Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

Leveraging nurse practitioner capacities to achieve global health for all: COVID-19 and beyond.

AIM: To argue that nurse practitioners have been under-utilized generally in the current global health environment, creating barriers to achieving universal health coverage and the Sustainable Development Goals. BACKGROUND: Nurse practitioners are advanced practice nurses possessing expert knowledge and leadership skills that can be optimized to narrow disparities and ensure access to high-quality health care globally. Nurses worldwide have been challenged to meet global public health needs in the context of COVID-19 (SARS-CoV-2 virus), and there are early indications that nurse practitioners are being called upon to the full extent of their capabilities in the current pandemic. SOURCES OF EVIDENCE: PubMed; Google Scholar; the International Council of Nurses; World Health Organization; United Nations; and the experiences of the authors. DISCUSSION: Several international reports, nursing and health organizations have called for continued investment in and development of nursing to improve mechanisms that promote cost-effective and universally accessible care. Expanding nurse practitioner scopes of practice across nations will leverage their clinical capacities, policy and advocacy skills, and talents to lead at all levels. CONCLUSION: Ongoing empirical data and policy change is needed to enable the full scope and strategic utilization of nurse practitioners across healthcare systems and contexts. IMPLICATIONS FOR NURSING PRACTICE, AND NURSING AND HEALTH POLICY: Widespread education regarding nurse practitioner capacities for interdisciplinary partners, policymakers and the public is needed. Policies that safely expand their roles are critical. Role titles and remuneration reflective of their scope and service are required to lead, sustain and grow the workforce internationally.

Beyond Penicillin: Rapid Desensitization for Specific Flucloxacillin Hypersensitivity.

Beta-lactam therapy for severe staphylococcal infections is associated with superior outcomes, compared to non-beta-lactam therapy. For patients with immediate hypersensitivity to beta-lactams, desensitization has been widely employed to allow beta-lactam therapy, but published protocols for antistaphylococcal beta-lactams such as flucloxacillin are lacking. Here, we report a case and describe the desensitization protocol successfully used for a patient with isolated flucloxacillin immediate hypersensitivity, for whom a penicillin desensitization protocol would likely have resulted in an adverse drug reaction.

Intra-articular injection of mesenchymal stem cells in treating knee osteoarthritis: a systematic review of animal studies.

PURPOSE: Mesenchymal stem cells (MSCs) injection has emerged as a novel treatment for knee osteoarthritis (KOA) but with inconsistent results in the experimental studies. Thus, the purpose of the present study is to evaluate the preclinical animal studies of MSCs injection for KOA and to determine the evidence for a role for MSCs in further clinical trials. METHODS: A systematic search of KOA animal studies published through Aug 2017 was conducted using the PubMed, Embase and Web of science. Criteria for eligibility were animal studies assessing the therapeutic effects of MSCs intra-articular injection to animals with KOA. The methodological quality of included studies was assessed by the SYRCLE tool for assessing risk of bias in animal intervention studies. Descriptive synthesis was performed. Evidence quality was evaluated based on the Confidence in the Evidence from Reviews of Qualitative research (CERQual) tool. RESULTS: Twenty-three KOA animal studies were eligible for inclusion. According to the SYRCLE's tool, all included studies had high risk of bias. Between-study heterogeneity was substantial. The included studies varied in terms of species, modeling methods, MSCs origin, treatment timing, injections frequency, transplantation type and dose of MSCs. The following outcomes, gross morphology, histological analysis, immunohistochemical analysis, radiological evaluation or behavior analysis, were reported in the primary studies. For all outcomes, the evidence quality was low or very low. CONCLUSIONS: We do not have absolute confidence to recommend use MSCs injection for KOA clinical trials. Based on the internal and external validity of current animal studies, high quality experimental studies and efforts for effective translation from preclinical studies to clinical trials are still required.

AAV-mediated and pharmacological induction of Hsp70 expression stimulates survival of retinal ganglion cells following axonal injury.

