In HFpEF with obesity, semaglutide improved health status and weight loss at 52 wk, regardless of initial health status.

SOURCE CITATION: Kosiborod MN, Verma S, Borlaug BA, et al; STEP-HFpEF Trial Committees and Investigators. Effects of semaglutide on symptoms, function, and quality of life in patients with heart failure with preserved ejection fraction and obesity: a prespecified analysis of the STEP-HFpEF trial. Circulation. 2024;149:204-216. 37952180.

Sodium-glucose co-transporter-2 inhibitors are associated with kidney benefits at all degrees of albuminuria: A retrospective cohort study of adults with diabetes.

AIM: To estimate the real-world effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) at reducing loss of kidney function and adverse kidney events in adults with varying levels of albuminuria. MATERIALS AND METHODS: In this retrospective cohort study using administrative data, we matched new SGLT2i users 1:2 to DPP4i users on diabetes therapy, chronic kidney disease (CKD) stage, albuminuria and time-conditional propensity score. Albuminuria was defined by spot urine albumin or equivalent as mild, moderate or severe. Linear regression was used to model the estimated glomerular filtration rate (eGFR), and Poisson regression for a composite kidney outcome (> 40% loss of eGFR, kidney replacement therapy or death from kidney causes) and all-cause mortality. RESULTS: SGLT2i users (n = 19 238, median age 57.9 years, female 40.9%) had mostly nil/mild albuminuria (70.7%). SGLT2is were associated with a 1.36 (95% CI 0.98-1.74) mL/min/1.73m2 (P < .001) acute (≤ 60 days) decline in eGFR, relative to DPP4is. Thereafter, SGLT2is were associated with 1.04 (95% CI 0.93-1.15) mL/min/1.73m2 (P < .001) less annual eGFR loss. SGLT2i users had fewer adverse kidney outcomes (incidence rate ratio [IRR] 0.58 [0.47-0.71]; P < .001), but not all-cause mortality (IRR 0.82 [0.66-1.01]; P = .06). Outcomes were similar considering only those with nil/mild albuminuria. CONCLUSIONS: SGLT2is may prevent eGFR decline and reduce the risk of adverse kidney events in adults with diabetes and nil or non-severe albuminuria.

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.

In obesity or overweight without diabetes, orforglipron increased weight loss at 26 wk.

SOURCE CITATION: Wharton S, Blevins T, Connery L, et al; GZGI investigators. Daily oral GLP-1 receptor agonist orforglipron for adults with obesity. N Engl J Med. 2023;389:877-880. 37351564.

In prediabetes, oral vitamin D reduces progression to new-onset diabetes.

SOURCE CITATION: Pittas AG, Kawahara T, Jorde R, et al. Vitamin D and risk for type 2 diabetes in people with prediabetes: a systematic review and meta-analysis of individual participant data from 3 randomized clinical trials. Ann Intern Med. 2023;176:355-363. 36745886.

Changing the Conversation: Empowering Community Pharmacists to Address Pneumococcal Vaccine Hesitancy.

BACKGROUND: Although pneumococcal vaccine is recommended for everyone 65 years of age and older, only 58% of Canadians in this age group have been vaccinated, well below the Public Health Agency of Canada's target of 80%. To improve uptake, a stepped-wedge cluster randomized trial testing the effectiveness of a community pharmacist intervention was developed. OBJECTIVE: This pre-specified sub-study aimed to uncover and quantify factors contributing to vaccine hesitancy by exploring the nature of patient-pharmacist conversations about pneumococcal vaccine. METHODS: Beginning each month (April to August 2023), participating pharmacies were randomly selected to receive an education package designed to enhance pharmacists' knowledge, skills, and abilities in promoting pneumococcal vaccination. Pharmacists provided usual care (control stage) until they received the educational package and transitioned to the intervention stage. Weekly scorecards tracked patient-pharmacist conversations about pneumococcal vaccination. Chi-squared tests compared time taken for each conversation and patient-reported reason(s) for refusal between control and intervention stages. RESULTS: Thirteen pharmacies from across Alberta were included in the analysis, reporting 656 patient-pharmacist conversations (control stage n=271, intervention stage n=385). Time taken for pneumococcal vaccine conversations decreased after pharmacies received the education package (65% of conversations resulting in vaccination took <20 minutes in the control stage, compared to 88% in the intervention stage (p=0.004)). The most common patient-reported reason for refusal, needing more time to think about the vaccine, remained similar between stages (p=0.23). However, during the intervention stage, fewer patients refused vaccination due to lack of time to receive it today (p=0.016) and perceived lack of benefit (p=0.035), but more patients refused vaccination due to cost barriers (p=0.026). CONCLUSION: The education provided in this study changed the reasons for refusing vaccines, suggesting the nature of patient-pharmacist conversations became more efficient and informed. Similar interventions could be adopted across Canada and the US to help combat vaccine hesitancy.

