A survey on the implementation of clinical medication reviews in community pharmacies within a multidisciplinary setting.

BACKGROUND: Polypharmacy is common in chronic medication users, which increases the risk of drug related problems. A suitable intervention is the clinical medication review (CMR) that was introduced in the Netherlands in 2012, but the effectiveness might be hindered by limited implementation in community pharmacies. Therefore our aim was to describe the current implementation of CMRs in Dutch community pharmacies and to identify barriers to the implementation. METHODS: An online questionnaire was developed based on the Consolidated Framework for Implementation Research (CFIR) and consisted of 58 questions with open ended, multiple choice or Likert-scale answering options. It was sent out to all Dutch community pharmacies (n = 1,953) in January 2021. Descriptive statistics were used. RESULTS: A total of 289 (14.8%) community pharmacies filled out the questionnaire. Most of the pharmacists agreed that a CMR has a positive effect on the quality of pharmacotherapy (91.3%) and on medication adherence (64.3%). Pharmacists structured CMRs according to available selection criteria or guidelines (92%). Pharmacists (90%) believed that jointly conducting a CMR with a general practitioner (GP) improved their mutual relationship, whereas 21% believed it improved the relationship with a medical specialist. Lack of time was reported by 43% of pharmacists and 80% (fully) agreed conducting CMRs with a medical specialist was complicated. Most pharmacists indicated that pharmacy technicians can assist in performing CMRs, but they rarely do in practice. CONCLUSIONS: Lack of time and suboptimal collaboration with medical specialists are the most important barriers to the implementation of CMRs.

The effect of combining therapeutic drug monitoring of antihypertensive drugs with personalised feedback on adherence and resistant hypertension: the (RHYME-RCT) trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined. METHODS: This is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling. DISCUSSION: This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adherence. Furthermore, if this trial shows positive outcomes for the intervention it can be directly implemented in clinical practice, which would be a great improvement in the treatment of RH. TRIAL REGISTRATION: RHYME-RCT is registered in the Dutch Trial Register on 27/12/2017 (NTR6914) and can be found in the International Clinical Trials Registry Platform.

Lessons learned from conducting a randomized controlled trial to improve non-adherence to antihypertensive drug treatment.

PURPOSE: Hypertension significantly contributes to cardiovascular diseases and premature deaths. Effective treatment is crucial to reduce cardiovascular risks, but poor adherence to antihypertensive drugs is a major issue. Numerous studies attempted to investigate interventions for identifying non-adherence, but often failed to address the issue effectively. The RHYME-RCT trial sought to bridge this gap by measuring non-adherence by determining antihypertensive drug concentrations in blood through a dried blood spot (DBS) method in patients with resistant hypertension. This measurement was followed by personalized feedback to improve adherence. During the course of this trial several challenges emerged, including selection bias, the gatekeeper role of physicians, the Hawthorne effect and the role of randomization. AIM: This communication aims to inform fellow researchers and clinicians of challenges that can arise when conducting clinical trials to improve adherence and offer insights for refining study designs to avoid these issues in forthcoming adherence studies.

Purpose: High blood pressure is a serious problem that can lead to heart and kidney problems and early deaths. Treating high blood pressure is therefore crucial. Initially, lifestyle changes are recommended, but if they don't work, medications are needed. However, taking these drugs daily can be challenging, and many patients miss doses which is called non-adherence. Despite numerous studies, a perfect solution hasn't been found to solve non-adherence to blood pressure lowering drugs.In the RHYME-RCT study, researchers aimed to improve drug adherence in patients with resistant hypertension. They monitored drug intake by measuring drug concentrations in the blood alongside 24-hour blood pressure monitoring. These data allowed healthcare providers to offer personalized advice to patients. The study encountered some important challenges in its design, including selection bias, where some participants shouldn't have been included or excluded in the study, and the Hawthorne effect, where patients changed their behavior because they knew they were being observed.Aim: This message is to inform fellow scientists and doctors about issues that can arise when conducting clinical trials to improve adherence and to encourage the exchange of ideas between scientists to improve future studies on medication adherence, which is essential for managing conditions like high blood pressure.

