The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire: predicting clinical arthritis development.

OBJECTIVE: There is a need to better define symptom characteristics associated with arthritis development in individuals at risk of rheumatoid arthritis (RA). We investigated whether reported symptoms in at-risk individuals could predict arthritis development and whether predictive symptoms differed between seropositive and seronegative at-risk individuals. METHOD: At-risk individuals from four cohorts (Netherlands, UK, Sweden, and Switzerland) completed the Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire. Participants had either (i) anti-citrullinated protein antibodies and/or rheumatoid factor, or (ii) relevant symptoms with or without RA antibodies. Follow up was ≥ 24 months or until clinical arthritis development. Stepwise forward selection created SPARRA prediction models for the combined group and for a seropositive subgroup. RESULTS: Of 214 participants, the mean age was 50 years, 67% were female, and 27% (n = 58) developed clinical arthritis after a median time of 7 months. Four symptoms predicted arthritis development: self-reported joint swelling, joint pain moving from side to side (combined group only), feeling pins and needles in the joints, and often feeling fatigued (predicting non-arthritis). CONCLUSION: Specific symptoms can provide useful information to estimate a person's RA risk. Differences in predictive symptoms between seropositive and seronegative at-risk individuals need to be further investigated. Future research is needed to determine whether changes in symptoms over time improve prediction and to determine the value of SPARRA in optimizing the selection of individuals who need to consult a rheumatologist.

Disease activity in women with ankylosing spondylitis remains higher under Tumour Necrosis Factor inhibitor treatment than in men: a five-year observational study.

OBJECTIVE: To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. METHOD: Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. RESULTS: Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (ß = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). CONCLUSION: Female AS patients show a lower response to TNFi and a higher disease activity compared to men.

Long-term effects on bone mineral density after four years of treatment with two intensive combination strategies, including initially high-dose prednisolone, in early rheumatoid arthritis patients: the COBRA-light trial.

In this study, no difference in bone loss was observed between patients with early RA initially treated with COmbinatietherapie Bij Reumatoide Artritis (COBRA) (including initially 60 mg/day prednisolone) and patients treated with COBRA-light (including initially 30 mg/day prednisolone) during 4-year observation. PURPOSE: To assess changes in bone mineral density (BMD) after 4 years in early rheumatoid arthritis (RA) patients initially treated with COBRA-light or COBRA therapy. METHODS: In a 1 year, open-label, randomised, non-inferiority trial, patients were assigned to COBRA-light (methotrexate 25 mg/week plus initially prednisolone 30 mg/day) or COBRA (methotrexate 7.5 mg/week, sulfasalazine 2 g/day plus initially prednisolone 60 mg/day) therapy. After 1 year, antirheumatic treatment was at the discretion of treating rheumatologists. BMD was measured at baseline and after 1, 2 and 4 years at hips and lumbar spine with dual-energy X-ray absorptiometry. BMD changes between treatment strategies on average over time were compared with GEE analysis. RESULTS: Data from 155 out of 162 patients could be analysed: 68% were female with a mean age of 52 (SD 13) years. Both COBRA-light and COBRA therapy showed declines in BMD at the total hip of -3.3% and -1.7%, respectively (p = 0.12), and the femoral neck, -3.7% and -3.0%, respectively (p = 0.95). At the lumbar spine, both treatment groups showed minor decline in BMD over 4 years: -0.5% and -1.0%, respectively (p = 0.10). CONCLUSION: In a treat-to-target design in early RA, over 4 years, no differences between groups were found in change in BMD at total hip, femoral neck and the lumbar spine. At the hip, bone loss was around 3% in both groups, while mild bone loss was observed at lumbar spine, both in patients starting prednisolone 60 and 30 mg/day. These data suggest that the well-known negative effects of prednisolone can be modulated by modern treatment of RA.

Accuracy of an algorithm to identify rheumatoid arthritis in the Longitudinal Ageing Study Amsterdam population: a validation study.

