Barriers and facilitators to implement the redispensing of unused oral anticancer drugs in clinical care: A hybrid-effectiveness type I study.

Background: Minimizing medication waste through the redispensing of oral anticancer drugs (OADs) that were unused by patients provides economic and environmental benefits, but this is not yet universally implemented in clinical care. ObjectiveS: To identify barriers and facilitators to the implementation of redispensing unused OADs in clinical care. Methods: A multicentre intervention study following a hybrid effectiveness-implementation type I design was conducted, consisting of semi-structured interviews with key stakeholders involved in the redispensing program: pharmacy employees, prescribing clinicians in oncology and haematology, patients who participated in redispensing and patients who declined trial participation. Questions encompassed experiences and suggestions for future implementation. The Consolidated Framework for Implementation Research (CFIR) guided data collection and categorisation of identified barriers and facilitators through thematic analysis. Results: In total, 35 interviews were conducted, identifying 15 themes encompassing barriers and facilitators, reflecting all CFIR domains. Facilitators encompassed: 1) convenient process requiring an acceptable time-investment; 2) support from project leaders and implementation champions; 3) being well-motivated by personal values and societal impact; 4) feeling ensured of medication quality upon redispensing; 5) endorsement by healthcare providers for patient participation; 6) clear and personal patient communication; 7) good visibility of intervention successes; and 8) implementation well supported through a collaborative network. Barriers encompassed: 1) unclear target population; 2) redispensing legally prohibited; 3) absence of financial compensation for pharmacies; 4) complexity arising from two parallel work processes; 5) widespread communication on adjustments within local teams challenging; 6) patient's low receptiveness due to burden of oncology treatment; and 7) lack of familiarization among pharmacy technicians. Conclusions: Facilitators for implementation of redispensing unused drugs mainly related to people's values, motivation, and societal demand, whereas barriers mainly encompassed practical issues, including knowledge, time, financial resources, and legal conditions. Strategies emphasizing the benefits of redispensing and further streamlining process compatibility could support implementation.

Medication Adherence to Direct Oral Anticoagulants: Extent and Impact of Side Effects.

Purpose: Arterial and venous thromboembolism are a leading cause of mortality. Direct oral anticoagulants (DOACs) are highly effective in both stroke prevention and prevention of venous thrombotic events. Medication adherence is a prerequisite for optimal protection against thromboembolic complications. Recent studies have shown that good adherence cannot be taken for granted by DOACs. In this cross-sectional study adherence among DOAC users was investigated and associations between beliefs about medication, perceived side effects and adherence were explored. Patients and Methods: We included 100 randomly selected adult DOAC users visiting one of the two participating Dutch community pharmacies in the summer of 2020. The self-reported adherence (primary outcome) was assessed with the Medication Adherence Rating Scale-5 (MARS-5) using three different cut-off scores. Beliefs about DOACs were assessed with the Beliefs about Medicine Questionnaire Specific (BMQ-S), while side effects and side effect burden were assessed with a self-developed questionnaire based on the Lareb Intensive Monitoring (LIM) system. Results: Of the participants, 9% reported non-adherence on the primary MARS-5 cut-off score <24. For the MARS-5 scores <23 and <25 non-adherence percentages of, respectively, 3 and 33% were calculated. Associations were found between adherence and both side effects and side effect burden, regardless of the MARS-5 cut-off score. Bruising and minor bleeds were the most reported side effects (both 20%). For all patients, the necessity beliefs outweighed the concern beliefs. No associations were found between adherence and either gender, indication, DOAC or dosage. Conclusion: This study confirms that adherence in patients on DOACs cannot be taken for granted. High necessity beliefs do not guarantee good adherence, as side effects impair adherence even in patients having high necessity beliefs. Therefore, we recommend that both physicians and pharmacists evaluate both adherence and side effects with these patients on a regular base.

The issue Thrombosis affects many people. Complications like stroke and lung embolism are a major cause of health damage, disability and even death. Direct oral anticoagulants (DOACs) are highly effective drugs at preventing these complications. However, patients need to take their medication properly to get the best protection. Recent studies showed that not all patients consistently take their DOACs. What's new? In this study, we discovered that patients experiencing bothersome side effect were less likely to stick to their medication schedule. The most common side effects reported were bruising and minor bleeding, by 20% each. There were no differences in how well patients took their medication based on gender, medical condition, type of DOAC or prescribed dosage. Most patients believed their medication was necessary for their health. Why is this important? This study shows that side effects hinder patients taking their medication correctly even when they believe their medication is necessary for their health. This means that patients on DOAC therapy who experience side effects may be less protected against stroke and lung embolism. Therefore, we recommend that doctors and pharmacists regularly check in with patients about any side effects they experience and how consistently they take their DOACs. What's next? This study highlights the importance of developing, testing, and implementing practical tools to find and help patients who do not take their DOACs correctly, to ensure they are better protected against blood clots.