We evaluated the effect of AAV2- and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin)-mediated upregulation of Hsp70 expression on the survival of retinal ganglion cells (RGCs) injured by optic nerve crush (ONC). AAV2-Hsp70 expression in the retina was primarily observed in the ganglion cell layer. Approximately 75% of all transfected cells were RGCs. RGC survival in AAV2-Hsp70-injected animals was increased by an average of 110% 2 weeks after the axonal injury compared with the control. The increase in cell numbers was not even across the retinas with a maximum effect of approximately 306% observed in the inferior quadrant. 17-AAG-mediated induction of Hsp70 expression has been associated with cell protection in various models of neurodegenerative diseases. We show here that a single intravitreal injection of 17-AAG (0.2 ug ul(-1)) results in an increased survival of ONC-injured RGCs by approximately 49% compared with the vehicle-treated animals. Expression of Hsp70 in retinas of 17-AAG-treated animals was upregulated approximately by twofold compared with control animals. Our data support the idea that the upregulation of Hsp70 has a beneficial effect on the survival of injured RGCs, and the induction of this protein could be viewed as a potential neuroprotective strategy for optic neuropathies.

Managing a nosocomial outbreak of carbapenem-resistant Klebsiella pneumoniae: an early Australian hospital experience.

BACKGROUND: Carbapenems are traditionally reserved as the last line of defence for treatment of serious infections with multiresistant Gram-negative bacilli. Reports of Klebsiella pneumoniae carbapenemase (KPC)-producing organisms have been emerging globally, but rare in Australasia to date. We describe an outbreak of KPC-2 producing K. pneumoniae at an Australian hospital. METHODS: After initial detection in October 2012, a retrospective review of patients with meropenem-resistant K. pneumoniae to June 2012, and ongoing prospective surveillance, was undertaken. Included patients were admitted to the hospital after June 2012 and had meropenem-resistant K. pneumoniae isolated from any site. Available isolates underwent detection of the KPC-2 gene by polymerase chain reaction and molecular typing was performed to determine genetic relatedness between isolates. Point-prevalence screening was performed on selected wards to detect asymptomatic carriage. Infection control procedures were implemented to contain the outbreak. RESULTS: Ten cases were identified in the initial cluster. Eight were localised to a single inpatient ward. Point-prevalence screening revealed one extra case. After temporary containment, re-emergence of KPC-producing isolates was observed post October 2013 with 18 further cases identified. Four K. pneumoniae isolates in the 2012 cluster and 16 from the 2013-2014 cluster were referred for further testing. All carried the KPC-2 beta-lactamase gene. The 2012 isolates were genetically similar to the 2014 isolates. CONCLUSION: KPC-2 mediated resistance is an emerging threat in Australia. The re-emergence of KPC despite initial containment emphasises the need for constant vigilance in the microbiology laboratory and ongoing maintenance of infection control and antimicrobial stewardship activity.

The association between obesity and outpatient visits for acute respiratory infections in Ontario, Canada.

OBJECTIVE: Recent evidence suggests that obesity increases the risk of severe outcomes following respiratory infection. It is less clear whether obesity is associated with the risk of being infected with influenza or other respiratory pathogens. Therefore, we examined the association between obesity and outpatient visits for acute respiratory infections (ARIs). DESIGN: We conducted a retrospective cohort study for a period of over 13 years on 104,665 individuals in Ontario, Canada who responded to population health surveys and agreed to linkage with health administrative data. Individuals aged 18-64 years who responded to a survey within 5 years prior to the start of an influenza season were included. Poisson regression, with adjustment for relevant confounders, was used to measure the association between self-reported body mass index (BMI) and outpatient visits for ARI. We conducted numerous sensitivity analyses to assess the robustness of our findings. RESULTS: We observed higher rates of outpatient visits for ARI during influenza season periods compared with normal weight individuals for those who were overweight (BMI 25-29.9; rate ratio (RR) 1.10; 95% confidence interval (95% CI) 1.07-1.13), obese class I (BMI 30-34.9; RR 1.17; 95% CI 1.13-1.22) and obese class II or III (BMI ≥35; RR 1.19; 95% CI 1.12-1.25). Associations of a similar magnitude were observed during non-influenza season periods. Obesity was a greater risk factor for ARIs managed in emergency departments than physician offices. CONCLUSIONS: Obese individuals are at an increased risk of outpatient visits for ARI during both influenza and non-influenza season periods, suggesting that the effect of obesity on the risk of respiratory infections is not limited to influenza. Interventions designed to reduce the prevalence of obesity may have the added benefit reducing the population burden of respiratory infections.

COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

Background rates of adverse events of special interest for COVID-19 vaccines: A multinational Global Vaccine Data Network (GVDN) analysis.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) project was established in 2021 under the multinational Global Vaccine Data Network (GVDN) consortium to facilitate the rapid assessment of the safety of newly introduced vaccines. This study analyzed data from GVDN member sites on the background incidence rates of conditions designated as adverse events of special interest (AESI) for COVID-19 vaccine safety monitoring. METHODS: Eleven GVDN global sites obtained data from national or regional healthcare databases using standardized methods. Incident events of 13 pre-defined AESI were included for a pre-pandemic period (2015-19) and the first pandemic year (2020). Background incidence rates (IR) and 95% confidence intervals (CI) were calculated for inpatient and emergency department encounters, stratified by age and sex, and compared between pre-pandemic and pandemic periods using incidence rate ratios. RESULTS: An estimated 197 million people contributed 1,189,652,926 person-years of follow-up time. Among inpatients in the pre-pandemic period (2015-19), generalized seizures were the most common neurological AESI (IR ranged from 22.15 [95% CI 19.01-25.65] to 278.82 [278.20-279.44] per 100,000 person-years); acute disseminated encephalomyelitis was the least common (<0.5 per 100,000 person-years at most sites). Pulmonary embolism was the most common thrombotic event (IR 45.34 [95% CI 44.85-45.84] to 93.77 [95% CI 93.46-94.08] per 100,000 person-years). The IR of myocarditis ranged from 1.60 [(95% CI 1.45-1.76) to 7.76 (95% CI 7.46-8.08) per 100,000 person-years. The IR of several AESI varied by site, healthcare setting, age and sex. The IR of some AESI were notably different in 2020 compared to 2015-19. CONCLUSION: Background incidence of AESIs exhibited some variability across study sites and between pre-pandemic and pandemic periods. These findings will contribute to global vaccine safety surveillance and research.

Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1.

MicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3'-untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression- and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.

Case of syndrome of headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) with focal slowing on electroencephalogram.

We describe a case of headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis in a patient presenting with a 3-week history of recurrent severe headaches associated with negative sensory symptoms and dysphasia. The patient had no cardiovascular risk factors and no family history of migraines. Neurological examination was unremarkable. Cerebral magnetic resonance imaging was unremarkable. CSF analysis revealed lymphocytosis (leucocytes 84 × 10(6)/L, 100% lymphocytes). Extensive laboratory investigations of CSF and serum did not reveal an infectious, autoimmune or metabolic cause. Visual evoked potentials were normal. Awake electroencephalogram revealed intermittent 3-5 Hz generalised slowing and frontal intermittent rhythmic delta activity, without epileptiform discharges. Repeat CSF analysis showed marked reduction of the total leucocyte count and remained negative for infectious aetiology. Propranolol was commenced, and no recurrence of headache or neurological symptoms was observed at follow-up. An extensive literature review on the topic is discussed.

Changes in Surgical Pathology Case Volume and Amendment Rates During the COVID-19 Pandemic.

OBJECTIVES: Surgical pathology volume decreased during the peak of the coronavirus disease 2019 (COVID-19) pandemic. We looked at the 4 months with the greatest reduction in surgical pathology volume during the COVID-19 pandemic and compared them with those same months in 2019 to determine changes in specimen volume. We compared the amendment rates during those periods and types of amendments issued (identification [ID], report defect [RD], diagnostic information [DI]). METHODS: All pathology reports between March to June 2019 and March to June 2020 were extracted from the pathology information system. All amendments issued were extracted over the same period and then subclassified by two pathologists. RESULTS: There was a 52.1% reduction in surgical pathology volume between the 4-month periods in 2019 and 2020 (P = .04). The amendment rate was 0.9% in 2019 compared with 1.4% in 2020, representing a 65.5% increase in amendments overall. There was a 53.3% reduction in amendments issued for ID, a 3.8% reduction in RD, and a 23.2% increase in amendments issued for DI. The change in amendments was not statistically significant. CONCLUSIONS: These findings suggest that a reduction in workload would not improve error rates. The circumstances of the pandemic highlight the many factors contributing to error rates in surgical pathology.

Development of a reporting guideline for systematic reviews of animal experiments in the field of traditional Chinese medicine.

