Secondary analysis of electronic opt-out consent in pragmatic research: A study design method to diversify clinical trials?

We conducted a multi-center pragmatic trial of a low-risk intervention focused on medication adherence using an opt-out consent approach, where patients could opt out by letter and then electronically. We focus on the cohort after opt-out by mail. Here, we describe that 8% of patients opted out electronically, resulting in a 92% participation rate. Patients who self-identify as Black or Hispanic were less likely to opt out in the study, and half the study cohort was female. This demographic data is useful for planning future trials employing this approach.

Description of patient questions received by clinical pharmacists in the Nudge Study.

PURPOSE: The Nudge Study is a patient level-randomized trial testing different text message medication refill reminders sent to patients assigned to 4 arms: (1) usual care, (2) generic text, (3) optimized text, and (4) optimized text plus chatbot. This report describes the frequency and types of patient questions sent to clinical pharmacists (CPs) following text reminders. METHODS: Patients were enrolled from Denver Health and Hospital Authority (DHHA) and Veterans Affairs Eastern Colorado Health Care System (VA ECHCS) from October 1, 2019, through May 30, 2021. Included patients responded to at least 1 text or interactive voice response (IVR) message. Patients were dichotomized as those who posed at least 1 question to a CP and those who posed no questions. RESULTS: Of the 6,325 patients enrolled in an intervention arm, 3,323 (52.5%) responded to at least 1 text or IVR message, and among those responding, 305 (9.2%) responded with a pharmacist question. Patient factors associated with submitting a CP question included age (45-74 years), enrollment from DHHA, and receipt of the optimized text or optimized text plus chatbot message versus the generic text. Questions to CP were in the following categories: medication related (48.2%), refill logistics (38.4%), cost (9.2%), and other (17.7%). CONCLUSION: In a text messaging intervention focused on medication refills, there were few questions directed to the CP. Patients assigned to receive optimized texts were more likely to have questions. We hypothesize that this may suggest greater patient engagement regarding their condition, resulting in more questions.

Nudge me: tailoring text messages for prescription adherence through N-of-1 interviews.

Almost 50% of patients with cardiovascular diseases face challenges in taking medications and increased morbidity and mortality. Text messaging may impact medication refill behavior and can be delivered at scale to patients by texting mobile phones. To obtain feedback from persons with chronic conditions on the design of interactive text messages and determine language of message for making messages that can motivate patients to refill medications on time. We purposively sampled 35 English and Spanish speaking patients with at least one chronic condition from three large healthcare delivery systems to participate in N-of-1 video-based synchronous interviews. Research assistants shared ideas for theory-informed text messages with content intended to persuade patients to refill their medication. We transcribed recorded interviews and conducted a content analysis to identify strategies to employ generating a dynamic interactive text message library intended to increase medication refill. Those interviewed were of diverse age and race/ethnicity and typical of persons with multiple chronic conditions. Several participants emphasized that personally tailored and positively framed messages would be more persuasive than generic and/or negative messages. Some patients appreciated humor and messages that could evoke a sense of social support from their providers and rejected the use of emojis. Messages to remind patients to refill medications may facilitate improvements in adherence, which in turn can improve chronic care. Designing messages that are persuasive and can prompt action is feasible and should be considered given the ease with which such messages can be delivered automatically at scale.

Leave me out: Patients' characteristics and reasons for opting out of a pragmatic clinical trial involving medication adherence.

ABSTRACT: Opt-out procedures are sometimes used instead of standard consent practices to enable patients to exercise their autonomous preferences regarding research participation while reducing patient and researcher burden. However, little is known about the characteristics of patients who opt-out of research and their reasons for doing so. We gathered such information in a large pragmatic clinical trial (PCT) evaluating the effect of theory informed text messages on medication adherence.Eligible patients, identified through electronic health records, were sent information about the study and provided with an opportunity to opt-out. Those opting out were asked to complete a voluntary survey regarding their reasons for doing so. Demographic data were compared among patients opting-out vs those included in the study using chi-squared tests and a log binomial regression model.Of 9046 patients receiving study packets, 906 (10.0%) patients returned opt-out forms. Of those, 451 (49.8%) returned the opt-out survey. Patients who opted out were more likely to be older, white, and nonHispanic than those who were included in the PCT. Survey respondents expressed high levels of trust in their health care providers, research, and system. Nearly half (46.6%) reported concerns about time as a reason to opt-out.In this PCT, 10% of patients receiving packets opted out, with significant differences in age, race, gender, and ethnicity compared to those included. Future trials should further investigate representativeness and reasons patients choose to opt-out of participating in research.

