species that cause diseases in plants, animals as well as humans (cystic fibrosis and airway infection). Here, we analyzed the proteomic data of 47 BCC strains by classifying them in three groups. Phylogenetic analyses were performed followed by individual core region identification for each group. Comparative analysis of the three individual core protein fractions resulted in 1766 ortholog/proteins. Non-human homologous proteins from the core region gave 1680 proteins. Essential protein analyses reduced the target list to 37 proteins, which were further compared to a closely related out-group, Burkholderia gladioli ATCC 10,248 strain, resulting in 21 proteins. 3D structure modeling, validation, and druggability step gave six targets that were subjected to further target prioritization parameters which ultimately resulted in two BCC targets. A library of 12,000 ZINC drug-like compounds was screened, where only the top hits were selected for docking orientations. These included ZINC01405842 (against Chorismate synthase aroC) and ZINC06055530 (against Bifunctional N-acetylglucosamine-1-phosphate uridyltransferase/Glucosamine-1-phosphate acetyltransferase glmU). Finally, dynamics simulation (200 ns) was performed for each ligand-receptor complex, followed by ADMET profiling. Of these targets, details of their applicability as drug targets have not yet been elucidated experimentally, hence making our predictions novel and it is suggested that further wet-lab experimentations should be conducted to test the identified BCC targets and ZINC scaffolds to inhibit them.

Public health emergency preparedness for infectious disease emergencies: a scoping review of recent evidence.

BACKGROUND: The COVID-19 pandemic continues to demonstrate the risks and profound health impacts that result from infectious disease emergencies. Emergency preparedness has been defined as the knowledge, capacity and organizational systems that governments, response and recovery organizations, communities and individuals develop to anticipate, respond to, or recover from emergencies. This scoping review explored recent literature on priority areas and indicators for public health emergency preparedness (PHEP) with a focus on infectious disease emergencies. METHODS: Using scoping review methodology, a comprehensive search was conducted for indexed and grey literature with a focus on records published from 2017 to 2020 onward, respectively. Records were included if they: (a) described PHEP, (b) focused on an infectious emergency, and (c) were published in an Organization for Economic Co-operation and Development country. An evidence-based all-hazards Resilience Framework for PHEP consisting of 11 elements was used as a reference point to identify additional areas of preparedness that have emerged in recent publications. The findings were analyzed deductively and summarized thematically. RESULTS: The included publications largely aligned with the 11 elements of the all-hazards Resilience Framework for PHEP. In particular, the elements related to collaborative networks, community engagement, risk analysis and communication were frequently observed across the publications included in this review. Ten emergent themes were identified that expand on the Resilience Framework for PHEP specific to infectious diseases. Planning to mitigate inequities was a key finding of this review, it was the most frequently identified emergent theme. Additional emergent themes were: research and evidence-informed decision making, building vaccination capacity, building laboratory and diagnostic system capacity, building infection prevention and control capacity, financial investment in infrastructure, health system capacity, climate and environmental health, public health legislation and phases of preparedness. CONCLUSION: The themes from this review contribute to the evolving understanding of critical public health emergency preparedness actions. The themes expand on the 11 elements outlined in the Resilience Framework for PHEP, specifically relevant to pandemics and infectious disease emergencies. Further research will be important to validate these findings, and expand understanding of how refinements to PHEP frameworks and indicators can support public health practice.

Navigating diagnostic options for inborn errors of immunity in children: a case-based illustration.

PURPOSE OF REVIEW: In recent years, there has been a dramatic increase in the number of recognized inborn errors of immunity (IEI), many of which present in childhood. This review discusses diagnostic approaches for some of the more common presentations of IEI in childhood. RECENT FINDINGS: Implementation of newborn screening (NBS) using the T cell receptor excision circle (TREC) assay has led to the timely identification of patients with severe combined immunodeficiency (SCID) as well as both syndromic and nonsyndromic forms of T cell lymphopenia, including DiGeorge syndrome. Improvements in the availability of immunophenotyping assays, genetic testing and advanced diagnostic techniques such as the artificial thymic organoid system can improve diagnostic clarity and impact management plans. Diagnostic improvements in humoral immunodeficiency include development of novel assays to quantify and functionally evaluate polysaccharide vaccine response. SUMMARY: IEI represent a rapidly growing field, particularly in paediatrics. Use of state-of-the-art diagnostic testing can facilitate rapid identification of IEI, hopefully allowing for initiation of prompt treatment and improved patient outcomes.

