Opportunities in the Postpartum Period to Reduce Cardiovascular Disease Risk After Adverse Pregnancy Outcomes: A Scientific Statement From the American Heart Association.

Adverse pregnancy outcomes are common among pregnant individuals and are associated with long-term risk of cardiovascular disease. Individuals with adverse pregnancy outcomes also have an increased incidence of cardiovascular disease risk factors after delivery. Despite this, evidence-based approaches to managing these patients after pregnancy to reduce cardiovascular disease risk are lacking. In this scientific statement, we review the current evidence on interpregnancy and postpartum preventive strategies, blood pressure management, and lifestyle interventions for optimizing cardiovascular disease using the American Heart Association Life's Essential 8 framework. Clinical, health system, and community-level interventions can be used to engage postpartum individuals and to reach populations who experience the highest burden of adverse pregnancy outcomes and cardiovascular disease. Future trials are needed to improve screening of subclinical cardiovascular disease in individuals with a history of adverse pregnancy outcomes, before the onset of symptomatic disease. Interventions in the fourth trimester, defined as the 12 weeks after delivery, have great potential to improve cardiovascular health across the life course.

Genome-wide oscillations in G + C density and sequence conservation.

Eukaryotic genomes typically show a uniform G + C content among chromosomes, but on smaller scales, many species have a G + C density that fluctuates with a characteristic wavelength. This oscillation is evident in many insect species, with wavelengths ranging between 700 bp and 4 kb. Measures of evolutionary conservation oscillate in phase with G + C content, with conserved regions having higher G + C. Loci with large regulatory regions show more regular oscillations; coding sequences and heterochromatic regions show little or no oscillation. There is little oscillation in vertebrate genomes in regions with densely distributed mobile repetitive elements. However, species with few repeats show oscillation in both G + C density and sequence conservation. These oscillations may reflect optimal spacing of cis-regulatory elements.

The Neutrophil Dynamic Mass Redistribution Assay as a Medium throughput Primary Cell Screening Assay.

In a typical G protein coupled receptor drug discovery campaign, an in vitro primary functional screening assay is often established in a recombinant system overexpressing the target of interest, which offers advantages with respect to overall throughput and robustness of compound testing. Subsequently, compounds are then progressed into more physiologically relevant but lower throughput ex vivo primary cell assays and finally in vivo studies. Here we describe a dynamic mass redistribution (DMR) assay that has been developed in a format suitable to support medium throughput drug screening in primary human neutrophils. Neutrophils are known to express both CXC chemokine receptor (CXCR) 1 and CXCR2 that are thought to play significant roles in various inflammatory disorders and cancer. Using multiple relevant chemokine ligands and a range of selective and nonselective small and large molecule antagonists that block CXCR1 and CXCR2 responses, we demonstrate distinct pharmacological profiles in neutrophil DMR from those observed in recombinant assays but predictive of activity in neutrophil chemotaxis and CD11b upregulation, a validated target engagement marker previously used in clinical studies of CXCR2 antagonists. The primary human neutrophil DMR cell system is highly reproducible, robust, and less prone to donor variability observed in CD11b and chemotaxis assays and thus provides a unique, more physiologically relevant, and higher throughput assay to support drug discovery and translation to early clinical trials. SIGNIFICANCE STATEMENT: Neutrophil dynamic mass redistribution assays provide a higher throughput screening assay to profile compounds in primary cells earlier in the screening cascade enabling a higher level of confidence in progressing the development of compounds toward the clinic. This is particularly important for chemokine receptors where redundancy contributes to a lack of correlation between recombinant screening assays and primary cells, with the coexpression of related receptors confounding results.

A single amino acid substitution in MdLAZY1A dominantly impairs shoot gravitropism in Malus.

