Association between sodium-glucose cotransporter-2 inhibitors and arrhythmic outcomes in patients with diabetes and pre-existing atrial fibrillation.

AIMS: Prior studies suggest that sodium-glucose cotransporter-2 inhibitors (SGLT2is) may decrease the incidence of atrial fibrillation (AF). However, it is unknown whether SGLT2i can attenuate the disease course of AF among patients with pre-existing AF and Type II diabetes mellitus (DM). In this study, our objective was to examine the association between SGLT2i prescription and arrhythmic outcomes among patients with DM and pre-existing AF. METHODS AND RESULTS: We conducted a population-based cohort study of adults with DM and AF between 2014 and 2019. Using a prevalent new-user design, individuals prescribed SGLT2i were matched 1:1 to those prescribed dipeptidyl peptidase-4 inhibitors (DPP4is) based on time-conditional propensity scores. The primary endpoint was a composite of AF-related healthcare utilization (i.e. hospitalization, emergency department visits, electrical cardioversion, or catheter ablation). Secondary outcome measures included all-cause mortality, heart failure (HF) hospitalization, and ischaemic stroke or transient ischaemic attack (TIA). Cox proportional hazard models were used to examine the association of SGLT2i with the study endpoint. Among 2242 patients with DM and AF followed for an average of 3.0 years, the primary endpoint occurred in 8.7% (n = 97) of patients in the SGLT2i group vs. 10.0% (n = 112) of patients in the DPP4i group [adjusted hazard ratio 0.73 (95% confidence interval 0.55-0.96; P = 0.03)]. Sodium-glucose cotransporter-2 inhibitors were associated with significant reductions in all-cause mortality and HF hospitalization, but there was no difference in the risk of ischaemic stroke/TIA. CONCLUSION: Among patients with DM and pre-existing AF, SGLT2is are associated with decreased AF-related health resource utilization and improved arrhythmic outcomes compared with DPP4is.

Patterns of metformin use and glycated haemoglobin trends among patients with newly diagnosed type 2 diabetes in Alberta, Canada.

AIM: Canadian guidelines recommend metformin as first-line therapy for incident uncomplicated type 2 diabetes and the vast majority of patients are treated accordingly. However, only 54% 65% remain on treatment after 1 year, with the highest discontinuation rates within the first 3 months. The purpose of this study was: (a) to identify individual and clinical factors associated with metformin discontinuation among patients with newly diagnosed uncomplicated type 2 diabetes in Alberta, Canada, and (b) describe glycated haemoglobin (HbA1c) trajectories in the first 12 months after initiation of pharmacotherapy, stratified by metformin usage pattern. MATERIALS AND METHODS: We conducted a retrospective cohort study using linked administrative datasets from 2012 to 2017 to define a cohort of individuals with uncomplicated incident type 2 diabetes. Using logistic regression, we determined individual and clinical characteristics associated with metformin discontinuation. We categorized individuals based on patterns of metformin use and then used mean HbA1c measurements over a 12-month follow-up period to determine glycaemic trajectories for each pattern. RESULTS: Characteristics associated with metformin discontinuation were younger age, lower baseline HbA1c and having fewer comorbidities. Sex, income and location (urban/rural) were not significantly associated with metformin discontinuation. Individuals who continued metformin with higher adherence and individuals who discontinued metformin entirely had lowest HbA1c values at 12 months from treatment initiation. Those who changed therapy or had additional therapies added had higher HbA1c values at 12 months. CONCLUSION: Identifying characteristics associated with discontinuation of metformin and individuals' medication usage patterns provide an opportunity for targeted interventions to support patients' glycaemic management.

Patterns and Patients' Characteristics Associated With Use of Sodium-Glucose Cotransporter-2 Inhibitors Among Adults With Type 2 Diabetes: A Population-based Cohort Study.

OBJECTIVES: Our aim in this study was to describe patterns and patient-level factors associated with use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) among adults with diabetes being treated in Alberta, Canada. METHODS: Using linked administrative data sets from 2014 to 2019, we defined a retrospective cohort of adults with prevalent or incident type 2 diabetes with indications for SGLT2i use and who did not have advanced kidney disease (glomerular filtration rate <30 mL/min per 1.73 m2) or previous amputation. We describe medication dispensation patterns of SGLT2is over time in the overall cohort and among the subgroup with cardiovascular disease (CVD). Multivariable logistic regression was used to determine patients' characteristics associated with SGLT2i use. RESULTS: Of the 341,827 patients with diabetes (mean age, 60.7 years; 45.6% female), 107,244 (31.3%) had CVD. The proportion of patients with an SGLT2i prescription increased in a linear fashion to a maximum of 10.8% (95% confidence interval [CI], 10.7% to 10.9%) of the eligible cohort by the end of the observation period (March 2019). The proportion of filled prescriptions was similar for patients with CVD (10.4%; 95% CI, 10.1% to 10.6%) and for those without CVD (10.9%; 95% CI, 10.8% to 11.0%). Patients' characteristics associated with lower odds of filling an SGLT2i prescription included female sex, older age and lower income. CONCLUSIONS: The use of SGLT2is is increasing among patients with diabetes but remains low even in those with CVD. Policy and practice changes to increase prescribing, especially in older adults, may help to reduce morbidity and mortality related to cardiovascular and renal complications.

