Abstract
Objective:
This primary objective of this pilot randomized, controlled trial was to determine whether a brief video intervention delivered after a pediatric office visit could improve inhaler technique in children with asthma immediately and one month later. The intervention’s effect on children’s inhaler self-efficacy and asthma control was also evaluated.
Methods:
Children (n = 91) ages 7–17 years with persistent asthma were recruited at two pediatric practices in North Carolina. Eligible children demonstrated their inhaler technique for metered dose inhalers (MDIs) either with or without a spacer. A trained research assistant used a validated inhaler technique checklist to record which steps children performed correctly. After a regularly scheduled office visit, children were randomized to watch either a 3-min MDI video (intervention group) or a nutrition video (control group) in English or Spanish. Children’s technique was assessed again after watching the video and one month later.
Results:
Children were primarily male (56%) and non-White (60%). When compared with the control group, children in the intervention group demonstrated a significant improvement in MDI technique post-intervention [mean = 1.12 steps, 95% CI (0.73, 1.50)] but the improvement was not sustained at 1-month follow-up. The intervention did not lead to significant improvements in inhaler self-efficacy or asthma control.
Conclusions:
A brief video intervention offered during pediatric clinic visits can lead to immediate improvements in children’s inhaler technique. Future studies should evaluate whether booster training videos can help maintain improvements in children’s inhaler technique over time.
Keywords: Asthma control, children, metered dose inhaler, self-efficacy, videos
Introduction
Nearly 6.7 million children in the USA have been diagnosed with asthma, which accounts for 3.4 million office visits and 500 000 emergency department visits each year [1,2]. Reducing morbid and costly exacerbations requires patient self-management, including proper medication use [3]. Inhaled corticosteroid medications are a critical component of asthma treatment; yet, incorrect inhaler technique can reduce therapeutic benefit by compromising delivery of medications to the lungs [4].
Children with asthma have demonstrated significant deficiencies in inhaler technique [5-7]. An observational study of children (ages 8–16 years) with persistent asthma at five pediatric practices found that only 8% of children used their metered dose inhaler (MDI) correctly [5]. Most children incorrectly performed at least two steps, and the steps that children missed were central to correct technique, such as forgetting to hold their breath for 10 s after inhaling the medication, which allows the medication to deposit in the lungs.
Since suboptimal inhaler technique has been linked with worse asthma control [4,8-10] and more emergency department visits [9], national guidelines recommend that inhaler technique skills should be demonstrated at every patient visit [11]. Yet providers rarely assess children’s technique [5,12] with demonstrations occurring in as a few as 6% of office visits [5]. Given the time constraints of a typical office visit and the number of health topics (e.g. diet, weight, vaccinations) providers must address, it may be difficult for providers to assess technique and provide detailed feedback at each office visit. Thus, innovative strategies for teaching children inhaler technique are needed. Prior work has shown that videos are a preferred intervention mode for children with asthma [13], making this mode an ideal candidate for teaching inhaler technique.
The primary purpose of this pilot randomized, controlled trial was to determine whether brief inhaler technique videos could improve children’s MDI technique immediately and at 1-month follow-up. A secondary purpose was to determine whether the video intervention could improve children’s confidence that they can use their inhalers correctly (inhaler self-efficacy) and asthma control at 1-month follow-up.
Methods
Participants
Study participants were recruited at two pediatric practices in a medium-sized metropolitan county (population ~171 000) in North Carolina [14]. Children were eligible if they: (i) were 7–17 years old, (ii) could speak English or Spanish, (iii) could read the assent form, (iv) were present at the visit with an adult (>18 years old) caregiver (parent or legal guardian) who could speak English or Spanish, (v) used a MDI, (vi) missed or incorrectly performed at least one step on an inhaler technique assessment and (vii) had mild, moderate or severe persistent asthma [11,15]. The study research assistant (RA) used an eligibility screening instrument to assess whether the child had persistent asthma, defined as experiencing asthma-related daytime symptoms more than twice a week, asthma-related nighttime symptoms more than twice a month, or receiving one or more long-term controller therapies for asthma [16,17]. The study was approved by the University of North Carolina at Chapel Hill Institutional Review Board and was registered with clinicaltrials.gov (NCT01641211).