Achievement of treatment targets among patients with type 2 diabetes in 2015 and 2020 in Canadian primary care.

BACKGROUND: An update on the degree to which patients with type 2 diabetes in Canada achieve treatment targets is needed to document progress and identify subgroups that need attention. We sought to estimate the frequency with which patients managed in primary care met treatment targets (i.e., HbA1c ≤ 7.0%, blood pressure < 130/80 mm Hg and low-density lipoprotein cholesterol [LDL-C] < 2.00 mmol/L), guideline-based use of statins and of angiotensin-convertingenzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and the effects of patient age and sex. METHODS: We conducted a cross-sectional study of 32 503 and 44 930 adults with diabetes in Canada on June 30, 2015, and 2020, respectively, using electronic medical record data from primary care practices across 5 provinces. We grouped achievement of diabetes targets by age and sex, and compared between groups using logistic regression with adjustment for cardiovascular comorbidities. RESULTS: In 2020, target HbA1c levels were achieved for 63.8% of women and 58.9% of men. Blood pressure and LDL-C targets were achieved for 45.6% and 45.8% of women, and for 43.1% and 59.4% of men, respectively. All 3 treatment targets were achieved for 13.3% of women and 16.5% of men. Overall, 45.3% and 54.0% of women and men, respectively, used statins; 46.5% of women used ACE inhibitors or ARBs, compared with 51.9% of men. With the exception of blood pressure and HbA1c levels among women, target achievement was lower among younger patients. Achievement of the LDL-C target, statin use and ACE inhibitor or ARB use were lower among women at any age. From 2015 to 2020, target achievement increased for HbA1c, remained consistent for LDL-C and declined for blood pressure; use of statins and of ACE inhibitors or ARBs also declined. INTERPRETATION: Target achievement for blood pressure and use of statins and of ACE inhibitors and ARBs declined between 2015 and 2020, and was suboptimal in all patient groups. Widespread quality improvement is needed to increase evidence-based therapy for people with diabetes.

In uninfected household contacts of patients with COVID-19, REGEN-COV reduced symptomatic COVID-19 at 28 d.

SOURCE CITATION: O'Brien MP, Forleo-Neto E, Musser BJ, et al. Subcutaneous REGEN-COV antibody combination to prevent Covid-19. N Engl J Med. 2021;385:1184-95. 34347950.

In adults with overweight or obesity, continued weekly semaglutide after a 20-wk run-in improved weight loss.

SOURCE CITATION: Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. JAMA. 2021;325:1414-25. 33755728.

Mycobacterium chimaera Encephalitis Following Cardiac Surgery: A New Syndrome.

We report the cases of 3 patients with fatal, disseminated Mycobacterium chimaera infections following cardiac surgeries. Progressive neurocognitive decline and death were explained by active granulomatous encephalitis, with widespread involvement of other organs. This syndrome is clinically elusive and, thus, may have caused deaths in prior reported series.

Atteinte des cibles thérapeutiques pour le diabète de type 2 en 2015 et 2020 en médecine de soins primaires au Canada.