Plant architecture is 1 of the most important factors that determines crop yield potential and productivity. In apple (Malus domestica), genetic improvement of tree architecture has been challenging due to a long juvenile phase and growth as complex trees composed of a distinct scion and a rootstock. To better understand the genetic control of apple tree architecture, the dominant weeping growth phenotype was investigated. We report the identification of MdLAZY1A (MD13G1122400) as the genetic determinant underpinning the Weeping (W) locus that largely controls weeping growth in Malus. MdLAZY1A is 1 of the 4 paralogs in apple that are most closely related to AtLAZY1 involved in gravitropism in Arabidopsis (Arabidopsis thaliana). The weeping allele (MdLAZY1A-W) contains a single nucleotide mutation c.584T>C that leads to a leucine to proline (L195P) substitution within a predicted transmembrane domain that colocalizes with Region III, 1 of the 5 conserved regions in LAZY1-like proteins. Subcellular localization revealed that MdLAZY1A localizes to the plasma membrane and nucleus in plant cells. Overexpressing the weeping allele in apple cultivar Royal Gala (RG) with standard growth habit impaired its gravitropic response and altered the growth to weeping-like. Suppressing the standard allele (MdLAZY1A-S) by RNA interference (RNAi) in RG similarly changed the branch growth direction to downward. Overall, the L195P mutation in MdLAZY1A is genetically causal for weeping growth, underscoring not only the crucial roles of residue L195 and Region III in MdLAZY1A-mediated gravitropic response but also a potential DNA base editing target for tree architecture improvement in Malus and other crops.

When a test is more than just a test: Findings from patient interviews and survey in the trial of a technology to measure antidepressant medication response (the PReDicT Trial).

BACKGROUND: A RCT of a novel intervention to detect antidepressant medication response (the PReDicT Test) took place in five European countries, accompanied by a nested study of its acceptability and implementation presented here. The RCT results indicated no effect of the intervention on depression at 8 weeks (primary outcome), although effects on anxiety at 8 weeks and functioning at 24 weeks were found. METHODS: The nested study used mixed methods. The aim was to explore patient experiences of the Test including acceptability and implementation, to inform its use within care. A bespoke survey was completed by trial participants in five countries (n = 778) at week 8. Semi-structured interviews were carried out in two countries soon after week 8 (UK n = 22, Germany n = 20). Quantitative data was analysed descriptively; for qualitative data, thematic analysis was carried out using a framework approach. Results of the two datasets were interrogated together. OUTCOMES: Survey results showed the intervention was well received, with a majority of participants indicating they would use it again, and it gave them helpful extra information; a small minority indicated the Test made them feel worse. Qualitative data showed the Test had unexpected properties, including: instigating a process of reflection, giving participants feedback on progress and new understanding about their illness, and making participants feel supported and more engaged in treatment. INTERPRETATION: The qualitative and quantitative results are generally consistent. The Test's unexpected properties may explain why the RCT showed little effect, as properties were experienced across both trial arms. Beyond the RCT, the qualitative data sheds light on measurement reactivity, i.e., how measurements of depression can impact patients.

Effectiveness of a home training program on improving pinch force perception in older adults.

BACKGROUND: Hand function is reduced with aging which can lead to impairments in the performance of daily activities and eventually loss of independence. The ability to perceive the forces being applied to an object is an important component of hand control that also declines with age. However, the extent to which force perception can be improved through training remains largely unknown. PURPOSE: This study evaluated the effectiveness of a home-training program focused on improving force perception in older adults. STUDY DESIGN: Quasi-experimental - Uncontrolled trial. METHODS: Eleven independent, healthy adults (mean age: 77.2 ± 6.8 years) participated in a home-based sensorimotor hand training program 6 days/week for 6 weeks. Force perception, the primary outcome variable, was measured as the ability to reproduce a pinch force equal to 25% maximum voluntary contraction in the absence of visual feedback using either the ipsilateral remembered or contralateral concurrent (CC) hand. We also measured hand strength, dexterity, tactile acuity, and cognition before and after training. RESULTS: After the program was completed, participants showed a 35% reduction in absolute (p < 0.01, confidence interval (CI): [7.3, 33.2], effect sizes (ES): 0.87) and constant (p = 0.05, CI: [0.0, 34.9], ES: 0.79) force matching errors in the CC condition. Improvements in dominant hand dexterity (Purdue pegboard test) (p < 0.05, CI: [0.2, 2.4], ES: 0.60) and tactile sensitivity (JVP thresholds) (p < 0.05, CI: [-1.7, -0.1], ES: 0.94), as well as cognition (Trail Making Test B) (p < 0.05, CI: [-24,1. -1.6], ES: 0.30) were also observed post-training. CONCLUSIONS: The results suggest that home-hand training can be an effective way to improve force perception among older adults.

