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.

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.

The added value of predictive biomarkers in treat-to-target strategies for rheumatoid arthritis patients: a conceptual modelling study.

OBJECTIVES: To quantify the additional value of a hypothetical biomarker predicting response to treatment for RA regarding efficacy and costs by using a modelling design. METHODS: A Markov model was built comparing a usual care T2T strategy with a biomarker-steered strategy for RA patients starting biologic therapy. Outcome measures include time spent in remission or low disease activity (LDA) and costs. Four additional scenario analyses were performed by varying biomarker or clinical care characteristics: (i) costs of the biomarker; (ii) sensitivity and specificity of the biomarker; (iii) proportion of eligible patients tapering; and (iv) medication costs. RESULTS: In the base model, patients spent 2.9 months extra in LDA or remission in the biomarker strategy compared with usual care T2T over 48 months. Total costs were €43 301 and €42 568 for, respectively, the usual care and biomarker strategy, and treatment costs accounted for 91% of total costs in both scenarios. Cost savings were driven due to patients in the biomarker strategy experiencing remission or LDA earlier, and starting tapering sooner. Cost-effectiveness was not so much driven by costs or test characteristics of the biomarker (scenario 1/2), but rather by the level of early and proactive tapering and drug costs (scenarios 3/4). CONCLUSIONS: The use of a biomarker for prediction of response to b/tsDMARD treatment in RA can be of added value to current treat-to-target clinical care. However, gains in efficacy are modest and cost gains are depending on a combination of early proactive tapering and high medication costs.

Seroconversion after a third COVID-19 vaccine is affected by rituximab dose but persistence is not in patients with rheumatoid arthritis.

OBJECTIVES: In patients with RA treated with (ultra-)low-dose rituximab (RTX), we investigated the association of dosing and timing of RTX on seroconversion after a third coronavirus disease 2019 (COVID-19) vaccination and the persistence of humoral response after a two-dose vaccination. MATERIAL AND METHODS: In this monocentre observational study, patients from the COVAC cohort were included in the third vaccine analysis if humoral response was obtained 2-6 weeks after a third vaccination in previous non-responders and in the persistence analysis if a follow-up humoral response was obtained before a third vaccination in previous responders. Dichotomization between positive and negative response was based on the assay cut-off. The association between the latest RTX dose before first vaccination, timing between the latest RTX dose and vaccination and response was analysed with univariable logistic regression. RESULTS: Of the 196 patients in the cohort, 98 were included in the third vaccine analysis and 23 in the persistence analysis. Third vaccination response was 19/98 (19%) and was higher for 200 mg RTX users [5/13 (38%)] than for 500 and 1000 mg users [7/37 (19%) and 7/48 (15%), respectively]. Non-significant trends were seen for higher response with lower dosing [200 vs 1000 mg: odds ratio (OR) 3.66 (95% CI 0.93, 14.0)] and later timing [per month since infusion: OR 1.16 (95% CI 0.97, 1.35)]. Humoral response persisted in 96% (22/23) and 89% (8/9) of patients who received RTX between the two measurements. CONCLUSIONS: Repeated vaccination as late as possible after the lowest RTX dose possible seems the best vaccination strategy. A once positive humoral response after COVID-19 vaccination persists irrespective of intercurrent RTX infusion. Study registration. Netherlands Trial Registry (https://www.trialregister.nl/), NL9342.

Adherence to prescription medication during pregnancy: Do pregnant women use pharmacological treatment as prescribed?