Accounting for concurrent antihyperglycemic medication changes in dietary and physical activity interventions: A focused literature review.

AIMS: To summarize methods used to account for antihyperglycemic medication changes in randomized controlled trials evaluating the effect of dietary and physical activity interventions on glycemia among adults with diabetes. METHODS: Using studies included in two recently published systematic reviews of randomized controlled trials examining the glycemic effects of dietary and physical activity interventions, we evaluated how each study accounted for antihyperglycemic medication changes. Data were analyzed using summary statistics, stratified by the type of intervention studied, and each was assigned a score from 0 to 6 reflecting the strength of medication controls employed. RESULTS: We evaluated 22 physical activity focused and 27 dietary focused articles. Our scoring system yielded a mean concurrent medication adjustment score of 3.9/6 for the physical activity studies and a score of 1.7/6 (p < 0.001) for the dietary studies. CONCLUSIONS: We found that randomized controlled trials included in recent systematic reviews of physical activity and dietary interventions did not robustly account or control for changes in antihyperglycemic medications, with physical activity interventions doing so more robustly than dietary interventions. This is a threat to the validity of study findings, as observed glycemic changes may in fact be attributable to imbalances in concurrent medication adjustments between groups.

First-line pharmacotherapy for incident type 2 diabetes: Prescription patterns, adherence and associated costs.

AIMS: To use real-world prescription data from Alberta, Canada to: (a) describe the prescribing patterns for initial pharmacotherapy for those with newly diagnosed uncomplicated type 2 diabetes; (b) describe medication-taking behaviours (adherence and persistence) in the first year after initiating pharmacotherapy; and (c) explore healthcare system costs associated with prescribing patterns. METHODS: We employed a retrospective cohort design using linked administrative datasets from 2012 to 2017 to define a cohort of those with uncomplicated incident diabetes. We summarized the initial prescription patterns, adherence and costs (healthcare and pharmaceutical) over the first year after initiation of pharmacotherapy. Using multivariable regression, we determined the association of these outcomes with various sociodemographic characteristics. RESULTS: The majority of individuals for whom metformin was indicated as first-line therapy received a prescription for metformin monotherapy (89%). Older individuals, those with higher baseline A1C and those with no comorbidities, were most likely to be started on non-metformin agents. Adherence with the initially prescribed regimen was suboptimal overall, with nearly half (48%) being non-adherent over the first year. One-third of those who started metformin discontinued it in the first 3 months. Those started on non-metformin agents had roughly twice the healthcare costs, and five to seven times higher medication costs, compared to those started on metformin, in the first year after starting therapy. CONCLUSIONS: With the addition of new classes of medications, healthcare providers who look after those with type 2 diabetes have more pharmaceutical options than ever. Most individuals continue to be prescribed metformin monotherapy. However, adherence is suboptimal, and drops off considerably within the first 3 months.

The prevalence of the defining features of primary ciliary dyskinesia within a cri du chat syndrome cohort.

BACKGROUND: Primary ciliary dyskinesia (PCD) and cri du chat syndrome (CdCS) are distinct disorders that can co-occur due to a common genetic locus on chromosome 5p. Chronic respiratory symptoms associated with PCD can occur in CdCS and are typically attributed to hypotonia, dysphagia, and aspiration. The prevalence of PCD among individuals with CdCS is not known. METHODS: An online survey assessing common features of PCD was distributed to members of the 5P Minus Society, a cri du chat patient advocacy group. Respondents who met criteria for elevated risk of PCD (at least 3 symptoms or other features highly suggestive of PCD) were offered PCD genetic testing. RESULTS: For the 123 respondents (median age 10.1 years with IQR 5.5-17.3 years; from 33 U.S. states and 10 other countries) chronic respiratory symptoms associated with PCD were prevalent, including unexplained neonatal respiratory distress, year-round nasal congestion beginning in infancy, and year-round, wet cough beginning in infancy in 35%, 32%, and 20% of respondents, respectively. Fifteen respondents (12%) met criteria for elevated risk for PCD and completed genetic analysis; however, none were diagnostic for PCD. A PCD clinical center evaluated an additional subject with CdCS who met criteria for likely PCD and had negative genetics, but had diagnostic electron microscopy of the respiratory cilia (missing outer dynein arms). CONCLUSION: Clinicians should be aware of the genetic connection between CdCS and PCD. Non-informative genetic testing does not rule out PCD. CdCS patients with chronic respiratory symptoms may benefit from referral to specialized PCD diagnostic centers.