Quantification of longitudinal patient-reported burden of adverse drug reactions attributed to the use of TNF-α inhibitors in inflammatory rheumatic diseases: an observational prospective cohort study.

BACKGROUND: There is a lack of knowledge on patient perspectives on adverse drug reactions (ADRs) attributed to the use of biologics. The aim of this study is to quantify the burden over time of ADRs attributed to TNF-α inhibitors in patients with inflammatory rheumatic diseases (IRDs) and investigate whether the burden over time differs between different types of ADRs. RESEARCH DESIGN AND METHODS: Data were used from the Dutch Biologic Monitor (DBM), an observational prospective cohort study for patient-reported ADRs attributed to biologics. Patients with an IRD using a TNF-α inhibitor reporting an ADR, lasting for three consecutive questionnaires, were included. Questionnaires were sent every 2 months and the burden was scored on a 5-point Likert-type scale. Burden scores were analyzed using linear mixed models. RESULTS: Data from 166 unique patients reporting 274 ADRs were included. The burden score decreased every month by 0.29 points (95% CI -0.34 - -0.24) on average on a 5-point Likert-type scale. The burden score for infections and infestations decreased significantly faster than the burden score for injection site reactions. CONCLUSIONS: Patient-reported burden of ADRs attributed to the use of a TNF-α inhibitor in patients with IRDs decreased significantly over time, especially for infections and infestations.

Patient reported medication-related problems, adherence and waste of oral anticancer medication over time.

OBJECTIVES: Patients on oral anticancer therapy regularly experience medication-related problems (MRPs), potentially leading to non-adherence and medication waste. Most studies reporting these experiences have cross-sectional designs. The aim of our study was to explore patient reported MRPs, adherence and waste of oral anticancer medication over time. METHODS: A prospective longitudinal quantitative interview study with 4 months follow-up was performed among patients on oral anticancer medication (mainly tyrosine kinase inhibitors, (anti)hormonal therapy, pyrimidine antagonists) using a semi-structured questionnaire. Patients from two Dutch university medical centres were included from March to December 2022 after informed consent was given. Four interviews were performed with 1 month in between. All interviews were audiotaped, after which the data were entered into an electronic case report form. The primary outcome was the mean number of MRPs per patient per interview round. Secondary outcomes were the proportion of patients with at least one MRP, types of MRPs, perceived non-adherence, medication waste (both in general and specifically for anticancer medication), costs of anticancer medication waste, and factors associated with medication waste as mentioned by the patient. Descriptive statistics were used to analyse the data. RESULTS: Forty patients were included with a mean (SD) age of 64 (9) years; 43% were male. The mean number of MRPs per patient was 2.1 in the first interview and 1.2, 1.0 and 0.9 in the second, third and fourth interviews, respectively. Adverse drug reactions were the most frequently reported type of MRPs (30 (75%) patients in the first interview and 19 (65%) in the last interview). Unintentional non-adherence was regularly reported, especially in the first interview. Medication changes were frequent and associated medication waste was mentioned in all interviews. CONCLUSIONS: Many patients using oral anticancer treatment report MRPs and this number remains substantial over time.

Model-Informed Precision Dosing Using Machine Learning for Levothyroxine in General Practice: Development, Validation and Clinical Simulation Trial.

Levothyroxine is one of the most prescribed drugs in the western world. Dosing is challenging due to high-interindividual differences in effective dosage and the narrow therapeutic window. Model-informed precision dosing (MIPD) using machine learning could assist general practitioners (GPs), but no such models exist for primary care. Furthermore, introduction of decision-support algorithms in healthcare is limited due to the substantial gap between developers and clinicians' perspectives. We report the development, validation, and a clinical simulation trial of the first MIPD application for primary care. Stable maintenance dosage of levothyroxine was the model target. The multiclass model generates predictions for individual patients, for different dosing classes. Random forest was trained and tested on a national primary care database (n = 19,004) with a final weighted AUC across dosing options of 0.71, even in subclinical hypothyroidism. TSH, fT4, weight, and age were most predictive. To assess the safety, feasibility, and clinical impact of MIPD for levothyroxine, we performed clinical simulation studies in GPs and compared MIPD to traditional prescription. Fifty-one GPs selected starting dosages for 20 primary hypothyroidism cases without and then with MIPD 2 weeks later. Overdosage and underdosage were defined as higher and lower than 12.5 µg relative to stable maintenance dosage. MIPD decreased overdosage in number (30.5 to 23.9%, P < 0.01) and magnitude (median 50 to 37.5 µg, P < 0.01) and increased optimal starting dosages (18.3 to 30.2%, P < 0.01). GPs considered lab results more often with MIPD and most would use the model frequently. This study demonstrates the clinical relevance, safety, and effectiveness of MIPD for levothyroxine in primary care.