Each clinic received $500 per month to serve as a recruitment site. Clinic staff informed patients with asthma about the study and referred interested families to a bilingual RA, who was located in the clinic waiting room. The RA read a study fact sheet to potentially eligible families. Those families who were interested in participating then verbally agreed to allow the RA to proceed with the eligibility screening process. As part of the screening process, children used placebo devices to demonstrate their MDI technique. Ineligible families were given a $5 cash incentive. If the child and caregiver were eligible, the RA explained the study and obtained written caregiver informed consent and child assent. Caregivers then completed a brief demographic questionnaire before the child’s regularly scheduled medical visit. All consent/assent forms and data collection instruments were available in English and Spanish.
After the child’s medical visit, the RA reconvened with the family in a private room. Using the randomization process described below, children were assigned to watch either an inhaler technique video (intervention) or a nutrition video (control) in their choice of English or Spanish. While children watched the video, caregivers completed a brief questionnaire. After watching the video, the RA observed and recorded each child’s technique again. Then the RA interviewed the child for 10 min. The child received a $15 cash incentive after the visit.
One month later, the same RA conducted a follow-up visit in which the child’s inhaler technique was observed again, the child was interviewed and the caregiver completed a questionnaire. Follow-up visits typically lasted 20 min and were conducted at a location (e.g. home, clinic, library) that was convenient for the caregiver. At the conclusion of the follow-up visit, the child received a $15 cash incentive.
Randomization and concealment
Immediately after the child’s medical visit, the RA opened a sequentially numbered, sealed envelope to determine whether the child had been allocated to the experimental or control group. The randomization sequence was prepared ahead of time by a statistician using computer-generated random numbers. Randomization was stratified by clinic.
Intervention
Children assigned to the experimental group watched a brief 3-min video in either English or Spanish. Separate videos were available for a MDI either with or without a spacer; children who indicated that they used a MDI with a spacer and without a spacer watched both MDI videos. Each inhaler video provided an overview of the device and specific instructions for how to use the device correctly. The video demonstrations are part of a multi-language educational software program called Meducation (Polyglot Systems, Inc., Morrisville, NC), which is designed to illustrate proper medication techniques for low health literate and limited English-speaking patients. The technique demonstrations were developed by Polyglot’s clinical instructional design team using a combination of best practice resources. Children watched the videos on a laptop computer and were given a wallet card with a web address and login information so they could watch the video again after leaving the clinic.
Control group
Control group children were allocated to an attentional control in which they watched a 3-min video about nutrition in English or Spanish. The nutrition video discussed the importance of balancing protein, carbohydrates and lipids in one’s diet.
Outcomes and blinding
The study RA was not blinded to children’s experimental group assignment. All children and caregivers were informed that the study was about how children use their asthma devices. Our primary outcome, children’s inhaler technique, was assessed at baseline as part of the eligibility screener, immediately after the office visit, and at 1-month follow-up. Our secondary outcomes, inhaler self-efficacy and asthma control, were assessed immediately after the office visit and at 1-month follow-up.
Measures
Inhaler technique
MDI technique was measured as the number of steps (out of eight possible steps) that the child performed correctly (Table 1) [5]. The RA used an inhaler technique checklist to document whether each step was performed correctly. If a child indicated that he/she used a MDI both with and without a spacer, then he/she was asked to demonstrate technique with and without a spacer.
Table 1.
Inhaler technique steps for a MDI with and without a spacer.
| Step | MDI with spacer | MDI without a spacer |
|---|---|---|
| 1 | Remove cap from inhaler | Remove cap from inhaler |
| 2 | Attach inhaler mouthpiece into holding chamber | Shake inhaler 4–6 times |
| 3 | Shake inhaler 4–6 times | Exhale normally |
| 4 | Exhale normally | Tilt head back slightly, place mouthpiece between lips or 1–2 inches in front of a wide open mouth |
| 5 | Tilt head back slightly, place holding chamber mouthpiece between lips, holding inhaler upright | Begin a slow, deep breath |
| 6 | Press inhaler canister once to place dose in holding chamber | Press inhaler canister once at beginning of breath |
| 7 | Begin a slow, deep inhalation immediately after placing dose in holding chamber (3–4 s) | Continue to inhale for 3–4s |
| 8 | Hold breath for 10 s | Hold breath for 10 s |
MDI=metered dose inhaler
The RA was taught how to assess inhaler technique using a validated training process that was developed by a pediatric pulmonologist and clinical pharmacist and used in a previous study [5]. For training purposes, the RA viewed a DVD that had examples of optimal MDI technique. After observing the optimal technique examples, the RA then watched recordings of three children using a MDI with and without a spacer with various omissions and errors. The RA viewed 18 examples of incorrect technique and used a checklist to score these techniques. The RA’s checklists were reviewed by a Certified Respiratory Therapist who provided feedback about the RA’s scoring on the basis of her clinical judgment. The RA continued to review the DVD recording until she could accurately identify all errors and omissions in technique.