Objective: In view of global ageing and the scarcity of knowledge about disease determinants in older individuals with rheumatoid arthritis (RA), an algorithm with optimal diagnostic accuracy was developed to identify RA patients in the Longitudinal Ageing Study Amsterdam (LASA).Method: Four case ascertainment algorithms were constructed and assessed for validity in LASA, an ongoing cohort study (≥ 55 years) representing the general older population of the Netherlands. Data sources used to identify the diagnosis RA were: self-reported morbidity, specialist diagnosis, and medication. A validation subsample of LASA participants was taken to verify RA diagnosis by a standard procedure using a checklist.Results: Data from 272/300 (91%) participants were verified. Four algorithms were developed: 'treatment', 'diagnosis', 'treatment or diagnosis', and 'treatment and diagnosis'. The algorithm 'treatment and diagnosis' showed the best measurement properties: specificity 100%, positive predictive value 100%, and area under the receiver operating characteristics curve 0.72. Applying this algorithm in the LASA sample (mean age 71 years) revealed a prevalence of RA of 1.0% (19/1908 participants).Conclusion: An algorithm for RA identification in the LASA population was developed, with high diagnostic accuracy. It provides an accurate tool to identify older adults with RA in LASA and, after validation, may be applicable in other large population-based studies.

Integration of a Dielectrophoretic Tapered Aluminum Microelectrode Array with a Flow Focusing Technique.

We present the integration of a flow focusing microfluidic device in a dielectrophoretic application that based on a tapered aluminum microelectrode array (TAMA). The characterization and optimization method of microfluidic geometry performs the hydrodynamic flow focusing on the channel. The sample fluids are hydrodynamically focused into the region of interest (ROI) where the dielectrophoresis force (FDEP) is dominant. The device geometry is designed using 3D CAD software and fabricated using the micro-milling process combined with soft lithography using PDMS. The flow simulation is achieved using COMSOL Multiphysics 5.5 to study the effect of the flow rate ratio between the sample fluids (Q1) and the sheath fluids (Q2) toward the width of flow focusing. Five different flow rate ratios (Q1/Q2) are recorded in this experiment, which are 0.2, 0.4, 0.6, 0.8 and 1.0. The width of flow focusing is increased linearly with the flow rate ratio (Q1/Q2) for both the simulation and the experiment. At the highest flow rate ratio (Q1/Q2 = 1), the width of flow focusing is obtained at 638.66 µm and at the lowest flow rate ratio (Q1/Q2 = 0.2), the width of flow focusing is obtained at 226.03 µm. As a result, the flow focusing effect is able to reduce the dispersion of the particles in the microelectrode from 2000 µm to 226.03 µm toward the ROI. The significance of flow focusing on the separation of particles is studied using 10 and 1 µm polystyrene beads by applying a non-uniform electrical field to the TAMA at 10 VPP, 150 kHz. Ultimately, we are able to manipulate the trajectories of two different types of particles in the channel. For further validation, the focusing of 3.2 µm polystyrene beads within the dominant FDEP results in an enhanced manipulation efficiency from 20% to 80% in the ROI.

Dielectrophoresis Prototypic Polystyrene Particle Synchronization toward Alive Keratinocyte Cells for Rapid Chronic Wound Healing.

Diabetes patients are at risk of having chronic wounds, which would take months to years to resolve naturally. Chronic wounds can be countered using the electrical stimulation technique (EST) by dielectrophoresis (DEP), which is label-free, highly sensitive, and selective for particle trajectory. In this study, we focus on the validation of polystyrene particles of 3.2 and 4.8 µm to predict the behavior of keratinocytes to estimate their crossover frequency (fXO) using the DEP force (FDEP) for particle manipulation. MyDEP is a piece of java-based stand-alone software used to consider the dielectric particle response to AC electric fields and analyzes the electrical properties of biological cells. The prototypic 3.2 and 4.8 µm polystyrene particles have fXO values from MyDEP of 425.02 and 275.37 kHz, respectively. Fibroblast cells were also subjected to numerical analysis because the interaction of keratinocytes and fibroblast cells is essential for wound healing. Consequently, the predicted fXO from the MyDEP plot for keratinocyte and fibroblast cells are 510.53 and 28.10 MHz, respectively. The finite element method (FEM) is utilized to compute the electric field intensity and particle trajectory based on DEP and drag forces. Moreover, the particle trajectories are quantified in a high and low conductive medium. To justify the simulation, further DEP experiments are carried out by applying a non-uniform electric field to a mixture of different sizes of polystyrene particles and keratinocyte cells, and these results are well agreed. The alive keratinocyte cells exhibit NDEP force in a highly conductive medium from 100 kHz to 25 MHz. 2D/3D motion analysis software (DIPP-MotionV) can also perform image analysis of keratinocyte cells and evaluate the average speed, acceleration, and trajectory position. The resultant NDEP force can align the keratinocyte cells in the wound site upon suitable applied frequency. Thus, MyDEP estimates the Clausius-Mossotti factors (CMF), FEM computes the cell trajectory, and the experimental results of prototypic polystyrene particles are well correlated and provide an optimistic response towards keratinocyte cells for rapid wound healing applications.