Elevating the Standard of Care for Patients with Axial Spondyloarthritis: 'Calls to Action' from Rheumacensus, a Multistakeholder Pan-European Initiative.

INTRODUCTION: Several barriers to optimal care in axial spondyloarthritis (axSpA) exist, which is detrimental to patient outcomes. The Rheumacensus programme aimed to identify how the standard of care (SoC) and treatment ambition for patients with axSpA could be elevated, from the unique perspective of three key stakeholders from across Europe: patients, healthcare professionals (HCPs) and payors. METHODS: Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in axSpA and an area of focus, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting to generate 'Calls to Action' (CTA) to highlight the changes needed to elevate the SoC for patients with axSpA. RESULTS: The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was patient empowerment through education on the disease and treatment options available, to enable patient involvement in management and ultimately increase treatment adherence. Four key themes emerged from the Delphi process: patient empowerment, patient knowledge, patient-HCP consultations and optimal initial treatment. These themes informed 11 overarching CTA, which demonstrate the need for a multistakeholder approach to implement a paradigm shift towards patient-centred care to elevate health outcomes in patients with axSpA. CONCLUSION: Rheumacensus identified CTA to help bridge the disparities observed in axSpA care. It is now imperative for all stakeholders to take practical steps towards addressing these CTA to elevate the SoC and treatment ambition in patients with axSpA.

Axial spondyloarthritis (axSpA) is a long-term inflammatory disease involving the spine and other joints of the body as well as where tendons and ligaments attach to bone. AxSpA is associated with a significant burden to patients which can be worsened by delays in diagnosis and poor disease management. This report is about a programme called Rheumacensus which has the overall aim of improving the standard of care (SoC) for patients with axSpA. Rheumacensus brings together the points of view of three key groups involved in the care of people with axSpA: patients, payors and healthcare professionals (HCPs) from across Europe. Together, these three groups agreed to focus on patient empowerment through education on the disease and treatment options to effectively enhance treatment adherence, as a way to raise the SoC. Through a series of exercises­to agree on the current SoC and what needs to be improved­and group discussions, four themes were established which were used by the groups to help them suggest 'Calls to action' (CTA). The CTAs were ideas of how improvements could be made or what needs to be done to improve the care patients receive. The four themes were (1) patient empowerment, (2) patient knowledge, (3) patient­HCP consultation and (4) optimal initial treatment. In total, 11 CTAs were developed across these themes that provide direction and practical next steps which patients, payors and HCPs could take to drive change and make a real difference to patients by improving their care.

Long-term clinical and radiological effectiveness and safety of ultralow doses of rituximab in rheumatoid arthritis: observational extension of the REDO trial.

BACKGROUND: The REDO trial (REtreatment with Rituximab in RhEmatoid arthritis: Disease Outcome after Dose Optimisation) showed similar disease activity for retreatment with ultralow doses (200 mg and 500 mg per 6 months) compared with standard low-dose rituximab (RTX, 1000 mg per 6 months). We performed an observational extension study of the REDO trial to assess long-term effectiveness. METHODS: Patients from the REDO trial were followed from start of the trial to censoring in April 2021. RTX use was at the discretion of patient and rheumatologist using treat to target. The primary outcome was disease activity (disease activity score in 28 joints C-reactive protein (DAS28-CRP)), analysed using a longitudinal mixed model by original randomisation and time-varying RTX dose. The original DAS28-CRP non-inferiority (NI) margin of 0.6 was used. RTX dose and persistence, safety and radiological outcomes were also assessed. FINDINGS: Data from 126 of 142 REDO patients was collected from 15 December 2016, up to 30 April 2021. Drop-outs continued treatment elsewhere (n=3) or did not consent (n=13).Disease activity did not differ by original randomisation group: 1000 mg mean DAS28-CRP (95% CI) of 2.2 (2.0 to 2.5), 500 mg 2.3 (2.1 to 2.4) and 200 mg 2.4 (2.2 to 2.5). Lower time-varying RTX dose was associated with higher DAS28-CRP (0.22 (95% CI 0.05 to 0.40) higher for 200 mg/6 months compared with 1000 mg/6 months), but remained within the NI-margin. RTX persistence was 93%. Median RTX dose was 978 mg (IQR 684-1413) per year, and no association was found between RTX dose and adverse events or radiological damage. INTERPRETATION: Long-term use of ultralow doses of RTX is effective in patients with rheumatoid arthritis responding to standard dose RTX.

Effect of a smart temperature logger on correctly storing biological disease-modifying antirheumatic drugs at home: a pre-post study.