Perioperative stroke during carotid endarterectomy: benefits of multimodal neuromonitoring - a case report.

BACKGROUND: Carotid endarterectomy is routinely performed after ischemic stroke due to carotid stenosis. Perioperative, cerebral blood flow and oxygenation can be monitored in different ways, but there is no clear evidence of a gold standard and a uniform guideline is lacking. Electroencephalography and near-infrared spectroscopy are among the most frequently used methods of neuromonitoring. Clinicians should be aware of their pitfalls and the added value of transcranial doppler. CASE PRESENTATION: We present the case of an 85-year old male with perioperative haemodynamic stroke during carotid endarterectomy. Ischemic stroke was caused by suddenly increased carotid stenosis resulting in major neurologic deficit. This was registered only by transcranial doppler, while surface electroencephalography and near-infrared spectroscopy failed to detect any significant change in cerebral perfusion, despite a large perfusion defect on computed tomography. Circulation was restored with endovascular treatment and neurologic deficit quickly resolved. CONCLUSION: We strongly advocate the practice of multimodal neuromonitoring including transcranial doppler whenever possible to minimize the risk of persistent neurologic deficit due to perioperative stroke during carotid endarterectomy.

From benchtop to clinic: a translational analysis of the immune response to submicron topography and its relevance to bone healing.

Proper regulation of the innate immune response to bone biomaterials after implantation is pivotal for successful bone healing. Pro-inflammatory M1 and anti-inflammatory M2 macrophages are known to have an important role in regulating the healing response to biomaterials. Materials with defined structural and topographical features have recently been found to favourably modulate the innate immune response, leading to improved healing outcomes. Calcium phosphate bone grafts with submicron-sized needle-shaped surface features have been shown to trigger a pro-healing response through upregulation of M2 polarised macrophages, leading to accelerated and enhanced bone regeneration. The present review describes the recent research on these and other materials, all the way from benchtop to the clinic, including in vitro and in vivo fundamental studies, evaluation in clinically relevant spinal fusion models and clinical validation in a case series of 77 patients with posterolateral and/or interbody fusion in the lumbar and cervical spine. This research demonstrates the feasibility of enhancing biomaterial-directed bone formation by modulating the innate immune response through topographic surface features.

Accelerated bone formation by biphasic calcium phosphate with a novel sub-micron surface topography.

Osteoinductive calcium phosphate (CaP) bone grafts have equivalent performance to autografts in repairing critical-size bone defects. The osteoinductive potential of CaP is linked to the size of the surface topographical features. In the present study, two novel biphasic calcium phosphate (BCP) bone grafts were synthesised with either sub-micron- (BCP<µm) or micron-scale (BCPµm) needle-shaped surface topography and compared to dimensionally similar tricalcium phosphate (TCP) with grain-shaped surface structures (TCP<µm and TCPµm). To clarify the possible function of the surface morphology (needle-like vs. grain-like) in initiating bone formation, the four CaP test materials were physicochemically characterised and implanted for 12 weeks in the dorsal muscle of beagles. The sub-micron needle-shaped topography of BCP<µm triggered earlier bone formation (3-6 weeks) as compared to the grain-shaped surface topography of TCP<µm, which formed bone at 6-9 weeks. After 12 weeks, the amount of induced bone formation in both materials was equivalent, based on histomorphometry. The micron-sized needle-shaped surface topography of BCPµm led to limited formation of new bone tissue, whereas its counterpart, TCPµm with grain-shaped surface topography, failed to trigger de novo bone formation. The relative strength of the parameters affecting CaP-driven bone induction was as follows: surface feature size > surface feature morphology > substrate chemistry. BCP materials with needle-shaped sub-micron surface topography gave rise to accelerated bone formation and slower rate of resorption than a comparable TCP. These characteristics may be translated to improve bone healing in orthotopic defects.

First report of a comparative patient-oriented perspective on the use of non-vitamin-K oral anticoagulants or vitamin-K antagonists in atrial fibrillation: patients' experiences, side-effects and practical problems leading to non-adherence.