Inborn errors of immunity associated with elevated immunoglobulin E.

OBJECTIVE: To review the characteristic clinical and laboratory features of inborn errors of immunity (IEI) that are associated with elevated immunoglobulin (Ig)E levels. DATA SOURCES: Primary peer-reviewed literature. STUDY SELECTIONS: Original research articles reviewed include interventional studies, retrospective studies, case-control studies, cohort studies, and review articles related to the subject matter. RESULTS: An extensive literature review was completed to allow for comprehensive evaluation of several monogenic IEI. This review includes a description of the classic clinical features, common infections, characteristic laboratory findings, specific diagnostic methods (when applicable), and genetic basis of disease of each syndrome. A comprehensive flow diagram was created to assist them in the diagnosis and evaluation of patients with elevated IgE levels who may require evaluation for an IEI. CONCLUSION: IEI should be considered in patients with elevated IgE levels, especially if they have recurrent infections, eczematous dermatitis, malignancy, lymphoproliferation, autoimmunity, or connective tissue abnormalities.

Rising through the pandemic: a scoping review of quality improvement in public health during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic generated a growing interest in and need for evidence-based tools to facilitate the implementation of emergency management strategies within public health practice. Quality improvement (QI) is a key framework and philosophy to guide organizational emergency response efforts; however, the nature and extent to which it has been used in public health settings during the COVID-19 pandemic remains unclear. METHODS: We conducted a scoping review of literature published January 2020 - February 2021 and focused on the topic of QI at public health agencies during the COVID-19 pandemic. The search was conducted using four bibliographic databases, in addition to a supplementary grey literature search through custom Google search engines and targeted website search methods. Of the 1,878 peer-reviewed articles assessed, 15 records met the inclusion criteria. An additional 11 relevant records were identified during the grey literature search, for a total of 26 records included in the scoping review. RESULTS: Records were organized into five topics: 1) collaborative problem solving and analysis with stakeholders; 2) supporting learning and capacity building in QI; 3) learning from past emergencies; 4) implementing QI methods during COVID-19; and 5) evaluating performance using frameworks/indicators. CONCLUSIONS: The literature indicates that QI-oriented activities are occurring at the organizational and program levels to enhance COVID-19 response. To optimize the benefits that QI approaches and methodologies may offer, it is important for public health agencies to focus on both widespread integration of QI as part of an organization's management philosophy and culture, as well as project level activities at all stages of the emergency management cycle.

Deep learning analysis of electrocardiogram for risk prediction of drug-induced arrhythmias and diagnosis of long QT syndrome.

AIMS: Congenital long-QT syndromes (cLQTS) or drug-induced long-QT syndromes (diLQTS) can cause torsade de pointes (TdP), a life-threatening ventricular arrhythmia. The current strategy for the identification of drugs at the high risk of TdP relies on measuring the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG). However, QTc has a low positive predictive value. METHODS AND RESULTS: We used convolutional neural network (CNN) models to quantify ECG alterations induced by sotalol, an IKr blocker associated with TdP, aiming to provide new tools (CNN models) to enhance the prediction of drug-induced TdP (diTdP) and diagnosis of cLQTS. Tested CNN models used single or multiple 10-s recordings/patient using 8 leads or single leads in various cohorts: 1029 healthy subjects before and after sotalol intake (n = 14 135 ECGs); 487 cLQTS patients (n = 1083 ECGs: 560 type 1, 456 type 2, 67 type 3); and 48 patients with diTdP (n = 1105 ECGs, with 147 obtained within 48 h of a diTdP episode). CNN models outperformed models using QTc to identify exposure to sotalol [area under the receiver operating characteristic curve (ROC-AUC) = 0.98 vs. 0.72, P ≤ 0.001]. CNN models had higher ROC-AUC using multiple vs. single 10-s ECG (P ≤ 0.001). Performances were comparable for 8-lead vs. single-lead models. CNN models predicting sotalol exposure also accurately detected the presence and type of cLQTS vs. healthy controls, particularly for cLQT2 (AUC-ROC = 0.9) and were greatest shortly after a diTdP event and declining over time (P ≤ 0.001), after controlling for QTc and intake of culprit drugs. ECG segment analysis identified the J-Tpeak interval as the best discriminator of sotalol intake. CONCLUSION: CNN models applied to ECGs outperform QTc measurements to identify exposure to drugs altering the QT interval, congenital LQTS, and are greatest shortly after a diTdP episode.

