Interventions supporting long term adherence and decreasing cardiovascular events after myocardial infarction (ISLAND): pragmatic randomised controlled trial.

OBJECTIVE: To test a scalable health system intervention to improve long term adherence to secondary prevention treatments among patients who have had a recent myocardial infarction. DESIGN: Three arm, pragmatic randomised controlled trial with blinded outcome assessment. SETTING: Nine cardiac centres in Ontario, Canada. PARTICIPANTS: 2632 patients with obstructive coronary artery disease after a myocardial infarction, identified from a centralised cardiac registry. INTERVENTIONS: Participants were randomised 1:1:1 to receive usual care, five mail-outs developed through a user centred design process, or mail-outs plus phone calls. The phone calls were delivered first by an interactive automated system to screen for non-adherence to treatment. Trained lay health workers followed up as necessary. Interventions were coordinated centrally but delivered from each patient's hospital site. MAIN OUTCOME MEASURES: Co-primary outcomes were completion of cardiac rehabilitation and adherence to recommended medication. Data were collected by blinded assessors through patient report and from administrative health databases at 12 months. RESULTS: 2632 patients (mean age 66, 71% male) were randomised: 878 to the full intervention (mail plus phone calls), 878 to mail only, and 876 to usual care. Of the respondents, 174 (27%) of 643 in the usual care group, 200 (32%) of 628 in the mail only group, and 196 (37%) of 531 allocated to the full intervention completed cardiac rehabilitation (adjusted odds ratio 1.55, 95% confidence interval 1.18 to 2.03). In the mail plus phone group, 11.7%, 6.0%, 14.4%, 32.9%, and 35.0% reported adherence to 0, 1, 2, 3, and 4 drug classes after one year, respectively, in comparison with 12.5%, 6.8%, 13.6%, 30.2%, and 36.8% in the mail only group, and 12.2%, 8.4%, 13.1%, 30.3%, and 36.1% in the usual care group, respectively (mail only v usual care, odds ratio 0.98, 95% confidence interval 0.81 to 1.19; full intervention v usual care, 0.99, 0.82 to 1.20). CONCLUSIONS: Scalable interventions delivered by mail plus phone can increase completion of cardiac rehabilitation after myocardial infarction but not adherence to medication. More intensive interventions should be tested to improve adherence to medication and to evaluate the association between attendance at cardiac rehabilitation and adherence to medication. TRIAL REGISTRATION: ClinicalTrials.gov NCT02382731, registered 9 March 2015 before any patient enrolment.

Two speeds of increasing milk feeds for very preterm or very low-birthweight infants: the SIFT RCT.

BACKGROUND: Observational data suggest that slowly advancing enteral feeds in preterm infants may reduce necrotising enterocolitis but increase late-onset sepsis. The Speed of Increasing milk Feeds Trial (SIFT) compared two rates of feed advancement. OBJECTIVE: To determine if faster (30 ml/kg/day) or slower (18 ml/kg/day) daily feed increments improve survival without moderate or severe disability and other morbidities in very preterm or very low-birthweight infants. DESIGN: This was a multicentre, two-arm, parallel-group, randomised controlled trial. Randomisation was via a web-hosted minimisation algorithm. It was not possible to safely and completely blind caregivers and parents. SETTING: The setting was 55 UK neonatal units, from May 2013 to June 2015. PARTICIPANTS: The participants were infants born at < 32 weeks' gestation or a weight of < 1500 g, who were receiving < 30 ml/kg/day of milk at trial enrolment. INTERVENTIONS: When clinicians were ready to start advancing feed volumes, the infant was randomised to receive daily feed increments of either 30 ml/kg/day or 18 ml/kg/day. In total, 1400 infants were allocated to fast feeds and 1404 infants were allocated to slow feeds. MAIN OUTCOME MEASURES: The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for gestational age. The secondary outcomes were mortality; moderate or severe neurodevelopmental disability at 24 months corrected for gestational age; death before discharge home; microbiologically confirmed or clinically suspected late-onset sepsis; necrotising enterocolitis (Bell's stage 2 or 3); time taken to reach full milk feeds (tolerating 150 ml/kg/day for 3 consecutive days); growth from birth to discharge; duration of parenteral feeding; time in intensive care; duration of hospital stay; diagnosis of cerebral palsy by a doctor or other health professional; and individual components of the definition of moderate or severe neurodevelopmental disability. RESULTS: The results showed that survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 out of 1224 (65.5%) infants allocated to faster increments and 848 out of 1246 (68.1%) infants allocated to slower increments (adjusted risk ratio 0.96, 95% confidence interval 0.92 to 1.01). There was no significant difference between groups in the risk of the individual components of the primary outcome or in the important hospital outcomes: late-onset sepsis (adjusted risk ratio 0.96, 95% confidence interval 0.86 to 1.07) or necrotising enterocolitis (adjusted risk ratio 0.88, 95% confidence interval 0.68 to 1.16). Cost-consequence analysis showed that the faster feed increment rate was less costly but also less effective than the slower rate in terms of achieving the primary outcome, so was therefore found to not be cost-effective. Four unexpected serious adverse events were reported, two in each group. None was assessed as being causally related to the intervention. LIMITATIONS: The study could not be blinded, so care may have been affected by knowledge of allocation. Although well powered for comparisons of all infants, subgroup comparisons were underpowered. CONCLUSIONS: No clear advantage was identified for the important outcomes in very preterm or very low-birthweight infants when milk feeds were advanced in daily volume increments of 30 ml/kg/day or 18 ml/kg/day. In terms of future work, the interaction of different milk types with increments merits further examination, as may different increments in infants at the extremes of gestation or birthweight. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76463425. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 18. See the NIHR Journals Library website for further project information.

