Relational Dynamics of Treatment Behavior Among Individuals with Tuberculosis in High-Income Countries: A Scoping Review.

Although tuberculosis (TB) incidence has significantly declined in high-income, low-incidence (HILI) countries, challenges remain in managing TB in vulnerable populations who may struggle to stay on anti-TB treatment (ATT). Factors associated with non-adherence to ATT are well documented; however, adherence is often narrowly conceived as a fixed binary variable that places emphasis on individual agency and the act of taking medicines, rather than on the demands of being on treatment more broadly. Further, the mechanisms through which documented factors act upon the experience of being on treatment are poorly understood. Adopting a relational approach that emphasizes the embeddedness of individuals within dynamic social, structural, and health systems contexts, this scoping review aims to synthesize qualitative evidence on experiences of being on ATT and mechanisms through which socio-ecological factors influence adherence in HILI countries. Six electronic databases were searched for peer-reviewed literature published in English between January 1990 and May 2020. Additional studies were obtained by searching references of included studies. Narrative synthesis was used to analyze qualitative data extracted from included studies. Of 28 included studies, the majority (86%) reported on health systems factors, followed by personal characteristics (82%), structural influences (61%), social factors (57%), and treatment-related factors (50%). Included studies highlighted three points that underpin a relational approach to ATT behavior: 1) individual motivation and capacity to take ATT is dynamic and intertwined with, rather than separate from, social, health systems, and structural factors; 2) individuals' pre-existing experiences of health-seeking influence their views on treatment and their ability to commit to long-term regular medicine-taking; and 3) social, cultural, and political contexts play an important role in mediating how specific factors work to support or hinder ATT adherence behavior in different settings. Based on our analysis, we suggest that person-centered clinical management of tuberculosis should 1) acknowledge the ways in which ATT both disrupts and is managed within the everyday lives of individuals with TB; 2) appreciate that individuals' circumstances and the support and resources they can access may change over the course of treatment; and 3) display sensitivity towards context-specific social and cultural norms affecting individual and collective experiences of being on ATT.

IMPACT study on intervening with a manualised package to achieve treatment adherence in people with tuberculosis: protocol paper for a mixed-methods study, including a pilot randomised controlled trial.

INTRODUCTION: Compared with the rest of the UK and Western Europe, England has high rates of the infectious disease tuberculosis (TB). TB is curable, although treatment is for at least 6 months and longer when disease is drug resistant. If patients miss too many doses (non-adherence), they may transmit infection for longer and the infecting bacteria may develop resistance to the standard drugs used for treatment. Non-adherence may therefore risk both their health and that of others. Within England, certain population groups are thought to be at higher risk of non-adherence, but the factors contributing to this have been insufficiently determined, as have the best interventions to promote adherence. The objective of this study was to develop a manualised package of interventions for use as part of routine care within National Health Services to address the social and cultural factors that lead to poor adherence to treatment for TB disease. METHODS AND ANALYSIS: This study uses a mixed-methods approach, with six study components. These are (1) scoping reviews of the literature; (2) qualitative research with patients, carers and healthcare professionals; (3) development of the intervention; (4) a pilot randomised controlled trial of the manualised intervention; (5) a process evaluation to examine clinical utility; and (6) a cost analysis. ETHICS AND DISSEMINATION: This study received ethics approval on 24 December 2018 from Camberwell St. Giles Ethics Committee, UK (REC reference 18/LO/1818). Findings will be published and disseminated through peer-reviewed publications and conference presentations, published in an end of study report to our funder (the National Institute for Health Research, UK) and presented to key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN95243114 SECONDARY IDENTIFYING NUMBERS: University College London/University College London Hospitals Joint Research Office 17/0726.National Institute for Health Research, UK 16/88/06.

Predictors of nonadherence in children and adolescents with epilepsy: A multimethod assessment approach.

