Impact of the COVID-19 Pandemic on Antihyperglycemic Prescriptions for Adults With Type 2 Diabetes in Canada: A Cross-sectional Study.

OBJECTIVES: Diabetes is a major public health problem in Canada and requires multifactorial, consistent clinical management. The COVID-19 pandemic has increased challenges in the management of many chronic ailments, including diabetes. Diabetes was associated with a higher risk of severe illness in the context of COVID-19. Pandemic restrictions also impacted diabetes care continuity, which may have contributed to an increased risk of diabetes-related complications and mortality. METHODS: This was a retrospective cross-sectional study of prescription patterns of antihyperglycemic medications claimed by individuals with type 2 diabetes (T2D) before and during the COVID-19 pandemic using the IQVIA Canada Longitudinal Prescription Claims database. The study period was from March 1, 2018, to February 28, 2021. The study outcomes are described on a monthly, quarterly, and yearly basis and overall, and by medication, medication class, and insurance coverage type. "New-to-molecule" patients were defined as those claiming a medication during the analysis period that they had no history of claiming in the database. Adults with at least 1 year of prescription history available and claiming their first prescription for an antihyperglycemic drug during the analysis period were classified as newly diagnosed with T2D. RESULTS: A similar number of people had at least 1 non-insulin antihyperglycemic prescription during the baseline, prepandemic, and pandemic periods in Canada (1,778,155, 1,822,403, and 1,797,272, respectively). However, the number of people initiating newer antihyperglycemic medications decreased at the beginning of the pandemic, in contrast to older medications, which remained consistent across the pandemic period. The number of people diagnosed with T2D decreased in the early months of the pandemic but recovered by October 2020. CONCLUSION: The COVID-19 epidemic in Canada impacted clinical care for at-risk Canadians, with fewer being prescribed newer antihyperglycemic drugs and a reduction in the number of diagnoses of T2D.

Phase 3 trial to evaluate the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, followed by 23-valent pneumococcal polysaccharide vaccine 6 months later, in at-risk adults 18-49 years of age (PNEU-DAY): A subgroup analysis by baseline risk factors.

Immunocompetent adults with certain medical and behavioral factors are at increased risk of pneumococcal disease. In some countries, sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults. This subgroup analysis from a phase 3 study evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults 18-49 years of age with pre-defined risk factors for pneumococcal disease. Safety and immunogenicity post-vaccination were analyzed by type and baseline number of risk factors for pneumococcal disease (1 and ≥2 risk factors). This analysis included 1,131 participants randomized 3:1 to receive either V114 or PCV13, followed by PPSV23. The majority (73.1%) of participants had at least one risk factor. Safety and tolerability profiles of V114 and PCV13 were similar across risk factor groups. V114 administered either alone or sequentially with PPSV23 6 months later was immunogenic for all 15 serotypes, including those not contained in PCV13, regardless of the number of baseline risk factors. V114 has the potential to broaden serotype coverage for at-risk adults.

Impact of the COVID-19 Pandemic on Adults With Type 2 Diabetes Care and Clinical Parameters in a Primary Care Setting in Ontario, Canada: A Cross-sectional Study.

OBJECTIVES: Diabetes requires ongoing monitoring and care to prevent long-term adverse health outcomes. In Canada, quarantine restrictions were put into place to address the coronavirus-2019 (COVID-19) pandemic in March 2020. Primary care diabetes clinics limited their in-person services and were advised to manage type 2 diabetes (T2D) through virtual visits and reduce the frequency of routine diabetes-related lab tests and screening. METHODS: This retrospective cross-sectional study used de-identified patient records from a primary care electronic medical records database in Ontario, Canada, to identify people with T2D who had at least 1 health-care touchpoint between March 1, 2018, and February 28, 2021. Outcomes were described on a monthly or yearly basis: 1) number of people with primary care visits (in-person vs virtual); 2) number of people with referrals; 3) number of people with each of the vital/lab measures; and 4) results of the vital/lab measures. RESULTS: A total of 16,845 individuals with T2D were included. Compared with the pre-pandemic period, the COVID-19 period had a 16.8% reduction in the T2D population utilizing any primary care and an increase of 330.4% in the number of people with at least 1 virtual visit. Compared with the pre-pandemic period, fewer people had vital/lab measures in the pandemic period. However, among the people with the test results available, the average values for all tests were similar in the pre- and pandemic periods. CONCLUSION: Further research is needed to understand the impact of the reduction of in-person clinical care on the entire population with T2D.