AIMS: Pregnant women are hypothesized to have low adherence to prescribed medication, because of concerns about harmful effects on the unborn child. However, very little is known about the actual adherence to prescribed medication during pregnancy. We determined to what extent women follow treatment recommendations regarding prescribed medication use in mid-pregnancy. METHODS: Dutch women participating in the PRIDE Study completed a 6-week diary on medication use. Additionally, pharmacy records were obtained. For each medication dispensed, we determined 3 measures of adherence: (i) whether use was reported in the diary (actual use); (ii) difference between dispensing date and date of first reported use (initiation time); and (iii) proportion of days with at least the correct number of doses taken (implementation adherence). RESULTS: During the 6-week study period, 235 of 816 women (29%) were dispensed medication. Actual use was highest for medications used for chronic conditions (88%; 95% confidence interval [95% CI] 81-93), followed by medication for pregnancy-related conditions (79%; 95% CI 71-86) and medication for occasional and short-time use (69%; 95% CI 60-77). We observed a ≥1-day delay in treatment initiation for 42% of medications dispensed for the first time in the study period. Mean implementation adherence was 74.2% (95% CI 69.3-79.2) for medications that were actually used. CONCLUSION: Although actual use of medications dispensed was high, many pregnant women did not adhere to treatment recommendations. This nonadherence may impact maternal and child health and lead to overestimation of medication use in studies in perinatal pharmacoepidemiology relying on administrative databases.

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.

Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab.

OBJECTIVES: The REDO trial (REtreatment with Rituximab in RhEumatoid arthritis: Disease Outcome after Dose Optimisation) showed that ultra-low-dose rituximab (500 mg or 200 mg) was similarly effective to a 1000 mg dosage in the majority of RA patients. This pre-planned secondary analysis investigated (1) associations between rituximab dosage, drug levels, anti-drug antibodies (ADAs) and B-cell counts and (2) the predictive value of pharmacokinetic and pharmacodynamic parameters, and of patient, disease and treatment characteristics in relation to response to ultra-low-dose rituximab. METHODS: For 140 RA patients from the REDO trial, differences in drug levels, ADAs and B-cell counts were examined at baseline, and at 3 and 6 months after dosing. Treatment response was defined as absence of flare and no extra rituximab or >1 glucocorticoid injection received during follow-up. The association between potential predictors and response was investigated using logistic regression analyses. RESULTS: Lower doses of rituximab resulted in lower drug levels but did not significantly affect ADA levels or B-cell counts, and 3 (10.7%), 12 (20.7%) and 7 (13.0%) patients failed to meet the response criteria in, respectively, the 1000 mg, 500 mg and 200 mg dosage groups. Drug levels, ADAs, B-cell counts, and patient, disease and treatment characteristics were not predictive for response to ultra-low-dose rituximab. CONCLUSION: The results of this study further support the hypothesis that continued treatment with 500 or 200 mg rituximab is similarly effective to a 1000 mg dosage in RA patients doing well on rituximab. These results, combined with lack of finding a clinical dose-response relationship in the original REDO study, suggest that 200 mg rituximab is not yet the lowest effective rituximab retreatment dose in RA.

Humoral response to coronavirus disease-19 vaccines is dependent on dosage and timing of rituximab in patients with rheumatoid arthritis.

OBJECTIVES: Humoral response to vaccines in RA patients treated with rituximab (RTX) in standard dosages (≥1000 mg) is decreased. Ultra-low dosages (500 or 200 mg) may have better response. Also, timing after latest RTX infusion may be an important variable. We aimed to investigate the influence of RTX dosage and timing on response to COVID-19 vaccination in RA patients. METHODS: A single-centre observational study (n = 196) investigated the humoral response, measured by total Ig anti-COVID-19 assay (positive response ≥1.1), 2-6 weeks after complete COVID-19 vaccination. A multivariable logistic regression model was built to study the effect of RTX dosage and time between latest rituximab and vaccination on response, adjusting for age and methotrexate use. RESULTS: After two-dose vaccination, the response rate was significantly better for patients receiving 200 mg (n = 31, 45%) rituximab compared with 1000 mg (n = 98, 26%; odds ratio 3.07, 95% CI 1.14-8.27) and for each additional month between latest rituximab and vaccination (OR 1.67, 1.39-2.01). CONCLUSION: Both increased time between latest rituximab infusion and complete vaccination, and 200 mg as latest dose were associated with a better response to COVID-19 vaccination and should be considered when trying to increase vaccine response after rituximab in RA patients. TRIAL REGISTRATION: Netherlands Trial Register, https://www.trialregister.nl/, NL9342.

