Internal and External Data Linkage of Complex Relational Database: Results from CorHealth Ontario

Introduction CorHealth Ontario, formerly Cardiac Care Network (CCN), maintains a registry of patients undergoing select cardiac procedures/surgeries in Ontario, Canada. This population-based database contains over 35 datasets with complex structure, linked by unique primary key or multiple keys. Objectives and Approach We aimed to simplify the complex CorHealth database so that research analysts could create study cohorts more efficiently and effectively, and to enrich the study cohort by getting more clinical information through database linkage. Through internal linkage, we could combine clinical fields from multiple CorHealth datasets. While the CorHealth dataset may not have all the clinical information needed for a given study, we may link the CorHealth study cohort externally to other administration databases to obtain additional fields via the probability matching (i.e., identical patient ID, hospital ID and procedure/surgery date). Results After identifying the primary keys on the relational database flowchart, we designed new data structures by combining similar topic datasets. The total number of datasets was reduced from 35 to 13. This simplified CorHealth dataset includes one main CorHealth dataset (including demographic information, referral data, comorbidities) plus 12 other linkable specific datasets (including stent, vessel, TAVI, STEMI). Through internal linkage, we can get the stent numbers, lengths and types of Percutaneous Coronary Interventions from the Stent dataset. Linking to Discharge Abstract Database (DAD), we can get the hospital length of stay and the episode of care of hospital transfer for each procedure; linking to The Ontario Health Insurance Plan database (OHIP), we can find the graft numbers and vessel types of Coronary Artery Bypass Graft. Conclusion/Implications To improve the research capacity and increase the value of the CorHealth database, analysts could create enhanced cardiovascular study cohorts derived from the simplified CorHealth database, plus internal linkage from other CorHealth datasets, and external data linkage from population-based administrative sources. We have accomplished three reports (PCI/CABG/TAVI) accordingly in 2017/18

Unplanned readmissions after hospital discharge among patients identified as being at high risk for readmission using a validated predictive algorithm

BACKGROUND: Unplanned hospital readmissions are common, expensive and often preventable. Strategies designed to reduce readmissions should target patients at high risk. The purpose of this study was to describe medical patients identified using a recently published and validated algorithm (the LACE index) as being at high risk for readmission and to examine their actual hospital readmission rates. METHODS: We used population-based administrative data to identify adult medical patients discharged alive from 6 hospitals in Toronto, Canada, during 2007. A LACE index score of 10 or higher was used to identify patients at high risk for readmission. We described patient and hospitalization characteristics among both the high-risk and low-risk groups as well as the 30-day readmission rates. RESULTS: Of 26 045 patients, 12.6% were readmitted to hospital within 30 days and 20.9% were readmitted within 90 days of discharge. High-risk patients (LACE ≥ 10) accounted for 34.0% of the sample but 51.7% of the patients who were readmitted within 30 days. High-risk patients were readmitted with twice the frequency as other patients, had longer lengths of stay and were more likely to die during the readmission. INTERPRETATION: Using a LACE index score of 10, we identified patients with a high rate of readmission who may benefit from improved post-discharge care. Our findings suggest that the LACE index is a potentially useful tool for decision-makers interested in identifying appropriate patients for post-discharge interventions

Potential Savings of Harmonising Hospital and Community Formularies for Chronic Disease Medications Initiated in Hospital

Hospitals in Canada manage their formularies independently, yet many inpatients are discharged on medications which will be purchased through publicly-funded programs. We sought to determine how much public money could be saved on chronic medications if hospitals promoted the initiation of agents with the lowest outpatient formulary prices.We used administrative databases for the province of Ontario to identify patients initiated on a proton pump inhibitor (PPI), angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) following hospital admission from April 1(st) 2008-March 31(st) 2009. We assessed the cost to the Ontario Drug Benefit Program (ODB) over the year following initiation and determined the cost savings if prescriptions were substituted with the least expensive agent in each class.The cost for filling all PPI, ACE inhibitor and ARB prescriptions was $2.48 million,$968 thousand and $325 thousand respectively. Substituting the least expensive agent could have saved$1.16 million (47%) for PPIs, $162 thousand (17$14 thousand (4%) for ARBs over the year following discharge.In a setting where outpatient prescriptions are publicly funded, harmonising outpatient formularies with inpatient therapeutic substitution resulted in modest cost savings and may be one way to control rising pharmaceutical costs

Significant Effects of Antiretroviral Therapy on Global Gene Expression in Brain Tissues of Patients with HIV-1-Associated Neurocognitive Disorders

Antiretroviral therapy (ART) has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing pathophysiological changes in the brain associated with HAND. Aberrantly expressed transcripts common to untreated and treated HAND may contribute to neurocognitive changes defying ART

Population dynamics of a salmonella lytic phage and its host : implications of the host bacterial growth rate in modelling