CONTEXTE: Une vérification du degré d'atteinte des cibles thérapeutiques pour le diabète de type 2 au Canada s'impose afin d'en documenter l'évolution et d'identifier les sousgroupes auprès desquels il est plus urgent d'intervenir. Nous avons voulu estimer la fréquence à laquelle les cas suivis en soins primaires atteignaient leurs cibles thérapeutiques (c.-a-d., HbA1c ≤ 7,0 %, tension artérielle (TA) < 130/80 mm Hg et cholestérol à lipoprotéines de basse densité [LDL-C] < 2,00 mmol/L), le recours aux statines et aux inhibiteurs de l'enzyme de conversion de l'angiotensine (IECA) ou aux bloqueurs des récepteurs de l'angiotensine (BRA) conformément aux lignes directrices, et les effets de l'âge et du sexe. MÉTHODES: Nous avons réalisé une étude transversale auprès de 32 503 et 44 930 adultes atteints de diabète au Canada le 30 juin 2015 et le 30 juin 2020, respectivement, à l'aide des données tirées des dossiers médicaux électroniques (DME) des milieux de soins primaires de 5 provinces. Nous avons regroupé l'atteinte des cibles thérapeutiques pour le diabète selon l'âge et le sexe et comparé les groupes à l'aide d'analyses de régression logistique en tenant compte des comorbidités cardiovasculaires. RÉSULTATS: En 2020, les taux cibles d'HbA1c ont été atteints par 63,8 % des femmes et 58,9 % des hommes. Les cibles de TA et de LDL-C ont été atteintes par 45,6 % et 45,8 % des femmes et par 43,1 % et 59,4 % des hommes, respectivement. Les 3 cibles thérapeutiques ont été atteintes par 13,3 % des femmes et 16,5 % des hommes. Globalement, 45,3 % et 54,0 % des femmes et des hommes, respectivement, ont utilisé des statines; 46,5 % des femmes ont utilisé des inhibiteurs de l'ECA ou des BRA, contre 51,9 % des hommes. À l'exception de la TA et des taux d'HbA1c chez les femmes, l'atteinte des cibles a été moindre chez les patientes plus jeunes. L'atteinte de la cible de LDL-C et l'utilisation de statines et d'IECA ou de BRA ont été moindres chez les femmes de toutes les catégories d'âge. Entre 2015 et 2020, l'atteinte des cibles a augmenté pour l'HbA1c, est demeurée constante pour le LDL-C et a diminué pour la TA; l'utilisation des statines et des IECA ou des BRA a aussi diminué. INTERPRÉTATION: L'atteinte des cibles de TA et l'utilisation des statines, des IECA et des BRA ont diminué entre 2015 et 2020 et étaient sous-optimales dans tous les groupes. Une amélioration à grande échelle de la qualité des soins s'impose pour promouvoir un traitement du diabète fondé sur des données probantes.

Association between frailty and 30-day outcomes after discharge from hospital.

BACKGROUND: Readmissions after hospital discharge are common and costly, but prediction models are poor at identifying patients at high risk of readmission. We evaluated the impact of frailty on readmission or death within 30 days after discharge from general internal medicine wards. METHODS: We prospectively enrolled patients discharged from 7 medical wards at 2 teaching hospitals in Edmonton. Frailty was defined by means of the previously validated Clinical Frailty Scale. The primary outcome was the composite of readmission or death within 30 days after discharge. RESULTS: Of the 495 patients included in the study, 162 (33%) met the definition of frailty: 91 (18%) had mild, 60 (12%) had moderate, and 11 (2%) had severe frailty. Frail patients were older, had more comorbidities, lower quality of life, and higher LACE scores at discharge than those who were not frail. The composite of 30-day readmission or death was higher among frail than among nonfrail patients (39 [24.1%] v. 46 [13.8%]). Although frailty added additional prognostic information to predictive models that included age, sex and LACE score, only moderate to severe frailty (31.0% event rate) was an independent risk factor for readmission or death (adjusted odds ratio 2.19, 95% confidence interval 1.12-4.24). INTERPRETATION: Frailty was common and associated with a substantially increased risk of early readmission or death after discharge from medical wards. The Clinical Frailty Scale could be useful in identifying high-risk patients being discharged from general internal medicine wards.