Predictors of sick leave and improved worker productivity after 52 weeks of intensive treatment in patients with early rheumatoid arthritis.

Objective: To identify predictors of sick leave and improved worker productivity in patients with early rheumatoid arthritis (RA) treated for 52 weeks with intensive combination strategies. Methods: Patients with early RA were included in the COmbinatietherapie Bij Reumatoïde Artritis (COBRA)-light trial and followed for 52 weeks. As the COBRA-light strategy proved to be non-inferior to the COBRA strategy, all patients were pooled. Predictors for sick leave and improved worker productivity were assessed through a 3 month time-lag multivariable logistic generalized estimating equations model. Results: At baseline, 97 patients had a paid job, 59 had no job, and for six patients the work status was unknown. During the trial, 13 patients stopped working (8%) and six started working (4%). Only sick leave in the past 3 months predicted sick leave. By excluding this variable, patient global assessment and actual hours of sick leave became predictors. Increased worker productivity was predicted by higher patient global assessment levels, Sharp van der Heijde score ≥ 1, actual hours on sick leave, and higher worker productivity in the past 3 months. Conclusion: Sick leave and improved worker productivity were mainly predicted by non-disease-specific variables. Both outcomes can be predicted on a 3 month basis, using the outcome over the past 3 months for the next 3 months. By applying this model in daily practice, decisions for therapy change could be based not solely on disease activity but also taking into account a possible high risk for sick leave in the upcoming 3 months.

Screening instruments for identification of vulnerable older adults at the emergency department: a critical appraisal.

BACKGROUND: Early detection of vulnerable older adults at the emergency department (ED) and implementation of targeted interventions to prevent functional decline may lead to better patient outcomes. OBJECTIVE: To assess the level of agreement between four frequently used screening instruments: ISAR-HP, VMS, InterRAI ED Screener and APOP. METHODS: Observational prospective cohort study in patients ≥ 70 years attending Dutch ED. RESULTS: The prevalence of vulnerability ranged from 19% (APOP) to 45% (ISAR-HP). Overall there was a moderate agreement between the screening instruments (Fleiss Kappa of 0.42 (p<0.001)). CONCLUSION: Depending on the screening instrument used, either only a small percentage or almost as many as half of the presenting patients will be eligible for targeted interventions, leading to large dissimilarities in working processes, resources and costs.

Indirect costs account for half of the total costs of an osteoporotic fracture: a prospective evaluation.

UNLABELLED: Data on direct and indirect costs of clinical fractures in 116 osteoporotic patients 50 years and older were prospectively collected using cost diaries. Indirect costs accounted for roughly half of the total costs, with a contribution of at least 81% of these costs in employed patients. INTRODUCTION: The aim of this prospective study was to gain insight into the current total costs of clinical fractures in osteoporotic patients aged 50 years and older. METHODS: In a study in the Netherlands, patients prospectively filled out cost diaries every 3 months, during 1 year after a clinical fracture. Primary analyses were performed on those patients with all four cost diaries returned. In-depth analyses of indirect costs were performed, dividing results for employed and unemployed patients. Sensitivity analyses using imputation techniques were performed on patients who returned two or three diaries RESULTS: Of the 116 included patients, 69 completed all four diaries, 24 only two or three, and 23 patient completed one or no diaries. For all fractures, approximately 50% of the total costs were due to indirect costs; employed patients contributed for at least 81% of the indirect cost. Humerus fractures were most expensive with a total 1-year cost of €16.841 per patient. Indirect costs in the group with clinical spine fractures were highest (12.522), accounting for 89.1% of the total costs for this fracture. CONCLUSION: Indirect costs account for roughly half of the total costs of clinical fractures, which are largely related to sick leave. When performing cost analyses in fracture patients, we advise a societal perspective in which indirect costs are also considered, and to apply a patient derived prospective data collection method to get a 'true' and complete image of the total costs due to clinical fractures.

A comparison of intramuscular diamorphine and intramuscular pethidine for labour analgesia: a two-centre randomised blinded controlled trial.