National evaluation of DNP students' use of the PICOT method for formulating clinical questions.

BACKGROUND: The intent of the PICOT (i.e., Population, Intervention, Comparison, Outcome, Time) method is to formulate focused clinical questions to facilitate the discovery of relevant evidence through systematic searching, with the components of the question serving as the foundation for the search. Doctor of Nursing Practice (DNP) graduates use evidence-based practices to institute changes in their organizations' systems and policies, thereby yielding positive effects on both patient and system outcomes. Given that the clinical question is the foundation of the evidence-based practice process, DNP graduates' competence in the PICOT method needs to be better understood. AIMS: This analysis aimed to describe how DNP students used the PICOT method to ask clinical questions in their DNP projects. METHODS: Project questions were retrieved from a subset (n = 129, 60.56%) of an existing national random sample of publicly available DNP projects spanning the years 2010 to 2021 from Commission on Collegiate Nursing Education-accredited schools (n = 213). Project questions using the PICOT method were further evaluated with a scoring system of 0 = no and 1 = yes for missing elements, formatting, directional outcome, and project purpose. Possible scores ranged from 0 to 8, with higher scores indicating more errors. Discussion among five researchers, until agreement was achieved, yielded consensus. RESULTS: Although the PICOT method was project author-identified in 66 (31.0%) projects, only four (6%) followed the PICOT method. All 66 (100%) were intervention questions. There were 2.74 (SD 1.55) mean errors, ranging from 0 to 6. No questions were missing P or O. Specific errors included missing I 3 (4.5%) or missing C 37 (56%), poor formatting 34 (51.5%), directional outcome 44 (66.7%), and project purpose 38 (57.6%). Thirty-three (50%) of the questions were missing T; however, T is not used for searching, so researchers recalculated the mean error without T (M = 2.24, SD = 1.28, range 0-5). LINKING EVIDENCE TO ACTION: Gaps in the accurate use of the PICOT method to construct clinical questions can lead to biased searches, inaccurate clinical problem identification, and, when used as the project purpose, jumping to non-evidence-based solutions. Academic faculty and clinical educators can mitigate these skewed outcomes and enhance their impact on quality outcomes by helping DNP-prepared nurses shore up this foundational skill.

Increasing clinician participation in tobacco cessation by an implementation science-based tobacco cessation champion program.

BACKGROUND: We designed a process to increase tobacco cessation in an academic center and its widely distributed network community sites using clinical champions to overcome referral barriers. METHODS: In 2020 a needs assessment was performed across the City of Hope Medical Center and its 32 community treatment sites. We reviewed information science strategies to choose elements for our expanded tobacco control plan, focusing on distributed leadership with tobacco cessation champions. We analyzed smoking patterns in patients with cancer before and following program implementation. We evaluated the champion experience and measured tobacco abstinence after 6 months of follow-up. RESULTS: Cancer center leadership committed to expanding tobacco control. Funding was obtained through a Cancer Center Cessation Initiative (C3I) grant. Multi-disciplinary leaders developed a comprehensive plan. Disease-focused clinics and community sites named cessation champions (a clinician and nurse) supported by certified tobacco treatment specialists. Patient, staff, clinician, and champion training/education were developed. Roles and responsibilities of the champions were defined. Implementation in pilot sites showed increased tobacco assessment from 80.8 to 96.6%, increased tobacco cessation referral by 367%, and moderate smoking abstinence in both academic (27.2%) and community sites (22.5%). 73% of champions had positive attitudes toward the program. CONCLUSION: An efficient process to expand smoking cessation in the City of Hope network was developed using implementation science strategies and cessation champions. This well-detailed implementation process may be helpful to other cancer centers, particularly those with a tertiary care cancer center and community network.

