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.

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.

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.

DASS Good: Explainable Data Mining of Spatial Cohort Data.

Developing applicable clinical machine learning models is a difficult task when the data includes spatial information, for example, radiation dose distributions across adjacent organs at risk. We describe the co-design of a modeling system, DASS, to support the hybrid human-machine development and validation of predictive models for estimating long-term toxicities related to radiotherapy doses in head and neck cancer patients. Developed in collaboration with domain experts in oncology and data mining, DASS incorporates human-in-the-loop visual steering, spatial data, and explainable AI to augment domain knowledge with automatic data mining. We demonstrate DASS with the development of two practical clinical stratification models and report feedback from domain experts. Finally, we describe the design lessons learned from this collaborative experience.

The perceived waning of biologics in severe asthma.

BACKGROUND: Biologics are highly effective in severe asthma and used at fixed dosing intervals. However, in clinical practice, dosing intervals are sometimes shortened if patients perceive a decreased biologic effect before the next administration. The occurrence and clinical relevance of this perceived waning of biological effect is unknown. OBJECTIVE: To explore (1) the frequency, severity and conditions, (2) associated symptoms and (3) relationship with clinical characteristics of the patient-perceived waning effect of biologics before the next administration. METHODS: Severe asthma patients receiving biological treatment ≥4 months were included. Based on 17 semi-structured patient interviews, we developed a questionnaire focusing on the waning effect of biologics before the next administration, which was distributed among 129 patients. Clinical characteristics, including asthma control (ACQ) and quality of life (AQLQ) scores, were collected from patient files. RESULTS: 65/101 patients who completed the questionnaire reported a waning of biological effect, graded as severe (median (IQR) 6.5 (5-7.5) on a 0-10 BORG-scale). Waning manifested in a broad spectrum of symptoms. Patients reporting waning had higher ACQ and lower AQLQ scores versus those without (p < 0.05) and higher BORG-scores were associated with higher exacerbation rate (ρ = 0.309, p = 0.013). A third of all patients were in favor of extending or shortening their dosing interval. CONCLUSION: Two-thirds of severe asthma patients report waning of biologic effect at the end of the dosing interval, which is associated with poorer asthma control and quality of life. The diversity in observed waning of effect opens the way for research into more individualized dosing of biologics.

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.

Dense 3D pressure discomfort threshold (PDT) map of the human head, face and neck: A new method for mapping human sensitivity.

When designing wearables that interface with the human head, face and neck, designers and engineers consider human senses, ergonomics and comfort. A dense 3D pressure discomfort threshold map could be helpful, but does not exist yet. Differences in pressure discomfort threshold for areas of the head, neck and face were recorded, to create a 3D pressure discomfort threshold map. Between 126 and 146 landmarks were placed on the left side of the head, face and neck of twenty-eight healthy participants (gender balanced). The positions of the landmarks were specified using an EEG 10-20 system-based landmark-grid on the head and a self-developed grid on the face and neck. A 3D scan was made to capture the head geometry and landmark coordinates. In a randomised order, pressure was applied on each landmark with a force gauge until the participant indicated experiencing discomfort. By interpolating all collected pressure discomfort thresholds based on their corresponding 3D coordinates, a dense 3D pressure discomfort threshold map was made. A relatively low-pressure discomfort threshold was found in areas around the nose, neck front, mouth, chin-jaw, cheek and cheekbone, possibly due to the proximate or direct location of nerves, blood veins and soft (muscular) tissue. Medium pressure discomfort was found in the neck back, forehead and temple regions. High pressure discomfort threshold was found in the back of the head and scalp, where skin is relatively thin and closely supported by bone, making these regions interesting for mounting or resting head, face and neck related equipment upon.

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.

Non-adherence to guideline recommendations for insulins: a qualitative study amongst primary care practitioners.