Clinical utility of combinatorial pharmacogenomic testing in depression: A Canadian patient- and rater-blinded, randomized, controlled trial.

The pharmacological treatment of depression consists of stages of trial and error, with less than 40% of patients achieving remission during first medication trial. However, in a large, randomized-controlled trial (RCT) in the U.S. ("GUIDED"), significant improvements in response and remission rates were observed in patients who received treatment guided by combinatorial pharmacogenomic testing, compared to treatment-as-usual (TAU). Here we present results from the Canadian "GAPP-MDD" RCT. This 52-week, 3-arm, multi-center, participant- and rater-blinded RCT evaluated clinical outcomes among patients with depression whose treatment was guided by combinatorial pharmacogenomic testing compared to TAU. The primary outcome was symptom improvement (change in 17-item Hamilton Depression Rating Scale, HAM-D17) at week 8. Secondary outcomes included response (≥50% decrease in HAM-D17) and remission (HAM-D17 ≤ 7) at week 8. Numerically, patients in the guided-care arm had greater symptom improvement (27.6% versus 22.7%), response (30.3% versus 22.7%), and remission rates (15.7% versus 8.3%) compared to TAU, although these differences were not statistically significant. Given that the GAPP-MDD trial was ultimately underpowered to detect statistically significant differences in patient outcomes, it was assessed in parallel with the larger GUIDED RCT. We observed that relative improvements in response and remission rates were consistent between the GAPP-MDD (33.0% response, 89.0% remission) and GUIDED (31.0% response, 51.0% remission) trials. Together with GUIDED, the results from the GAPP-MDD trial indicate that combinatorial pharmacogenomic testing can be an effective tool to help guide depression treatment in the context of the Canadian healthcare setting (ClinicalTrials.gov NCT02466477).

Immunogenicity, Safety, and Tolerability of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Immunocompetent Adults Aged 18-49 Years With or Without Risk Factors for Pneumococcal Disease: A Randomized Phase 3 Trial (PNEU-DAY).

BACKGROUND: Adults with certain medical and behavioral factors are at increased risk for pneumococcal disease (PD). Sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults in some countries. METHODS: This phase 3 trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults aged 18-49 years with or without predefined risk factors for PD (NCT03547167). Overall, 1515 participants were randomized 3:1 to receive either V114 or PCV13, followed by PPSV23. RESULTS: Most common solicited adverse events (AEs) following administration of V114 or PCV13 as well as PPSV23 were injection-site pain and fatigue. The proportion of participants with AEs was comparable in both groups. V114 and PCV13 were immunogenic based on opsonophagocytic activity (OPA) geometric mean titers (GMTs) 30 days postvaccination for all serotypes contained in each respective vaccine. OPA GMTs to the 2 unique serotypes in V114 were robust in the V114 group. PPSV23 was immunogenic for all 15 serotypes contained in V114 in both vaccination groups, including 22F and 33F. CONCLUSIONS: V114 administered alone or sequentially with PPSV23 is well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, in immunocompetent adults aged 18-49 years with or without certain medical or behavioral risk factors for PD. CLINICAL TRIALS REGISTRATION: NCT03547167 and EudraCT 2017-004915-38.

Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose. CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.

Obesity in adults: a clinical practice guideline

Obesity is a complex chronic disease in which abnormal or excess body fat (adiposity) impairs health, increases the risk of long-term medical complications and reduces lifespan.1 Epidemiologic studies define obesity using the body mass index (BMI; weight/height2), which can stratify obesity-related health risks at the population level. Obesity is operationally defined as a BMI exceeding 30 kg/m2 and is subclassified into class 1 (30­34.9), class 2 (35­39.9) and class 3 (≥ 40). At the population level, health complications from excess body fat increase as BMI increases.2 At the individual level, complications occur because of excess adiposity, location and distribution of adiposity and many other factors, including environmental, genetic, biologic and socioeconomic factors.