Barriers and facilitators for the usage of a personal health record for medication reconciliation: A qualitative study among patients.

AIMS: Personal health records (PHRs) are more often used for medication reconciliation (MR). However, patients' adoption rate is low. We aimed to provide insight into patients' barriers and facilitators for the usage of a PHR for MR prior to an in- or outpatient visit. METHODS: A qualitative study was conducted among PHR users and non-users who had a planned visit at the outpatient rheumatology department or the inpatient cardiology or neurology department. About 1 week after the hospital visit, patients were interviewed about barriers and facilitators for the usage of a PHR for MR using a semi-structured interview guide based on the theoretical domains framework. Afterwards, data were analysed following thematic analysis. RESULTS: Ten PHR users and non-users were interviewed. Barriers and facilitators were classified in four domains: patient, application, process and context. We identified 14 barriers including limited (health) literacy and/or computer skills, practical and technical issues, ambiguity about who is responsible (the patient or the healthcare provider) and lack of data exchange and connectivity between applications. Besides that, ten facilitators were identified including being place and time independent, improve usability, target patients who benefit most and/or have sufficient skills, and integration of different applications. CONCLUSION: Barriers and facilitators identified at the patient, application, process and context level, need to be addressed to effectively develop and implement PHRs for MR.

Implementation of a pharmacist-led transitional pharmaceutical care programme: Process evaluation of Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH).

WHAT IS KNOWN AND OBJECTIVE: The recently conducted Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH) transitional care programme, which aimed to test the effectiveness of a transitional care programme on the occurrence of ADEs post-discharge, did not show a significant effect. To clarify whether this non-significant effect was due to poor implementation or due to ineffectiveness of the intervention as such, a process evaluation was conducted. The aim of the study was to gain more insight into the implementation fidelity of MARCH. METHODS: A mixed methods design and the modified Conceptual Framework for Implementation Fidelity was used. For evaluation, the implementation fidelity and moderating factors of four key MARCH intervention components (teach-back, the pharmaceutical discharge letter, the post-discharge home-visit and the transitional medication review) were assessed. Quantitative data were collected during and after the intervention. Qualitative data were collected using semi-structured interviews with MARCH healthcare professionals (community pharmacists, clinical pharmacists, pharmacy assistants and pharmaceutical consultants) and analysed using thematic analysis. RESULTS AND DISCUSSION: Not all key intervention components were implemented as intended. Teach-back was not always performed. Moreover, 63% of the pharmaceutical discharge letters, 35% of the post-discharge home-visits and 44% of the transitional medication reviews were not conducted within their planned time frames. Training sessions, structured manuals and protocols with detailed descriptions facilitated implementation. Intervention complexity, time constraints and the multidisciplinary coordination were identified as barriers for the implementation. WHAT IS NEW AND CONCLUSION: Overall, the implementation fidelity was considered to be moderate. Not all key intervention components were carried out as planned. Therefore, the non-significant results of the MARCH programme on ADEs may at least partly be explained by poor implementation of the programme. To successfully implement transitional care programmes, healthcare professionals require full integration of these programmes in the standard work-flow including IT improvements as well as compensation for the time investment.

Usability and perceived usefulness of patient-centered medication reconciliation using a personalized health record: a multicenter cross-sectional study.