TREC Screening for WHIM Syndrome.

PURPOSE: T cell receptor excision circle (TREC) quantification is a recent addition to newborn screening (NBS) programs and is intended to identify infants with severe combined immunodeficiencies (SCID). However, other primary immunodeficiency diseases (PID) have also been identified as the result of TREC screening. We recently reported a newborn with a low TREC level on day 1 of life who was diagnosed with WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome, a non-SCID primary immunodeficiency caused by mutations in the chemokine receptor CXCR4. METHODS: We have now retrospectively reviewed the birth and clinical histories of all known WHIM infants born after the implementation of NBS for SCID. RESULTS: We identified six infants with confirmed WHIM syndrome who also had TREC quantification on NBS. Three of the six WHIM infants had low TREC levels on NBS. All six patients were lymphopenic but only one infant had a T cell count below 1,500 cells/µL. The most common clinical manifestation was viral bronchiolitis requiring hospitalization. One infant died of complications related to Tetralogy of Fallot, a known WHIM phenotype. CONCLUSION: The results suggest that WHIM syndrome should be considered in the differential diagnosis of newborns with low NBS TREC levels. TRIAL REGISTRATION: Not applicable.

Insights into the role of estrogens and androgens in glial tumorigenesis.

Gliomas are more common in males than in females. Emerging evidence from several studies in vitro and in vivo have shown the role of estrogens and androgens in glial tumorigenesis. In recent times, studies have also shed light on the actions of estrogen receptors, alpha and beta, and androgen receptor. Here, we provide a comprehensive overview of the research hitherto on estrogens and androgens along with an emphasis on their receptors in glioma pathophysiology. Studies with conflicting results are discussed and future possibilities are put forward. A collective understanding of the studies on these steroid hormones in glioma may serve to create an amalgamated therapeutic approach; and thereby, augment the efforts in tackling this deadly disease.

The Management of Diabetes in Conflict Settings: Focus on the Syrian Crisis.

Humanitarian crises represent a major global health challenge as record numbers of people are being displaced worldwide. The Syrian crisis has resulted in >4 million refugees and 6 million people who are internally displaced within Syria. In 2017, there were 705,700 reported cases of adult diabetes in Syria. During periods of conflict, people with diabetes face numerous challenges, including food insecurity, inadequate access to medications and testing supplies, and a shortage of providers with expertise in diabetes care. Access to insulin represents a major challenge during a crisis, especially for individuals with type 1 diabetes, for whom the interruption of insulin constitutes a medical emergency. In the short term (days to weeks) during a crisis, it is vital to 1) prioritize insulin for patients with type 1 diabetes, 2) ensure continuous access to essential diabetes medications, and 3) provide appropriate diabetes education for patients, with a focus on hypoglycemia and sick-day guidelines. In the long term (weeks to months) during a crisis, it is important to 1) provide access to quality diabetes care and medications, 2) train local and international health care providers on diabetes care, and 3) develop clinical guidelines for diabetes management during humanitarian crises. It is imperative that we work across all sectors to promote the health of people with diabetes during humanitarian response.

Heterotrimeric kinesin-2, together with kinesin-1, steers vesicular acetylcholinesterase movements toward the synapse.

Acetylcholinesterase (AChE), which is implicated in the pathophysiology of neurological disorders, is distributed along the axon and enriched at the presynaptic basal lamina. It hydrolyses the neurotransmitter acetylcholine, which inhibits synaptic transmission. Aberrant AChE activity and ectopic axonal accumulation of the enzyme are associated with neurodegenerative disorders, such as Alzheimer's disease. The molecular mechanism that underlies AChE transport is still unclear. Here, we show that expression of Drosophila AChE tagged with photoactivatable green fluorescent protein and m-Cherry (GPAC) in cholinergic neurons compensates for the RNA interference-mediated knockdown of endogenous AChE activity. GPAC-AChE, which is enriched in the neuropil region of the brain, moves in the apparently vesicular form in axons with an anterograde bias in Drosophila larvae. Two anterograde motors, kinesin-1 and -2, propel distinct aspects of GPAC-AChE movements. Total loss of kinesin-2 reduces the density of anterograde traffic and increases bidirectional movements of GPAC-AChE vesicles without altering their speed. A partial loss of kinesin-1 reduces both the density and speed of anterograde GPAC-AChE traffic and enhances the pool of stationary vesicles. Together, these results suggest that combining activity of a relatively weak kinesin-2 with that of a stronger kinesin-1 motor could steer AChE-containing vesicles toward synapse, and provides a molecular basis for the observed subcellular distribution of the enzyme.-Kulkarni, A., Khan, Y., Ray, K. Heterotrimeric kinesin-2, together with kinesin-1, steers vesicular acetylcholinesterase movements toward the synapse.