OBJECTIVE: Intramuscular (i.m.) pethidine is used worldwide for labour analgesia and i.m. diamorphine usage has increased in the UK in the last 15 years. This trial aims to ascertain the relative efficacy and adverse effects of diamorphine and pethidine for labour pain. DESIGN: Prospective, parallel-arm randomised controlled trial with blinding of participants, care-givers and outcome assessors. SETTING: Maternity units in two District General Hospitals in the UK. POPULATION: After written informed consent, 484 women were randomised and recruited (244 diamorphine, 240 pethidine). Inclusion criteria included women 16 years or older, established labour, singleton pregnancy, 37-42 weeks of gestation and weight 60-120 kg. METHODS: On request of i.m. analgesia, participants received either 150 mg pethidine or 7.5 mg diamorphine based on computer-generated block randomisation. MAIN OUTCOME MEASURES: Maternal-reduction in pain intensity from baseline (10-cm visual analogue scale) at 60 minutes and over the 3-hour period after drug administration. Neonatal-requirement for resuscitation and Apgar score at 1 minute. RESULTS: Diamorphine provided modestly improved pain relief at 60 minutes, mean difference 1 cm (95% confidence interval [CI] 0.5-1.5), and over the 3 hours, mean difference 0.7 cm (95% CI 0.3-1.1). However, average length of labour in women receiving diamorphine was 82 minutes longer (95% CI 39-124) and therefore they experienced more pain overall. There were no statistically significant differences in primary neonatal outcomes. CONCLUSIONS: There is a modest difference between the analgesia provided by diamorphine or pethidine for labour analgesia but diamorphine is associated with significantly longer labours.

A national survey of obstetric early warning systems in the United Kingdom: five years on.

The Confidential Enquiries into Maternal Deaths in the UK have recommended obstetric early warning systems for early identification of clinical deterioration to reduce maternal morbidity and mortality. This survey explored early warning systems currently used by maternity units in the UK. An electronic questionnaire was sent to all 205 lead obstetric anaesthetists under the auspices of the Obstetric Anaesthetists' Association, generating 130 (63%) responses. All respondents reported use of an obstetric early warning system, compared with 19% in a similar survey in 2007. Respondents agreed that the six most important physiological parameters to record were respiratory rate, heart rate, temperature, systolic and diastolic blood pressure and oxygen saturation. One hundred and eighteen (91%) lead anaesthetists agreed that early warning systems helped to prevent obstetric morbidity. Staffing pressures were perceived as the greatest barrier to their use, and improved audit, education and training for healthcare professionals were identified as priority areas.

Antibody elution with 2-me/SDS solution: Uses for multi-layer immunohistochemical analysis of wholemount preparations of human colonic myenteric plexus.

Indirect immunofluorescence is usually restricted to 3-5 markers per preparation, limiting analysis of coexistence. A solution containing 2-mercaptoethanol and sodium dodecyl sulfate (2-ME/SDS) can elute indirect immunofluorescence labelling (i.e. primary antisera followed by fluorophore-conjugated secondary antisera) and has been used for sequential staining of sections. The aim of this study was to test whether 2-ME/SDS is effective for eluting indirect immunofluorescent staining (with primary antisera visualised by fluorophore-coupled secondary antisera) in wholemount preparations. We also analysed how 2-ME/SDS may work and used this understanding to devise additional uses for immunofluorescence in the nervous system. 2-ME/SDS appears to denature unfixed proteins (including antisera used as reagents) but has much less effect on antigenicity of formaldehyde-fixed epitopes. Moieties linked by strong biotin-streptavidin bonds are highly resistant to elution by 2-ME/SDS. Two primary antisera raised in the same species can be applied without spurious cross-reactivity, if a specific order of labelling is followed. The first primary antiserum is followed by a biotinylated secondary, then a tertiary of fluorophore-conjugated streptavidin. The preparation is then exposed to 2-ME/SDS, which has minimal impact on labelling by the first primary/secondary/tertiary combination. However, when this is followed by a second primary antiserum (raised in the same species), followed by a fluorophore-conjugated secondary antiserum, the intervening 2-ME/SDS exposure prevents cross-reactivity between primary and secondary antisera of the two layers. A third property of 2-ME/SDS is that it reduces lipofuscin autofluorescence, although it also raises background fluorescence and strongly enhances autofluorescence of erythrocytes. In summary, 2-ME/SDS is easy to use, cost-effective and does not require modified primary antisera. It can be used as the basis of a multi-layer immunohistochemistry protocol and allows 2 primary antisera raised in the same species to be used together.