DnaB helicase dynamics in bacterial DNA replication resolved by single-molecule studies.

In Escherichia coli, the DnaB helicase forms the basis for the assembly of the DNA replication complex. The stability of DnaB at the replication fork is likely important for successful replication initiation and progression. Single-molecule experiments have significantly changed the classical model of highly stable replication machines by showing that components exchange with free molecules from the environment. However, due to technical limitations, accurate assessments of DnaB stability in the context of replication are lacking. Using in vitro fluorescence single-molecule imaging, we visualise DnaB loaded on forked DNA templates. That these helicases are highly stable at replication forks, indicated by their observed dwell time of ∼30 min. Addition of the remaining replication factors results in a single DnaB helicase integrated as part of an active replisome. In contrast to the dynamic behaviour of other replisome components, DnaB is maintained within the replisome for the entirety of the replication process. Interestingly, we observe a transient interaction of additional helicases with the replication fork. This interaction is dependent on the τ subunit of the clamp-loader complex. Collectively, our single-molecule observations solidify the role of the DnaB helicase as the stable anchor of the replisome, but also reveal its capacity for dynamic interactions.

Patterns and cost of care according to keratinocyte cancer risk stratification in a volunteer population screening clinic: Real-world data from the TRoPICS study.

BACKGROUND: Risk prediction tools have been developed for keratinocyte cancers (KCs) to effectively categorize individuals with different levels of skin cancer burden. Few have been clinically validated nor routinely used in clinical settings. OBJECTIVES: To assess whether risk prediction tool categories associate with interventions including chemoprophylaxis for skin cancer, and health-care costs in a dermatologist-run screening clinic. METHODS: Adult participants who presented to a walk-in screening facility were invited to participate. A self-completed KC risk prediction tool was used to classify participants into one of the five risk categories. Participants subsequently underwent full skin examination by a dermatologist. Dermatological interventions and skin cancer-related medical prescriptions were documented. Total health-care costs, both to the health-care system and patients were evaluated. RESULTS: Of the 507 participants recruited, 5-fluorouracil cream and nicotinamide were more frequently prescribed in the higher risk groups as chemoprophylaxis (p < 0.005). A significant association with high predicted risk was also observed in the use of cryotherapy and curettage and cautery (p < 0.05). The average health-care costs associated with a skin check visit increased from $90 ± 37 (standard deviation) in the lowest risk group to $149 ± 97 in the highest risk group (p < 0.0001). CONCLUSIONS: We observed a positive association between higher predicted risk of skin cancer and the prescription of chemoprophylaxis and health-care costs involved with opportunistic community skin cancer screening. A clinical use of risk stratification may be to provide an opportunity for clinicians to discuss skin cancer prevention and chemoprophylaxis with individual patients.

Examination of the validity of the Injury-Psychological Readiness to Return to Sport (I-PRRS) scale in male professional football players: A worldwide study of 29 professional teams.