Child inhaler self-efficacy
Child inhaler self-efficacy was measured using one item from the Bursch et al. [18] asthma management self-efficacy measure, “How sure are you that you can use your inhaler correctly?” Response options included: 1 = “not at all sure”, 2 = “a little bit sure”, 3 = “fairly sure”, 4 = “quite sure” and 5 = “completely sure”.
Asthma control
The Asthma Control Test (ACT) is a 5-item questionnaire that assesses asthma symptoms, use of rescue medications, and the effect of asthma on daily functioning [19]. Scores range from 5 (poor control) to 25 (complete control). The ACT is reliable, valid and responsive to temporal changes in asthma control [20].
Demographic and other measures
We also measured: (i) child age (in years), gender, race and ethnicity; (ii) caregiver age (in years); gender, race, ethnicity and educational level; (iii) type of health insurance; (iv) annual household income and (v) years child has had asthma.
Sample size and power
We decided a priori that anything less than a one-step difference in inhaler technique was not clinically meaningful. Assuming that, on average, the children in the intervention group would improve by one step between baseline and post-visit and that the standard deviation for these change scores was 1.8 (based on prior data [5]), enrolling 100 children (50 per group) would provide ~80% power using a two-sided test at the 0.05 significance level. Over an 8-month recruitment period, we enrolled 91 children, which was 9 children short of our 100 child recruitment target and reduced power to 75% under these same assumptions.
Statistical analyses
Analyses were conducted using SAS software (version 9.2; SAS Institute, Cary, NC). Analyses included all available data for all children in the group to which they were randomized (intention-to-treat). We assessed change in the number of inhaler technique steps performed properly using a linear mixed model that included fixed effects for intervention group, time (pre-visit/post-visit/1-month follow-up), group-by-time interactions, whether or not a spacer was used, and practice site. The model also included separate random effects to account for correlation between responses from the same subject over time as well as within time for those children who demonstrated technique both with and without a spacer. Appropriate contrasts were tested at the two-sided 0.05 significance level with no adjustment for multiple comparisons. For our secondary outcomes of inhaler self-efficacy and asthma control, we used similar linear mixed models to explore whether the intervention affected these outcomes at 1-month follow-up.
Results
Flow of participants through the trial
Figure 1 summarizes participant flow through the trial for the primary outcome of inhaler technique. Participants were enrolled from July 2012 to March 2013. Due to expiration of the study funding, we had to terminate the study before reaching our enrollment target of 100 families. Ninety-one of 143 screened families (64%) were eligible and enrolled. Of note, no child was excluded because of their inhaler technique; all of the 143 screened children missed at least one step on the inhaler technique assessment. Of the 91 eligible families, 46 were randomly allocated to the intervention group and 45 were allocated to the control group. Eight families were lost to follow-up, leaving 83 families (91%) who completed the 1-month follow-up visit.
Figure 1.
Flow diagram of participant progress through the trial.
Baseline characteristics for the children and caregivers in the intervention and control group are presented in Table 2. The majority of children in the sample were non-White (60%). Immediately after the office visit, children were very confident they could use their inhalers correctly and reported that their asthma was well-controlled. Only four children (4%) watched the video in Spanish. A majority (91%) of children reported using a MDI that was a rescue medication (i.e. albuterol) while 42% used a MDI that was a control medication. Three children (3%) reported that they used their MDI both with and without a spacer.
Table 2.