OBJECTIVES: Biological disease-modifying antirheumatic drugs (bDMARDs) require specific storage temperatures, but are frequently stored outside the recommended range of 2-8°C. As incorrect storage may affect therapy effectiveness and consequently lead to higher disease activity, compliance with recommended storage temperatures should be improved. eHealth interventions can provide insight into storage temperatures and alerts in case of deviations from recommended temperatures. Therefore, this study aims to assess the effect of a smart temperature logger on correctly storing bDMARDs at home by patients with rheumatic diseases. METHODS: A pre-post study was performed in a hospital in the Netherlands. The baseline period consisted of 12 weeks of storage temperature measurement with a passive temperature logger, and the intervention period consisted of 12 weeks of storage temperature measurement with a smart temperature logger. This smart logger included a smartphone application which provided insight into storage temperatures and real-time alerts when exceeding recommended temperatures. The main outcome measure was the difference in the number of patients who stored their bDMARDs correctly between baseline and intervention. Secondary outcomes were the difference in the proportion of measurement time within 2-8°C between baseline and intervention, the distribution of measurement time among temperature categories, and the patient's acceptance measured using a questionnaire based on the Technology Acceptance Model. RESULTS: In total, 48 participants (median age 55 years (IQR 47-64), 53% male) were analysed. The proportion of participants correctly storing bDMARDs increased from 18.8% (n=9) during baseline to 39.6% (n=19) during intervention (p=0.004). The median proportion of measurement time between 2-8°C improved by 6% (IQR 0-34%) (p<0.0001). Technology acceptance was scored as moderate. CONCLUSIONS: Temperature monitoring and real-time feedback with a smart temperature logger shows potential to improve at-home storage of bDMARDs, provided that continuous connection is realised to ensure real-time alerts and data collection.

The Use of Remote Consultations and Associated Factors in Rheumatology: A Large Retrospective Cohort Study of Follow-Up Consultations Before, During, and After COVID-19.

OBJECTIVE: To investigate the use of remote consultations (RCs) and the influence of consultation, health care provider (HCP), and patient characteristics on the choice for remote or face-to-face consultation. METHODS: A monocenter retrospective cohort study was conducted on follow-up consultations of patients with rheumatic diseases from January 1, 2019 to January 16, 2023, using data from electronic health records. Trends in the proportion of RCs before, during, and after COVID-19 were studied. Cross-classified multilevel logistic regression models were built to account for clustering of consultations (level 1) within both patients and HCPs (level 2). The influence of consultation, patient, and HCP characteristics on the type of consultation was assessed. RESULTS: 157,028 consultations of 30,215 unique patients seen by 64 HCPs were included in the data set. After an initial sharp increase in RC use at the beginning of the COVID-19 pandemic, the proportion of RCs decreased toward a seemingly steady state at around 30%. 90% of the variance in the use of RCs can be attributed to the consultation level, whereas 4% and 6% can be attributed to the patient and HCP level. Longer consultation durations and time since last consultation decreased the odds for a RC, as did higher patient age, shared care, and longer disease duration. Higher travel distance, consultation density, and patient digital access increased the odds for a RC. CONCLUSION: The COVID pandemic resulted in a structural increase in the use of RCs. Although several patient characteristics are associated with the type of consultation, most variance resulted from consultation characteristics compared with patients and HCPs.

Cost Savings and Waste Reduction Through Redispensing Unused Oral Anticancer Drugs: The ROAD Study.

Importance: New strategies targeting waste are required to improve financial and ecologic sustainability of expensive therapies, such as oral anticancer drugs, that frequently remain unused by patients. Redispensing unused oral anticancer drugs seems to be a promising strategy when drug quality is guaranteed. Objectives: To determine the waste reduction and net cost savings attained by redispensing oral anticancer drugs that go unused by patients compared with the standard practice of disposal. Design, Settings, and Participants: The ROAD study was a prospective single-group intervention conducted in the outpatient pharmacies of 4 hospitals in the Netherlands from February 1, 2021, to February 1, 2023, with 12-month follow-up of each patient. Patients with cancer and who had a prescription for an oral anticancer drug that could be stored at room temperature were included. Of 2426 eligible patients, 602 did not consent and 601 did not respond. Data analyses were performed from August 25, 2022, to April 19, 2023. Intervention: Participants received oral anticancer drugs for use at home in special packaging (ie, sealed packaging with time-temperature indicator), to be returned to the pharmacy should these remain unused. The pharmacy ensured quality of returned drugs based on authenticity, appearance, remaining shelf life and adequate storage temperature. Drugs fulfilling quality requirements were redispensed to other patients. Main Outcome and Measure: Total waste reduction and mean net annual cost savings per patient compared with the standard practice of disposal. Optimization of cost savings was explored by introducing variations in the quality assurance procedure and patient population. All analyses used the average exchange rate for 2021 €1 = US $1.18. Results: Of 1223 patients with cancer who consented, 1071 participated (median [IQR] age, 70 [62-75] years; 622 [58.1%] were male). In all, 171 patients (16.0%; 95% CI, 13.8%-18.3%) returned 335 unused oral anticancer drug packages. Of the returned drugs, 228 packages were redispensed, which reduced waste by 68.1% (95% CI, 67.7%-68.5%) compared with the standard practice (disposal). Redispensing unused oral anticancer drugs comprised 2.4% (95% CI, 2.2%-2.5%) of total drug costs, providing mean net annual cost savings of US $680 (95% CI, $524-$837) up to $1591 (95% CI, $1226-$2002) per participant. Conclusions and Relevance: The findings of this multicenter intervention study indicate that redispensing unused oral anticancer drugs is associated with waste reduction and cost savings, which in turn may improve the affordability and sustainability of cancer treatment. Trial Registration: World Health Organization International Clinical Trials Registry Platform Identifier: NL9208.