BACKGROUND: Guideline adherence is generally high in Dutch general practices. However, the prescription of insulins to type 2 diabetes mellitus patients is often not in line with the guideline, which recommends NPH insulin as first choice and discourages newer insulins. This qualitative study aimed to identify the reasons why primary care healthcare professionals prescribe insulins that are not recommended in guidelines. METHODS: Digital focus groups with primary care practitioners were organised. A topic list was developed, based on reasons for preferred insulins obtained from literature and a priori expert discussions. The discussions were video and audio-recorded, transcribed verbatim and coded with a combination of inductive and deductive codes. Codes were categorized into an existing knowledge, attitudes and behaviour model for guideline non-adherence. RESULTS: Four focus groups with eleven general practitioners, twelve practice nurses, six pharmacists, four diabetes nurses and two nurse practitioners were organised. The prescription of non-recommended insulins was largely driven by argumentation in the domain of attitudes. Lack of agreement with the guideline was the most prominent category. Most of those perspectives did not reflect disagreement with the guideline recommendations in general, but were about advantages of non-recommended insulins, which led, according to the healthcare professionals, to better applicability of those insulins to specific patients. The belief that guideline-recommended insulins were less effective, positive experience with other insulins and marketing from pharmaceutical companies were also identified as attitude-related barriers to prescribe guideline-recommended insulins. One additional category in the domain of attitudes was identified, namely the lack of uniformity in policy between healthcare professionals in the same practice. Only a small number of external barriers were identified, focusing on patient characteristics that prevented the use of recommended insulins, the availability of contradictory guidelines and other, mostly secondary care, healthcare providers initiating non-recommended insulins. No knowledge-related barriers were identified. CONCLUSIONS: The prescription of non-recommended insulins in primary care is mostly driven by lack of agreement with the guideline recommendations and different interpretation of evidence. These insights can be used for the development of interventions to stimulate primary care practitioners to prescribe guideline-recommended insulins.

Indications related to antidepressant prescribing in the Nivel-PCD database and the SIDIAP database.

BACKGROUND: Antidepressant drug consumption has increased, mainly in the elderly. This trend could be explained by the use for indications other than depression. We aimed to describe the indications related to antidepressant drug new users in two primary care settings. METHODS: A longitudinal study of new antidepressant users aged ≥65 was conducted, with data from the Nivel-PCD (The Netherlands) and SIDIAP (Catalonia) databases (2010-2015). As a proxy for indication, diagnoses registered around the 3 months of antidepressant prescribing were collected. Indications were classified in seven categories and an additional one of non-selected indications. The percentage and incidence calculated over the total population registered was described. RESULTS: A total of 16,537 and 199,168 new antidepressant users were identified in the Nivel-PCD and SIDIAP databases, respectively (women aged 65-69 were the most prevalent). Depression was the most frequent indication (24.0% and 31.3%), followed by anxiety (12.5% and 19.5%) and sleep disorders (10.2% and 26.4%). Tricyclic antidepressants were the most commonly prescribed in Nivel-PCD (48.7%), mainly associated with neuropathic pain, and selective serotonin reuptake inhibitor antidepressants in SIDIAP (63.1%), associated with depression. The non-selected indications category showed an upward trend in the Nivel-PCD database while in the SIDIAP database it decreased. LIMITATIONS: It is not mandatory for physicians to register a diagnosis with each prescription. CONCLUSIONS: Depression was the most common prescribing indication in The Netherlands and Spain, followed by anxiety and sleep disorders. The most commonly prescribed antidepressant differed between the countries and is likely explained by differences in local guidelines.

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.

How are medication related problems managed in primary care? An exploratory study in patients with diabetes and primary care providers.

BACKGROUND: Medication self-management is important for patients who are controlling diabetes. Achieving medication self-management goals, may depend on treatment complexity and patients' capacities such as health literacy, knowledge and attitude. OBJECTIVES: The aims of this study were to explore how patients with diabetes self-manage their medications, how patients seek support when experiencing problems and how primary healthcare providers identify patients' medication related problems and provide support. METHODS: Semi-structured interviews were conducted among patients with diabetes receiving primary care and with their primary healthcare providers - GPs, nurses, pharmacists and technicians - between January and June 2017. A purposive sampling strategy was used to identify and select participants. An interview guide based on the Cycle of Complexity model was developed. Interviews were audiotaped and transcribed verbatim. Transcripts were coded with a combination of deductive and inductive codes. A thematic analysis was performed to identify categories and themes in the data. Findings were compared with the Cycle of Complexity model. RESULTS: Twelve patients and 27 healthcare providers were included in the study. From the transcripts 95 codes, 6 categories and 2 major themes were extracted. Patients used practical solutions and gaining knowledge to manage their medication. Their problems were often related to stress and concerns about using medications. A trusted relationship with the healthcare provider was essential for patients to share problems and ask for support. Informal support was sought from family and peer-patients. Healthcare providers perceive problem identification as challenging. They relied on patients coming forward, computer notifications, clinical parameters and gut-feeling. Healthcare providers were able to offer appropriate support if a medication management problem was known. CONCLUSION: Patients are confident of finding their way to manage their medications. However, sharing problems with healthcare providers requires a trusted relationship. This is acknowledged by both patients and healthcare providers.

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.

Implicit and explicit attitudes towards disease-modifying antirheumatic drugs as possible target for improving medication adherence.