Baseline characteristics of participants in the control and experimental groups.
| Control group (N = 45) |
Intervention group (N = 46) |
|
|---|---|---|
| Child characteristics | ||
| Age, years, mean (SD) | 10.8 (2.9) | 10.9 (2.6) |
| (range) | (7–17) | (7–17) |
| Gender, n (%) | ||
| Male | 25 (56) | 24 (52) |
| Female | 20 (44) | 22 (48) |
| Race, n (%) | ||
| Non-Hispanic White | 18 (40) | 19 (41) |
| Black | 6 (13) | 14 (30) |
| Hispanic/Latino | 12 (27) | 10 (22) |
| Other | 9 (20) | 3 (7) |
| Asthma severity, n (%) | ||
| Mild persistent | 22 (49) | 24 (52) |
| Moderate/severe persistent | 23 (51) | 20 (44) |
| Years living with asthma, mean (SD) | 3.7 (3.3) | 3.5 (3.8) |
| (range) | (0–14) | (0–17) |
| Taking a control MDI medication, n (%) | 19 (42) | 19 (41) |
| Watched video in Spanish, n (%) | 3 (7) | 1 (2) |
| Caregiver characteristics | ||
| Age, years, mean (SD) | 39.8 (11.3) | 41.0 (8.4) |
| (range) | (27–84) | (27–69) |
| Gender, n (%) | ||
| Male | 8 (18) | 7 (15) |
| Female | 37 (82) | 39 (85) |
| Race, n (%) | ||
| White | 23 (51) | 18 (39) |
| Black | 6 (13) | 12 (26) |
| Hispanic/Latino | 13 (29) | 13 (28) |
| Other | 3 (7) | 3 (7) |
| Education, years, mean (SD) | 11.8 (2.7) | 11.6 (3.2) |
| (range) | (6–18) | (6–18) |
| Insurance type, n (%) | ||
| None | 0 | 1 (2) |
| Private | 6 (13) | 10 (22) |
| Medicaid | 30 (67) | 27 (59) |
| North Carolina Health Choice for Children | 8 (18) | 8 (17) |
| Other | 1 (2) | 0 |
| Total household income, n (%) | ||
| <$10 000 | 10 (22) | 11 (24) |
| $10 000–19 999 | 15 (33) | 11 (24) |
| $20 000–$29 999 | 5 (11) | 12 (26) |
| $30 000–$49 999 | 10 (22) | 8 (17) |
| >$50 000 | 5 (11) | 4 (9) |
MDI=metered dose inhaler
Only 5 (11%) intervention group children used the wallet card to access and watch the technique video online again after their office visit. Of these five children, three watched the video once, one watched the video twice and one watched the video 15 times.
Primary outcome: change in inhaler technique
Table 3 shows the mean number of MDI steps performed correctly for children in the intervention and control group at baseline, immediately post-intervention, and 1-month follow-up. On average, at baseline, children incorrectly performed two steps regardless of whether they used an MDI with or without a spacer. The steps children were most likely to miss or perform incorrectly at baseline were: forgetting to shake the inhaler (69% for MDI with a spacer and 57% for MDI without a spacer) and not holding their breath for 10 s (96% for MDI with a spacer and 94% for MDI without a spacer).
Table 3.
Summary of outcome measures by study visit for the control and intervention groups.
| Parameter | Control (N = 45) |
Intervention (N = 46) |
||
|---|---|---|---|---|
| n | Mean (SD) | n | Mean (SD) | |
| MDI steps performed correctly with spacer | ||||
| Baseline | 15 | 6.2 (0.8) | 11 | 5.6 (1.0) |
| Post-intervention | 17 | 6.1 (0.7) | 11 | 6.7 (1.0) |
| 1-month follow-up | 9 | 6.6 (0.5) | 8 | 6.9 (0.8) |
| MDI steps performed correctly without spacer | ||||
| Baseline | 31 | 5.8 (1.0) | 37 | 5.7 (1.2) |
| Post-intervention | 29 | 6.0 (1.1) | 34 | 6.9 (0.9) |
| 1-month follow-up | 31 | 6.2 (1.0) | 35 | 6.5 (1.2) |
| Inhaler self-efficacy | ||||
| Baseline | 45 | 4.6 (0.8) | 46 | 4.4 (1.2) |
| 1-month follow-up | 40 | 4.6 (0.7) | 43 | 4.8 (0.5) |
| Asthma control | ||||
| Baseline | 45 | 18.4 (3.8) | 46 | 18.6 (4.6) |
| 1-month follow-up | 40 | 19.4 (4.4) | 42 | 20.3 (3.3) |
Lower inhaler self-efficacy scores indicate less self-efficacy. Lower asthma control scores indicate worse asthma control.