BACKGROUND: Non-vitamin­K oral anticoagulants (NOACs) are recommended as the first-choice therapy for stroke prevention in patients with non-valvular atrial fibrillation (AF). However, the lack of monitoring may impact patients' adherence, and non-adherence to medication is a potential hazard to safe and efficacious use. This is the first report with a 'comparative patient-oriented perspective' regarding the use of anticoagulant medication in the NOACs era. Our aim was to compare patients' self-reported practical problems, adverse events and non-adherence to anticoagulation therapy. METHODS: A survey was conducted among patients with AF on either NOACs or vitamin­K antagonists (VKAs). The outcomes were self-reported non-adherence to anticoagulant medication, and patients' experiences, adverse events and practical problems correlated with the intake of the drug itself. RESULTS: A total of 765 patients filled out the questionnaire, of which 389 (50.9%) were on VKAs and 376 (49.1%) on NOACs. Age (70.6 ± 8.8 vs 70.3 ± 9.1 years) and male gender (70.4% vs 64.6%) were similar in the two groups. A significantly higher proportion of VKA users than NOAC users reported having frequent (16.2% vs 3.7%, p > 0.001) or occasional (4.1% vs 1.3%, p > 0.001) practical issues with medication intake. Self-reported non-adherence was significantly higher (24.4% vs 18.1%, p = 0.03) among VKA users. The incidence of self-reported adverse events was similar. CONCLUSION: Patient experiences support the current guideline recommendations for NOACs as the first-choice therapy: NOAC therapy resulted in a higher practical feasibility and better adherence when compared with VKA therapy, with a similar incidence of adverse events in both groups.

Adult periodontitis treated with a new device for subgingival lavage-a randomized controlled clinical trial using a split-mouth design.

OBJECTIVES: To evaluate in patients with untreated adult periodontitis, the effect of treatment with a novel pocket irrigator/evacuator device (IED) compared to conventional subgingival debridement (CPT), both provided during the initial phase of active periodontal therapy. METHODS: This study was an examiner-blind, randomized controlled clinical trial using a split-mouth design. Systemically healthy patients with adult periodontitis were selected. Full-mouth probing pocket depth (PPD), gingival bleeding on pocket probing scores (BOPP), gingival recession (REC) and dental plaque (PI) were assessed at baseline. All participants received oral hygiene instructions and supragingival prophylaxis including polishing. In 2 randomly assigned contra-lateral quadrants, approximal sites were irrigated with the IED, whereas in the other quadrants, CPT was provided. The CPT consisted of subgingival debridement using ultrasonic devices followed by the use of hand instruments. At 3 months post-treatment, the clinical parameters were re-assessed. RESULTS: Twenty-five patients met the inclusion criteria and were willing to participate. At 3 months post-treatment, the PPD and BOPP had significantly improved for both treatment modalities. Pockets of ≥5 mm reduced by 0.64 mm in the IED group (P < .001), compared to a reduction of 0.82 mm for the CPT group (P < .001). With respect to the primary outcome parameter (PPD) and BI, the results with the IED were less pronounced. Between the test and control groups, no significant differences were observed for REC and PI. CONCLUSIONS: Oral hygiene instructions, supragingival prophylaxis and subgingival lavage with the IED resulted in a significant reduction in PPD and BOPP. However, the effect does not reach the results of CPT which included the subgingival use of ultrasonic and hand instruments.

Variability in market uptake of psychotropic medications in Europe reflects cultural diversity.

