Effect and usability of mobile health applications for medication adherence in patients with heart failure: A systematic review.

BACKGROUND: This review aimed to evaluate the effect of mobile health applications (apps) use on medication adherence in heart failure (HF) patients, and to verify their quality of use. METHODS: We searched MEDLINE, Embase, Web of Science, Scopus, CINAHL, LILACS, Cochrane, Clinical Trial Registries, Google Scholar, ProQuest, Open Access Theses and dissertations (OATD), Annual Symposium Proceedings of the American Medical Informatics Association (AMIA). RESULTS: Of the 836 records identified, eight studies (five randomized clinical trials (RCTs) and three observational studies) were included, totaling 484 participants, with a mean age ranging from 51.1 to 72 years and 65% were male. The apps improved medication adherence when compared with their comparators in only two RCTs (n = 111, Cohen d = 3.23, 95% confidence interval (CI) 2.66; 3.80 and n = 80, d = 1.20, 95% CI 0.71; 1.66), and two observational studies, one of them with large effect size (n = 142, Cohen d = 1.51, 95% CI 1.12; 1.90). Apps proved to be more effective interventions than their comparators allowed continuous monitoring of patients. All included studies used self-report measures to assess medication adherence behaviors and their results should be interpreted with caution, as such tools may cause social desirability bias or recall bias. CONCLUSION: The included studies indicate a possible outcome in favor of the use of apps to improve medication adherence in HF patients, but with very low quality level of evidence. Further studies are needed to investigate the effects of the use of apps, optimal frequency and duration of its use in HF patients.

Influence of polymorphisms in CYP2C9, VKORC1, MDR1 and APOE genes on the warfarin maintenance dose in Brazilian patients.

Background: Polymorphisms in the CYP2C9, VKORC1, MDR1 and APOE genes may impact warfarin dose. Aim: To investigate the influence of sociodemographic, clinical factors and polymorphisms *1, *2 and *3 for CYP2C9, -1639G>A for VKORC1, 3435C>T for MDR1, and ϵ2, ϵ3 and ϵ4 for APOE genes on the mean weekly warfarin maintenance dose in adults. Methods: This cross-sectional study recruited a calculated sample of 315 patients in three anticoagulation clinics in Brazil. A model containing the variables significantly associated with warfarin dose was estimated. Results: The mean age of patients was 64.1 ± 13.1 years, with 173 (54.9%) women. Age, use of amiodarone, genotype VKORC1 GA, genotype VKORC1 AA, genotypes CYP2C9*1/*2 or *1/*3 and genotypes CYP2C9*2/*2 or *2/*3 or *3/*3 were associated with a reduced warfarin dose. Conclusion: This study pointed out factors that could impact the management of oral anticoagulation.

Telemedicine-Based Management of Oral Anticoagulation Therapy: Systematic Review and Meta-analysis.

BACKGROUND: Oral anticoagulation is the cornerstone treatment of several diseases. Its management is often challenging, and different telemedicine strategies have been implemented to support it. OBJECTIVE: The aim of the study is to systematically review the evidence on the impact of telemedicine-based oral anticoagulation management compared to usual care on thromboembolic and bleeding events. METHODS: Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection and data extraction. Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models. RESULTS: In total, 25 randomized controlled trials were included (n=25,746 patients) and classified as moderate to high risk of bias by the Cochrane tool. Telemedicine resulted in lower rates of thromboembolic events, though not statistically significant (n=13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I2=42%), comparable rates of major bleeding (n=11 studies, RR 0.94, 95% CI 0.82-1.07; I2=0%) and mortality (n=12 studies, RR 0.96, 95% CI 0.78-1.20; I2=11%), and an improved time in therapeutic range (n=16 studies, mean difference 3.38, 95% CI 1.12-5.65; I2=90%). In the subgroup of the multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48). CONCLUSIONS: Telemedicine-based oral anticoagulation management resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events, and better anticoagulation quality compared to standard care. Given the potential benefits of telemedicine-based care, such as greater access to remote populations or people with ambulatory restrictions, these findings may encourage further implementation of eHealth strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases. Meanwhile, researchers should develop higher-quality evidence focusing on hard clinical outcomes, cost-effectiveness, and quality of life. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020159208; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=159208.