A study to examine the ageing behaviour of cold plasma-treated agricultural seeds.

Cold plasma (low pressure) technology has been effectively used to boost the germination and growth of various crops in recent decades. The durability of these plasma-treated seeds is essential because of the need to store and distribute the seeds at different locations. However, these ageing effects are often not ascertained and reported because germination and related tests are carried out within a short time after the plasma-treatment. This research aims to fill that knowledge gap by subjecting three different types of seeds (and precursors): Bambara groundnuts (water), chilli (oxygen), and papaya (oxygen) to cold plasma-treatment. Common mechanisms found for these diverse seed types and treatment conditions were the physical and chemical changes induced by the physical etching and the cold plasma on the seeds and subsequent oxidation, which promoted germination and growth. The high glass transition temperature of the lignin-cellulose prevented any physical restructuring of the surfaces while maintaining the chemical changes to continue to promote the seeds germination and growth. These changes were monitored over 60 days of ageing using water contact angle (WCA), water uptake, electrical conductivity, field emission scanning electron microscopy (FE-SEM) and X-ray photoelectron spectroscopy (XPS). The vacuum effect was also investigated to separate its effect from cold plasma (low pressure). This finding offers a framework for determining how long agricultural seeds that have received plasma treatment can be used. Additionally, there is a need to transfer this research from the lab to the field. Once the impact of plasma treatment on seeds has been estimated, it will be simple to do so.

Atmospheric Pressure Plasma Polymerisation of D-Limonene and Its Antimicrobial Activity.

Antibacterial coating is necessary to prevent biofilm-forming bacteria from colonising medical tools causing infection and sepsis in patients. The recent coating strategies such as immobilisation of antimicrobial materials and low-pressure plasma polymerisation may require multiple processing steps involving a high-vacuum system and time-consuming process. Some of those have limited efficacy and durability. Here, we report a rapid and one-step atmospheric pressure plasma polymerisation (APPP) of D-limonene to produce nano-thin films with hydrophobic-like properties for antibacterial applications. The influence of plasma polymerisation time on the thickness, surface characteristic, and chemical composition of the plasma-polymerised films was systematically investigated. Results showed that the nano-thin films deposited at 1 min on glass substrate are optically transparent and homogenous, with a thickness of 44.3 ± 4.8 nm, a smooth surface with an average roughness of 0.23 ± 0.02 nm. For its antimicrobial activity, the biofilm assay evaluation revealed a significant 94% decrease in the number of Escherichia coli (E. coli) compared to the control sample. More importantly, the resultant nano-thin films exhibited a potent bactericidal effect that can distort and rupture the membrane of the treated bacteria. These findings provide important insights into the development of bacteria-resistant and biocompatible coatings on the arbitrary substrate in a straightforward and cost-effective route at atmospheric pressure.

Characterization of Dual-Layer Hybrid Biomatrix for Future Use in Cutaneous Wound Healing.

A skin wound without immediate treatment could delay wound healing and may lead to death after severe infection (sepsis). Any interruption or inappropriate normal wound healing, mainly in these wounds, commonly resulted in prolonged and excessive skin contraction. Contraction is a common mechanism in wound healing phases and contributes 40-80% of the original wound size post-healing. Even though it is essential to accelerate wound healing, it also simultaneously limits movement, mainly in the joint area. In the worst-case scenario, prolonged contraction could lead to disfigurement and loss of tissue function. This study aimed to fabricate and characterise the elastin-fortified gelatin/polyvinyl alcohol (PVA) film layered on top of a collagen sponge as a bilayer hybrid biomatrix. Briefly, the combination of halal-based gelatin (4% (w/v)) and PVA ((4% (w/v)) was used to fabricate composite film, followed by the integration of poultry elastin (0.25 mg/mL) and 0.1% (w/v) genipin crosslinking. Furthermore, further analysis was conducted on the composite bilayer biomatrix's physicochemical and mechanical strength. The bilayer biomatrix demonstrated a slow biodegradation rate (0.374967 ± 0.031 mg/h), adequate water absorption (1078.734 ± 42.33%), reasonable water vapour transmission rate (WVTR) (724.6467 ± 70.69 g/m2 h) and porous (102.5944 ± 28.21%). The bilayer biomatrix also exhibited an excellent crosslinking degree and was mechanically robust. Besides, the elastin releasing study presented an acceptable rate post-integration with hybrid biomatrix. Therefore, the ready-to-use bilayer biomatrix will benefit therapeutic effects as an alternative treatment for future diabetic skin wound management.