BACKGROUND: In the last 20-30 years, many international studies have found substantial differences in the use of (older) psychotropic medication between European countries. The majority mentioned an important role for attitudes and beliefs towards psychotropic medication. So far, no studies have looked into the effects of cultural diversity on the use of new medications entering the market. As national cultures relate deeply to held values regarding, for example, what is seen as effective versus ineffective or safe versus dangerous, (cultural) diversity in decision making around the role of new medications in clinical practice may already be expected from the first day after market authorization. METHODS: This study examined the relation between cultural diversity, described in Hofstede's model of cultural dimensions (Power Distance, Individualism, Masculinity, Uncertainty Avoidance, Indulgence and Long-Term Orientation) and utilization of three new psychotropic medications, namely aripiprazole, duloxetine and pregabalin in Europe. Country level sales data of the case study medications were correlated to country-specific scores of Hofstede's cultural dimensions. IMS Health's MIDAS database has been used for sales data (converted to Defined Daily Doses/1000 inhabitants/day) for the case study medications from the market authorization date in 2004 until December 2009 for 23 EU member states. RESULTS: Consumption of the case study medications was seen in all countries. In general, pregabalin was used more often than aripiprazole and duloxetine. In 2 years after market authorization, approximately 80% of all countries have reported use of all three molecules. Correlations between Hofstede dimensions individualism, long-term orientation and indulgence and total use of the case study medications tended to become stronger over time, but they were only statistically significant for indulgence at two years after market authorization (rho = 0.51, p = 0.014) and three years after market authorization (rho = 0.54, p = 0.008). A more detailed analysis showed (slight) variation by molecule. CONCLUSIONS: This study is a first step in including cultural dimensions when explaining cross-national variation in the use of new medications. The results indicate that indulgence, however marginally, is a cultural aspect that relates to the utilization of new psychotropic medications, suggesting that within the cultural context, less regulation of social norms is a main factor in explaining cross-national variation in uptake of these medications.

Predictors of Failure of Closure in Percutaneous EVAR Using the Prostar XL Percutaneous Vascular Surgery Device.

OBJECTIVE: To identify predictors of failure in percutaneous endovascular aneurysm repair (P-EVAR) using the Prostar XL Percutaneous Vascular Surgery Device (Abbot Vascular, Santa Clara, CA, USA) and the need for conversion to conventional femoral cutdown (O-EVAR). METHODS: Consecutive patients who underwent P-EVAR with the Prostar XL device between January 2009 and April 2012 were included in this series. Patients with a circular calcified common femoral artery (CFA) oncomputed tomography angiography were operated using O-EVAR and were therefore excluded. To identify predictors of success of closure in P-EVAR, artery characteristics, sheath size used, and comorbidities were analyzed in a univariate logistic regression model. RESULTS: Percutaneous access was achieved in 154 femoral access sites with conversion to O-EVAR was needed in10 (6.5%). Significant predictors of conversion included sheath size (continuous, relative risk [RR] 1.50, p < .03)and the ratio between sheath size and CFA diameter >0.75 (RR 8.93, p < .01). Variables such as calcification quantity scores, CFA diameter, body mass index, and comorbidities were not significant. CONCLUSION: The data demonstrate that sheath size, in particular, combined with CFA diameter predicts failure of closure in P-EVAR using the Prostar XL device. This ratio can be utilized to help in decision making with regard to the EVAR approach. A ratio of >0.75 would favor a primary open groin approach.

Primary-care patients' trade-off preferences with regard to antidepressants.

BACKGROUND: Antidepressants are frequently prescribed but results regarding their efficacy have been equivocal for different spectra of the severity continuum and their side-effects are often burdensome. Non-adherence is a likely consequence. The objective was therefore to examine patients' trade-offs between the efficacy, side-effects and other drawbacks of antidepressants and whether these trade-offs predicted non-adherence. METHOD: Trade-offs from 225 antidepressant users, recruited through community pharmacies, were assessed with an Adaptive Conjoint Analysis (ACA) choice task that was customized to each individual patient. From the estimated utilities, relative importance scores of treatment properties were calculated. Non-adherence was measured through self-report and pharmacy refill data. RESULTS: Relapse prevention and symptom relief were on average equally important. Side-effects were as important and the side-effect stomach and intestine complaints was on average even slightly more important than relapse prevention and symptom relief. Additional treatment with psychotherapy was preferred by 61% of the patients. A benefit/drawback ratio revealed that 18% of the patients did not consider the efficacy to outweigh the drawbacks. A higher benefit/drawback ratio was associated with a decreased odds of intentional non-adherence [odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07-0.7, Wald = 6.7, p = 0.01). CONCLUSIONS: For nearly one in five patients, the efficacy of antidepressants does not outweigh their drawbacks. Knowing patients' trade-offs is likely to aid both physicians and patients to identify important treatment preferences, to improve adherence and to make more deliberate decisions on whether or not to continue treatment.