Public health emergency preparedness: a framework to promote resilience.

BACKGROUND: Emergencies and disasters impact population health. Despite the importance of upstream readiness, a persistent challenge for public health practitioners is defining what it means to be prepared. There is a knowledge gap in that existing frameworks lack consideration for complexity relevant to health systems and the emergency context. The objective of this study is to describe the essential elements of a resilient public health system and how the elements interact as a complex adaptive system. METHODS: This study used a qualitative design employing the Structured Interview Matrix facilitation technique in six focus groups across Canada. Focus group participants were practitioners from public health and related sectors. Data collection generated qualitative data on the essential elements, and interactions between elements, for a resilient public health system. Data analysis employed qualitative content analysis and the lens of complexity theory to account for the complex nature of public health emergency preparedness (PHEP). The unit of study was the local/regional public health agency. Ethics and values were considered in the development of the framework. RESULTS: A total of 130 participants attended the six focus groups. Urban, urban-rural and rural regions from across Canada participated and focus group size ranged from 15 to 33 across the six sites. Eleven elements emerged from the data; these included one cross-cutting element (Governance and leadership) and 10 distinct but interlinked elements. The essential elements define a conceptual framework for PHEP. The framework was refined to ensure practice and policy relevance for local/regional public health agencies; the framework has ethics and values at its core. CONCLUSIONS: This framework describes the complexity of the system yet moves beyond description to use tenets of complexity to support building resilience. This applied public health framework for local/regional public health agencies is empirically-derived and theoretically-informed and represents a complex adaptive systems approach to upstream readiness for PHEP.

Promoting Adolescent Girls' Well-Being in Pakistan: a Mixed-Methods Study of Change Over Time, Feasibility, and Acceptability, of the COMPASS Program.

Promoting resilience among displaced adolescent girls in northern Pakistan may buffer against developmental risks such as violence exposure and associated longer-term consequences for physical and mental well-being. However, girls' access to such programming may be limited by social norms restricting movement. A mixed-method evaluation examined change over time, feasibility, and acceptability of the COMPASS program in three districts of Khyber-Pakhtunkhwa province through a single-group within-participant pretest-posttest of adolescent girls aged 12-19 enrolled in the intervention (n = 78), and qualitative in-depth interviews with girls following posttest completion (n = 15). Primary outcomes included improvements in movement, safety, and comfort discussing life skills topics with caregivers, operationalized quantitatively as number of places visited in the previous month, number of spaces that girls felt safe visiting, and comfort discussing puberty, education, working outside the home, and marriage, respectively. Secondary outcomes included psychosocial well-being, gendered rites of passage, social support networks, perceptions of support for survivors of violence, and knowledge of services. Quantitative pretest-posttest findings included significant improvements in movement, psychosocial well-being, and some improvements in social support, knowledge of services, and gendered rites of passage; findings on safety and comfort discussing life skills topics were not significant. Qualitative findings illuminated themes related to definitions of safety and freedom of movement, perceptions and acceptability of program content, perceptions of social support, and perceptions of blame and support and knowledge of services in response to violence. Taken together, findings illustrate positive impacts of life skills programming, and the need for societal changes on gender norms to improve girls' safety in public spaces and access to resources.

Effective communication of public health guidance to emergency department clinicians in the setting of emerging incidents: a qualitative study and framework.