BACKGROUND: Adoption of a personal health record (PHR) depends on its usability and perceived usefulness. Therefore, we aimed to assess the usability and perceived usefulness of an online PHR used for medication reconciliation and to assess the association between patient-, clinical-, hospital-, and ICT-related factors and the usability and perceived usefulness at both the in- and outpatient clinics. METHODS: A multicenter cross-sectional study was conducted with patients with either an outpatient visit (rheumatology ward) or planned admission in the hospital (cardiology, neurology, internal medicine or pulmonary wards). All patients received an invitation to update their medication list in the PHR 2 weeks prior to their appointment. One month after the hospital visit, PHR-users were asked to rate usability (using the System Usability Scale (SUS)) and perceived usefulness on a 5-point Likert scale. The usability and perceived usefulness were classified according to the adjective rating scale of Bangor et al. The usability was furthermore dichotomized in the categories: low (SUS between 0 and 51) and good (SUS 51-100) usability. Associations between patient-, clinical-, hospital-, and ICT-related factors and the usability and perceived usefulness were analysed. RESULTS: 255 of the 743 invited PHR-users completed the questionnaire. 78% inpatients and 83% outpatients indicated that usability of the PHR was good. There were no significant association between patient-, clinical-, hospital-, and ICT-related factors and the usability of the PHR. The majority of the patients (57% inpatients and 67% outpatients) classified perceived usefulness of the PHR as good, excellent, or best imaginable. Outpatients who also used the PHR for other drug related purposes reported a higher perceived usefulness (adjusted odds ratio 20.0; 95% confidence interval 2.36-170). Besides that, there was no significant association between patient-, clinical-, hospital-, and ICT-related factors and the perceived usefulness of the PHR. CONCLUSIONS: The majority of the patients indicated that the PHR for medication reconciliation was useful and easy to use, but there is still room for improvement. To improve the intervention, further research should explore patients' barriers and facilitators of using a PHR for medication reconciliation.

The effect of Patient's Own Medication use on patient's self-reported medication knowledge during hospitalisation: a pre-post intervention study.

BACKGROUND: Improving patient's medication knowledge and consequently medication use is essential for optimal treatment outcomes. As patient knowledge about medication is currently suboptimal, interventions to optimise medication knowledge are necessary. Implementation of Patient's Own Medication (POM) in which patients bring their outpatient medication to the hospital, and nurses administer these during admission, may increase medication knowledge. The aim of this study is to explore the impact of POM use on self-reported medication knowledge of hospitalised patients compared to standard care. Patient's sense of medication safety, attitude to the provision of information, and to inpatient medication use were studied in both standard care and during POM use too. METHOD: In this nationwide intervention study perceived medication knowledge was assessed with a questionnaire pre and post implementing POM use. The questionnaire assessed perceived medication knowledge at admission and discharge, medication safety during hospitalisation, the provision of information during hospitalisation and at discharge, and inpatient medication use during hospitalisation. Patients' answers were categorised into positive and negative/neutral. The proportion of patients with adequate medication knowledge, in the standard care and POM use group at hospital admission and discharge, were calculated and compared with adjustment for potential confounders. RESULTS: Among the 731 patients (393 received standard care and 338 POM) who completed the questionnaire (80.2%), POM use seemed to be positively associated with self-reported knowledge on how to use medication at discharge (adjusted OR: 3.22 [95% CI 2.01-5.16]). However, for the other two knowledge related statements POM use was not associated. Medication knowledge at admission was the most important variable associated with perceived medication knowledge at discharge. The majority perceived POM use to be safer (52.9% of standard care patients versus 74.0% POM users; P <  0.01), POM users knew better which medicines they still used during hospitalisation (85.8% versus 92.3% resp.; P = 0.01), and most patients preferred POM use regardless of having experienced it (68.2% versus 82.2% resp.; P <  0.01). CONCLUSION: POM use positively affects patient's medication knowledge about how to use medication and patients' perception of medication safety. With POM use more patients have a positive attitude towards the provision of information. The majority of patients prefer POM use. In conclusion, POM use seems a valuable intervention and requires further investigation.

The value of incorporating patient-consulted medication reconciliation in influencing drug-related actions in the outpatient rheumatology setting.