Building an antimicrobial stewardship program: A narrative of six years under the Donabedian perspective.

Introduction: Antimicrobial resistance (AMR) is increasing and represents one of the world's major challenges. AMR increase morbimortality, length of hospital stay and costs. Antimicrobial Stewardship Programs (ASP) are one of the key strategies to promote the rational use of antimicrobials since AMR is mostly driven by antimicrobial consumption. Objective: To describe the ASP implementation in a teaching hospital from the perspective of Donabedian quality assessment and the Brazilian regulatory requirements. Method: This was a descriptive study with secondary data collection, including document review of the ASP. The study setting was a general public 392-bed hospital. The ASP activities were performed by the hospital infection control committee (HICC), hospital pharmacy (HP) and diagnostic support laboratory (DSL). The description of the three services mainly involved in the ASP was based on a quality assessment model involving the dimensions of "structure", "process" and "result" proposed by Donabedian. The distribution among dimensions was guided by the checklist of essential elements of the ASP that compose the Brazilian regulatory requirements. The checklist was applied in July, 2022, and the ASP results described from 2016 to 2021. Results: ASP actions have been gradually implemented since 2008 with the implementation of HICC and improved over the years. Regarding structure, the investments in technology were mapped, quantifying 26 computers and three software programs employed to computerize the ASP processes performed in specific physical areas by HICC, HP and DSL. Institutional guidelines used by HICC, HP and DSL guided clinical practices to operationalize ASP. The evaluation metrics improved for 10 indicators and worsened for four indicators. From the 60 items composing the checklist, the hospital met the requirements in 73.3% of the items (n = 44). Conclusion: This study described the implementation of ASP in a teaching hospital, applying the Donabedian perspective. Although the hospital still does not have a classic ASP model, there were investments to improve structure, processes and results, aiming to comply with international guidelines. A high proportion of key elements of ASP in the hospital were followed according to the Brazilian regulatory requirements. Aspects related to antimicrobial consumption and the emergence of microbial resistance deserve further investigations.

Quality management tools applied to drug dispensing in hospital pharmacy: A scoping review.

BACKGROUND: The process of drug dispensing in hospital pharmacies (HPs) is one of the essential steps in health care, but presents high complexity due to the diversity of professionals and clinical conditions of patients. Therefore, the use of quality management tools may be an important strategy to improve patient safety and to achieve institutional goals, including user satisfaction and reduction of costs. OBJECTIVE: This scoping review sought to describe quality management tools applied to drug dispensing in HPs; quality indicators used and results obtained. METHODS: This scoping review was developed according to the Cochrane methodology and reported according to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA), being registered at Open Science Framework (https://doi.org/10.17605/OSF.IO/KP3AJ). The searches were performed in electronic databases Medline, Cochrane Library, Embase, CINAHL and Lilacs, with no limit of date or language. Studies on quality management tools applied to drug dispensing in HPs were assessed for eligibility, extracted and compiled in a narrative form. RESULTS: From the 1318 studies identified, 11 were eligible for this review. The quality management tools more frequently reported were those related to the definition of root cause (n = 4; 36%), e.g. DMAIC (Define, Measure, Analyze, Improve and Control) and the cause and effect diagram; tools for risk management, such as FMEA (Failure Mode and Effect Analysis) and its variations (n = 4; 36%); and tools related to the LSS (LEAN Six Sigma) principles (n = 3; 27%). The quality indicators used to monitor the results were, mainly, work team satisfaction, time spent performing activities and reduction of errors and costs. CONCLUSIONS: The use of quality management tools showed a tendency to improve the indicators of the drug dispensing process in HPs, such as increase in work team satisfaction, reduction of time spent performing activities, errors and costs, improving the quality of services.

Factors associated with nonadherence to the use of coumarin derivatives or direct oral anticoagulants: A systematic review of observational studies.