Perceived confidence is an important dimension of an athlete's psychological readiness to return-to-play. However, there is no established and validated tool to evaluate confidence in professional football. This study aimed to provide preliminary evaluation of the internal structure of the Injury-Psychological Readiness to Return-to-Sport scale (I-PRRS) in a cohort of injured male professional footballers. Over an 18-month period, 29 teams from 17 leagues participated. Players sustaining injuries eliciting ≥ 3 weeks' time-loss were recruited. Cross culturally adapted to 4 further languages, the I-PRRS was administered on two occasions: 1) day before returning-to-training and 2) day before returning-to-match-play. In total, 113 injuries were recorded with 96 completed I-PRRS data sets collected. Confirmatory factor analysis indicated the I-PRRS was a unidimensional scale, with all items measuring the same construct. The scale demonstrated good internal consistency (ω = .88). When examining longitudinal invariance of the I-PRRS across administration time-points, indices of model fit supported scalar invariance. There was preliminary evidence of good internal structure for the I-PRRS in professional male footballers. However, before further research involving the I-PRRS can be endorsed, efforts to confirm or refute empirical developments pertaining to psychological readiness are necessary.

A Cohort Comparison of Midlife Marital Quality: A Quarter Century of Change.

Marital quality has been declining among recent cohorts, but whether this pattern characterizes middle-aged and older married adults is largely unknown. The doubling of the divorce rate among persons over the age of 50 years foretells poorer quality marriages for today's midlife adults than a generation ago. Combining data on married individuals aged 50-65 years from the 1987-88 National Survey of Families and Households (NSFH) and the 2013 Families and Relationships Study, we conduct a cohort comparison of five dimensions of midlife marital quality. Today's older adults report more marital disagreement and instability as well as less fairness and interaction with their spouses than their counterparts did a generation ago. The two cohorts report comparable levels of marital happiness. Consistent with the upward trend in divorce during the second half of life, the quality of midlife marriages appears to have declined over the past quarter century.

An intergenerational service-learning approach to improve hand function in older adults.

Homebound older adults are at greater risk for functional impairments, social isolation, and loss of independence. Adequate hand function is needed to perform many daily activities, yet is understudied, particularly in the homebound population. The purpose of this study was to pilot test an intergenerational program in which pre-health college students were trained to deliver hand exercises to homebound older adults receiving Meals on Wheels (MOW) services. Eight MOW clients (mean age: 80.1 ± 12.9y) and 17 students completed the program. Students visited clients 2×/week for 6 weeks and engaged in hand exercises and meaningful conversations. Measures of hand strength, dexterity, self-reported function, self-efficacy, depression, and social isolation were taken before and after the program. Clients and students also completed a post-program experience survey. Significant improvements in pinch strength were observed, and 75% of clients reported better upper limb mobility after training. Survey feedback was positive with clients saying they enjoyed interacting with college students, while students praised the hands-on nature of the program and engagement with older adults. Results from this pilot study demonstrate an intergenerational approach to deliver hand training is feasible and underscores the value of using such models to increase access to care for homebound older adults.

Improving Maternal Cardiovascular Health in Underserved Populations: a Narrative Review of Behavioral Intervention Trials Targeting Postpartum Weight Retention.

PURPOSE OF REVIEW: Racial/ethnic minority and socioeconomically disadvantaged individuals experience greater postpartum weight retention, which has been linked to the development of cardiovascular disease. This article reviews recent literature on behavioral interventions targeting postpartum weight retention in these populations. RECENT FINDINGS: Seven randomized controlled trials published since 2010 were selected for this review. Four were successful in reducing or preventing postpartum weight retention. Recruitment primarily occurred in low-income urban areas. All interventions reported using the Social Cognitive Theory and targeted mostly individual-level behavior change focused on diet and physical activity. Four were technology-based, and most implemented strategies to increase cultural relevance of the intervention. Opportunities for future interventions include expand target population to enroll individuals starting in pregnancy and address rural populations; incorporate empirically tested retention strategies; increase focus on psychosocial factors, particularly chronic stress; utilize multilevel approaches; continue to leverage technology; and maximize efforts to increase cultural relevancy.

Is maximum grip strength a reliable predictor of hand limitations among older adults?