Short- and long-term effects of real-time medication monitoring with short message service (SMS) reminders for missed doses on the refill adherence of people with Type 2 diabetes: evidence from a randomized controlled trial.

AIMS: To investigate short- and long-term effects of real-time monitoring medication use combined with short message service (SMS) reminders for missed doses on refill adherence to oral anti-diabetic medication. METHODS: A randomized controlled trial with two intervention groups and one control group involving 161 participants with Type 2 diabetes with suboptimal adherence. For 6 months, participants in the SMS group (n = 56) were monitored and received SMS reminders if they missed their medication. Participants in the non-SMS group (n = 48) were only monitored. The control group (n = 57) was not exposed to any intervention. Primary outcome measure was refill adherence to oral anti-diabetic medication. Multi-level regression analyses were performed to examine intervention effects on adherence between and within groups after 1 and 2 years of follow-up. RESULTS: At baseline, mean refill adherence was comparable between the groups. After 1 year, adherence in the SMS group was significantly higher than in the control group (79.5% vs. 64.5%; P < 0.001) and showed a significant improvement from baseline (+16.3%; P < 0.001). Mean adherence in the non-SMS group reached 73.1% (+7.3%; P < 0.05), but did not differ from the control group (P = 0.06). After 2 years, the improved adherence in the SMS group persisted and remained significantly higher than in the control group (80.4% vs. 68.4%; P < .01), contrary to the non-SMS group whose adherence approached baseline level again (65.5%). CONCLUSIONS: This study shows the long-term effectiveness of real-time medication monitoring combined with SMS reminders in improving refill adherence. This new reminder system can strengthen the self-management of people with diabetes.

Antidepressant prescribing in five European countries: application of common definitions to assess the prevalence, clinical observations, and methodological implications.

PURPOSE: Drug utilization studies have applied different methods to various data types to describe medication use, which hampers comparisons across populations. The aim of this study was to describe the time trends in antidepressant prescribing in the last decade and the variation in the prevalence, calculated in a uniform manner, in seven European electronic healthcare databases. METHODS: Annual prevalence per 10,000 person-years (PYs) was calculated for 2001-2009 in databases from Spain, Germany, Denmark, the United Kingdom (UK), and the Netherlands. Prevalence data were stratified according to age, sex, antidepressant type (selective serotonin re-uptake inhibitors [SSRIs] or tricyclic antidepressants [TCAs]) and major indications. RESULTS: The age- and sex-standardized prevalence was lowest in the two Dutch (391 and 429 users per 10,000 PYs) and highest in the two UK (913 and 936 users per 10,000 PYs) populations in 2008. The prevalence in the Danish, German, and Spanish populations was 637, 618, and 644 users per 10,000 PY respectively. Antidepressants were prescribed most often in 20- to 60-year-olds in the two UK populations compared with the others. SSRIs were prescribed more often than TCAs in all except the German population. In the majority of countries we observed an increasing trend of antidepressant prescribing over time. Two different methods identifying recorded indications yielded different ranges of proportions of patients recorded with the specific indication (15-57% and 39-69% for depression respectively). CONCLUSION: Despite applying uniform methods, variations in the prevalence of antidepressant prescribing were obvious in the different populations. Database characteristics and clinical factors may both explain these variations.

General practitioners' and community pharmacists' beliefs and practices on opioids for non-malignant pain.