Nonadherence to thromboprophylaxis treatment with oral anticoagulants (OAC) is a public health problem and may be associated with high mortality rates. We sought to synthesize the factors associated with nonadherence to therapy with coumarin derivatives or direct oral anticoagulants. A systematic review was performed at electronic databases Medline, Embase, CINAHL, Lilacs and grey literature (Google Scholar, MedNar, OpenGray, ProQuest Dissertations and Theses, and hand search). This study was conducted according to Cochrane's method and PRISMA. The registration on PROSPERO is CRD42020223555. Overall, 1270 studies were identified and nine studies were selected for this review. In hand searching, 77 studies were found, but none included. The associated factors with nonadherence were heterogeneous, and some factors were described as both risk and protection for nonadherence, with few variables showing consistent results among the studies. Variables reported only as risk factors were "male sex", "hospitalization", "Charlson score" and "bleeding", while "white race", CHA2 DS2 VASc (score range 2-9)" and "polypharmacy" were reported only as protective factors. Most studies did not present details in the description of concepts and methods to assess nonadherence. In clinical practice, the knowledge on factors associated with nonadherence is helpful to identifying patients at higher risk of complications that would benefit from individualized interventions.

Medication literacy: A conceptual model.

BACKGROUND: Medication literacy reflects the specific literacy skills necessary to act on medication-related information. A comprehensive and clear conceptual model that reflects medication literacy is lacking. Conceptual models describe the components that represent a construct, allowing for its understanding and providing a rationale for its measurement. OBJECTIVES: To propose a conceptual model to support the development of an instrument to measure medication literacy. METHODS: This is a three-phase methodological study. A literature review was conducted to identify the components that should be part of the preliminary conceptual model. Subsequently, the importance of its components was judged on a Likert-5 scale. Then, the model was refined, and the dimensions and subdimensions of medication literacy were defined. RESULTS: Forty-five experts were included, with a mean age of 39.9 (SD = 10.5) years, most of them females (86.7%) and pharmacists (80%). All components of the preliminary conceptual model were considered important to extremely important by most experts. "Dosing information", "medication name", and "processing the information received about their medication and acting upon medication instructions" were the components considered most important. In the refinement phase, we identified that the construct has four dimensions - functional literacy, communicative literacy, critical literacy, and numeracy, which include the subdimensions to access, understand, evaluate, calculate, and communicate medication-related information. CONCLUSIONS: The conceptual model allowed identifying the components that represent medication literacy, which will support the development of an instrument for measuring the construct in Brazil.

Effectiveness of local hemostatic to prevent bleeding in dental patients on anticoagulation: A systematic review and network meta-analysis.

This study aimed to determine the effectiveness of hemostatic protocols to prevent bleeding in dental procedures among individuals undergoing oral anticoagulation therapy. A systematic review and network meta-analysis were accomplished. Searches of literature and grey literature were performed in different electronic databases. Clinical trials were considered as part of the inclusion criteria. Data extraction and assessment of the risk of bias of the included articles were performed. Assessment of the certainty of evidence was also performed. As results we find that the N-butyl-2-cyanoacrylate [RR -35.00 (95% CI - 107.12, -5.78)], calcium sulfate (CaSO4) [RR -5.62 (95% CI -11.41, -1.03)], and tranexamic acid (TXA) [RR -3.46 (95% CI -7.63, -0.77)] showed beneficial effects compared to placebo. However, only TXA presented beneficial effects with moderate certainty evidence. N-butyl-2-cyanoacrylate and CaSO4 presented very low certainty evidence. In the comparisons between the hemostatic agents, no differences were observed. For the mean bleeding time, no significant difference in the comparisons was observed as well. Concluding, bleeding events in individuals on oral anticoagulation decreased with the use of TXA compared to placebo. N-butyl-2-cyanoacrylate and CaSO4 were also superior to placebo, but the certainty of evidence was low. For the mean bleeding time, no significant difference in hemostatic agents was observed.

Sex-influence on the time in therapeutic range (TTR) during oral anticoagulation with coumarin derivatives: Systematic review and meta-analysis.

