Understanding strategies to improve medication adherence among persons with type 2 diabetes: A scoping review.

AIMS: The objectives of this scoping review were to: (1) identify the target audience and contexts in which strategies to improve type 2 diabetes mellitus (T2DM) medication adherence have been used, (2) provide an overview of behaviour change techniques (BCTs) used, (3) describe the determinants of behaviour targeted by strategies and (4) to identify current gaps in strategies. METHODS: A systemic search for articles related to T2DM, medication adherence and strategies was conducted in EMBASE, Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily using the OvidSP platform on 11 March 2021. All publications involving strategies to overcome medication non-adherence among adults with T2DM were included. Strategies were categorized according to the BCT taxonomy and the determinants of behaviour targeted by each strategy were classified by using the Theoretical Domains Framework (TDF). RESULTS: The search identified 58 articles and 61 strategies. The BCT categories Antecedents and Natural consequences and BCTs Feedback on outcome(s) of behaviour, Adding objects to the environment and Information about health consequences were identified most frequently as components of strategies resulting in statistically significant improvement in medication adherence. Strategies targeting the TDF domains Reinforcement and Beliefs about Consequences most often resulted in statistically significant improvements in adherence measures. CONCLUSIONS: The findings from this review identify BCTs and targeted behaviours with demonstrated success. Further exploration of the myriad of BCTs and the corresponding determinants of behaviour which were not accessed may be warranted for the development of future strategies to improve medication adherence in type 2 diabetes.

A Cross-sectional Survey to Assess Reasons for Therapeutic Inertia in People With Type 2 Diabetes Mellitus and Preferred Strategies to Overcome It From the Perspectives of Persons With Diabetes and General/Family Practitioners: Results From the MOTION Study.

OBJECTIVES: Although multiple causes of therapeutic inertia in type 2 diabetes mellitus (T2DM) have been identified, few studies have addressed the behavioural aspects of treatment-intensification decisions among persons with type 2 diabetes (PwT2DM) and general practitioners/family practitioners (GPFPs). METHODS: A quantitative online survey was developed to capture from 300 PwT2DM and 100 GPFPs the following information: 1) perspectives on shared decision-making (SDM) related to treatment intensification, using the 9-item Shared Decision Making Questionnaire and the Shared Decision Making Questionnaire---physician version; 2) intentions to intensify treatments, using the Theory of Planned Behaviour (TPB); and 3) preferred strategies to overcome causes of therapeutic inertia in T2DM. Regression methods were applied post hoc to examine correlations with SDM scores, behavioural intentions and behaviours. RESULTS: SDM scores showed a significantly lower level of perceived involvement in decision-making related to treatment intensification among PwT2DM compared with GPFPs. The TPB identified that, for PwT2DM, attitudes, perceived behavioural control and age were associated with variation in intention to intensify treatment and, for GPFPs, perceived behavioural control and not being in a shared/group practice were associated with intentions to intensify treatment. PwT2DM behaviour, measured as hesitancy to intensify treatment, was associated with age. PwT2DM want more information to become more comfortable with the treatment decision-making process, whereas GPFPs desired support from other health professionals, and more time to address issues among PwT2DM. CONCLUSIONS: Strategies directed at providing GPFPs with tools/approaches to increase PwT2DM involvement in the decision-making process, such as behavioural coaching, decision aids and goal setting, may increase acceptance of treatment intensification, leading to a reduction in therapeutic inertia in T2DM.

Persons With Diabetes and General/Family Practitioner Perspectives Related to Therapeutic Inertia in Type 2 Diabetes Mellitus Using Qualitative Focus Groups and the Theoretical Domains Framework: Results From the MOTION Study.

OBJECTIVES: Therapeutic inertia in type 2 diabetes (T2DM) is the failure to receive timely treatment intensification as indicated according to T2DM treatment guidelines. Multifactorial causes of therapeutic inertia in T2DM have been documented at the level of persons with diabetes (PwD), health-care providers and health-care systems. METHODS: We developed a 3-part mixed-methods research program, called the Moving to Overcome Therapeutic Inertia Obstacles Now in T2DM (MOTION) study, to inform the development of strategies to address therapeutic inertia in T2DM. We present the results from focus groups with the following objectives: 1) understanding PwD and general practitioner/family practitioner (GPFP) determinants of behaviour related to treatment intensification using the Theoretical Domains Framework (TDF); and 2) identifying the sources of behaviours contributing to therapeutic inertia in T2DM, as proposed by the Behaviour Change Wheel (BCW). Two focus groups with PwD and 4 with GPFPs were conducted. Transcripts from the focus groups were coded independently by 2 investigators to identify themes, then mapped to TDF domains and linked using the BCW. RESULTS: For PwD, the most commonly coded TDF domains were intentions, goals, knowledge, beliefs about consequences and social influences. For GPFPs, the most common domains were intentions, environmental context and resources and social/professional role and identity. The BCW identified that PwD interventions should include reflective motivation, psychological capability and social opportunity; GPFP interventions should include physical opportunity, social opportunity and reflective motivation. CONCLUSIONS: Comprehensive strategies that target both PwD and GPFP barriers would encourage a more collaborative approach toward treatment intensification decisions and reducing therapeutic inertia.