OBJECTIVE: This study aims to explore the contribution of implicit attitudes and associations towards conventional disease-modifying antirheumatic drugs (cDMARDs), alongside explicit measures, on medication-taking behaviour and clinical outcomes in adult patients with rheumatoid arthritis (RA). METHODS: In this observational study, implicit attitudes (positive-negative) and health-related associations (health-sickness) were measured with Single Category Implicit Association Tests, whereas explicit outcomes were measured with a bipolar evaluative adjective scale and the Beliefs about Medicines Questionnaire Specific. The primary outcome of this study was medication-taking behaviour subjectively measured by self-report (i.e. validated Compliance Questionnaire on Rheumatology) and objectively measured with electronic drug monitors over a 3 month period. Spearman rank correlations were used to describe correlations between implicit and explicit outcomes. Nested linear regression models were used to assess the additional value of implicit measures over explicit measures and patient-, clinical-, and treatment-related characteristics. RESULTS: Of the 1659 initially-invited patients, 254 patients with RA agreed to participate in this study. Implicit attitudes correlated significantly with necessity-concerns differential (NCD) scores (ρ = 0.13, P = 0.05) and disease activity scores (ρ = -0.17, P = 0.04), whereas implicit health-related associations correlated significantly with mean scores for explicitly reported health-related associations (ρ = 0.18, P = 0.004). Significant differences in age, number of DMARDs, biologic DMARD use, NCD-scores, and self-reported correct dosing were found between the four attitudinal profiles. Nested linear regression models revealed no additional value of implicit measures in explaining self-reported medication-taking behaviour and clinical outcomes, over and above all other variables. CONCLUSION: Implicit attitudes and associations had no additional value in explaining medication-taking behaviour and clinical outcomes over and above often used explicitly measured characteristics, attitudes and outcomes in the studied population. Only age and NCD scores contributed significantly when the dependent variable was correct dosing measured with self-report.

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.

Case report: direct revascularization in acute mesenteric ischemia by an endovascular approach.

BACKGROUND: Acute mesenteric ischemia is a relatively rare but life-threatening clinical condition. Outcome depends on early diagnosis and prompt intervention. CASE PRESENTATION: A 85-year-old man and a 75-year-old woman developed acute mesenteric ischemia due to cardiac embolism. The first patient received an insufficient dose of anticoagulants for atrial fibrillation and the second patient dicontinued her anticoagulantia to avoid bleeding during a routine colonoscopy. Both patients presented with severe abdominal pain and computed tomography showed thrombus in de superior mesenteric artery. Successfulrevascularization with good clinical outcome was achieved by means of an endovascular first approach. CONCLUSION: This case report shows that an endovascular approach - in contrast to open surgery - not only enables to revascularize main trunk lesions but can also facilitate revascularization of side branches. Endovascular treatment used to be limited to a selected group of patients without signs of bowel necrosis, but there is a tendency to initiate endovascular revascularization in all patients because it is associated with a reduced mortality, a reduced laparotomy rate and reduction in the resected length of bowel.

Long-term outcomes following the medial approach for open reduction of the hip in children with developmental dysplasia.

Aims Open reduction is required following failed conservative treatment of developmental dysplasia of the hip (DDH). The Ludloff medial approach is commonly used, but poor results have been reported, with rates of the development of avascular necrosis (AVN) varying between 8% and 54%. This retrospective cohort study evaluates the long-term radiographic and clinical outcome of dislocated hips treated using this approach. Patients and Methods Children with a dislocated hip, younger than one year of age at the time of surgery, who were treated using a medial approach were eligible for the study. Radiographs were evaluated for the degree of dislocation and the presence of an ossific nucleus preoperatively, and for the degree of AVN and residual dysplasia at one and five years and at a mean of 12.7 years (4.6 to 20.8) postoperatively. Radiographic outcome was assessed using the Severin classification, after five years of age. Further surgical procedures were recorded. Functional outcome was assessed using the Pediatric Outcomes Data Collection Instrument (PODCI) or the Hip Disability and Osteoarthritis Outcome Score (HOOS), depending on the patient's age. Results A total of 52 children (58 hips) were included. At the latest follow-up, 11 hips (19%) showed signs of AVN. Further surgery was undertaken in 13 hips (22%). A total of 13 hips had a poor radiological outcome with Severin type III or higher. Of these, the age at the time of surgery was significantly higher (p < 0.05) than in those with a good Severin type (I or II). The patient-reported outcomes were significantly worse (p < 0.05) in children with a poor Severin classification. Conclusion This retrospective long-term follow-up study shows that one in five children with DDH who undergo open reduction using a medial surgical approach has poor clinical and/or radiological outcome. The poor outcome is not related to the presence of AVN (19%), but due to residual dysplasia. Cite this article: Bone Joint J 2018;100-B:822-7.