Clinical Outcomes With Electronic Nudges to Increase Influenza Vaccination : A Prespecified Analysis of a Nationwide, Pragmatic, Registry-Based, Randomized Implementation Trial.

BACKGROUND: In the NUDGE-FLU (Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake) trial, electronic letters incorporating cardiovascular (CV) gain-framing and repeated messaging increased influenza vaccination by approximately 1 percentage point. OBJECTIVE: To evaluate the effects of the successful nudging interventions on downstream clinical outcomes. DESIGN: Prespecified exploratory analysis of a nationwide randomized implementation trial. (ClinicalTrials.gov: NCT05542004). SETTING: The 2022 to 2023 influenza season. PARTICIPANTS: 964 870 Danish citizens aged 65 years or older. INTERVENTION: Usual care or 9 different electronically delivered behavioral nudging letters. MEASUREMENTS: Cardiovascular, respiratory, and other clinical end points during follow-up from intervention delivery (16 September 2022) through 31 May 2023. RESULTS: The analysis set included 691 820 participants. Hospitalization for pneumonia or influenza occurred in 3354 of 346 327 (1.0%) participants in the usual care group, 396 of 38 586 (1.0%) in the CV gain-framing group (hazard ratio [HR], 1.06 [95% CI, 0.95 to 1.18]; versus usual care), and 403 of 38 231 (1.1%) in the repeated letter group (HR, 1.09 [CI, 0.98 to 1.21]; versus usual care). In the usual care group, 44 682 (12.9%) participants were hospitalized for any cause, compared with 5002 (13.0%) in the CV gain-framing group (HR, 1.00 [CI, 0.97 to 1.03]; versus usual care) and 4965 (13.0%) in the repeated letter group (HR, 1.01 [CI, 0.98 to 1.04]; versus usual care). A total of 6341 (1.8%) participants died in the usual care group, compared with 721 (1.9%) in the CV gain-framing group (HR, 1.02 [CI, 0.94 to 1.10]; versus usual care) and 646 (1.7%) in the repeated letter group (HR, 0.92 [CI, 0.85 to 1.00]; versus usual care). LIMITATION: Prespecified but exploratory analysis, potential misclassification of events in routinely collected registry data, and results may not be generalizable to other health systems or countries with other racial compositions and/or cultural or societal norms. CONCLUSION: In a prespecified exploratory analysis, modest increases in influenza vaccination rates seen with electronic nudges did not translate into observable improvements in clinical outcomes. Seasonal influenza vaccination should remain strongly recommended. PRIMARY FUNDING SOURCE: Sanofi.

Effect of Electronic Nudges on Influenza Vaccination Rate in Older Adults With Cardiovascular Disease: Prespecified Analysis of the NUDGE-FLU Trial.

BACKGROUND: Influenza vaccines have been demonstrated to effectively reduce the incidence of influenza infection and potentially associated risks of cardiovascular events in patients with cardiovascular disease (CVD). Despite strong guideline and public health endorsements, global influenza vaccination rates in patients with CVD are highly variable. This prespecified analysis of NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) examined the effect of digital behavioral nudges on influenza vaccine uptake based on the presence of CVD. METHODS: NUDGE-FLU was a randomized, pragmatic, nationwide, register-based trial that included Danish citizens 65 years of age or older during the 2022 to 2023 influenza season. Households were randomized in a 9:1:1:1:1:1:1:1:1:1 ratio to usual care or 9 electronic letters with designs based on behavioral concepts. Danish nationwide registers were used to collect baseline and outcome data. The primary end point was receipt of an influenza vaccine on or before January 1, 2023. The effects of the intervention letters were examined according to the presence of CVD and across cardiovascular subgroups that included heart failure, ischemic heart disease, and atrial fibrillation. RESULTS: Of 964 870 NUDGE-FLU participants from 691 820 households, 264 392 (27.4%) had CVD. During follow-up, 83.1% of participants with CVD versus 79.2% of participants without CVD received an influenza vaccination (P<0.001). Compared with usual care, a letter emphasizing the potential cardiovascular benefits of influenza vaccination increased vaccination rates; this effect was consistent in participants with CVD (absolute difference, +0.60 percentage points [99.55% CI, -0.48 to 1.68]) and without CVD (+0.98 percentage points [99.55% CI, 0.27-1.70; P for interaction=0.41). A repeated letter strategy with a reminder follow-up letter 14 days later was also effective in increasing influenza vaccination, irrespective of CVD (CVD: absolute difference, +0.80 percentage points [99.55% CI, -0.27 to 1.86]; no CVD: +0.67 percentage points [99.55% CI, -0.06 to 1.40]; P for interaction=0.77). Effectiveness of both nudging strategies was consistent across all major CVD subgroups. None of the other 7 nudging strategies were effective, regardless of CVD status. CONCLUSIONS: Electronic letter interventions emphasizing the potential cardiovascular benefits of influenza vaccination and using a reminder letter strategy were similarly beneficial in increasing influenza vaccination rates among older adults with and without CVD and across cardiovascular subgroups. Electronic nudges may improve influenza vaccine uptake in individuals with CVD. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05542004.