BACKGROUND: There is a lack of a standardized tool for adherence measurement in patients with epilepsy. Studies in children with epilepsy have reported adherence in 50-96.5%. The primary objective of this study was to identify predictors of nonadherence to antiepileptic drugs (AEDs) using two different methods in Jordanian children and adolescents with epilepsy. METHODS: Participants included 63 children and adolescents with epilepsy and their primary caregivers. Adherence measures included a subjective approach (using parent and child self-reports via Medication Adherence Report Scale (MARS)) and an objective method (measuring plasma levels of AEDs coupled with the application of population pharmacokinetic models to predict AED concentrations in the children). The Beliefs about Medicines Questionnaire (BMQ) was used to examine the association beliefs about medicines with nonadherence in the participating patients. RESULTS: Measuring AEDs in plasma samples captured the highest percentage of nonadherence (36.2%). No significant agreement was found between the AED plasma level method and both the MARS (parent) and MARS (child). The overall nonadherence (combined methods) to AED therapy in children with epilepsy was 44.4%. Logistic regression analysis indicated that children with longer duration of disease were more likely (odds ratio [OR]: 1.54, 95% confidence interval [CI]: 1.16-2.04) to be classified as nonadherent as were children whose parents have lower AED Necessity scores (OR: 0.68, 95% CI: 0.53-0.87) and higher AED Concerns (OR: 1.6, 95% CI: 1.26-2.04) as measured by the BMQ. CONCLUSION: The use of a multimethod approach for assessing adherence increases sensitivity for detection of nonadherence to AEDs. Disease duration and parental necessity beliefs and concerns assessed by the BMQ-specific questionnaire were significant predictors of nonadherence to the AED therapy. The need for the development and implementation of interventions that can be employed to improve adherence within this pediatric population has been highlighted by the high levels of nonadherence identified.

Biochemical Screening for Nonadherence Is Associated With Blood Pressure Reduction and Improvement in Adherence.

We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.

Developing an Economic Case of Clinical Pharmacists' Interventions on Venous Thromboembolism Prophylaxis Through Service Evaluation.

OBJECTIVE: Venous thromboembolism (VTE) has become a huge health problem as well as a financial burden for the National Health Service. The objective of this study was to characterize current practice of VTE prophylaxis (VTEP) and evaluate the economic impact of clinical pharmacists' interventions (CPIs) on VTEP. METHODS: A prospective service evaluation was conducted in a medical and surgical ward at a tertiary teaching hospital in London from 23 May to 08 June 2016. Appropriateness of risk assessment (RA) and VTEP and CPIs were categorized and assessed. Based on the results of the service evaluation, a pharmacoeconomic analysis was undertaken to estimate the cost savings by CPIs for inappropriate pharmacological VTEP. FINDINGS: A total of 203 cases were analyzed. The rates of appropriateness for RA on admission, RA at 24 h and pharmacological VTEP were 58.6%, 39.7%, and 75.4%, respectively. In the medical ward, there was a significant difference of appropriate RAs between on admission and at 24 h (70.3% vs. 23.8%, respectively). Whereas, the rate of appropriate pharmacological VTEP accounted for 75.4% and the rate of appropriate prophylaxis was significantly higher in the medical ward than surgical ward (80.5% vs. 68.2%, P = 0.045). Of 50 cases of inappropriate pharmacological prophylaxis, 39 cases (78.0%) were corrected by clinical pharmacists. These CPIs resulted in £1,286.23 cost savings during the study and it was estimated to be £517,522/annum. CONCLUSION: CPIs had significant positive clinical and economic impacts on VTEP. There is more scope for the improvement of RA at 24 h through CPIs.

Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial.

BACKGROUND: Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens. However, it is not clear how best to treat patients with antibodies. This trial will test a combined screening and treatment protocol in renal transplant recipients. METHODS/DESIGN: Recipients>1 year post-transplantation, aged 18 to 70 with an estimated glomerular filtration rate>30 mL/min will be randomly allocated to blinded or unblinded screening arms, before being screened for the presence of antibodies. In the unblinded arm, test results will be revealed. Those with antibodies will have biomarker-led care, consisting of a change in their anti-rejection drugs to prednisone, tacrolimus and mycophenolate mofetil. In the blinded arm, screening results will be double blinded and all recruits will remain on current therapy (standard care). In both arms, those without antibodies will be retested every 8 months for 3 years. The primary outcome is the 3-year kidney failure rate for the antibody-positive recruits, as measured by initiation of long-term dialysis or re-transplantation, predicted to be approximately 20% in the standard care group but <10% in biomarker-led care. The secondary outcomes include the rate of transplant dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of adherence with medication and a health economic analysis of the combined screening and treatment protocol. Blood samples will be collected and stored every 4 months and will form the basis of separately funded studies to identify new biomarkers associated with the outcomes. DISCUSSION: We have evidence that the biomarker-led care regime will be effective at preventing graft dysfunction and expect this to feed through to graft survival. This trial will confirm the benefit of routine screening and lead to a greater understanding of how to keep kidney transplants working longer. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46157828.