Plasma-Polymerised Antibacterial Coating of Ovine Tendon Collagen Type I (OTC) Crosslinked with Genipin (GNP) and Dehydrothermal-Crosslinked (DHT) as a Cutaneous Substitute for Wound Healing.

Tissue engineering products have grown in popularity as a therapeutic approach for chronic wounds and burns. However, some drawbacks include additional steps and a lack of antibacterial capacities, both of which need to be addressed to treat wounds effectively. This study aimed to develop an acellular, ready-to-use ovine tendon collagen type I (OTC-I) bioscaffold with an antibacterial coating for the immediate treatment of skin wounds and to prevent infection post-implantation. Two types of crosslinkers, 0.1% genipin (GNP) and dehydrothermal treatment (DHT), were explored to optimise the material strength and biodegradability compared with a non-crosslinked (OTC) control. Carvone plasma polymerisation (ppCar) was conducted to deposit an antibacterial protective coating. Various parameters were performed to investigate the physicochemical properties, mechanical properties, microstructures, biodegradability, thermal stability, surface wettability, antibacterial activity and biocompatibility of the scaffolds on human skin cells between the different crosslinkers, with and without plasma polymerisation. GNP is a better crosslinker than DHT because it demonstrated better physicochemical properties (27.33 ± 5.69% vs. 43 ± 7.64% shrinkage), mechanical properties (0.15 ± 0.15 MPa vs. 0.07 ± 0.08 MPa), swelling (2453 ± 419.2% vs. 1535 ± 392.9%), biodegradation (0.06 ± 0.06 mg/h vs. 0.15 ± 0.16 mg/h), microstructure and biocompatibility. Similarly, its ppCar counterpart, GNPppCar, presents promising results as a biomaterial with enhanced antibacterial properties. Plasma-polymerised carvone on a crosslinked collagen scaffold could also support human skin cell proliferation and viability while preventing infection. Thus, GNPppCar has potential for the rapid treatment of healing wounds.

Load-induced deformation of the tibia and its effect on implant loosening detection.

CT imaging under external valgus and varus loading conditions and consecutive image analysis can be used to detect tibial implant loosening after total knee arthroplasty. However, the applied load causes the tibia to deform, which could result in an overestimation of implant displacement. This research evaluates the extent of tibia deformation and its effect on measuring implant displacement. Ten cadaver specimen with TKA were CT-scanned under valgus/varus loading (20 Nm), first implanted without bone cement fixation (mimicking a loose implant) and subsequently with bone cement fixation (mimicking a fixed implant). By means of image analysis, three relative displacements were assessed: (1) between the proximal and distal tibia (measure of deformation), (2) between the implant and the whole tibia (including potential deformation effect) and (3) between the implant and the proximal tibia (reduced deformation effect). Relative displacements were quantified in terms of translations along, and rotations about the axes of a local coordinate system. As a measure of deformation, the proximal tibia moved relative to the distal tibia by, on average 1.27 mm (± 0.50 mm) and 0.64° (± 0.25°). Deformation caused an overestimation of implant displacement in the cemented implant. The implant displaced with respect to the whole tibia by 0.45 mm (± 0.22 mm) and 0.79° (± 0.38°). Relative to the proximal tibia, the implant moved by 0.23 mm (± 0.10 mm) and 0.62° (± 0.34°). The differentiation between loose and fixed implants improved when tibia deformation was compensated for by using the proximal tibia rather than the whole tibia.

The effect of biological agents on work participation in rheumatoid arthritis patients: a systematic review.