Electronic nudges to increase influenza vaccination uptake in Denmark: a nationwide, pragmatic, registry-based, randomised implementation trial.

BACKGROUND: Influenza vaccination rates remain suboptimal despite effectiveness in preventing influenza infection and related complications. We investigated whether behavioural nudges, delivered via a governmental electronic letter system, would increase influenza vaccination uptake among older adults in Denmark. METHODS: We did a nationwide, pragmatic, registry-based, cluster-randomised implementation trial during the 2022-23 influenza season in Denmark. All Danish citizens aged 65 years or older or turning 65 years by Jan 15, 2023 were included. We excluded individuals living in nursing homes and individuals who had an exemption from the Danish mandatory governmental electronic letter system. Households were randomly assigned (9:1:1:1:1:1:1:1:1:1) to usual care or nine different electronic letters designed on the basis of different behavioural nudging concepts. Data were sourced from nationwide Danish administrative health registries. The primary endpoint was receipt of influenza vaccination on or before Jan 1, 2023. The primary analysis assessed an analytical set of one randomly selected individual per household, and a sensitivity analysis included all randomly assigned individuals and accounted for within-household correlation. The trial is registered with ClinicalTrials.gov, NCT05542004. FINDINGS: We identified 1 232 938 individuals aged 65 years or older in Denmark and excluded 56 436 (4·6%) individuals living in nursing homes and 211 632 (17·2%) with an exemption from the electronic letter system. We randomly assigned 964 870 (78·3%) participants across 691 820 households. Compared with usual care, influenza vaccination rates were higher in the group receiving an electronic letter highlighting potential cardiovascular benefits of vaccination (81·00% vs 80·12%; difference 0·89 percentage points [99·55% CI 0·29-1·48]; p<0·0001) and the group receiving repeated letters at randomisation and at day 14 (80·85% vs 80·12%; difference 0·73 percentage points [0·13-1·34]; p=0·0006). These strategies improved vaccination rates across major subgroups including those with and without established cardiovascular disease. The cardiovascular gain-framed letter was particularly effective among participants who had not been vaccinated for influenza in the previous season (pinteraction=0·0002). A sensitivity analysis of all randomly assigned individuals accounting for within-household clustering yielded similar findings. INTERPRETATION: Electronically delivered letters highlighting potential cardiovascular benefits of influenza vaccination or sent again as a reminder significantly increased vaccination uptake across Denmark. Although the magnitude of effectiveness was modest, the low-touch, inexpensive, and highly scalable nature of these electronic letters might be informative for future public health campaigns. FUNDING: Sanofi.

Nationwide Utilization of Danish Government Electronic letter system for increasing inFLUenza vaccine uptake (NUDGE-FLU): Study protocol for a nationwide randomized implementation trial.

BACKGROUND: Annual influenza vaccination is widely recommended in older adults and other high-risk groups including patients with cardiovascular disease. The real-world effectiveness of influenza vaccination is limited by suboptimal uptake and effective strategies for increasing vaccination rates are therefore needed. The purpose of this trial is to investigate whether behavioral nudges digitally delivered via the Danish nationwide mandatory governmental electronic letter system can increase influenza vaccination uptake among older adults. METHODS: The NUDGE-FLU trial is a randomized implementation trial randomizing all Danish citizens aged 65 years and above without an exemption from the Danish mandatory governmental electronic letter system to receive no digitally delivered behavioral nudge (usual care arm) or to receive one of 9 electronic letters (intervention arms) each leveraging different behavioral science strategies. The trial has randomized 964,870 participants with randomization clustered at the household level (n = 691,820 households). Intervention letters were delivered on September 16, 2022, and follow-up is currently ongoing. All trial data are captured using the nationwide Danish administrative health registries. The primary end point is the receipt of an influenza vaccine on or before January 1, 2023. The secondary end point is time to vaccination. Exploratory end points include clinical events such as hospitalization for influenza or pneumonia, cardiovascular events, all-cause hospitalization, and all-cause mortality. DISCUSSION: The nationwide randomized NUDGE-FLU trial is one of the largest implementation trials ever conducted and will provide important insights into effective communication strategies to maximize vaccination uptake among high-risk groups. TRIAL REGISTRATION: Clinicaltrials.gov: NCT05542004, registered September 15, 2022, https://clinicaltrials.gov/ct2/show/NCT05542004.