Working-age adults with diabetes experience greater susceptibility to seasonal influenza: a population-based cohort study.

AIMS/HYPOTHESIS: The aim of this work was to compare the incidence of illness attributable to influenza in working-age adults (age <65 years) with and without diabetes. METHODS: We performed a cohort study using administrative data from Manitoba, Canada, between 2000 and 2008. All working-age adults with diabetes were identified and matched with up to two non-diabetic controls. We analysed the rates of influenza-like illness physician visits and hospitalisations, pneumonia and influenza hospitalisations, and all-cause hospitalisations. Multivariable regressions were used to estimate the influenza-attributable rate of each outcome. RESULTS: We included 745,777 person-years of follow-up among 166,715 subjects. The median age was 50-51 years and 48-49% were women; adults with diabetes had more comorbidities and were more likely to be vaccinated for influenza than those without diabetes. Compared with similar adults without diabetes, those with diabetes had a 6% greater (RR 1.06, 95% CI 1.02, 1.10; absolute risk difference 6 per 1,000 adults per year) increase in all-cause hospitalisations associated with influenza, representing a total of 54 additional hospitalisations. There were no differences in the influenza-attributable rates of influenza-like illness (p = 0.06) or pneumonia and influenza (p = 0.11). CONCLUSIONS/INTERPRETATION: Guidelines calling for influenza vaccinations in diabetic, in addition to elderly, adults implicitly single out working-age adults with diabetes. The evidence supporting such guidelines has hitherto been scant. We found that working-age adults with diabetes appear more susceptible to serious influenza-attributable illness. These findings represent the strongest available evidence for targeting diabetes as an indication for influenza vaccination, irrespective of age.

Inter-observer reliability and anatomical landmarks for arm circumference to determine cuff size for blood pressure measurement.

Accurate arm circumference (AC) measurement is required for accurate blood pressure (BP) readings. Standards stipulate measuring arm circumference at the midpoint between the acromion process (AP) and the olecranon process. However, which part of the AP to use is not stipulated. Furthermore, BP is measured sitting but arm circumference is measured standing. We sought to understand how landmarking during AC measurement and body position affect cuff size selection. Two variations in measurement procedure were studied. First, AC was measured at the top of the acromion (TOA) and compared to the spine of the acromion (SOA). Second, standing versus seated measurements using each landmark were compared. AC was measured to the nearest 0.1 cm at the mid-point of the upper arm by two independent observers, blinded from each other's measurements. In 51 participants, the mean (±SD) mid-AC measurement using the anchoring landmarks TOA and SOA in the standing position were 32.4 cm (±6.18) and 32.1 cm (±6.07), respectively (mean difference of 0.3 cm). In the seated position, mean arm circumference was 32.2 (±6.10) using TOA and 31.1 (±6.03) using SOA (mean difference 1.1 cm). Kappa agreement for cuff selection in the standing position between TOA and SOA was 0.94 (p < 0.001). The landmark on the acromion process can change the cuff selection in a small percentage of cases. The overall impact of this landmark selection is small. However, standardizing landmark selection and body position for AC measurement could further reduce variability in cuff size selection during BP measurement and validation studies.

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

BACKGROUND: We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. METHODS AND RESULTS: This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. CONCLUSIONS: In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Stroke Risk Reduction in Atrial Fibrillation Through Pharmacist Prescribing: A Randomized Clinical Trial.