BACKGROUND: Unintentional changes to patients' medicine regimens and drug non-adherence are discovered by medication reconciliation. High numbers of outpatient visits and medication reconciliation being time-consuming, make it challenging to perform medication reconciliation for all outpatients. Therefore, we aimed to get insight into the proportion of outpatient visits in which information obtained with medication reconciliation led to additional drug-related actions. METHODS: In October and November 2018, we performed a cross-sectional observational study at the rheumatology outpatient clinic. Based on a standardized data collection form, outpatient visits were observed by a pharmacy technician trained to observe and report all drug-related actions made by the rheumatologist. Afterwards, the nine observed rheumatologists and an expert panel, consisting of two rheumatologists and two pharmacists, were individually asked which drug information reported on the drug list composed by medication reconciliation was required to perform the drug-related actions. The four members of the expert panel discussed until consensus was reached about their assessment of the required information. Subsequently, a researcher determined if the required information was available in digital sources: electronic medical record (electronic prescribing system plus physician's medical notes) or Dutch Nationwide Medication Record System. RESULTS: Of the 114 selected patients, 83 (73%) patients were included. If both digital drug sources were available, patient's input during medication reconciliation resulted in additional information to perform drug-related actions according to the rheumatologist in 0% of the visits and according to the expert panel in 14%. If there was only access to the electronic medical record, the proportions were 8 and 29%, respectively. Patient's input was especially required for starting a new drug and discussing drug-related problems. CONCLUSIONS: If rheumatologists only had access to the electronic medical record, in 1 out of 3 visits the patient provided additional information during medication reconciliation which was required to perform a drug-related action. When rheumatologists had access to two digital sources, patient's additional input during medication reconciliation was at most 14%. As the added value of patient's input was highest when rheumatologists prescribe a new drug and/or discuss a drug-related problem, it may be considered that rheumatologists only perform medication reconciliation during the visit when performing one of these actions.

2020 EULAR points to consider for the prevention, screening, assessment and management of non-adherence to treatment in people with rheumatic and musculoskeletal diseases for use in clinical practice.

BACKGROUND: Non-adherence to treatment could preclude reaching an optimal outcome. Thirty to 80% of patients with rheumatic and musculoskeletal diseases (RMDs) do not adhere to the agreed treatment. OBJECTIVES: The objective was to establish points to consider (PtCs) for the prevention, screening, assessment and management of non-adherence to (non-)pharmacological treatments in people with RMDs. METHODS: An EULAR task force (TF) was established, and the EULAR standardised operating procedures for the development of PtCs were followed. The TF included healthcare providers (HCPs), comprising rheumatologists, nurses, pharmacists, psychologists, physiotherapists, occupational therapists and patient-representatives from 12 European countries. A review of systematic reviews was conducted in advance to support the TF in formulating the PtCs. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtCs were formulated. The PtCs reflect the phases of action on non-adherence. HCPs should assess and discuss adherence with patients on a regular basis and support patients to treatment adherence. As adherence is an agreed behaviour, the treatment has to be tailored to the patients' needs. The level of agreement ranged from 9.5 to 9.9 out of 10. CONCLUSIONS: These PtCs can help HCPs to support people with RMDs to be more adherent to the agreed treatment plan. The basic scheme being prevent non-adherence by bonding with the patient and building trust, overcoming structural barriers, assessing in a blame-free environment and tailoring the solution to the problem.

Effectiveness and tolerability of oral vs subcutaneous methotrexate in patients with rheumatoid arthritis.

OBJECTIVES: The aim of this study was to compare the effectiveness and tolerability between oral MTX and s.c. MTX in a large group of RA patients in a real-life setting. METHODS: In this retrospective cohort study, adult patients with clinical diagnosis of RA who started MTX treatment (monotherapy or combined with HCQ) started with either oral or s.c. MTX. The primary outcome was superiority testing of between group difference in change in DAS28CRP between baseline and 3-6 months, and subsequent non-inferiority (non-inferiority margin 0.6) testing analyses in case of non-superiority. Secondary outcomes included MTX dose, side effects, laboratory abnormalities and use of comedication. RESULTS: Six hundred and forty RA patients were included: 259 started with oral MTX and 381 with s.c. MTX. There was no significant difference in ΔDAS28CRP [after adjusting for confounding, 0.13 (95% CI: -0.14, 0.40)], and oral MTX strategy was non-inferior to s.c. The mean MTX dose was slightly lower for the oral strategy [18.0 (6.9) vs 19.9 (8.2), P = 0.002], which was accompanied by a lower cumulative incidence of adverse events (41% vs 52%, P = 0.005). No differences were seen in use of other comedication. CONCLUSION: Starting with oral MTX in RA in a real-life setting is non-inferior to a s.c. MTX treatment with regard to disease activity control, at least when used in dosages up to 25 mg and on a background of HCQ co-treatment and a treat-to-target approach. In addition, tolerability was better. This supports the strategy of starting with oral MTX.