This study reviewed the effect of biological agents on participation in paid work among patients with rheumatoid arthritis (RA). A systematic literature search was performed to identify published articles reporting the effect of biological agents on employment status, sick leave and/or presenteeism. The quality of included articles was assessed according to the guidelines as proposed by the Dutch Cochrane Centre. Narrative summaries were used to present the data separately for randomised controlled trials (RCTs) as well as controlled and uncontrolled cohort studies. 19 studies (six uncontrolled cohorts, seven controlled cohorts and six RCTs) were included, in which 11 259 patients were treated with biological agents. Employment status improved in four out of 13 studies, absence from work in all 10 studies and presenteeism in seven out of nine studies that reported this outcome. For absenteeism and presenteeism the statistical significance of change or difference was not always provided and results within studies were sometimes conflicting when using different time frames or alternative outcomes. The large heterogeneity in terms of population, design, analyses and most important in outcome measures limits interpretation of the data. RCTs as well as cohort studies showed positive results of biological agents on both absenteeism and presenteeism compared with other disease-modifying antirheumatic drugs (DMARD), continuing the failing DMARD, the general population or the situation before the start of biological agents. The effect on employment status was more conflicting, but 50% of studies that addressed patients with early methotrexate-naive RA showed a positive result on employment status.

Who stop telemonitoring disease activity and who adhere: a prospective cohort study of patients with inflammatory arthritis.

BACKGROUND: The use of frequent electronic patient reported outcome measures (ePRO's) enables monitoring disease activity at a distance (telemonitoring) in patients with inflammatory arthritis. However, telemonitoring studies report declining long-term adherence to reporting ePRO's, which may oppose the benefits of telemonitoring. Therefore, the objective was to investigate what factors are associated with (non-)adherence to telemonitoring with a weekly ePRO in patients with inflammatory arthritis (IA). METHODS: We performed a prospective cohort study in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) at Reade Amsterdam, The Netherlands. Patients telemonitored their disease activity weekly for 6 months with a modified Multidimensional Health Assessment Questionnaire completed in a smartphone application. The primary outcome was time to dropout, defined as ≥ 4 weeks of consecutively nonresponse. Based on literature and through expert meetings, a predefined set of 13 baseline factors were selected to assess the association with time to dropout through a multivariable Cox-regression analysis. RESULTS: A total of 220 consecutive patients were included (mean age 54, SD 12; 55% females; 99 RA, 81 PsA, and 40 AS). A total of 141 patients (64%) dropped out, with a median time to dropout of 17 weeks (IQR 9-26). Women had a significant higher chance to dropout over 6 months compared to men (HR 1.58, 95% CI 1.06-2.36). CONCLUSION: In the set of investigated factors, women stopped reporting the weekly ePRO sooner than men. Future focus group discussions will be performed to investigate the reasons for dropout, and in specific why women dropped out sooner. Trial registration This trials was prospectively registered at www.trialregister.nl (NL8414).

The RAPID3 questionnaire as a screening tool to reduce the number of outpatient clinic visits: a retrospective cohort study.

BACKGROUND: Treat-to-target strategies require frequent on-site evaluations of disease activity in patients with rheumatoid arthritis (RA), burdening patients and caregivers. However, this frequency may not be required in patients in a stable low disease activity state. The Routine Assessment of Patient Index Data 3 (RAPID3) is a reliable tool to detect such states in groups but has not been tested to reduce the frequency of on-site evaluations in individual patient care. In Reade, an outpatient rheumatology clinic, patients can complete the questionnaire online prior to consultation, and the results are directly fed into the electronic patient record. Focusing on low disease activity, we retrospectively studied the test characteristics of RAPID3 and its agreement with the DAS28 in our database of routine patient care. OBJECTIVE: To assess the test characteristics and agreement between de DAS28 and the RAPID3 in patients with RA, with a focus on the low disease activity categories. METHODS: We performed a retrospective database study with available clinical data collected as part of usual care from the electronic medical record at Reade Amsterdam. The dataset comprised RAPID3 assessments followed by a DAS28 within 2 weeks, obtained between June 2014 and March 2021. We dichotomized the disease activity categories for both the RAPID3 and DAS28 into low (remission and low disease activity) and high (moderate and high disease activity). With cutoff values of 2.0 for RAPID3 and 3.2 for DAS28, we calculated test characteristics and agreement (Cohen's kappa). RESULTS: A total of 5009 combined RAPID3 and DAS28 measurements were done at Reade in 1681 unique RA patients. The mean age was 60 years, and 76% of patients were female with a median disease duration of 4 years. Agreement was considered fair (kappa = 0.26). In total, 1426 (28%) of the RAPID3 measurements were classified as low and could be potentially targeted to skip their consultations. The sensitivity to detect low disease activity was 0.39, specificity was 0.93, and the positive predictive value was 0.92. CONCLUSION: We showed that when the RAPID3 classifies a patient into low disease activity state, the accuracy is 92%. Of all consultations, 28% could possibly be postponed following the screening with RAPID3.