5p deletions: Current knowledge and future directions.

Disorders resulting from 5p deletions (5p-) were first recognized by Lejeune et al. in 1963 [Lejeune et al. (1963); C R Hebd Seances Acad Sci 257:3098-3102]. 5p- is caused by partial or total deletion of the short arm of chromosome 5. The most recognizable phenotype is characterized by a high-pitched cry, dysmorphic features, poor growth, and developmental delay. This report reviews 5p- disorders and their molecular basis. Hemizygosity for genes located within this region have been implicated in contributing to the phenotype. A review of the genes on 5p which may be dosage sensitive is summarized. Because of the growing knowledge of these specific genes, future directions to explore potential targeted therapies for individuals with 5p- are discussed. © 2015 Wiley Periodicals, Inc.

Temporal and spatial profile of brain diffusion-weighted MRI after cardiac arrest.

BACKGROUND AND PURPOSE: Diffusion-weighted magnetic resonance imaging of the brain is a promising technique to help predict functional outcome in comatose survivors of cardiac arrest. We aimed to evaluate prospectively the temporal-spatial profile of brain apparent diffusion coefficient changes in comatose survivors during the first 8 days after cardiac arrest. METHODS: Apparent diffusion coefficient values were measured by 2 independent and blinded investigators in predefined brain regions in 18 good- and 15 poor-outcome patients with 38 brain magnetic resonance imaging scans and were compared with those of 14 normal controls. The same brain regions were also assessed qualitatively by 2 other independent and blinded investigators. RESULTS: In poor-outcome patients, cortical structures, in particular the occipital and temporal lobes, and the putamen exhibited the most profound apparent diffusion coefficient reductions, which were noted as early as 1.5 days and reached a nadir between 3 and 5 days after the arrest. Conversely, when compared with normal controls, good-outcome patients exhibited increased diffusivity, in particular in the hippocampus, temporal and occipital lobes, and corona radiata. By qualitative magnetic resonance imaging readings, 1 or more cortical gray matter structures were judged to be moderately to severely abnormal in all poor-outcome patients except for the 3 patients imaged within 24 hours after the arrest. CONCLUSIONS: Brain diffusion-weighted imaging changes in comatose, postcardiac arrest survivors in the first week after the arrest are region and time dependent and differ between good- and poor-outcome patients. With increasing use of magnetic resonance imaging in this context, it is important to be aware of these relations.

Associations between demographic factors and provider structures on cost and length of stay for hemodialysis patients with vascular access failure.

Vascular access failure (VAF) is a major determinant of morbidity and cost for hemodialysis patients, but little is known about the care patterns and cost implications that are associated with VAF. A total of 952 episodes of VAF in 348 patients were identified using specific procedure codes. Demographic and care pattern characteristics were available as were detailed costs for each episode. The determinants of several important performance measures were evaluated: Cost per episode, inpatient versus outpatient treatment, and length of stay (LOS). Over 5 yr of study, the proportion of VAF episodes that were treated on an outpatient basis increased from 31 to 63%. Average costs of outpatient versus inpatient episodes were $1491 and $8265, respectively. Men were more likely to be treated as outpatients (odds ratio [OR] 1.56; 95% confidence interval [CI] 1.17 to 2.08), but once admitted, their LOS was longer (difference LOS +1.3; 95% CI +0.32 to +2.28) and more costly (delta$ +2603; 95% CI +632 to +4573). Nonblack, nonwhite patients were more likely to be treated as outpatients than were white patients (OR 2.07; 95% CI 1.27 to 3.36) and had shorter LOS once admitted (deltaLOS -2.37; 95% CI -4.23 to -0.49). Compared with Medicare, non-Medicare case-managed insurance was associated with a higher likelihood of outpatient treatment (OR 1.40; 95% CI 1.01 to 1.94) for VAF and shorter LOS (deltaLOS -1.36; 95% CI -2.48 to -0.24) and lower costs (delta$ -2742; 95% CI -5012 to -472) for inpatient treatment. It is concluded that gender and racial factors may influence VAF care. Over time, more VAF episodes are being treated in outpatient settings. Case management may lead to more outpatient treatment and shorter inpatient treatment of VAF.