BACKGROUND: Grip strength is commonly used to assess hand function among older adults. While shown to be associated with disability, the degree to which grip strength specifically predicts hand limitations is unknown. AIMS: The primary aim of this study was to evaluate grip strength as a predictor of hand limitations. METHODS: Using the 2011-14 National Health and Nutrition Examination Survey (NHANES), we classified older adults reporting one or more hand limitations versus those with no limitations. Odds ratios were used to assess the association between grip strength (separated into quartiles) and the likelihood of a hand limitation while controlling for sex, race/ethnicity, education level, income, and pain. Receiver operator characteristic (ROC) curves were used to evaluate the degree to which grip strength discriminates between older adults with and without a hand limitation. RESULTS: We identified 2064 older adults (age ≥ 65), 31% of whom reported a hand-related limitation. Older adults with very low grip strength (weakest quartile) were more likely to report at least one limitation (OR: 6.1, 95% CI: 3.2, 11.8) than those with high grip strength (strongest quartile). However, grip strength had poor to moderate discrimination of hand limitations (ROC area under curves: 0.65-0.81). DISCUSSION: While self-reported hand limitations were associated with lower grip strength; overall, it is a relatively poor predictor of hand impairments among older adults. CONCLUSION: Better assessments are needed to adequately evaluate upper extremity impairments to help older adults maintain functional independence.

Equity in Psychosocial Outcomes and Care for Racial and Ethnic Minorities and Socioeconomically Disadvantaged People With Diabetes.

The role of social determinants of health (SDOH) in promoting equity in diabetes prevalence, incidence, and outcomes continues to be documented in the literature. Less attention has focused on disparities in psychosocial aspects of living with diabetes and the role of SDOH in promoting equity in psychosocial outcomes and care. In this review, the authors describe racial/ethnic and socioeconomic disparities in psychosocial aspects of living with diabetes, discuss promising approaches to promote equity in psychosocial care, and provide future research directions.

Union Formation Expectations among Older Adults Who Live Apart Together in the USA.

There is an ongoing debate over whether living apart together (LAT) relationships are simply long-term relationships or alternatives to cohabitation or marriage. This study examined cohabitation and marriage expectations among older adults who LAT in the United States to address the debate. The analyses also compared the marriage expectations of older adults who LAT and cohabitors. Using data from the 2011 Wisconsin Longitudinal Study (WLS), we examined the union expectations of 250 individuals who LAT and 234 cohabitors. After providing a demographic portrait of older adults who LAT, we used ordered logistic regression models to predict their cohabitation and marriage expectations. Additional models predicted marriage expectations for older adults who LAT versus cohabitors. Older adults who LAT were unlikely to expect to formalize their unions. Adults who LAT were less likely to expect marriage than cohabitors. LAT relationships appear to be long-term partnerships in the United States.

High contiguity de novo genome assembly and DNA modification analyses for the fungus fly, Sciara coprophila, using single-molecule sequencing.

BACKGROUND: The lower Dipteran fungus fly, Sciara coprophila, has many unique biological features that challenge the rule of genome DNA constancy. For example, Sciara undergoes paternal chromosome elimination and maternal X chromosome nondisjunction during spermatogenesis, paternal X elimination during embryogenesis, intrachromosomal DNA amplification of DNA puff loci during larval development, and germline-limited chromosome elimination from all somatic cells. Paternal chromosome elimination in Sciara was the first observation of imprinting, though the mechanism remains a mystery. Here, we present the first draft genome sequence for Sciara coprophila to take a large step forward in addressing these features. RESULTS: We assembled the Sciara genome using PacBio, Nanopore, and Illumina sequencing. To find an optimal assembly using these datasets, we generated 44 short-read and 50 long-read assemblies. We ranked assemblies using 27 metrics assessing contiguity, gene content, and dataset concordance. The highest-ranking assemblies were scaffolded using BioNano optical maps. RNA-seq datasets from multiple life stages and both sexes facilitated genome annotation. A set of 66 metrics was used to select the first draft assembly for Sciara. Nearly half of the Sciara genome sequence was anchored into chromosomes, and all scaffolds were classified as X-linked or autosomal by coverage. CONCLUSIONS: We determined that X-linked genes in Sciara males undergo dosage compensation. An entire bacterial genome from the Rickettsia genus, a group known to be endosymbionts in insects, was co-assembled with the Sciara genome, opening the possibility that Rickettsia may function in sex determination in Sciara. Finally, the signal level of the PacBio and Nanopore data support the presence of cytosine and adenine modifications in the Sciara genome, consistent with a possible role in imprinting.