AIMS: We sought to investigate the association between sex and oral anticoagulation control employing coumarin derivatives. METHODS: Electronic sources were MEDLINE, Biblioteca Virtual em Saúde (BVS), The Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central and Web of Science. Inclusion criteria were: observational and experimental studies; age ≥18 years; both sexes; treatment with any coumarin derivative for ≥3 months; any indication of long-term use; quality of oral anticoagulation measured by time in therapeutic range (TTR). The meta-analysis was developed with odds ratios (OR) for binary variables and mean differences (MD) for continuous variables, using random-effects models (DerSimonian and Laird) with 95% confidence intervals (CI). RESULTS: Overall, 22 articles were selected, comprising 16 cohort studies, four cross-sectional studies and two clinical trials. The number of participants ranged from 110 to 104 505 (183 612; women: 45%). The main indication of oral anticoagulation was atrial fibrillation. Most studies reported the use of warfarin. In the meta-analysis, 15 studies were analysed using TTR as a binary variable (OR = 0.87; 95% CI = 0.78, 0.96; z = -2.75; P = .006.; I2  = 67%) and seven studies as a continuous variable (MD = -2.97; 95% CI = -4.80, -1.14; z = -3.19; P = .0014; I2  = 75%). The pooled estimates indicated that women were associated with lower TTR than men. CONCLUSIONS: Our findings revealed an association between female sex and worse oral anticoagulation control. Further studies are needed with primary design to investigate sex-related factors influencing oral anticoagulation control with coumarin derivatives. Innovative strategies focused on women's health may be useful to improve patient-centred care.

Oral Health-Related Quality of Life in Anticoagulated Patients with Warfarin Treatment: A Cross-Sectional Study.

To evaluate factors associated with oral health-related quality of life (OHRQoL) in patients under oral anticoagulant therapy with warfarin, a cross-sectional study was conducted. Validated questionnaires assessed self-reported periodontal disease, demographic variables, and OHRQoL using the short version of the Oral Health Impact Profile (OHIP-14) instrument. After calibration (Kappa > 0.60), an examiner evaluated patients' experience with dental caries and the need for dental prostheses. Statistical analysis involved proportions and measures of central tendency. Negative binomial regression models were used to estimate the rate ratios (RR) and the corresponding 95% confidence interval (CI). The sample consisted of 158 individuals, with a mean age of 58.8 years (SD = 12.1), of which 62.7% of the participants were women. The OHIP-14 mean was 10.62 (SD = 10.92). A higher OHIP-14 total score (worse OHRQoL) was associated with ethnic group, age, periodontal disease self-report, dental caries, and oral health self-report. Demographic and clinical factors can negatively influence the perception of anticoagulated patients on OHRQoL.

Empowerment-oriented strategies to identify behavior change in patients with chronic diseases: An integrative review of the literature.

BACKGROUND: Chronic diseases in the Americas account for about 80 % (5.2 million) of all deaths. Instruments are needed to enhance knowledge, skills, behavior change and self-care attitudes drawing on patient autonomy. OBJECTIVE: To identify empowerment-oriented strategies focused on behavioral change in patients with chronic diseases. PATIENT INVOLVEMENT: None. METHODS: This is an integrative review of articles published from any period until June 2020 by journals indexed in the following databases: National Library of Medicine National Institutes of Health (PubMed), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Biblioteca Virtual em Saúde (BVS). RESULTS: Out of 1,287 articles, 25 met our selection criteria. Reported health interventions were based on self-management and behavior change, shared decisions and a personalized collaborative process, peer support and self-confidence, as well as strategies involving educational media and health literacy. DISCUSSION: Over 80 % of health interventions were patient-centered and focused on patient knowledge and skill development towards personal goal setting, including effective problem-solving strategy development. Behavior change is not only an outcome of education, but also implicates revisiting values, attitudes, and experiences. Knowledge is important to facilitate decision-making leading to positive outcomes in chronic disease management. PRACTICAL VALUE: Empowerment-oriented strategies are important tools for providing trust and motivation to people with chronic diseases. Healthcare professionals should support and encourage patient empowerment as a strategy for behavior change and able to offer qualified care for shared decision making. Thus, patients will be able to participate more actively in their own health condition management and to make decisions to promote self-care.

Causality assessment of adverse drug reactions by applying a global introspection method in a high complexity hospital.