Innovative Remote Management Solutions for the Control of Hypertension.

We stand at a critical juncture in the delivery of health care for hypertension. Blood pressure control rates have stagnated, and traditional health care is failing. Fortunately, hypertension is exceptionally well-suited to remote management, and innovative digital solutions are proliferating. Early strategies arose with the spread of digital medicine, long before the COVID-19 pandemic forced lasting changes to the way medicine is practiced. Highlighting one contemporary example, this review explores salient features of remote management hypertensive programs, including: an automated algorithm to guide clinical decisions, home (as opposed to office) blood pressure measurements, an interdisciplinary care team, and robust information technology and analytics. Dozens of emerging hypertension management solutions are contributing to a highly fragmented and competitive landscape. Beyond viability, profit and scalability are critical. We explore the challenges impeding large-scale acceptance of these programs and conclude with a hopeful look to the future when remote hypertension care will have dramatic impact on global cardiovascular health.

Remote Cardiovascular Hypertension Program Enhanced Blood Pressure Control During the COVID-19 Pandemic.

Background The COVID-19 pandemic disrupted traditional health care; one fallout was a drastic decrease in blood pressure (BP) assessment. We analyzed the pandemic's impact on our existing remote hypertension management program's effectiveness and adaptability. Methods and Results This retrospective observational analysis evaluated BP control in an entirely remote management program before and during the pandemic. A team of pharmacists, nurse practitioners, physicians, and nonlicensed navigators used an evidence-based clinical algorithm to optimize hypertensive treatment. The algorithm was adapted during the pandemic to simplify BP control. Overall, 1256 patients (605 enrolled in the 6 months before the pandemic shutdown in March 2020 and 651 in the 6 months after) were a median age of 63 years old, 57% female, and 38.2% non-White. Among enrolled patients with sustained hypertension, 51.1% reached BP goals. Within this group, rates of achieving goal BP improved to 94.6% during the pandemic from 75.8% prepandemic (P<0.0001). Mean baseline home BP was 141.7/81.9 mm Hg during the pandemic and 139.8/82.2 prepandemic, and fell ≈16/9 mm Hg in both periods (P<0.0001). Maintenance during the pandemic was achieved earlier (median 11.8 versus 19.6 weeks, P<0.0001), with more frequent monthly calls (8.2 versus 3.1, P<0.0001) and more monthly home BP recordings per patient (32.4 versus 18.9, P<0.0001), compared with the prepandemic period. Conclusions A remote clinical management program was successfully adapted and delivered significant improvements in BP control and increased home BP monitoring despite a nationally observed disruption of traditional hypertension care. Such programs have the potential to transform hypertension management and care delivery.

Electronic nudges to increase influenza vaccination uptake among patients with heart failure: A pre-specified analysis of the NUDGE-FLU trial.

AIMS: Seasonal influenza vaccination is strongly recommended in patients with heart failure (HF). The NUDGE-FLU trial recently found two electronic behavioural nudging letter strategies - a letter highlighting potential cardiovascular benefits of vaccination and a repeated letter at day 14 -effective in increasing influenza vaccination in Denmark. The aims of this pre-specified analysis was to further examine vaccination patterns and effects of these behavioural nudges in patients with HF including potential off-target effects on guideline-directed medical therapy (GDMT) use. METHODS AND RESULTS: The nationwide NUDGE-FLU trial randomized 964 870 Danish citizens ≥65 years to usual care or nine different electronic nudging letter strategies. Letters were delivered through the official Danish electronic letter system. The primary endpoint was the receipt of an influenza vaccine; additional outcomes for this analysis included GDMT use. In this analysis, we also assessed influenza vaccination rates in the overall Danish HF population including those <65 years (n = 65 075). During the 2022-2023 season, influenza vaccination uptake was 71.6% in the overall Danish HF population but this varied considerably with only 44.6% uptake in those <65 years. A total of 33 109 NUDGE-FLU participants had HF at baseline. Vaccination uptake was higher among those on higher levels of baseline GDMT (≥3 classes: 85.3% vs. ≤2 classes: 81.9%; p < 0.001). HF status did not modify the effects of the two overall successful nudging strategies on influenza vaccination uptake (cardiovascular gain-framed letter: pinteraction = 0.37; repeated letter: pinteraction = 0.55). No effect modification was observed across GDMT use levels for the repeated letter (pinteraction = 0.88), whereas a trend towards attenuated effect among those on low levels of GDMT was observed for the cardiovascular gain-framed letter (pinteraction = 0.07). The letters had no impact on longitudinal GDMT use. CONCLUSIONS: Approximately one in four patients with HF did not receive influenza vaccination with a pronounced implementation gap in those <65 years where less than half were vaccinated. HF status did not modify the effectiveness of cardiovascular gain-framed and repeated electronic nudging letters in increasing influenza vaccination rates. No unintended negative effects on longitudinal GDMT use were observed. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT05542004.