Table 4 presents the results of our linear mixed model comparing the change in inhaler technique over time for the intervention and control groups. Within the control group, the change in inhaler technique was not statistically significant at post-intervention [mean = 0.03, 95% CI (−0.36, 0.42)] or at 1-month follow-up [mean = 0.32, 95% CI (−0.09, 0.73)]. In contrast, the intervention group had significant improvements in MDI technique post-intervention [mean = 1.12, 95% CI (0.73, 1.50)] and at 1-month follow-up [mean = 0.87, 95% CI (0.47, 1.26)]. The between-groups mean difference of 1.08 steps was statistically significant [95% CI (0.53, 1.63)] post-intervention, but the 0.55-step mean difference at 1-month follow-up was not statistically significant [95% CI (−0.02, 1.11)].
Table 4.
Mean change in MDI technique steps (primary outcome), inhaler self-efficacy and asthma control post-intervention and at 1-month follow-up for the control (n = 45) and intervention group (n = 46).
| Control |
Intervention |
Between-group difference in change from baseline |
||
|---|---|---|---|---|
| Parameter | Mean change (SE) | Mean change (SE) | Mean difference (95% CI) | p |
| MDI technique | ||||
| Post-intervention | 0.03 (0.16) | 1.12 (0.16) | 1.08 (0.53, 1.63) | 0.003 |
| 1-month follow-up | 0.32 (0.17) | 0.87 (0.16) | 0.55 (−0.02, 1.11) | 0.056 |
| Inhaler self-efficacy | ||||
| 1-month follow-up | −0.10 (0.14) | 0.28 (0.13) | 0.38 (−0.00, 0.76) | 0.052 |
| Asthma control | ||||
| 1-month follow-up | 1.20 (0.63) | 1.93 (0.61) | 0.73 (−1.02, 2.49) | 0.407 |
Included fixed effects for intervention group, time (pre-visit/post-visit/1-month follow-up), group-by-time interactions, whether or not a spacer was used, and practice site. The model also included separate random effects to account for correlation between responses from the same subject over time as well as within time for those children who demonstrated technique both with and without a spacer.
Secondary outcomes: inhaler self-efficacy and asthma control
Table 4 also presents the between-group comparisons over time for inhaler self-efficacy and asthma control. Within the control group, the change in inhaler self-efficacy was not statistically significant [mean = −0.10, 95% CI (−0.38, 0.18)]. In contrast, there was a significant improvement in self-efficacy for the intervention group [mean 0.28, 95% CI (0.01, 0.55)]. The mean difference in self-efficacy between the control and intervention group over time was not statistically significant [mean = 0.38, 95% CI (−0.00, 0.76)].
Regarding asthma control, the intervention group showed a statistically significant improvement in asthma control from post-office visit to 1-month follow-up [mean = 1.93, 95% CI (0.70, 3.16)]; whereas, change in asthma control in the control group [mean = 1.20, 95% CI (−0.06, 2.46)] was not significant. The mean difference in asthma control between the control and intervention group over time was not statistically significant [mean = 0.73, 95% CI (−1.02, 2.49)].
Discussion
We found that a 3-min video delivered after a regularly scheduled pediatric office visit resulted in an immediate statistically significant one-step mean improvement in inhaler technique for children with asthma. However, this improvement was not maintained at 1-month follow-up. Previous research has shown that provider assessment and demonstration of inhaler technique can improve children’s inhaler technique [12]; however, providers rarely educate children about inhaler technique [5]. To our knowledge, this is the first randomized controlled trial to assess whether videos, a preferred intervention mode for children with asthma [13], can be used to teach children proper inhaler technique.
National guidelines recommend that providers ask patients to demonstrate inhaler technique at each medical visit [11]; yet, this rarely occurs in practice [5]. Technique videos may offer a method for streamlining the education process for providers while also meeting national guidelines for technique education. For example, if a trained office staff member or medical technician were available to assess children’s technique during pre-visit wait time, they could document the steps children missed, have children watch the inhaler technique video and also notify the provider of which steps the child missed. During the office visit, providers could then use the information about missed steps to provide tailored feedback to children about their technique. Thus, children could receive generic information about proper technique from the video and also receive tailored feedback from their provider. In cases where a trained office staff member or medical technician are unavailable, technique videos could simply be shown to all children with asthma during pre-visit wait time, and providers could be prompted to ask children if they had any questions about the video or how to use their inhaler correctly.
