Characteristics of new users of recent antidiabetic drugs in Canada and the United Kingdom.

Background: Characteristics of patients using newer 2 and 3 line antidiabetic drugs in a real-world setting are poorly understood. We described the characteristics of new users of sodium-glucose co-transporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitors (DPP-4i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in Canada and the United Kingdom (UK) between 2016 and 2018.

Methods: We conducted a multi-database cohort study using administrative health databases from 7 Canadian provinces and the UK Clinical Practice Research Datalink.

Economic Burden of Chronic Obstructive Pulmonary Disease and Lung Cancer Between 2000 and 2015 in Saskatchewan: Study Protocol.

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are both detrimental diseases that present great burdens on society. Years of life lost (YLL), premature years of life lost (PYLL), working years lost (WYL), and productivity loss are all effective measures in identifying economic burden of disease.

Objective: We propose a population-based study to analyze comprehensive provincial cohorts of Saskatchewan residents with COPD, lung cancer, and combined COPD and lung cancer in order to identify the burden these diseases present.

Validity of an algorithm to identify cardiovascular deaths from administrative health records: a multi-database population-based cohort study.

Background: Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data.

Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study.

Objective: To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice.

Design: Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis.

Setting: Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18.

Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Below-Knee Amputation: A Multicenter Observational Study.

Objective: Reports of amputations associated with sodium-glucose cotransporter 2 (SGLT2) inhibitors have been inconsistent. We aimed to compare the risk of below-knee amputation with SGLT2 inhibitors versus dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes.

Research Design And Methods: This multicenter observational study used administrative health care databases from seven Canadian provinces and the U.

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis : A Multicenter Cohort Study.

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA).

Objective: To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes.

Design: Population-based cohort study; prevalent new-user design between 2013 and 2018.

Sodium-glucose co-transporter-2 inhibitors and the risk of urosepsis: A multi-site, prevalent new-user cohort study.

Aim: To compare urosepsis rates in patients with type 2 diabetes treated using sodium-glucose co-transporter-2 inhibitors (SGLT2i) with dipeptidyl peptidase-4 inhibitors (DPP4i) in a real-world setting.

Methods: We conducted a matched cohort study using a prevalent new-user design with time-conditional propensity scores. New users of SGLT2i from seven Canadian provinces and the UK were matched to DPP4i users.

A population-based analysis of antidiabetic medications in four Canadian provinces: Secular trends and prescribing patterns.

Purpose: To use the Canadian Network for Observational Drug Effect Studies (CNODES) to describe drug utilization of antidiabetic medications in four Canadian provinces.

Methods: With the use of data from CNODES, we constructed cohorts of patients with type 2 diabetes in four Canadian provinces (Manitoba, Ontario, Quebec, and Saskatchewan) who received their first-ever prescription for a noninsulin antidiabetic medication during the study period, defined as the earliest date of data availability in each province (range: 1993-1998) to the latest date of the data extraction in each province (range: 2013-2014). Prescriptions rates were calculated for all prescriptions by class and described over time.

Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis.

Importance: The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial.

Objective: To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis.

Design, Setting, And Participants: A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom.

A Multicenter Observational Study of Incretin-based Drugs and Heart Failure.

Background: There is concern that antidiabetic incretin-based drugs, including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues, can increase the risk of heart failure. Ongoing clinical trials may not have large enough samples to effectively address this issue.

Methods: We applied a common protocol in the analysis of multiple cohorts of patients with diabetes.

Agreement between administrative data and the Resident Assessment Instrument Minimum Dataset (RAI-MDS) for medication use in long-term care facilities: a population-based study.

Background: Prescription medication use, which is common among long-term care facility (LTCF) residents, is routinely used to describe quality of care and predict health outcomes. Data sources that capture medication information, which include surveys, medical charts, administrative health databases, and clinical assessment records, may not collect concordant information, which can result in comparable prevalence and effect size estimates. The purpose of this research was to estimate agreement between two population-based electronic data sources for measuring use of several medication classes among LTCF residents: outpatient prescription drug administrative data and the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.

Validity of the RAI-MDS for ascertaining diabetes and comorbid conditions in long-term care facility residents.

Background: This study assessed the validity of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) Version 2.0 for diagnoses of diabetes and comorbid conditions in residents of long-term care facilities (LTCFs).

Methods: Hospital inpatient, outpatient physician billing, RAI-MDS, and population registry data for 1997 to 2011 from Saskatchewan, Canada were used to ascertain cases of diabetes and 12 comorbid conditions.

Potential therapeutic applications of phosphodiesterase inhibition in prostate cancer.

Objective: Phosphodiesterases (PDEs) play a role in controlling cyclic nucleotide action, including cyclic guanosine monophosphate (cGMP). Previous studies have ascribed a protective role of cGMP signaling on hypoxia-mediated cancer progression. Herein, we determine their potential role in hypoxia-mediated chemoresistance and immune escape.

Immunohistochemical Assessment of Expression of Centromere Protein-A (CENPA) in Human Invasive Breast Cancer.

Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein -A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)-the 70 gene signature MammaPrint® and the five gene Molecular Grade Index (MGISM).

Hypoxia increases tumor cell shedding of MHC class I chain-related molecule: role of nitric oxide.

The MHC class I chain-related (MIC) molecules play important roles in tumor immune surveillance through their interaction with the NKG2D receptor on natural killer and cytotoxic T cells. Thus, shedding of the MIC molecules from the tumor cell membrane represents a potential mechanism of escape from NKG2D-mediated immune surveillance. Tumor hypoxia is associated with a poor clinical outcome for cancer patients.

ER stress-regulated translation increases tolerance to extreme hypoxia and promotes tumor growth.

Tumor cell adaptation to hypoxic stress is an important determinant of malignant progression. While much emphasis has been placed on the role of HIF-1 in this context, the role of additional mechanisms has not been adequately explored. Here we demonstrate that cells cultured under hypoxic/anoxic conditions and transformed cells in hypoxic areas of tumors activate a translational control program known as the integrated stress response (ISR), which adapts cells to endoplasmic reticulum (ER) stress.