Electronically Delivered Nudges to Increase Influenza Vaccination Uptake in Older Adults With Diabetes: A Secondary Analysis of the NUDGE-FLU Trial.

Importance: Influenza vaccination is associated with a reduced risk of mortality in patients with diabetes, but vaccination rates remain suboptimal. Objective: To assess the effect of electronic nudges on influenza vaccination uptake according to diabetes status. Design, Setting, and Participants: The NUDGE-FLU (Nationwide Utilization of Danish Government Electronic Letter System for Increasing Influenza Vaccine Uptake) trial was a nationwide clinical trial of Danish citizens 65 years or older that randomized participants at the household level to usual care or 9 different electronic nudge letters during the 2022 to 2023 influenza season. End of follow-up was January 1, 2023. This secondary analysis of the NUDGE-FLU trial was performed from May to July 2023. Intervention: Nine different electronic nudge letters designed to boost influenza vaccination were sent in September to October 2022. Effect modification by diabetes status was assessed in a pooled analysis of all intervention arms vs usual care and for individual letters. Main Outcomes and Measures: The primary end point was receipt of a seasonal influenza vaccine. Results: The trial included 964 870 participants (51.5% female; mean [SD] age, 73.8 [6.3] years); 123 974 had diabetes. During follow-up, 83.5% with diabetes vs 80.2% without diabetes received a vaccine (P < .001). In the pooled analysis, nudges improved vaccination uptake in participants without diabetes (80.4% vs 80.0%; difference, 0.37 percentage points; 99.55% CI, 0.08 to 0.66), whereas there was no evidence of effect in those with diabetes (83.4% vs 83.6%; difference, -0.19 percentage points; 99.55% CI, -0.89 to 0.51) (P = .02 for interaction). In the main results of NUDGE-FLU, 2 of the 9 behaviorally designed letters (cardiovascular benefits letter and a repeated letter) significantly increased uptake of influenza vaccination vs usual care; these benefits similarly appeared attenuated in participants with diabetes (cardiovascular gain letter: 83.7% vs 83.6%; difference, 0.04 percentage points; 99.55% CI, -1.52 to 1.60; repeated letter: 83.5% vs 83.6%; difference, -0.15 percentage points; 99.55% CI, -1.71 to 1.41) vs those without diabetes (cardiovascular gain letter: 81.1% vs 80.0%; difference, 1.06 percentage points; 99.55% CI, 0.42 to 1.70; repeated letter: 80.9% vs 80.0%; difference, 0.87 percentage points; 99.55% CI, 0.22 to 1.52) (P = .07 for interaction). Conclusions and Relevance: In this exploratory subgroup analysis, electronic nudges improved influenza vaccination uptake in persons without diabetes, whereas there was no evidence of an effect in persons with diabetes. Trials are needed to investigate the effect of digital nudges specifically tailored to individuals with diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT05542004.

Ethnic differences in body composition and obesity related risk factors: study in Chinese and white males living in China.

The purpose of this cross-sectional observational study was to identify ethnic differences in body composition and obesity-related risk factors between Chinese and white males living in China. 115 Chinese and 114 white male pilots aged 28-63 years were recruited. Fasting body weight, height and blood pressure were measured following standard procedures. Whole-body and segmental body composition were measured using an 8-contact electrode bioimpedance analysis (BIA) system. Fasting serum glucose, fasting plasma total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed using automatic biochemistry analyzer. After adjusting for age and body mass index (BMI), Chinese males had significantly higher percentage of body fat (PBF) both with respect to whole body (Chinese: 23.7%±0.2% vs. Whites: 22.4%±0.2%) and the trunk area (Chinese: 25.0%±0.3% vs. Whites: 23.2%±0.3%) compared to their white counterparts. At all BMIs, Chinese males had significantly higher fasting glucose levels (Chinese: 5.7±1.0 mmol/L vs. Whites: 5.2±1.0 mmol/L) but lower high-density lipoprotein levels (Chinese: 0.8±1.0 mmol/L vs. Whites: 1.0±1.0 mmol/L) than white males. In addition, a marginally significantly higher diastolic blood pressure was found among Chinese men than that among white men (Chinese: 80±1.0 mmHg vs. Whites: 77±1.0 mmHg). Chinese males had more body fat and a greater degree of central fat deposition pattern than that seen in white males in the present study. Furthermore, data on blood pressure, fasting glucose and blood lipids suggest that Chinese men may be more prone to obesity-related risk factors than white men.