The difference in inhaler technique between the intervention and control group did not remain statistically significant at 1-month follow-up. Deterioration in inhaler technique over time has been observed in previous studies [4,21]. Despite this deterioration, the intervention group still maintained an average half-step improvement that was of borderline statistical significance (p = 0.056) when compared with the control group. This suggests that educational booster sessions may be necessary to maintain improvements in technique. In the case of our intervention, a booster session could be as simple as showing the video at a subsequent office visit. Because repeated technique instruction may improve other self-management behaviors like medication adherence [22], booster instruction could potentially improve children’s medication adherence and asthma control. Future studies should include boosters to reinforce proper technique and assess changes in children’s technique in the longer term, such as up to 1 year. Additionally, because caregivers are able to monitor children’s inhaler technique at home, future studies could test whether having both the child and his/her caregiver watch the video leads to greater long-term improvements in technique.
The intervention group reported improved inhaler self-efficacy at 1-month follow-up, although the difference between the intervention and control group was not statistical significant. Social cognitive theory asserts that individuals who have higher self-efficacy to perform a specific behavior (e.g. using an inhaler correctly) are more likely to engage in that behavior [23,24]. One possible method for further enhancing children’s inhaler self-efficacy is to create tailored technique videos. These videos could be targeted to children’s gender and race and tailored to the specific steps that children perform incorrectly. Interventions that use a personalized source (e.g. someone who looks like the study participant) to deliver in-depth tailored information have been shown to positively affect even addictive behaviors like smoking [25]. Thus, there is great potential for tailored videos to improve children’s inhaler self-efficacy and self-management behaviors.
Within the intervention group, children reported an almost two-point improvement in asthma control at 1-month follow-up, although the difference between the intervention and control group was not statistically significant. Moreover, the two-step improvement did not meet the minimally important difference for clinical significance [26]. This insignificant result could be due to the fact that only 42% of our sample was taking an MDI-administered control medication. Improved technique can only be expected to affect control if the child is taking a control medication. Previous studies have shown that improved technique for inhaled corticosteroids is associated with improved asthma control [4,8-10]. It is also possible that children in our sample were non-adherent to their MDI-administered control medications. Control medication adherence rates are generally low for pediatric patients, ranging from 50 to 70% [27,28]. Future studies should control for adherence to control medications when examining the relationship between inhaler technique and asthma control.
Our study has several limitations, and as such, the results should be interpreted with caution. First, the RA who assessed inhaler technique was not blinded to control or experimental group assignment. To mitigate this, future studies could video record children’s technique and have videos reviewed by RAs who are blinded to group assignment. Second, the study was conducted in two pediatric clinics in a moderately populated county in North Carolina and thus may not be generalizable to other pediatric care settings. Third, due to expiration of funding, we did not reach our recruitment goal of 100 participants; thus, we may have been underpowered to detect a significant difference in inhaler technique at 1-month follow-up. Additionally, we did not assess whether children were present for an asthma-related visit or a routine visit; thus, we could not control for this variable in our analyses. Also, we did not use the childhood Asthma Control Test (c-ACT) to measure asthma control for children who were <12 years old [29]. Future studies should use the c-ACT for patients who are <12 years since this version of the ACT has better validity in this age group. Last, because an inhaler self-efficacy scale has not been reported in the literature, our measure of inhaler self-efficacy was limited to one-item from a larger asthma management self-efficacy scale [18].
Conclusions
We found that a brief video intervention offered after a pediatric office visit can lead to an immediate improvement in the inhaler technique of children with asthma. However, the immediate benefits of the video seemed to attenuate over a 1-month period, suggesting that booster sessions may be necessary to maintain technique improvements over time. We did not find evidence that the intervention significantly improved children’s inhaler self-efficacy or asthma control. Future studies should explore whether videos are a viable and cost-effective method for teaching children inhaler technique in pediatric office settings.
Acknowledgments
This pilot project was supported by Award Number ULTR000083 from the National Center for Advancing Translational Sciences. Dr. Carpenter’s salary was partially supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant KL2TR000084.
Footnotes
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health.
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