Importance: Major gaps in the delivery of appropriate oral anticoagulation therapy (OAC) exist, leaving a large proportion of persons with atrial fibrillation (AF) unnecessarily at risk for stroke and its sequalae. Objective: To investigate whether pharmacist-led OAC prescription can increase the delivery of stroke risk reduction therapy in individuals with AF. Design, Setting, and Participants: This prospective, open-label, patient-level randomized clinical trial of early vs delayed pharmacist intervention from January 1, 2019, to December 31, 2022, was performed in 27 community pharmacies in Alberta, Canada. Pharmacists identified patients 65 years or older with 1 additional stroke risk factor and known, untreated AF (OAC nonprescription or OAC suboptimal dosing) or performed screening using a 30-second single-lead electrocardiogram to detect previously unrecognized AF. Patients with undertreated or newly diagnosed AF eligible for OAC therapy were considered to have actionable AF. Data were analyzed from April 3 to November 30, 2023. Interventions: In the early intervention group, pharmacists prescribed OAC using guideline-based algorithms with follow-up visits at 1 and 3 months. In the delayed intervention group, which served as the usual care control, the primary care physician (PCP) was sent a notification of actionable AF along with a medication list (both enhancement over usual care). After 3 months, patients without OAC optimization in the control group underwent delayed pharmacist intervention. Main Outcomes and Measures: The primary outcome was the difference in the rate of guideline-concordant OAC use in the 2 groups at 3-month follow-up ascertained by a research pharmacist blinded to treatment allocation. Results: Eighty patients were enrolled with actionable AF (9 [11.3%] newly diagnosed in 235 individuals screened). The mean (SD) age was 79.7 (7.4) years, and 45 patients (56.3%) were female. The median CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack) score was 2 (IQR, 2-3). Seventy patients completed follow-up. Guideline-concordant OAC use at 3 months occurred in 36 of 39 patients (92.3%) in the early intervention group vs 23 of 41 (56.1%) in the control group (P < .001), with an absolute increase of 34% and number needed to treat of 3. Of the 23 patients who received appropriate OAC prescription in the control group, the PCP called the pharmacist for prescribing advice in 6 patients. Conclusions and Relevance: This randomized clinical trial found that pharmacist OAC prescription is a potentially high-yield opportunity to effectively close gaps in the delivery of stroke risk reduction therapy for AF. Scalability and sustainability of pharmacist OAC prescription will require larger trials demonstrating effectiveness and safety. Trial Registration: ClinicalTrials.gov Identifier: NCT03126214.

Effectiveness of influenza vaccination in working-age adults with diabetes: a population-based cohort study.

BACKGROUND: Guidelines recommend influenza vaccinations in all diabetic adults, but there is limited evidence to support vaccinating working-age adults (<65 years) with diabetes. We examined the effectiveness of influenza vaccine in this subgroup, compared with elderly adults (≥ 65 years) for whom vaccination recommendations are well accepted. METHODS: We identified all adults with diabetes, along with a sample of age-matched and sex-matched comparison subjects without diabetes, from 2000 to 2008, using administrative data from Manitoba, Canada. With multivariable Poisson regression, we estimated vaccine effectiveness (VE) on influenza-like illnesses (ILIs), pneumonia and influenza (PI) hospitalisations and all-cause (ALL) hospitalisations during periods of known circulating influenza. Analyses were replicated outside of influenza season to rule out residual confounding. RESULTS: We included 543 367 person-years of follow-up, during which 223 920 ILI, 5422 PI and 94 988 ALL occurred. The majority (58%) of adults with diabetes were working age. In this group, influenza vaccination was associated with relative reductions in PI (43%, 95% CI 28% to 54%) and ALL (28%, 95% CI 24% to 32%) but not ILI (-1%, 95% CI -3% to 1%). VE was similar in elderly adults for ALL (33-34%) and PI (45-55%), although not ILI (12-13%). However, similar estimates of effectiveness were also observed for all three groups during non-influenza control periods. CONCLUSIONS: Working-age adults with diabetes experience similar benefits from vaccination as elderly adults, supporting current diabetes-specific recommendations. However, these benefits were also manifest outside of influenza season, suggesting residual bias. Vaccination recommendations in all high-risk adults would benefit from randomised trial evidence.