Background: Causality assessment of adverse drug reactions (ADRs) is an essential approach in pharmacovigilance. The World Health Organization-Uppsala Monitoring Center (WHO-UMC) system has been considered one of the most adequate method for establishing causal relationship in hospitalized patients. Objective: To describe the causality of potential ADRs in hospitalized patients assessed by the WHO-UMC system and by different healthcare professionals. Methods: Three healthcare professionals, with different backgrounds, acted as judges to adjudicate the causality categories for potential ADRs according to WHO-UMC system, in a Brazilian high complexity hospital. Judges' agreement was evaluated by using Fleiss' and Cohen's kappa coefficients. Results: Ninety potential ADRs identified in 300 participants were adjudicated by each judge, comprising a total of 270 assessments. Most potential ADRs were classified as probable or possible (77.8%). Fleiss´ kappa revealed slight concordance among judges (k = 0.096;CI:95%;0.01-0.18). Conclusions: Diverse backgrounds may have influenced the results for causality assessment of ADRs by employing the WHO-UMC system. Despite the slight concordance found for the method, this result suggests potential opportunity to enrich the ADRs management by engaging multiprofessional teams in the process. Further studies should be considered to investigate the performance of methods for ADRs assessment in hospitalized patients in low- and middle-income countries.

Preparedness of pharmacists to respond to the emergency of the COVID-19 pandemic in Brazil: a comprehensive overview.

The outbreak of COVID-19 in low- and middle-income countries is worrisome due to the social inequalities in these countries, their limited health budgets and the significant burden of other acute and chronic diseases. The leap in the number of cases in Brazil has imposed a huge strain on the healthcare system. We sought to provide a comprehensive overview of the challenges encountered by pharmacy services in responding to the COVID-19 pandemic emergency in Brazil and discuss the role of clinical pharmacists in this context. Pharmaceutical services play a key role in the emergency response to the pandemic. The pharmacy workforce has been actively working to manage drug shortages, redesign workflow, and review drug formularies/protocols to improve safety for patients and healthcare professionals (HCPs). COVID-19 patients may present high risk in the use of medications and clinical pharmacists can contribute substantially as part of a multidisciplinary team to improve outcomes in drug therapy in severe and critical illness. The participation of pharmacists as members of antimicrobial stewardship programs should be enhanced to ensure appropriate and safe use of antibiotics in this context. HCPs should be encouraged to seek improvements in the performance of pharmaceutical services and innovative practices to respond to the pandemic. Further studies are needed to generate knowledge on COVID-19 to improve patient care in vulnerable populations.

A simple and sensitive HPLC-FL method for simultaneous determination of angiotensin II receptor antagonists in human plasma.

Angiotensin II receptor antagonists are one of the most widely used classes of antihypertensive drugs. In this study, an HPLC fluorescence method after protein precipitation (PPT) extraction was developed and validated for determination of olmesartan, losartan, irbesartan, and valsartan in human plasma. The separation was carried out on a Luna cyano (250 × 4.6 mm i.d.; 5 µm particle size) column and the mobile phase was composed of acetonitrile and 0.1 % phosphoric acid in gradient elution, at a flow rate of 1.2 mL min-1. A PPT method was optimized by a two-level factorial design with triplicate at the central point. The parameters that could affect the extraction (sample volume and acetonitrile/plasma volume ratio) were evaluated and the method was compared to microextraction by packed sorbent (MEPS) and liquid-liquid extraction (LLE). The developed method allowed the simultaneous quantification of the analytes employing a simple and cheap sample preparation method and a short chromatographic run (13 min). This method was fully validated showing selectivity, precision, accuracy, and linearity over the range of 25.0-1500.0 ng mL-1 for olmesartan and valsartan, 25.0-2500.0 ng mL-1 for irbesartan, and 35.0-2500.0 ng mL-1 for losartan. Finally, the method was successfully applied in the analysis of human plasma from volunteers.

Acute kidney injury biomarkers in the critically ill.