Effectiveness and tolerability of a trandolapril-based antihypertensive treatment regimen over 12 months in actual clinical care across Canada.

BACKGROUND AND OBJECTIVES: There is little information on the effects of trandolapril on renal function when used in Canadian general practice. We evaluated the use and blood pressure (BP) lowering effectiveness of trandolapril-based therapies in Canadian conditions of actual care and attempted to capture assessments of urinary albumin concentration (UAC) and estimated glomerular filtration rate (eGFR) in clinical practice. METHODS: This was a prospective, non-interventional, observational study in adults with uncontrolled hypertension, with or without co-morbidities, either treatment-naïve or uncontrolled on existing antihypertensive medications. Hypertension was not defined per protocol. Trandolapril doses (0.5, 1, 2, 4 mg) and subjects' continued medical care were all at the discretion of the treating physician. Data were gathered after 3, 6 and 12 months. RESULTS: 7,993 patients entered the study and 4,983 patients attended the Month 12 visit. Most patients (91.7 %) received trandolapril as a new prescription. At 12 months, 72.9 % of patients without diabetes and 34.4 % with diabetes were controlled (targets <140/90 and 130/80 mmHg, respectively) and 79.2 % of patients with diabetes had BP below 140/90 mmHg. Evaluable eGFR data were available for 25.1, 21.2 and 21.7 % of patients at Months 3, 6 and 12, respectively, and UAC data for 9.6, 8.2 and 9.0 % of patients at the same time points. Treatment was well tolerated. Dropout rates were 37.7 % after 12 months. CONCLUSION: Effective, sustained and well-tolerated double-digit BP reduction is achievable with a trandolapril-based treatment regimen for all patient groups. It appears that for diabetic patients blood pressure control as per Canadian Hypertension Education Program recommendations is yet challenging. The results also illuminate the persistent gap between treatment guidelines and actual care.

Blood pressure control rates with an antihypertensive regimen including trandolapril in a Canadian usual-care setting.

INTRODUCTION: The aim of the study was to assess the effects on blood pressure (BP) levels and control rates in hypertensive subjects receiving trandolapril as monotherapy or as part of an antihypertensive regimen in everyday Canadian clinical practice. METHODS: The MAVIKtory study was a multicenter, single-arm observational study in 601 primary-care centers in Canada. Diabetic and nondiabetic subjects were included, who were treated with trandolapril for hypertension in accordance with usual practices and national guidelines. Subjects received trandolapril as a new prescription, alone, or in combination with prior therapy. Treatment regimens were at the discretions of the treating physicians. Subjects were followed for 6 months. The primary outcomes measures were the percentage of subjects reaching BP targets set by their physicians after 6 months of therapy, and the percentage of subjects reaching the guidelines targets (systolic blood pressure [SBP]/diastolic blood pressure [DBP] < 140/90 mm Hg) after 6 months as assessed by their physicians. Other outcomes were the percentage of diabetic subjects reaching BP targets, and tolerability. RESULTS: A total of 8787 subjects were enrolled and included in the intention-to-treat population. Starting doses of trandolapril were 1 or 2 mg in the majority of subjects and remained unchanged in 51.9% of the population at 6 months. The target of < 140/90 (< 130/80) mm Hg was reached by 67.3% of the population. The lower mean physician-set target of 133.4/83.3 mm Hg for nondiabetic subjects and 128.6/79.3 mm Hg for diabetic subjects was reached by 52.2%. Mean reductions from baseline to month 6 were 19.4 mm Hg (95% CI: [-19.9 to -19.0]) in SBP, and 10.1 mm Hg (95% CI: [-10.4 to -9.8]) in DBP. Cough was the most commonly reported adverse event, reported in 4.2% of all subjects. CONCLUSION: Trandolapril demonstrated a favorable safety and effectiveness profile. SBP reductions of approximately 20 mm Hg and control rates > 65% could be achieved over 6 months.

Effectiveness of a trandolapril-based treatment regimen in subjects with isolated systolic hypertension in Canada.