OBJECTIVE: In recent years, there are several systematic reviews published on animal experiments of Traditional Chinese medicine (TCM). PRISMA (preferred reporting items for systematic reviews and meta-analysis) guidelines provide a guarantee for significantly improving the reporting quality of systematic reviews (SRs) and meta-analysis (MAs) to a certain extent; however, there are still certain defects found in the quality of SRs/MAs of animal experiments of TCM. It has been found that especially, the descriptions of the rationale and animal characteristics of TCM interventions are inadequate. As a result, we have developed a novel reporting guideline for SRs/MAs of animal experimental in the field of TCM (PRISMA-ATCM) to overcome these problems. METHODS: PRISMA-ATCM reporting guidelines were formed by analyzing both the status and quality of published SRs/MAs of animal experiments and consulting experts in the related fields, and then by Delphi consultation, consensus meeting and revision. RESULTS: Among the 27 items on the PRISMA checklist, Title (1), Structured summary (2), Rationale (3), Objectives (4), Protocol and registration (5), Eligibility criteria (6), Data items (11), Planned methods of analysis (14), Study characteristics (18), Summary of evidence (24), Limitations (25), and Funding (27) have been extensively revised and expanded, to specifically include the details about TCM intervention and animal characteristics. In addition, illustrative examples and explanations have been provided for each item. CONCLUSION: PRISMA-ATCM could markedly improve the quality SRs/MAs of animal experiments in the field of TCM.

Search for light dark matter in XENON10 data.

We report results of a search for light (≲10 GeV) particle dark matter with the XENON10 detector. The event trigger was sensitive to a single electron, with the analysis threshold of 5 electrons corresponding to 1.4 keV nuclear recoil energy. Considering spin-independent dark matter-nucleon scattering, we exclude cross sections σ(n)>7×10(-42) cm(2), for a dark matter particle mass m(χ)=7 GeV. We find that our data strongly constrain recent elastic dark matter interpretations of excess low-energy events observed by CoGeNT and CRESST-II, as well as the DAMA annual modulation signal.

Influenza increases invasive meningococcal disease risk in temperate countries.

OBJECTIVES: Invasive meningococcal disease (IMD) is a severe bacterial infection that displays wintertime seasonality in temperate countries. Mechanisms driving seasonality are poorly understood and may include environmental conditions and/or respiratory virus infections. We evaluated the contribution of influenza and environmental conditions to IMD risk, using standardized methodology, across multiple geographical regions. METHODS: We evaluated 3276 IMD cases occurring between January 1999 and December 2011 in 11 jurisdictions in Australia, Canada, France and the United States. Effects of environmental exposures and normalized weekly influenza activity on IMD risk were evaluated using a case-crossover design. Meta-analytic methods were used to evaluate homogeneity of effects and to identify sources of between-region heterogeneity. RESULTS: After adjustment for environmental factors, elevated influenza activity at a 2-week lag was associated with increased IMD risk (adjusted odds ratio (OR) per standard deviation increase 1.29; 95% confidence interval, 1.04-1.59). This increase was homogeneous across the jurisdictions studied. By contrast, although associations between environmental exposures and IMD were identified in individual jurisdictions, none was generalizable. CONCLUSIONS: Using a self-matched design that adjusts for both coseasonality and case characteristics, we found that surges in influenza activity result in an acute increase in population-level IMD risk. This effect is seen across diverse geographic regions in North America, France and Australia. The impact of influenza infection on downstream meningococcal risk should be considered a potential benefit of influenza immunization programmes.

Redox proteins thioredoxin 1 and thioredoxin 2 support retinal ganglion cell survival in experimental glaucoma.

We investigated the neuroprotective effect of thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) which play critical roles in the regulation of oxidative stress on retinal ganglion cells (RGCs) in a rat glaucoma model. Expression of Trx1 and Trx2 and Trx-interacting protein (Txnip) was observed in the RGC layer (GCL), nerve fiber layer and inner nuclear layer. Txnip-, Trx1- and Trx2-expressing cells in the GCL were primarily colocalized with RGCs. The increased Txnip protein level was observed 2 and 5 weeks after glaucoma induction. Trx1 level decreased 2 weeks after glaucoma induction and more prominently after 5 weeks. No change in Trx2 levels was detected. The effects of Trx1 and Trx2 overexpression on RGC survival were evaluated 5 weeks after glaucoma induction. In nontransfected and EGFP-transfected (used as a negative control) retinas, RGC loss was approximately 27% compared with control. The loss of RGCs in Trx1- and Trx2- transfected retinas was approximately 15 and 17%, respectively. Thus, Trx1 and Trx2 preserved 45 and 37% of cells, respectively that were destined to die in glaucomatous retinas. The results of this study provide evidence for the involvement of oxidative stress in RGC degeneration in experimental glaucoma and point to potential strategies to reduce its impact.