Text Message Medication Adherence Reminders Automated and Delivered at Scale Across Two Institutions: Testing the Nudge System: Pilot Study.

BACKGROUND: Medication refill behavior in patients with cardiovascular diseases is suboptimal. Brief behavioral interventions called Nudges may impact medication refill behavior and can be delivered at scale to patients using text messaging. METHODS: Patients who were prescribed and filled at least one medication for hypertension, hyperlipidemia, diabetes, atrial fibrillation, and coronary artery disease were identified for the pilot study. Patients eligible for the pilot (N=400) were enrolled with an opportunity to opt out. In phase I of the pilot, we tested text message delivery to 60 patients. In phase II, we tested intervention feasibility by identifying those with refill gap of ≥7 days and randomized them to intervention or control arms. Patients were texted Nudges and assessed whether they refilled their medications. RESULTS: Of 400 patients sent study invitations, 56 (14%) opted out. In phase I, we successfully delivered text messages to 58 of 60 patients and captured patient responses via text. In phase II, 207 of 286 (72.4%) patients had a medication gap ≥7 days for one or more cardiovascular medications and were randomized to intervention or control. Enrolled patients averaged 61.7 years old, were primarily male (69.1%) and White (72.5%) with hypertension being the most prevalent qualifying condition (78.7%). There was a trend towards intervention patients being more likely to refill at least 1 gapping medication (30.6% versus 18.0%; P=0.12) and all gapping medications (17.8% versus 10.0%; P=0.27). CONCLUSIONS: It is possible to set up automated processes within health care delivery systems to identify patients with gaps in medication adherence and send Nudges to facilitate medication refills. Text message Nudges could potentially be a feasible and effective method to facilitate medication refills. A large multi-site randomized trial to determine the impact of text-based Nudges on overall CVD morbidity and mortality is now underway to explore this further. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03973931.

Exploring Vitamin B12 Deficiency in Sleeve Gastrectomy from a Histological Study of a Cadaveric Stomach and Ileum.

INTRODUCTION: Vitamin B12 deficiency is more commonly found among patients who have undergone Roux-en-Y gastric bypass (RYGB) as compared to those with post-sleeve gastrectomies (SG). The major difference between SG and RYGB is that the latter greatly bypasses the stomach whereas the former simply reduces the gastric volume. PURPOSE: The aim of this article was to study the stomach and the distal ileum histologically in a cadaver with SG to explain the higher rate of incidences of vitamin B12 deficiency seen in patients post-RYGB relative to patients post-SG. Since the stomach is the major variable in these two procedures, we hypothesize that it has the ability to regenerate and increase its surface area to compensate for the loss of its volume in SG patients. MATERIAL AND METHODS: Tissue biopsies and hematoxylin and eosin stains were performed from various anatomical locations of the GI tract, specifically the gastric fundus, body, and antrum, and from the distal ileum of the small intestine of a cadaver with SG and another without SG (control). RESULTS: Compared with the control, the SG cadaver's gastric tissue biopsies were significant for chronic gastritis and hypertrophy of the muscularis externa layer. More importantly, parietal cell hyperplasia and deeper mucosal glands were also noted in the SG cadaver supporting the hypothesis. CONCLUSIONS: The compensatory role of an intact stomach, given its ability to regenerate parietal cells and increase its numbers in the gastric fundus and body, can be better appreciated in a gastric-sparing procedure such as SG versus RYGB in terms of limiting vitamin B12 deficiencies.

Mercury and lead blood concentrations in pregnant women from 10 caribbean countries.

Maternal mercury (Hg) and lead (Pb) blood concentrations were measured in a total of 442 samples taken from pregnant and delivering women in 10 Caribbean countries. Hg was detected in all 10 countries with the geometric mean ranging from a low of 0.83 µg L(-1) (Jamaica) to a high of 3.13 µg L(-1) (Grenada). When compared to comparable U.S. and Canadian data, Hg concentrations in Caribbean women are on average more than 2 times higher. With the exception of St. Kitts & Nevis, Pb was detected in at least one of the samples taken from the other 9 countries with two countries-Grenada and St. Vincent - having Pb detected in ≥60% of those sampled. In these two countries, the Pb concentrations ranged from a low of 1.17 µg dL(-1) (Grenada) to a high of 1.98 µg dL(-1) (St. Vincent). Compared to comparable U.S. and Canadian data, Pb concentrations in Caribbean women are generally higher than that measured in North America. This study confirms that neonates in the Caribbean are being exposed to both Hg and Pb and highlights the need to implement surveillance programs that continuously monitor, intervene, and evaluate the levels of these toxic elements to ensure that they are reduced as far as possible.