BACKGROUND: Evidence to inform communication between emergency department clinicians and public health agencies is limited. In the context of diverse, emerging public health incidents, communication is urgent, as emergency department clinicians must implement recommendations to protect themselves and the public. The objectives of this study were to: explore current practices, barriers and facilitators at the local level for communicating public health guidance to emergency department clinicians in emerging public health incidents; and develop a framework that promotes effective communication of public health guidance to clinicians during emerging incidents. METHODS: A qualitative study was conducted using semi-structured interviews with 26 key informants from emergency departments and public health agencies in Ontario, Canada. Data were analyzed inductively and the analytic approach was guided by concepts of complexity theory. RESULTS: Emergent themes corresponded to challenges and strategies for effective communication of public health guidance. Important challenges related to the coordination of communication across institutions and jurisdictions, and differences in work environments across sectors. Strategies for effective communication were identified as the development of partnerships and collaboration, attention to specific methods of communication used, and the importance of roles and relationship-building prior to an emerging public health incident. Following descriptive analysis, a framework was developed that consists of the following elements: 1) Anticipate; 2) Invest in building relationships and networks; 3) Establish liaison roles and redundancy; 4) Active communication; 5) Consider and respond to the target audience; 6) Leverage networks for coordination; and 7) Acknowledge and address uncertainty. The qualities inherent in local relationships cut across framework elements. CONCLUSIONS: This research indicates that relationships are central to effective communication between public health agencies and emergency department clinicians at the local level. Our framework which is grounded in qualitative evidence focuses on strategies to promote effective communication in the emerging public health incident setting and may be useful in informing practice.

Binding to and Inhibition of Insulin-Regulated Aminopeptidase by Macrocyclic Disulfides Enhances Spine Density.

Angiotensin IV (Ang IV) and related peptide analogs, as well as nonpeptide inhibitors of insulin-regulated aminopeptidase (IRAP), have previously been shown to enhance memory and cognition in animal models. Furthermore, the endogenous IRAP substrates oxytocin and vasopressin are known to facilitate learning and memory. In this study, the two recently synthesized 13-membered macrocyclic competitive IRAP inhibitors HA08 and HA09, which were designed to mimic the N terminus of oxytocin and vasopressin, were assessed and compared based on their ability to bind to the IRAP active site, and alter dendritic spine density in rat hippocampal primary cultures. The binding modes of the IRAP inhibitors HA08, HA09, and of Ang IV in either the extended or γ-turn conformation at the C terminus to human IRAP were predicted by docking and molecular dynamics simulations. The binding free energies calculated with the linear interaction energy method, which are in excellent agreement with experimental data and simulations, have been used to explain the differences in activities of the IRAP inhibitors, both of which are structurally very similar, but differ only with regard to one stereogenic center. In addition, we show that HA08, which is 100-fold more potent than the epimer HA09, can enhance dendritic spine number and alter morphology, a process associated with memory facilitation. Therefore, HA08, one of the most potent IRAP inhibitors known today, may serve as a suitable starting point for medicinal chemistry programs aided by MD simulations aimed at discovering more drug-like cognitive enhancers acting via augmenting synaptic plasticity.

Assessing health impacts of the December 2013 Ice storm in Ontario, Canada.

BACKGROUND: Ice, or freezing rain storms have the potential to affect human health and disrupt normal functioning of a community. The purpose of this study was to assess acute health impacts of an ice storm that occurred in December 2013 in Toronto, Ontario, Canada. METHODS: Data on emergency department visits were obtained from the National Ambulatory Care Reporting System. Rates of visits in Toronto during the storm period (December 21, 2013 - January 1, 2014) were compared to rates occurring on the same dates in the previous five years (historical comparison) and compared to those in a major unaffected city, Ottawa, Ontario (geographic comparison). Overall visits and rates for three categories of interest (cardiac conditions, environmental causes and injuries) were assessed. Rate ratios were calculated using Poisson regression with population counts as an offset. Absolute counts of carbon monoxide poisoning were compared descriptively in a sub-analysis. RESULTS: During the 2013 storm period, there were 34 549 visits to EDs in Toronto (12.46 per 1000 population) compared with 10 794 visits in Ottawa (11.55 per 1000 population). When considering year and geography separately, rates of several types of ED visits were higher in the storm year than in previous years in both Toronto and Ottawa. Considering year and geography together, rates in the storm year were higher for overall ED visits (RR: 1.10, 95 % CI: 1.09-1.11) and for visits due to environmental causes (RR: 2.52, 95 % CI: 2.21-2.87) compared to previous years regardless of city. For injuries, visit rates were higher in the storm year in both Toronto and Ottawa, but the increase in Toronto was significantly greater than the increase in Ottawa, indicating a significant interaction between geography and year (RR: 1.23, 95 % CI: 1.16-1.30). CONCLUSIONS: This suggests that the main health impact of the 2013 Ice Storm was an increase in ED visits for injuries, while other increases could have been due to severe weather across Ontario at that time. This study is one of the first to use a population-level database and regression modeling of emergency visit codes to identify acute impacts resulting from ice storms.