The correlation between 4 adherence measurements methods in patients with rheumatoid arthritis using methotrexate.

AIMS: Methotrexate (MTX) is the cornerstone in the treatment of rheumatoid arthritis (RA) patients. However, adherence to MTX therapy is not optimal, and instruments to assess medication nonadherence are warranted. To date there is no consensus on the best method to determine adherence to MTX. The aim of this study was to assess the correlation between adherence assessed with a Medication Event Monitoring System (MEMS) vs. pill count, MTX-polyglutamate (PG) concentration and Compliance Questionnaire-Rheumatology (CQR) in patients with established RA. Second, the correlations between these methods and the Disease Activity Scores of 28 joints (DAS28) were examined. METHODS: Adult RA patients currently treated with MTX were included. Multivariable linear and logistic regression were used, with adherence assessed with MEMS as dependent variable vs. pill count, MTX-PG concentrations, CQR as independent variables and DAS28 vs. each of the 4 adherence measurements. Covariates were included, such as comedication, age and use of corticosteroids. RESULTS: In total, 190 consecutive RA patients were included. Pill count was correlated with adherence assessed with MEMS (linear regression, ß = 0.588, 95% confidence interval = 0.255-0.921, P < .001), whereas CQR and MTX-PGs were not. Logistic regression confirmed the correlation between dichotomized adherence and pill count only (ß = 4.47, 95% confidence interval = 1.31-7.64, P =  .006). No other correlations were found, either for all adherence outcomes or DAS28. CONCLUSION: Measuring adherence with MEMS is correlated with pill count, whereas other methods were not correlated with MEMS or with DAS28. Pill count can be used to estimate adherence to MTX therapy, in case MEMS is not achievable.

Long-term postoperative opioid use in orthopaedic patients.

BACKGROUND: The prevalence of long-term opioid use after orthopaedic surgery varies from 1.4% to 24% and has mostly been studied with prescription data, making it difficult to estimate the size and impact of the problem. This study aims to assess the prevalence and predictors of long-term postoperative opioid use in a high volume and tertiary orthopaedic centre by using online patient reported measures. METHODS: This Dutch prospective cohort study was conducted among adult patients who underwent any type of orthopaedic surgery from June to August 2021. Six months after surgery patients were invited to complete an online survey on current opioid use and patients' willingness to taper opioids. The demographics, clinical factors and preoperative opioid use were extracted from the patient file. RESULTS: In total, 607 patients (mean age 61.2 years, 63.4% female) completed the survey. Seventy-six patients (12.5%) used opioids 6 months after surgery of which 20 (3.3%) did not use opioids before surgery. The median (Q1-Q3) postoperative daily dose after 6 months was 29.9 mg (10.0-76.1) morphine equivalents. Most of them (88.2%) wanted to taper opioids. Affected body region (OR's: 6.84-12.75) and pre-operative opioid use (OR = 35.33) were significant predictors of long-term opioid use. CONCLUSION: The prevalence of long-term postoperative opioid use was 12.5%; one in thirty patients became a new long-term opioid user. Pre-operative opioid use and affected body region were predictive for long-term opioid use. These findings, together with the observation that long-term opioid users want to taper opioids, emphasize the relevance of prevention, recognition and tapering support in the perioperative setting. LEVEL OF EVIDENCE: Level II. SIGNIFICANCE: Short-term opioid use can unintentionally progress to long-term opioid use. The prevalence of long-term opioid use after orthopaedic surgery varies widely and is mostly prescription-based, making it difficult to estimate the magnitude of the problem. This study assessed long-term postoperative opioid use in a full breadth orthopaedic population using patient reported measures, making conclusions much more robust. The prevalence of long-term postoperative opioid use in this study was 12.5%.

Implementing medication adherence interventions in four Dutch living labs; context matters.