BACKGROUND: In Europe, opioid use has surged, largely due to prescriptions for chronic non-malignant pain (CNMP). General practitioners (GPs) and community pharmacists (CPs) play a major role in opioid prescribing for non-malignant pain. Exploring their personal beliefs and practices might reveal underlying mechanisms to identify measures that could halt the further escalation of opioid use. METHODS: Guided by the health belief model, a survey was designed and distributed nationwide to examine the practices and beliefs of GPs and CPs in the domains: threats, benefits, barriers and self-efficacy. The results of GPs and CPs were compared at the statement level using chi-square analysis. RESULTS: Of 214 GPs and 212 CPs who completed the survey, the majority agreed that too many opioids are used in the treatment of chronic non-malignant pain (66.8% GPs and 66.5% CPs). Furthermore, they were concerned about the addictive potential of opioids (83.1% GPs and 71.7% CPs). In general, both professions have concerns about opioid use. GPs report a slightly higher degree of self-efficacy and perceive fewer benefits from opioids in treating CNMP. GPs and CPs valued the recommended measures to reduce opioid prescribing, yet less than half actively implement these strategies in their clinics. CONCLUSION: GPs and CPs believe that opioids are being used too frequently to treat CNMP. However, both professions lack the actions to improve opioid-related care. GPs and CPs require education, collaboration and tools to implement guidelines on non-malignant pain and opioids. SIGNIFICANCE: This study, guided by the health belief model, reveals that general practitioners and community pharmacists have serious concerns about opioid use in chronic non-malignant pain. Despite shared concerns, both professions differ in their beliefs about opioid benefits and perceived self-efficacy. Both professions have in common that they value recommended measures to reduce opioid prescribing. Also, they both struggle to implement strategies, emphasizing the urgent need for education, collaboration and tools to align practices with guidelines on non-malignant pain and opioids.

Evaluation of guideline implementation for dispensing driving-impairing medicines by National Pharmacy Organizations.

Background: In 2004, the International Pharmaceutical Federation (FIP) adopted a Statement of Professional Standard on the supply of medicines affecting driving performance, transformed to FIP guidelines in 2014. In 2011, the final report from the European initiative on Driving Under the Influence of Drugs, Alcohol and Medicines (DRUID) was published. Both documents provided recommendations for improving dispensing guidelines for driving-impairing medicines for patients who use psychoactive medicines. Objective: This study investigated the extent that European professional organizations of pharmacists (POPs) implemented existing guidelines and DRUID results. Methods: An online questionnaire survey was conducted in April-May 2022. Questionnaires were sent by e-mail to POPs in 46 European countries. The questionnaire addressed the following topics: awareness of FIP guidelines and DRUID outcomes (a), development of dispensing guidelines (b), target groups for information materials (c), evaluations of dispensing practices (d), examples of projects on medicines affecting driving fitness (e), development of ICT (Information and Communication Technology) -support (f), collaboration with organizations of physicians (g), and patients (h). The data were analyzed by indicating implementation initiatives in different countries. Open-ended questions were assessed qualitatively. Results: POPs in 23 European countries responded to the invitation (response rate: 50%). Guidelines for improving dispensing practices were available in 5 countries targeted at professionals, patients, and the general population. Patient and physician organizations were involved in 4 and 3 countries, respectively. Implementation was supported by computerized dispensing systems (5 countries) and public campaigns (5 countries). Conclusions: Twenty years after the introduction of FIP guidelines and ten years after the DRUID outcomes, only 5 European POPs have implemented this knowledge. Different activities were performed to support implementation, resulting in examples of successful use of recommendations for driving-impairing medicines in pharmacy practice. Implementation needs further attention. The successful practices that have been developed are an example for dissemination to other countries.

Clubfoot patients show more anterior-posterior displacement during one-leg-standing and less ankle power and plantarflexor moment during one-leg-hopping than typically developing children.

BACKGROUND: Clubfoot patients show good-to-excellent foot correction after the Ponseti method. Nevertheless, underlying functional problems that limit motor abilities such as one-leg-standing and one-leg-hopping still persist. These restrictions have been proposed to arise due to problems with maintaining balance and the limited force-generating capacity of clubfoot patients. More insight is needed to understand the underlying limiting factors to improve overall motor ability in clubfoot patients. RESEARCH QUESTION: The aim of this study was to determine the differences between clubfoot patients and typically developing children (TDC) in force and balance parameters during walking, one-leg-standing and hopping. METHODS: Three-dimensional motion analysis was performed in 19 TDC and 16 idiopathic Ponseti-treated clubfoot patients between 5-9 years old. Kinematic and kinetic parameters were calculated during walking and one-leg-hopping. To describe the balance parameters, center of pressure (CoP) data was assessed during walking, one-leg-hopping and one-leg-standing. Mean group values were calculated and compared using nonparametric statistical tests. A general linear model with repeated measures was used to determine which activity showed the largest group differences. RESULTS: Clubfoot patients showed lower peak plantarflexor moment and peak ankle power absorption and generation during one-leg-hopping compared to TDC. Furthermore, clubfoot patients showed a lower hop length and velocity than TDC. The difference in peak plantarflexor moment and ankle power between the study groups was larger during one-leg-hopping than during walking. Finally, clubfoot patients showed a higher anterior-posterior CoP range during one-leg-standing. SIGNIFICANCE: Deviations in force parameters seemed to limit one-leg-hopping in clubfoot patients, and impaired anterior-posterior static balance was thought to be the underlying cause of problems with one-leg-standing. Furthermore, one-leg-hopping was more sensitive to distinguish between clubfoot patients and TDC than walking. Individualized physiotherapy targeting static balance and force parameters, with extra emphasis on including eccentric contractions, might improve the overall motor abilities of clubfoot patients.

Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension: a randomized controlled trial.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension. METHODS: We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12. RESULTS: Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm ( P  = 0.008, n  = 40) and remained the same in the SoC arm (71.4%, n  = 42). The difference in adherence between the arms was statistically significant ( P  = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm ( P  < 0.001, n  = 40) and 59.5% in the SoC arm ( P  < 0.001, n  = 42) at t12; the difference between the arms was statistically nonsignificant ( P  = 0.14). CONCLUSION: Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

Trade-off preferences regarding adjuvant endocrine therapy among women with estrogen receptor-positive breast cancer.

BACKGROUND: There is substantial nonadherence to effective adjuvant endocrine therapy for breast cancer prevention. We therefore examined patients' trade-offs between the efficacy, side-effects, and regimen duration, and whether trade-offs predicted nonadherence. PATIENTS AND METHODS: Trade-offs from 241 women were assessed with an Adaptive Conjoint Analysis (ACA) choice task that was customized to each individual patient. From the estimated ACA utilities, the relative importance of each treatment property was calculated and a benefit/drawback ratio between the importance of the efficacy versus that of the side-effects and other treatment properties. Nonadherence was assessed through composites of validated self-report measures. RESULTS: Efficacy was most important. The side-effects joint and muscle pain and risk of endometrial cancer were almost as important. The benefit/drawback ratio showed 16% of the women to value the efficacy less than the side-effects and other treatment properties. A higher benefit/drawback ratio was associated with decreased nonadherence [adjusted odds ratio (OR) 0.1, 95% confidence interval 0.03-0.3]. CONCLUSIONS: One in six women do not consider the efficacy of endocrine therapy to outweigh its drawbacks. Knowing women's trade-offs is likely to identify women at risk for nonadherence and to help clinicians in tailoring their communication and care to different needs of individual women.

Lazy sunday afternoons: the negative impact of interruptions in patients' daily routine on adherence to oral antidiabetic medication. A multilevel analysis of electronic monitoring data.

PURPOSE: Considerable variability in adherence over time exists. The aim of this study was to investigate to what extent deviations from the prescribed regimen in type 2 diabetes patients can be explained by characteristics of the individual 'medication intake moments' and the patient. METHODS: Medication intake of 104 non-adherent type 2 diabetes patients from 37 community pharmacies was electronically monitored for 6 months. The primary outcome measures were: (1) whether or not the intake occurred and (2) whether or not the intake occurred within the agreed-upon time period (correct timing). Multilevel logistic regression analyses were performed to account for the nested structure of the data. RESULTS: Medication intakes in the evening and during weekends and holidays were more likely to be incorrectly timed and also more likely to be completely missed. Irrespective of timing, most intakes occurred in the mornings of Monday through Thursday (96 %), and least intakes occurred on Saturday evening (82 %). Correctly timed intakes most often occurred on Monday and Tuesday mornings (61 %) in contrast to Sunday evenings (33 %). A patient's medication regimen was significantly associated with adherence. CONCLUSION: Based on our results, among patients who already have difficulties in taking their oral antidiabetic medication, interruptions in the daily routine negatively influence the intake of their medication. Professionals need to be aware of this variation in adherence within patients. As regular medication intake is important to maintain glycaemic control, healthcare professionals and patients should work together to find strategies that prevent deviations from the prescribed regimen at these problematic dosing times.