The prevalence and impact of bacteriophages in the ecology of bacterial communities coupled with their ability to control pathogens turn essential to understand and predict the dynamics between phage and bacteria populations. To achieve this knowledge it is essential to develop mathematical models able to explain and simulate the population dynamics of phage and bacteria. We have developed an unstructured mathematical model using delay-differential equations to predict the interactions between a broad-host-range Salmonella phage and its pathogenic host. The model takes into consideration the main biological parameters that rule phage-bacteria interactions likewise the adsorption rate, latent period, burst size, bacterial growth rate, and substrate uptake rate, among others. The experimental validation of the model was performed with data from phage-interaction studies in a 5 L bioreactor. The key and innovative aspect of the model was the introduction of variations in the latent period and adsorption rate values that are considered as constants in previous developed models. By modelling the latent period as a normal distribution of values and the adsorption rate as a function of the bacterial growth rate it was possible to accurately predict the behaviour of the phage-bacteria population. The model was shown to predict simulated data with a good agreement with the experimental observations and explains how a lytic phage and its host bacteria are able to coexist.Financial support was received through the Strategic Project PEst-OE/EQB/LA0023/2013 from the FCT-Fundacao para a Ciencia e Tecnologia (http://www.fct.pt) and the projects "BioHealth - Biotechnology and Bioengineering approaches to improve health quality'', Ref. NORTE-07-0124 FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 - O Novo Norte), QREN, FEDER and "Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB'', Ref. FCOMP-01-0124-FEDER-027462. Silvio B. Santos was supported by the grant SFRH/BPD/75311/2010 and Carla Carvalho was supported by the grant SFRH/BPD/79365/2011 both from the FCT-Fundacao para a Ciencia e Tecnologia (http://www.fct.pt). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Upper Gastrointestinal Hemorrhage During Warfarin Therapy Associated with Co-Trimoxazole and other Urinary Tract Anti-infectives

Some antibiotics, including co-trimoxazole, inhibit warfarin’s metabolism and may be associated with greater risk of hemorrhage in warfarin-treated patients. This thesis examines the risk of upper gastrointestinal (UGI) hemorrhage in older patients receiving warfarin and antibiotics commonly used to treat urinary tract infections, with a focus on co-trimoxazole. This population-based nested case-control study using Ontario healthcare databases, identified residents aged 66 years or older continuously on warfarin (n=134,637). Cases were those hospitalized with UGI hemorrhage (n=2151). Cases were nearly 4 times more likely than controls to have recently received co-trimoxazole (adjusted odds ratio (OR), 3.84; 95% confidence interval (CI) 2.33 – 6.33). Ciprofloxacin was also associated with an increased risk (adjusted OR 1.94; 95% CI 1.28 – 2.95), but no significant association was observed with amoxicillin, ampicillin, nitrofurantoin or norfloxacin. Among older patients receiving warfarin, co-trimoxazole is associated with a significantly higher risk of UGI hemorrhage than other commonly used antibiotics.MAS

Syncope and Its consequences in patients with dementia receiving cholinesterase inhibitors: A population-based cohort study

Background Cholinesterase inhibitors are commonly prescribed to treat dementia, but their adverse effect profile has received little attention. These drugs can provoke symptomatic bradycardia and syncope, which may lead to permanent pacemaker insertion. Drug-induced syncope may also precipitate fall-related injuries, including hip fracture. Methods In a population-based cohort study, we investigated the relationship between cholinesterase inhibitor use and syncope-related outcomes using health care databases from Ontario, Canada, with accrual from April 1, 2002, to March 31, 2004. We identified 19 803 community-dwelling older adults with dementia who were prescribed cholinesterase inhibitors and 61 499 controls who were not. Results :Hospital visits for syncope were more frequent in people receiving cholinesterase inhibitors than in controls (31.5 vs 18.6 events per 1000 person-years; adjusted hazard ratio [HR], 1.76; 95% confidence interval [CI], 1.57-1.98). Other syncope-related events were also more common among people receiving cholinesterase inhibitors compared with controls: hospital visits for bradycardia (6.9 vs 4.4 events per 1000 person-years; HR, 1.69; 95% CI, 1.32-2.15), permanent pacemaker insertion (4.7 vs 3.3 events per 1000 person-years; HR, 1.49; 95% CI, 1.12-2.00), and hip fracture (22.4 vs 19.8 events per 1000 person-years; HR, 1.18; 95% CI, 1.04-1.34). Results were consistent in additional analyses in which subjects were either matched on their baseline comorbidity status or matched using propensity scores. Conclusions: Use of cholinesterase inhibitors is associated with increased rates of syncope, bradycardia, pacemaker insertion, and hip fracture in older adults with dementia. The risk of these previously underrecognized serious adverse events must be weighed carefully against the drugs' generally modest benefits