Impact of Fasting on Cardiovascular Outcomes in Patients With Hypertension.

ABSTRACT: Fasting has been frequently practiced for religious or medical purposes worldwide. However, limited literature assesses the impact of different fasting patterns on the physiologic and cardiac-related parameters in patients with hypertension. This review aims to examine the effect of fasting on cardiovascular outcomes in hypertensive patients. Medline, Embase, and Cochrane library were systematically screened until March 2021 for observational prospective cohorts investigating the effect of fasting on cardiovascular outcomes. Articles were assessed by searching for hypertension and fasting, both as Medical Subject Headings (MeSH) terms and text words. The review included studies assessing Ramadan, intermittent, and water-only fasting. Water-only fasting reduces body weight, blood pressure, and lipolytic activity of fasting hypertensive patients without affecting average heart rate. Ramadan fasting enhances lipid profile, although it shows conflicting results for body weight, blood pressure, and heart rate variability. Considering the limited studies in this field, further research should be conducted to support the clinical impact of fasting on the cardiovascular health of patients with hypertension.

Effect of Interactive eHealth Interventions on Improving Medication Adherence in Adults With Long-Term Medication: Systematic Review.

BACKGROUND: Medication nonadherence leads to suboptimal treatment outcomes, making it a major priority in health care. eHealth provides an opportunity to offer medication adherence interventions with minimal effort from health care providers whose time and resources are limited. OBJECTIVE: The aim of this systematic review is twofold: (1) to evaluate effectiveness of recently developed and tested interactive eHealth (including mHealth) interventions on medication adherence in adult patients using long-term medication and (2) to describe strategies among effective interventions. METHODS: MEDLINE, EMBASE, Cochrane Library, PsycINFO, and Web of Science were systematically searched from January 2014 to July 2019 as well as reference lists and citations of included articles. Eligible studies fulfilled the following inclusion criteria: (1) randomized controlled trial with a usual care control group; (2) a total sample size of at least 50 adult patients using long-term medication; (3) applying an interactive eHealth intervention aimed at the patient or patient's caregiver; and (4) medication adherence as primary outcome. Methodologic quality was assessed using the Cochrane risk of bias tool. Selection and quality assessment of studies were performed by 2 researchers (BP and BvdB or JV) independently. A best evidence synthesis was performed according to the Cochrane Back Review Group. RESULTS: Of the 9047 records screened, 22 randomized clinical trials were included reporting on 29 interventions. Most (21/29, 72%) interventions specified using a (mobile) phone for calling, SMS text messaging, or mobile apps. A majority of all interactive interventions (17/29) had a statistically significant effect on medication adherence (P<.05). Of these interventions, 9 had at least a small effect size (Cohen d ≥ 0.2) and 3 showed strong odds for becoming adherent in the intervention group (odds ratio > 2.0). Our best evidence synthesis provided strong evidence for a positive effect of interventions using SMS text messages or interactive voice response, mobile app, and calls as mode of providing adherence tele-feedback. Intervention strategies "to teach medication management skills," "to improve health care quality by coordinating medication adherence care between professionals," and "to facilitate communication or decision making between patients and health care providers" also showed strong evidence for a positive effect. CONCLUSIONS: Overall, this review supports the hypothesis that interactive eHealth interventions can be effective in improving medication adherence. Intervention strategies that improve patients' treatment involvement and their medication management skills are most promising and should be considered for implementation in practice.

Shared decision making in routine clinical care of patients with rheumatoid arthritis: an assessment of audio-recorded consultations.