Some infants who are born early need to be fed through a tube into their stomach. A small volume of milk is given to begin with, which is gradually increased. To determine whether infants do better if they are fed faster or slower, this study compared increasing the milk feeds by 30 ml/kg/day with increasing the milk feeds by 18 ml/kg/day, aiming to get to full feeds (when other fluids are not needed) in 5 or 9 days. We compared results from the two groups at discharge from hospital and at 24 months of age, after correcting for prematurity. We also assessed the economic impact of the two daily feed increments, interviewed parents about taking part in multiple studies and tested methods for improving questionnaire returns. The faster-fed group reached full milk feeds sooner and needed less intravenous nutrition, and the proportion of infants developing bowel inflammation or bloodstream infection were similar. At 24 months of age, we found an unexpected increase in the risk of moderate or severe motor impairment in the faster-fed group, which is difficult to explain. We also saw that other types of disability were more frequent in the faster group, although this was not significantly different mathematically. This means that no clear advantage of increasing feeds at faster or slower rates was identified and health professionals will need to carefully consider how to increase feeds. After accepting the increased risk of disability, an economic evaluation showed that increasing milk feed volumes at a faster rate was not a cost-effective strategy. Interviews with parents showed that they valued opportunities for their infant to take part in studies, but this interaction is complex and difficult to remember at a stressful and confusing time and made worse by considering multiple studies. More questionnaires were returned when vouchers were given before rather than after receiving them.

Feasibility of an Electronic Health Tool to Promote Physical Activity in Primary Care: Pilot Cluster Randomized Controlled Trial.

BACKGROUND: Physical inactivity is associated with increased health risks. Primary care providers (PCPs) are well positioned to support increased physical activity (PA) levels through screening and provision of PA prescriptions. However, PCP counseling on PA is not common. OBJECTIVE: This study aimed to assess the feasibility of implementing an electronic health (eHealth) tool to support PA counseling by PCPs and estimate intervention effectiveness on patients' PA levels. METHODS: A pragmatic pilot study was conducted using a stepped wedge cluster randomized trial design. The study was conducted at a single primary care clinic, with 4 pre-existing PCP teams. Adult patients who had a periodic health review (PHR) scheduled during the study period were invited to participate. The eHealth tool involved an electronic survey sent to participants before their PHR via an email or a tablet; data were used to automatically produce tailored resources and a PA prescription in the electronic medical record of participants in the intervention arm. Participants assigned to the control arm received usual care from their PCP. Feasibility was assessed by the proportion of completed surveys and patient-reported acceptability and fidelity measures. The primary effectiveness outcome was patient-reported PA at 4 months post-PHR, measured as metabolic equivalent of task (MET) minutes per week. Secondary outcomes assessed determinants of PA, including self-efficacy and intention to change based on the Health Action Process Approach behavior change theory. RESULTS: A total of 1028 patients receiving care from 34 PCPs were invited to participate and 530 (51.55%) consented (intervention [n=296] and control [n=234]). Of the participants who completed a process evaluation, almost half (88/178, 49.4%) stated they received a PA prescription, with only 42 receiving the full intervention including tailored resources from their PCP. A cluster-level linear regression analysis yielded a non-statistically significant positive difference in MET-minutes reported per week at follow-up between intervention and control conditions (mean difference 1027; 95% CI -155 to 2209; P=.09). No statistically significant differences were observed for secondary outcomes. CONCLUSIONS: Our results suggest that it is feasible to build an eHealth tool that screens and provides tailored resources for PA in a primary care setting but suboptimal intervention fidelity suggests greater work must be done to address PCP barriers to resource distribution. Participant responses to the primary effectiveness outcome (MET-minutes) were highly variable, reflecting a need for more robust measures of PA in future trials to address limitations in patient-reported data. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181295; https://clinicaltrials.gov/ct2/show/NCT03181295.

Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants.

BACKGROUND: Observational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited. METHODS: We randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy. RESULTS: Among 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P = 0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16). CONCLUSIONS: There was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.).

How should family physicians provide physical activity advice? Qualitative study to inform the design of an e-health intervention.