Whole-genome classification of rotavirus C and genetic diversity of porcine strains in the USA.

Rotavirus C (RVC) is associated with acute diarrhoea in both children and young animals. Because of its frequent occurrence, additional sequences have recently been generated. In this study, we sequenced 21 complete genomes from porcine diarrhoea samples and analysed them together with all available reference sequences collected from the GenBank database [National Center for Biotechnology Information (NCBI)]. Based on phylogenetic analysis and genetic distance calculation, the number of each segment was identified as 31G, 26P, 13I, 5R, 5C, 5M, 12A, 10 N, 9T, 8E and 4 H for genotypes encoding VP7, VP4, VP6, VP1, VP2, VP3 and NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. From the analysis, genotypes G19-G31, P[22]-P[26], R5, A9-A12, N9-N10, T7-T9 and E6-E8 were defined as newly identified genotypes, and genotype C6 was combined with C5, and M6 was combined with M1, due to their closely related nature. Estimated with the identity frequency ratio between the intergenotype and intragenotype, the nucleotide identity cutoff values for different genotypes were determined as 85, 85, 86, 84, 83, 84, 82, 87, 84, 81 and 79 % for VP7, VP4, VP6, VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5, respectively. Genotyping of the 49 US strains indicated possible segment reassortment in 9 of the 11 segments, with the exceptions being VP1 and NSP5, and the most prevalent genotypes for each segment genes in the USA were G6/G5/G21/G9-P5/P4-I6/I5-R1-C5-M1-A8-N1/N10-T1-E1-H1. Our study updated the genotypes of RVC strains and provided more evidence of RVC strain diversity that may be relevant to better understand genetic diversity, and the distribution and evolution of RVC strains.

A Randomized Encouragement Trial to Increase Mail Order Pharmacy Use and Medication Adherence in Patients with Diabetes.

BACKGROUND: Mail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence. OBJECTIVE: To assess an intervention to encourage MOP services to increase its use and medication adherence. DESIGN: Randomized encouragement trial. PATIENTS: 63,012 diabetes patients from three health care systems: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Hawaii (KPHI), and Harvard Pilgrim Health Care (HPHC) who were poorly adherent to at least one class of cardiometabolic medications and had not used MOP in the prior 12 months. INTERVENTION: Patients were randomized to receive either usual care (control arm) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use (intervention arm). HPHC intervention patients received the letter only. MEASUREMENTS: We compared the percentages of patients that began using MOP and that became adherent to cardiometabolic medication classes during a 12-month follow-up period. We also conducted a race/ethnicity-stratified analysis. RESULTS: During follow-up, 10.6% of intervention patients began using MOP vs. 9.3% of controls (p < 0.01); the percent of cardiometabolic medication delivered via mail was 42.1% vs. 39.8% (p < 0.01). Metformin adherence improved in the intervention arm relative to control at the two KP sites (52% vs. 49%, p < 0.01). Stratified analyses suggested a significant positive effect of the intervention in White (RR: 1.12, 95% CI: 1.03, 1.22) and Asian (RR: 1.30, 95% CI: 1.17, 1.45) patients. CONCLUSION: This pragmatic trial showed that simple outreach to encourage MOP modestly increased its use and improved adherence measured by refills to a key class of diabetes medications in some settings. Given its minimal cost, clinicians and health systems should consider outreach interventions to actively promote MOP use among diabetes patients. TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT02621476.