OBJECTIVE: This report evaluates the effectiveness of a titration-based, escalating dose regimen based on trandolapril in subjects with isolated systolic hypertension (ISH) treated in Canadian clinical practice. METHODS: Substudy of the TRAIL (Trandolapril Regimen Applied In real Life) study; a prospective, open-label, single cohort, multicentre study in 192 Canadian primary care practices. Subjects with ISH received trandolapril therapy, initiated at 1 mg/day (0.5 mg/day in subjects on diuretics) and increased to 2 or 4 mg at 4 and 9 weeks, respectively, in those not achieving blood-pressure (BP) targets, subject to tolerability. If BP was not controlled after 14 weeks of treatment subjects could be put on trandolapril 4 mg/verapamil 240 mg while continuing the diuretic, or verapamil could be added to the existing regimen. The observation period was 26 weeks. The primary outcome measure was the achievement of target BP levels after 14 weeks. RESULTS: Systolic BP (SBP) was significantly (p < 0.01) reduced from 167.3 +/- 8.7 mmHg at baseline to 136.8 +/- 14.0 mmHg (means +/- SD) at Week 14. The reductions were maintained at Week 26: mean SBP at this time point was 137.4 +/- 12.5 mmHg. The target BP levels of < or =140/90 mmHg at Week 14 was reached by 67% of subjects with ISH. Among study limitations were the observational design; the lack of randomisation and control group, and the fact that subjects with ISH represented a comparatively small number of subjects. CONCLUSIONS: A titration-based, escalating-dose regimen based on trandolapril is effective in subjects with ISH under treatment conditions seen in general clinical practice in Canada.

A 26-week, prospective, open-label, uncontrolled, multicenter study to evaluate the effect of an escalating-dose regimen of trandolapril on change in blood pressure in treatment-naive and concurrently treated adult hypertensive subjects (TRAIL).

OBJECTIVE: This study evaluated the effectiveness of an escalating-dose regimen of trandolapril in subjects with stage 1 or stage 2 hypertension. METHODS: This was a 26-week, prospective, open-label,multicenter study in Canadian primary care centers. Subjects with hypertension who were treatment naive or whose disease was uncontrolled on current first-line antihypertensive monotherapy were treated with trandolapril for 26 weeks alone or in addition to their current treatment. Uncontrolled hypertension was defined as systolic/diastolic blood pressure (SBP/DBP) >or=140/90 mm Hg in subjects with no other risk factors or >or=130/80 mm Hg in subjects with diabetes or kidney disease. Trandolapril therapy was initiated at 1 mg/d and was titrated as required to 2 or 4 mg at 4 and 9 weeks after initiation of treatment, respectively, in those not achieving BP targets. At 14 weeks after treatment initiation, subjects not achieving BP targets could receive a combination of trandolapril 4 mg plus a calcium channel blocker (verapamil 240 mg) with or without a diuretic. Primary outcome was the percentage of patients reaching target BP after 14 weeks. RESULTS: A total of 1683 subjects from 192 general practice clinics across Canada completed the 14-week trandolapril dose-optimization phase, and 1650 completed the full 26-week follow-up. Mean (SD) age was 56.6 (12.6) years, and 49.2% of the subjects were men. At baseline, 82.4% (1359/1650) of subjects were antihypertensive-treatment naive. At the trial end, 73.4% (95% CI, 70.9-75.9) of subjects achieved a target level of SBP/DBP <140/90 mm Hg. The mean (SD) reductions in SBP and DBP were -21.5 (14.0) and -11.9 (9.1) mm Hg, respectively (P < 0.001), and -22.4 (14.0) and -12.7 (9.0) mm Hg, respectively (P < 0.001), at 26 weeks. A total of 343 predominantly mild, nonserious adverse events were attributed to the study drugs, reported by 252 (15.3%) of the 1650 subjects. The most frequently reported nonserious adverse events were cough (6.3%); gastrointestinal disorders (2.3%), predominantly nausea; and headache (2.1%). No serious adverse events were attributed to the study treatment. Trandolapril was generally well tolerated. CONCLUSIONS: A titration-based, escalating-dose regimen of trandolapril was effective and well tolerated in the management of these subjects who were antihypertensive-treatment naive or whose disease was uncontrolled on a diuretic or a calcium channel blocker in this open-label, uncontrolled, multicenter study. Overall, 73.4% of subjects achieved their target blood pressure goal (<140/90 mm Hg).