Cysteine3 of Src family protein tyrosine kinase determines palmitoylation and localization in caveolae.

Recent work has demonstrated that p56lck, a member of the Src family of protein tyrosine kinases (PTKs), is modified by palmitoylation of a cysteine residue(s) within the first 10 amino acids of the protein (in addition to amino-terminal myristoylation that is a common modification of the Src family of PTKs). This is now extended to three other members of this family by showing incorporation of [3H]palmitate into p59fyn, p55fgr, and p56hck, but not into p60src. The [3H]palmitate was released by treatment with neutral hydroxylamine, indicating a thioester linkage to the protein. Individual replacement of the two cysteine residues within the first 10 amino acids of p59fyn and p56lck with serine indicated that Cys3 was the major determinant of palmitoylation, as well as association of the PTK with glycosyl-phosphatidylinositol-anchored proteins. Introduction of Cys3 into p60src led to its palmitoylation. p59fyn but not p60src partitioned into Triton-insoluble complexes that contain caveolae, microinvaginations of the plasma membrane. Mapping of the requirement for partitioning into caveolae demonstrated that the amino-terminal sequence Met-Gly-Cys is both necessary and sufficient within the context of a Src family PTK to confer localization into caveolae. Palmitoylation of this motif in p59fyn also modestly increased its overall avidity for membranes. These results highlight the role of the amino-terminal motif Met-Gly-Cys in determining the structure and properties of members of the Src family of PTKs.

Impact of availability of direct-acting antivirals for hepatitis C on Canadian hospitalization rates, 2012-2016.

BACKGROUNDS: Hospitalizations associated with hepatitis C virus (HCV) infection and liver disease increased on average by 6.0% per year from 2004 to 2010 in Canada and were projected (in 2010) to increase by another 4% by 2016. The first generation of direct-acting antivirals (DAAs) became available in 2012. In 2014, a second generation of effective and well-tolerated DAA therapy was authorized in Canada. The impact of DAA therapy on the HCV-associated disease burden in Canada has not been documented. OBJECTIVES: To assess the potential impact of DAA therapy on the disease burden by a) comparing the actual hospitalization rates associated with HCV infection and liver disease following the introduction of DAAs in Canada with the 2010 baseline projection and b) documenting the associated uptake of anti-HCV therapy. METHODS: The hospital records of inpatients diagnosed with chronic HCV and chronic liver disease were extracted from the Canadian Discharge Abstract Database (DAD) by fiscal year for 2004-2016. We compared the actual number of hospitalizations to the baseline projection by year and for selected 5-year birth cohorts (1925-1989). The monthly number of new prescriptions for anti-HCV regimens was extracted from the IQVIA CDH CompuScript database (formerly IMS Health), aggregated to annual levels by age group and compared with hospitalization trends. RESULTS: Compared to the baseline projection, there was a slight reduction in hospitalizations in 2014/15 and 2015/16. This slight reduction was followed by a more significant decline in 2016/17 (32% below expected; 95% confidence interval [CI]: 27%-37%). The largest declines were observed for patients born before 1960 (age 55 or older) at 40% below expected in 2016/17. The number of new anti-HCV prescriptions increased from 5,484 in fiscal year 2012/13 to a peak of 17,775 in 2015/2016. The number of new prescriptions corresponds to approximately 1.3 and five times the number of hospitalizations in 2012/13 and 2015/16, respectively. CONCLUSIONS: In Canada there has been a modest decrease in HCV and liver-related hospitalizations following a significant increase in uptake of second-generation DAAs in 2015. However, the burden is still high. Linked health administrative databases created to monitor the disease burden in the new treatment era should provide additional insight with the linkage of treatment history and disease stage to individual outcomes.