OBJECTIVES: Although shared decision making (SDM) is advocated in rheumatoid arthritis (RA) treatment, it is largely unclear when, how and to what extent SDM is applied in routine clinical care of patients with RA. This study aimed to investigate the level of SDM in RA treatment from an observer perspective and to assess associations between the level of SDM and characteristics of the clinician, patient and consultation. METHODS: The level of SDM was investigated by scoring audio-recordings of 168 routine consultations with unique patients with the observer patient involvement (OPTION) scale (scale 0-100, higher OPTION scores indicating higher levels of SDM). Associations between the level of SDM and characteristics of the clinician, patient and consultation were assessed using multilevel modelling. Statistical significance was set at p<0.05. RESULTS: The mean OPTION score was 28.3 (SD=15.1). The multilevel model included four characteristics: clinician age, patient age, consultation duration and type of treatment decision. There were significant, positive associations between the level of SDM and the consultation duration (b=0.63, 95% CI 0.16 to 1.11), decision for stopping and/or starting medication (b=14.30, 95% CI 5.62 to 22.98), decision for adjusting medication doses (b=8.36, 95% CI 3.92 to 12.81) and decision for administering single dose glucocorticoids (b=15.03, 95% CI 9.12 to 20.93). Thus, a higher level of SDM was significantly associated with a longer consultation duration and the type of treatment decision. No other significant associations were found. CONCLUSIONS: Overall, the level of SDM in RA treatment leaves room for improvement. To foster SDM in routine clinical care, training programmes on patient-centred communication skills may be helpful.

Patients with inflammatory rheumatic diseases: quality of self-reported medical information in a prospective cohort event monitoring system.

OBJECTIVES: Assessment of the quality of patient-reported medical information in the Dutch Biologic Monitor and evaluation of the representativeness of the sampled participants. METHODS: Consecutive adult patients using a biologic DMARD (bDMARD) for an immune-mediated inflammatory disease were included in eight Dutch centres. For this substudy, data of 550 patients with inflammatory rheumatic diseases were used. Patient-reported bDMARD prescription, indication and combination therapy were verified for patients that permitted access to their electronic health record using percentage agreement and/or Cohen's kappa (n = 483). Conservative post hoc sensitivity analysis was performed to account for missing data. Population representativeness was tested for the entire substudy population by comparing age, gender and prescribed bDMARD to the centres' reference populations using Mann-Whitney U-test, χ2 goodness-of-fit or Fisher's exact test with Monte Carlo simulation (n = 550). RESULTS: The correct bDMARD was reported by 95.8% of the participants. Agreement between patients and electronic health record was almost perfect for indications (κ = 0.832) and substantial for combination therapies (κ = 0.725). Agreement on combination therapies remained substantial after post hoc sensitivity analysis (κ = 0.640). Gender distribution (P > 0.05) and bDMARD use (P > 0.05) were similar to the reference populations. Median age was different (58.0 vs 56.0 years, P = 0.04), but considered clinically irrelevant. CONCLUSION: The Dutch Biologic Monitor seems to be a valid tool to obtain patient-reported medical information. Reported medical information generally corresponded to the electronic health records and the participants represented their reference populations regarding age, gender and prescribed bDMARD.

Diagnostic accuracy of a single-lead portable ECG device for measuring QTc prolongation.

BACKGROUND: To assess the diagnostic accuracy of a single-lead portable ECG device for measuring QTc-intervals in comparison with a standard 12-lead ECG. METHODS: Adult patients visiting the cardiology outpatient clinic for a 12-lead recording were also measured with a portable single-lead ECG recorder (HeartcheckTM). QTc-intervals were determined by two cardiologists. Perfect agreement was defined as a limit of ≤10 ms between the two measurement methods. RESULTS: Hundred one ECGs were recorded. QTc-interval mean differences between the two measurement methods was substantially outside our definition of perfect agreement (-31.9 [SD±41.3] ms). CONCLUSION: In conclusion, the Heartcheck single-lead ECG device is not accurate for measuring QTc-intervals.