Acute kidney injury (AKI) is a highly common complication in intensive care units (ICUs). Novel biomarkers might accelerate the detection and management of AKI. We performed a systematic review aiming to evaluate the performance of biomarkers for early AKI diagnosis in ICUs. MEDLINE, BVS, CINAHL, COCHRANE and EMBASE were searched for studies (2006-2019) on the use of biomarkers for AKI diagnosis. Preselected biomarkers were cystatin C, chitinase-3-like protein-1 (UCHI3L1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1) and interferon-gamma-inducible protein 10 (IP-10/CXCL-10), measured in plasma or urine. Eleven articles with total of 2,289 patients were included. The most cited biomarker was NGAL (n = 7 studies; 63.6%). Biomarkers with the highest sensitivity (se) and specificity (sp) were urinary heat shock protein (HSP-72) (se = 100%; sp = 90%) and urinary IL-18 (se = 92%; sp = 100%). All biomarkers' performance was influenced by the presence of comorbidities or AKI etiology. Although some biomarkers showed good performance, there was no externally validated biomarker for early AKI diagnosis. Thus, from this review, we did not indicate a novel biomarker to be promptly used in clinical practice. Prospective studies with a large number of patients are needed to expand knowledge in this field. PROSPERO registration number CRD42016037325.

Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects.

Warfarin exhibits a wide variation in dose requirements. We sought to evaluate the association of polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) and nongenetic factors with maintenance doses of warfarin <17.5 mg/week and to create an algorithm to predict drug sensitivity. This is a retrospective cohort study including 312 patients assisted at an anticoagulation clinic in Brazil. The mean age of participants was 60.4 ± 13.5 years and 59.9% were female. The logistic regression model included: age [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06], genotype VKORC1 AA (OR 31.61, 95% CI 11.20-100.15) and genotype CYP2C9 2/2, 2/3 or 3/3 (OR 16.48, 95% CI 3.37-81.79). The creation of our algorithm involved warfarin-experienced patients on stable doses, identifying factors associated with drug sensitivity. The validation of this algorithm allows its use in future populations to determine the initial dose distinguishing patients with dose requirements <17.5 mg and reducing time to achieve stable doses.

Adverse reactions to meglumine antimoniate in Brazilian inpatients with visceral leishmaniases: A case series.

WHAT IS KNOWN AND OBJECTIVES: Adverse drug reactions (ADR) related to the treatment of visceral leishmaniasis (VL) can cause severe clinical complications. We report a case series of ADR in hospitalized VL patients on meglumine antimoniate (MA). CASE DESCRIPTION: Seven cases of patients taking MA had at least one objective evidence for suspected ADR, including electrocardiographic, laboratory or clinical alteration. WHAT IS NEW AND CONCLUSION: Meglumine antimoniate is highly toxic. Adherence to treatment guidelines is important. Pharmacists working in multidisciplinary teams may contribute to early detection and management of MA therapy-related ADR.

Instruments for the assessment of patient adherence to oral anticoagulation with warfarin protocol for a systematic review.

BACKGROUND: Non-adherence can be highlighted as one of the main contributors to the occurrence of adverse events in patients treated with warfarin. The usefulness of self-reporting measures of drug adherence could be improved by following psychometric properties in the development of the measurement scales. Thus, we aimed to describe the protocol of a systematic literature review designed to investigate and describe validated instruments used to assess adherence to warfarin therapy. METHODS: We will perform a systematic review will include observational and experimental studies involving the use of validated instruments to assess adherence to warfarin therapy. Dimensions of adherence raised by the selected studies will be extracted to be compared. We will systematically search electronic databases including MEDLINE, LILACS, EMBASE, and Cochrane Library using a comprehensive strategy from inception to June 31, 2019. Two reviewers will revise the literature independently using a standardized form and assess the potential bias. After the comparison of results, discrepancies will be solved after the analysis of a third reviewer. RESULT: The development of the present systematic will help to summarize and evaluate the validated instruments that have been previously published to assess adherence to warfarin therapy. CONCLUSION: This review will substantiate the discussion of relevant topics that should be assessed while providing care to patients taking warfarin. This knowledge will enable a comprehensive approach for healthcare professionals to improve treatment outcomes and the design of future investigations. REGISTRATION: The systematic review is registered in the PROSPERO international prospective register of systematic review (PROSPERO# CRD42019128324).