BACKGROUND: Despite the abundant availability of effective medication adherence interventions, uptake of these interventions into routine care often lacks. Examples of effective medication adherence interventions include telephone counseling, consult preparation and the teach-back method. Assessing context is an important step in understanding implementation success of interventions, but context is often not reported or only moderately described. This study aims to describe context-specific characteristics in four living labs prior to the implementation of evidence-based interventions aiming to improve medication adherence. METHODS: A qualitative study was conducted within four living labs using individual interviews (n = 12) and focus groups (n = 4) with project leaders and involved healthcare providers. The four living labs are multidisciplinary collaboratives that are early adopters of medication adherence interventions in the Dutch primary care system. Context is defined as the environment or setting in which the proposed change is to be implemented. Interview topics to assess context were formulated based on the 'inner setting' and 'outer setting' domains of the Consolidated Framework for Implementation Research (CFIR). Interviews were recorded and transcribed verbatim. Transcripts were deductively analyzed. RESULTS: A total of 39 community pharmacists, pharmacy technicians, general practitioners and a home care employee participated in the (focus group) interviews. All four living labs proved to be pharmacy-driven and characterized by a high regard for innovation by staff members, a positive implementation climate, high levels of leadership engagement and high compatibility between the living labs and the interventions. Two living labs were larger in size and characterized by more formal communication. Two living labs were characterized by higher levels of cosmopolitanism which resulted in more adaptable interventions. Worries about external policy, most notably lack of reimbursement for sustainment and upscaling of the interventions, were shared among all living labs. CONCLUSIONS: Contextual characteristics of four living labs that are early adopters of medication adherence interventions provide detailed examples of a positive implementation setting. These can be used to inform dissemination of medication adherence interventions in settings less experienced in implementing medication adherence interventions.

Preferences of Patients With Musculoskeletal Disorders Regarding the Timing and Channel of eHealth and Factors Influencing Its Use: Mixed Methods Study.

BACKGROUND: Implementation of eHealth is progressing slowly. In-depth insight into patients' preferences and needs regarding eHealth might improve its use. OBJECTIVE: This study aimed to describe when patients want to use eHealth, how patients want to communicate and receive information digitally, and what factors influence the use of eHealth in clinical practice. METHODS: A multimethod study was conducted. Two meetings of ~5.5 hours with plenary information sessions and focus groups were held with 22 patients from the rheumatology, orthopedics, and rehabilitation departments of a Dutch hospital specialized in musculoskeletal disorders. Assignments were performed during the focus groups in which qualitative (eg, semistructured interview questions) and quantitative (ie, voting and ranking factors) data were collected. RESULTS: The way patients want to use eHealth varies between patients and moments of a patient's care pathway. Patients' digital channel preferences depended on the need for interaction with a health care provider (HCP). The interaction need is in turn influenced by the degree to which information or communication is specific to an individual patient and leads to consequences for the patient. The 5 most important factors influencing the use of eHealth were access to medical information (eg, electronic health records), perceived control over disease management, correctness and completeness of information, data security, and access to information or an HCP at any time. The 5 least important factors influencing eHealth use were help with using digital devices, having internet or equipment, digital skills, attitude or emotions toward eHealth, and societal benefits. CONCLUSIONS: Patients identified opportunities for using eHealth during all moments of their care pathway. However, preferences for eHealth varied between patients and phases in the care pathway. As a consequence, eHealth should be tailored to fit individual patients' preferences but also the need for interaction regarding different topics by offering a variety of digital channels with a gradient of interaction possibilities. Furthermore, digital skills and access to the internet might become less important to focus on in the future. Improving eHealth use by patients may be achieved by providing patients access to correct and safe (medical) information and more control over their care.

Impaired cardiac structure and systolic function in athletes using supra-physiological doses of anabolic androgenic steroids.

OBJECTIVES: Athletes are increasingly using supra-physiological doses of anabolic androgenic steroids without weighing health side effects. This study aims to conjointly evaluate the effect of supraphysiological doses of anabolic androgenic steroids on global cardiovascular structure and functional capacity. DESIGN: Cross-sectional study. METHODS: 92 males enrolled in the study, including 18 sedentary subjects, 26 anabolic androgenic steroid non-user athletes, and 48 anabolic androgenic steroid-user athletes. Two-dimensional echocardiography was done to evaluate the cardiovascular structure and function. RESULTS: Anabolic androgenic steroid-users presented increased cardiac remodeling of the left ventricle and left atrium compared to control groups (p < 0.001). Anabolic androgenic steroid-users showed increased left ventricular mass/body surface area versus control groups (p < 0.001), with 28 steroid-users (58.3 %) having cardiac remodeling, which is more than control groups (p < 0.001). Anabolic androgenic steroid-users presented lower diastolic function (E and E/A) compared to non-users (p = 0.003 and <0.001, respectively). Ejection fraction was decreased among anabolic androgenic steroid-users versus the sedentary group only (p = 0.020), while anabolic androgenic steroid-users presented reduced global longitudinal strain of 15.43 % compared to both control groups (p < 0.001). Moreover, anabolic androgenic steroid-users experienced more tricuspid valve regurgitation (p = 0.001). CONCLUSIONS: Anabolic androgenic steroid consumption is associated with global cardiac remodeling with increased dimensions of the left ventricle, and atrium. Anabolic androgenic steroid-users present left ventricular hypertrophy with reduced subclinical systolic function. Moreover, anabolic androgenic steroid consumption is correlated with valve regurgitation and dilation of the sino-tubular junction.