Real-world persistence of erenumab for preventive treatment of chronic and episodic migraine: Retrospective real-world study.

OBJECTIVE: To describe the real-world treatment persistence (defined as the continuation of medication for the prescribed treatment duration), demographics and clinical characteristics, and treatment patterns for patients prescribed erenumab for migraine prevention in Canada. BACKGROUND: The effectiveness of prophylactic migraine treatments is often undermined by poor treatment persistence. In clinical trials, erenumab has demonstrated efficacy and tolerability as a preventive treatment, but less is known about the longer term treatment persistence with erenumab. METHODS: This is a real-world retrospective cohort study where a descriptive analysis of secondary patient data was conducted. Enrollment and prescription data were extracted from a patient support program for a cohort of patients prescribed erenumab in Canada between September 2018 and December 2019 and analyzed for persistence, baseline demographics, clinical characteristics, and treatment patterns. Descriptive analyses and unadjusted Kaplan-Meier (KM) curves were used to summarize the persistence and dose escalation/de-escalation at different timepoints. RESULTS: Data were analyzed for 14,282 patients. Median patient age was 47 years, 11,852 (83.0%) of patients were female, and 9443 (66.1%) had chronic migraine at treatment initiation. Based on KM methods, 71.0% of patients overall were persistent to erenumab 360 days after treatment initiation. Within 360 days of treatment initiation, it is estimated that 59.3% (KM-derived) of patients who initiated erenumab at 70 mg escalated to 140 mg, and 4.4% (KM-derived) of patients who initiated at 140 mg de-escalated to 70 mg. CONCLUSIONS: The majority of patients prescribed erenumab remained persistent for at least a year after treatment initiation, and most patients initiated or escalated to a 140 mg dose. These results suggest that erenumab is well tolerated, and its uptake as a new class of prophylactic treatment for migraine in real-world clinical practice is not likely to be undermined by poor persistence when coverage for erenumab is easily available.

Strategies to Overcome Therapeutic Inertia in Type 2 Diabetes Mellitus: A Scoping Review.

The objectives of this review were to: 1) examine recent strategies and component interventions used to overcome therapeutic inertia in type 2 diabetes mellitus (T2DM), 2) map strategies to the causes of therapeutic inertia they target and 3) identify causes of therapeutic inertia in T2DM that have not been targeted by recent strategies. A systematic search of the literature published from January 2014 to December 2019 was conducted to identify strategies targeting therapeutic inertia in T2DM, and key strategy characteristics were extracted and summarized. The search identified 46 articles, employing a total of 50 strategies aimed at overcoming therapeutic inertia. Strategies were composed of an average of 3.3 interventions (range, 1 to 10) aimed at an average of 3.6 causes (range, 1 to 9); most (78%) included a type of educational strategy. Most strategies targeted causes of inertia at the patient (38%) or health-care professional (26%) levels only and 8% targeted health-care-system-level causes, whereas 28% targeted causes at multiple levels. No strategies focused on patients' attitudes toward disease or lack of trust in health-care professionals; none addressed health-care professionals' concerns over costs or lack of information on side effects/fear of causing harm, or the lack of a health-care-system-level disease registry. Strategies to overcome therapeutic inertia in T2DM commonly employed multiple interventions, but novel strategies with interventions that simultaneously target multiple levels warrant further study. Although educational interventions are commonly used to address therapeutic inertia, future strategies may benefit from addressing a wider range of determinants of behaviour change to overcome therapeutic inertia.

Direct visualization of ligand-protein interactions using atomic force microscopy.

1. Streptavidin is a 60-kDa tetramer which binds four molecules of biotin with extremely high affinity (K(A) approximately 10(14) M(-1)). We have used atomic force microscopy (AFM) to visualize this ligand-protein interaction directly. 2. Biotin was tagged with a short (152-basepair; 50-nm) DNA rod and incubated with streptavidin. The resulting complexes were then imaged by AFM. The molecular volume of streptavidin calculated from the dimensions of the protein particles (105+/-3 nm(3)) was in close agreement with the value calculated from its molecular mass (114 nm(3)). Biotinylation increased the apparent size of streptavidin (to 133+/-2 nm(3)), concomitant with an increase in the thermal stability of the tetramer. 3. Images of streptavidin with one to four molecules of DNA-biotin bound were obtained. When two ligands were bound, the angle between the DNA rods was either acute or obtuse, as expected from the relative orientations of the biotin binding sites. The ratio of acute : obtuse angles (1 : 3) was lower than the expected value (1 : 2), indicating a degree of steric hindrance in the binding of the DNA-biotin. The slight under-representation of higher occupancy states supported this idea. 4. Streptavidin with a single molecule of DNA-biotin bound was used to tag biotinylated beta-galactosidase, a model multimeric enzyme. 5. The ability to image directly the binding of a ligand to its protein target by AFM provides useful information about the nature of the interaction, and about the effect of complex formation on the structure of the protein. Furthermore, the use of DNA-biotin/streptavidin tags could potentially shed light on the architecture of multi-subunit proteins.