The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.

The cost effectiveness of a telephone-based pharmacy advisory service to improve adherence to newly prescribed medicines.

OBJECTIVE: This "proof of concept" study aimed to assess the cost effectiveness of pharmacists giving advice via telephone, to patients receiving a new medicine for a chronic condition, in England. METHODS: The self-regulatory model (SRM) theory was used to guide development of our intervention and used in training pharmacists to adopt a patient-centred approach. Non-adherence to new medicines for chronic conditions develops rapidly so we developed a study intervention in which a pharmacist telephoned patients two weeks after they had started a new medicine for a chronic condition. Patients were included if they were 75 or older, or were suffering from stroke, cardiovascular disease, asthma, diabetes or rheumatoid arthritis, and were randomized into treatment or control arms. Main outcome measures were non-adherence and cost to the UK NHS, obtained via a questionnaire sent two months after starting therapy. Cost of the intervention was also included. Incremental cost effectiveness ratios (ICERs) were generated. RESULTS: Five hundred patients were recruited. At 4-week follow-up, non-adherence was significantly lower in the intervention group (9% vs 16%, p=0.032). The number of patients reporting medicine-related problems was significantly lower in the intervention group compared to the control, (23% vs 34% p=0.021). Mean total patient costs at 2-month follow-up (median, range) were intervention: pound sterling 187.7 (40.6, 4.2-2484.3); control: pound sterling 282.8 (42, 0-3804) (p<0.0001). The intervention was dominant (less costly and more effective). If the decision maker is not willing to pay anything for one extra adherent patient, there is still a 90% probability that the intervention is cost effective. CONCLUSIONS: These findings suggest that pharmacists can meet patients' needs for information and advice on medicines, soon after starting treatment. While a larger trial is needed to confirm that the effect is real and sustained, these initial findings suggest the study intervention may be effective, at least in the short term, with a reduced overall cost to the health provider.

A conceptually based approach to understanding chronically ill patients' responses to medication cost pressures.

Prescription medications enhance the well-being of most chronically ill patients. Many individuals, however, struggle with how to pay for their treatments and as a result experience problems with self-care and health maintenance. Although studies have documented that high out-of-pocket costs are associated with medication non-adherence, little research on prescription cost sharing has been theoretically grounded in knowledge of the more general determinants of patients' self-management behaviors and chronic disease outcomes. We present a conceptual framework for understanding the influence of patient, medication, clinician, and health system factors on individuals' responses to medication costs. We review what is known about how these factors influence medication adherence, identify possible strategies through which clinicians, health systems, and policy-makers may assist patients burdened by their medication costs, and highlight areas in need of further research. Although medication costs represent a burden to chronically ill patients worldwide, most patients report using their medication as prescribed despite the costs, and others report cost-related underuse despite an apparent ability to afford those treatments. The cost-adherence relationship is modified by contextual factors, including patients' characteristics (e.g., age, ethnicity, and attitudes toward medications), the type of medications they are using (e.g., the complexity of dosing and the drug's clinical target), clinician factors (e.g., choice of first-line agent and communication about medication costs), and health system factors (e.g., efforts to influence clinicians' prescribing and to help patients apply for financial assistance programs). Understanding these relationships will enable clinicians and policy-makers to better design pharmacy benefits and assist patients in taking their medication as prescribed. The next generation of studies examining the consequences of prescription drug costs should expand our knowledge of the ways in which these co-factors influence patients' responses to medication cost pressures.