Development of a Framework Structuring Themes in the Course of Adverse Drug Reactions from a Patient's Perspective.

INTRODUCTION: There is a need for more extensive information about adverse drug reactions (ADRs) for patients than currently available, including information on the course of ADRs. Aspects characterising the course of ADRs from the patient perspective have not been identified before. OBJECTIVE: We aimed to develop a framework based on common themes in the course of ADRs identified from patient descriptions in patient-reported ADRs. METHODS: In this qualitative study, patient descriptions of the course of patient-reported ADRs were analysed by a thematic analysis with an inductive approach using three different existing datasets containing patient-reported ADRs. Two datasets included patient-reported ADRs from cohort event monitoring of biologics and direct oral anticoagulants and one dataset included spontaneous reports from patients concerning medication for lower urinary tract symptoms. A conceptual framework was developed from the identified main themes and subthemes. RESULTS: Patient-reported data concerning 3888 ADRs were analysed. Six main themes with multiple subthemes were identified from patient descriptions of the course of ADRs. Four themes were descriptive: frequency of an ADR episode, duration of an ADR episode, moment or period of ADR occurrence, and development in the intensity of the ADR. Two themes concerned factors influencing the course of ADRs: triggering factors and improving factors. CONCLUSIONS: The presented framework illustrates that patients describe extensive details on the course and timeframe of ADRs. The identified themes provide a basis for improving the systematic data collection of more extensive details about ADRs from patients as a first step towards the provision of more comprehensive ADR information to patients.

Factors Influencing Preferences of Patients With Rheumatic Diseases Regarding Telehealth Channels for Support With Medication Use: Qualitative Study.

BACKGROUND: Patients with rheumatic diseases are known to experience drug-related problems at various times during their treatment. As these problems can negatively influence patients' health, they should be prevented or resolved as soon as possible, for which patients might benefit from additional support. Telehealth has the potential to continuously provide information and offers the possibility to easily contact a health care provider in order to support patients with medication use. Knowledge of factors influencing the patient's preference for telehealth channels can improve the actual use of telehealth channels. OBJECTIVE: This study aims to identify factors that influence the preferences of patients with rheumatic diseases regarding telehealth channels for support with medication use. METHODS: A qualitative study with face-to-face interviews was performed among patients with an inflammatory rheumatic disease in the Netherlands. A total of 4 telehealth channels were used: a frequently asked questions page, a digital human, an app for SMS text messaging with health care providers, and an app for video-calling with health care providers. Using a semistructured interview guide based on domains of the Capability, Opportunity, Motivation, and Behavior (COM-B) model, participants were questioned about (1) their general opinion on the 4 telehealth channels, (2) factors influencing preference for individual telehealth channels, and (3) factors influencing preference for individual telehealth channels in relation to the other available channels. Interviews were recorded, transcribed, and categorically analyzed. RESULTS: A total of 15 patients were interviewed (female: n=8, 53%; male: n=7, 47%; mean age 55, SD 16.8 years; median treatment duration of 41, IQR 12-106 months). The following 3 categories of factors influencing patient preference regarding telehealth channels were identified: (1) problem-related factors included problems needing a visual check, problems specifically related to the patient, and urgency of the problem; (2) patient-related factors included personal communication preference and patient characteristics; and (3) channel-related factors included familiarity with the telehealth channel, direct communication with a health care provider, methods of searching, and conversation history. CONCLUSIONS: Preference for telehealth channels is influenced by factors related to the problem experienced, the patient experiencing the problem, and telehealth channel characteristics. As the preference for telehealth channels varies between these categories, multiple telehealth channels should be offered to enable patients to tailor the support with their medication use to their needs.

Non-Medical Switching from Tocilizumab to Sarilumab in Rheumatoid Arthritis Patients with Low Disease Activity, an Observational Study.

Tocilizumab and sarilumab are IL-6-receptor antagonists registered for rheumatoid arthritis (RA), with equal effectiveness and safety. Switching from tocilizumab to sarilumab could be a strategy to reduce injection burden, in case of drug shortages, and to reduce costs. This study therefore aims to investigate the effectiveness and safety of switching patients with RA with well-controlled disease under tocilizumab treatment to sarilumab. Patients with RA with low Disease Activity Score 28 (DAS28;-CRP < 2.9 or < 3.5 with clinical judgment), on stable dose tocilizumab (> 6 months) were offered to switch to sarilumab. Patients who switched and consented were followed for 6 months. Sarilumab was started at 200 mg and double the last tocilizumab interval. Co-primary outcomes at 6 months were (i) the 90% confidence interval (CI) of DAS28-CRP change from baseline compared with the non-inferiority margin of 0.6 and (ii) the 90% CI of the proportion of patients persisting with sarilumab, compared with a prespecified minimum of 70%. Of 50 invited patients, 25 agreed to switch to sarilumab, and 23 patients switched and were included. One patient was lost to follow-up immediately after inclusion, therefore 22 patients are included in the analyses. At 6 months, mean change in DAS28-CRP was 0.48 (90% CI: 0.11-0.87), compared with the non-inferiority margin of 0.6. Sarilumab persistence was 68% (90% CI: 51-82%, 15 out of 22 patients), compared with the prespecified minimum of 70%. Non-medical switching from tocilizumab to sarilumab in patients doing well on tocilizumab failed to show non-inferiority regarding disease activity and drug persistence.