OBJECTIVE: To explore patient attitudes toward interacting with family physicians regarding physical activity in order to inform the development of an e-health intervention aimed at helping family physicians support patients in becoming more physically active. DESIGN: Qualitative study. SETTING: Women's College Hospital in Toronto, Ont. PARTICIPANTS: Ten patients recruited from the academic family practice health centre. METHODS: Semistructured interviews were conducted with patients using maximum variation sampling until thematic saturation was reached. Interviews explored past experiences and preferences for receiving physical activity advice from family physicians, and tools or techniques that might support increasing physical activity. Interviews were audiorecorded, transcribed, and coded independently by members of the research team before undergoing thematic analysis. MAIN FINDINGS: Patient interviews revealed 4 overarching themes that offered insight to physical activity discussions. Family physicians might provide more meaningful and useful physical activity advice to patients by providing individualized recommendations focused on proximal (ie, near-term) health and functional goals; recognizing and addressing unique environmental and social factors influencing physical activity levels; balancing candour and sensitivity in advice provision while incorporating a broad definition of physical activity; and recommending tools that incorporate planning, goal-setting, and goal-monitoring features. CONCLUSION: Ultimately, physical activity recommendations from family physicians cannot make a difference if patients do not act on them. This study elicits input from patients to develop preliminary strategies that might help family physicians provide physical activity advice in a more patient-centred fashion. Further research is needed to test interventions that help implement these strategies and to assess their effect.

Interventions Supporting Long-term Adherence aNd Decreasing cardiovascular events (ISLAND): Pragmatic randomized trial protocol.

BACKGROUND: Guidelines recommend cardiac rehabilitation and long-term use of cardiac medications for most patients who have had a myocardial infarction (MI), but adherence to these secondary prevention treatments is suboptimal. METHODS: This is a multicenter, pragmatic, 3-arm randomized trial. Eligible patients (n = 2,742) with obstructive coronary artery disease are randomized post-MI to usual care or 1 of 2 intervention arms. Patients in the first intervention arm receive mail-outs sent on behalf of their cardiologist at 4, 8, 20, 32, and 44 weeks post-MI; content is designed to address determinants of adherence and facilitate discussion between the patient and their health care team. Patients in the second intervention arm receive mail-outs plus automated interactive voice response system telephone calls 2 weeks after each letter, as well as a telephone call by trained lay health workers if the interactive voice response system identifies challenges with adherence. Outcomes are assessed 12 months post-MI via patient self-report and administrative data sources. Co-primary outcomes are adherence to cardiac medications and completion of cardiac rehabilitation. Secondary outcomes include cardiovascular events and mortality. An embedded, theory-informed process evaluation will explore the mechanism of action; an economic evaluation is also planned. CONCLUSIONS: We describe a complete program evaluation of a highly pragmatic, health-system intervention to support adherence to recommended treatments. Research ethics boards approved waiver of consent for patients enrolled in the trial with provision of multiple opportunities to opt out and a debrief at the time of outcome assessment. The methods used here may provide a model for similar interventions.

Negotiating Tensions Between Theory and Design in the Development of Mailings for People Recovering From Acute Coronary Syndrome.

BACKGROUND: Taking all recommended secondary prevention cardiac medications and fully participating in a formal cardiac rehabilitation program significantly reduces mortality and morbidity in the year following a heart attack. However, many people who have had a heart attack stop taking some or all of their recommended medications prematurely and many do not complete a formal cardiac rehabilitation program. OBJECTIVE: The objective of our study was to develop a user-centered, theory-based, scalable intervention of printed educational materials to encourage and support people who have had a heart attack to use recommended secondary prevention cardiac treatments. METHODS: Prior to the design process, we conducted theory-based interviews and surveys with patients who had had a heart attack to identify key determinants of secondary prevention behaviors. Our interdisciplinary research team then partnered with a patient advisor and design firm to undertake an iterative, theory-informed, user-centered design process to operationalize techniques to address these determinants. User-centered design requires considering users' needs, goals, strengths, limitations, context, and intuitive processes; designing prototypes adapted to users accordingly; observing how potential users respond to the prototype; and using those data to refine the design. To accomplish these tasks, we conducted user research to develop personas (archetypes of potential users), developed a preliminary prototype using behavior change theory to map behavior change techniques to identified determinants of medication adherence, and conducted 2 design cycles, testing materials via think-aloud and semistructured interviews with a total of 11 users (10 patients who had experienced a heart attack and 1 caregiver). We recruited participants at a single cardiac clinic using purposive sampling informed by our personas. We recorded sessions with users and extracted key themes from transcripts. We held interdisciplinary team discussions to interpret findings in the context of relevant theory-based evidence and iteratively adapted the intervention accordingly. RESULTS: Through our iterative development and testing, we identified 3 key tensions: (1) evidence from theory-based studies versus users' feelings, (2) informative versus persuasive communication, and (3) logistical constraints for the intervention versus users' desires or preferences. We addressed these by (1) identifying root causes for users' feelings and addressing those to better incorporate theory- and evidence-based features, (2) accepting that our intervention was ethically justified in being persuasive, and (3) making changes to the intervention where possible, such as attempting to match imagery in the materials to patients' self-images. CONCLUSIONS: Theory-informed interventions must be operationalized in ways that fit with user needs. Tensions between users' desires or preferences and health care system goals and constraints must be identified and addressed to the greatest extent possible. A cluster randomized controlled trial of the final intervention is currently underway.