How to engage healthcare providers in preventing medication waste through individualized prescribing and dispensing: A qualitative study.

BACKGROUND: Medication waste is a threat to healthcare's sustainability. To prevent medication waste in patients' homes, medication quantities prescribed and dispensed to patients could be individualized. Perspectives of healthcare providers on engaging in this strategy however remain unclear. OBJECTIVE(S): To identify factors influencing healthcare providers in preventing medication waste through individualized prescribing and dispensing. METHODS: Individual semi-structured interviews were conducted via conference calls with pharmacists and physicians prescribing and dispensing medication to outpatients of eleven Dutch hospitals. An interview guide based on the Theory of Planned Behaviour was developed. Questions related to participant's view on medication waste, current prescribing/dispensing behaviour and intention to personalising prescribing/dispensing quantities. Data was thematically analysed, following a deductive approach based on the Integrated Behavioural Model. RESULTS: Nineteen out of 45 (42%) healthcare providers were interviewed, of whom eleven were pharmacists and eight physicians. Factors influencing individualized prescribing and dispensing by healthcare providers were identified and categorized in seven themes: (1) attitude: beliefs about consequences of waste, as well as perceived benefits and concerns of the intervention; (2) perceived norm: professional and social responsibilities; (3) personal agency: available resources; (4) knowledge and skills: intervention complexity; (5) salience of behaviour: perceived need from past experiences and evaluation of actions; (6) habit: prescribing and dispensing habits; and (7) situational factors: support for change, momentum for sustainable actions, need for guidance, triad collaboration and information provision. CONCLUSIONS: Healthcare providers perceive a strong professional and social responsibility to prevent medication waste yet feel bound by limited resources available to engage in individualized prescribing and dispensing. Situational factors, including leadership, organizational awareness and strong collaborations, could help healthcare providers to engage in individualized prescribing and dispensing. Through the identified themes, this study offers directions for designing and implementing an individualized prescribing and dispensing program to prevent medication waste.

Association of Low-Dose Colchicine With Incidence of Knee and Hip Replacements : Exploratory Analyses From a Randomized, Controlled, Double-Blind Trial.

BACKGROUND: Osteoarthritis is a major contributor to pain and disability worldwide. Given that inflammation plays an important role in the development of osteoarthritis, anti-inflammatory drugs may slow disease progression. OBJECTIVE: To examine whether colchicine, 0.5 mg daily, reduces incident total knee replacements (TKRs) and total hip replacements (THRs). DESIGN: Exploratory analysis of the LoDoCo2 (Low-Dose Colchicine 2) randomized, controlled, double-blind trial. (Australian New Zealand Clinical Trials Registry: ACTRN12614000093684). SETTING: 43 centers in Australia and the Netherlands. PATIENTS: 5522 patients with chronic coronary artery disease. INTERVENTION: Colchicine, 0.5 mg, or placebo once daily. MEASUREMENTS: The primary outcome was time to first TKR or THR since randomization. All analyses were performed on an intention-to-treat basis. RESULTS: A total of 2762 patients received colchicine and 2760 received placebo during a median follow-up of 28.6 months. During the trial, TKR or THR was performed in 68 patients (2.5%) in the colchicine group and 97 (3.5%) in the placebo group (incidence rate, 0.90 vs. 1.30 per 100 person-years; incidence rate difference, -0.40 [95% CI, -0.74 to -0.06] per 100 person-years; hazard ratio, 0.69 [CI, 0.51 to 0.95]). In sensitivity analyses, similar results were obtained when patients with gout at baseline were excluded and when joint replacements that occurred in the first 3 and 6 months of follow-up were omitted. LIMITATION: LoDoCo2 was not designed to investigate the effect of colchicine in osteoarthritis of the knee or hip and did not collect information specifically on osteoarthritis. CONCLUSION: In this exploratory analysis of the LoDoCo2 trial, use of colchicine, 0.5 mg daily, was associated with a lower incidence of TKR and THR. Further investigation of colchicine therapy to slow disease progression in osteoarthritis is warranted. PRIMARY FUNDING SOURCE: None.