Male rheumatoid arthritis patients at substantially higher risk for cardiovascular mortality in comparison to women.

BACKGROUND: Patients with rheumatoid arthritis (RA) are at an increased risk for developing cardiovascular diseases. While advice regarding cardiovascular risk screening and management in RA patients has been incorporated in several guidelines in recent years, its implementation and adherence is still poor. OBJECTIVES: To assess the cardiovascular disease risk in new diagnosed RA patients and evaluate whether advice to initiate preventive medical treatment of high risk patients was followed. METHODS: All patients with a recent diagnosis of RA, aged 40-70 years, were screened between May 2019 and December 2022 for cardiovascular diseases and risk factors within the first year after diagnosis at the outpatient rheumatology clinic, as part of standard care. Screening included a physical examination with blood pressure measurement, and laboratory tests with lipid profile tests. All patients and their general practitioner (GP) received an overview with their cardiovascular risk profile and a calculated 10-year cardiovascular mortality risk. Cardiovascular risk was defined as low (<1%), intermediate (1-5%), high (5-10%) and very high (>10%). The national pharmacy network was consulted to check whether or not patients started preventive medication after screening. RESULTS: A total of 125 RA patients was included in this study. The mean age was 56 years and 78% was female. Median RA disease duration at screening was 6 months. Six patients (5%) indicated to have been screened before, and used antihypertensive medication. During screening, hypertension was found in 57% of male patients and 43% of female patients and dyslipidemia was found in 36% in male and 32% in female patients. 46% of male patients and 21% of female patients currently smoked. A high or very high 10-year cardiovascular mortality risk was found in 50% of male patients, but in only 4% of female patients. Only 26% of (very) high risk patients started antihypertensive or statin medication after screening. CONCLUSIONS: An increased cardiovascular disease risk is often present in newly diagnosed RA patients, especially male patients, with a large proportion having undiagnosed and untreated hypertension and hypercholesterolemia. Even with structural screening and informing of the patients and GPs, treatment of cardiovascular risk factors in high risk patients remains insufficient. CV risk screening needs to be part of standard care for RA patients, with clear agreement on the responsibilities between primary and secondary care. Awareness of the importance of CVD risk screening needs to improve among both RA patients themselves and the GPs to ultimately reduce the cardiovascular burden of our patients. Obviously, a better collaboration between GPs and rheumatologists is urgently needed to lower the cardiovascular burden of our patients.

The addition of the MEP amplitude of finger extension muscles to clinical predictors of hand function after stroke: A prospective cohort study.

BACKGROUND: Within the first 72 hours after stroke, active finger extension is a strong predictor of long-term dexterity. Transcranial magnetic stimulation may add prognostic value to clinical assessment, which is especially relevant for patients unable to follow instructions. OBJECTIVE: The current prospective cohort study aims at determining whether amplitude of motor evoked potentials of the extensor digitorum communis (EDC) can improve clinical prediction after stroke when added to clinical tests. METHODS: the amplitude of motor evoked potentials of the affected EDC muscle at rest was measured in 18 participants within 4 weeks after stroke, as were the ability to perform finger extension and the Fugl-Meyer Motor Assessment of the upper extremity (FMA_UE). These three determinants were related to the FMA_UE at 26 weeks after stroke (FMA_UE26), both directly, and via the proportional recovery prediction model. The relation between amplitude of the motor evoked potentials and FMA_UE26 was evaluated for EDC. For comparison, also the MEP amplitudes of biceps brachii and adductor digiti minimi muscles were recorded. RESULTS: Patients' ability to voluntarily extend the fingers was strongly related to FMA_UE26, in our cohort there were no false negative results for this predictor. Our data revealed that the relation between amplitude of motor evoked potential of EDC and FMA_UE26 was significant, but moderate (rs = 0.58) without added clinical value. The other tested muscles did not correlate significantly to FMA_UE26. CONCLUSIONS: Our study demonstrates no additional value of motor evoked potential amplitude of the affected EDC muscle to the clinical test of finger extension, the latter being more strongly related to FMA_UE26.

Adherence to etanercept therapy in rheumatoid arthritis patients during 3 years of follow-up.

OBJECTIVES: To determine the percentage non-adherence to etanercept in patients with rheumatoid arthritis during three years of follow-up. METHODS: During study visits in this prospective cohort study, blood samples were taken to determine serum etanercept concentrations using ELISA and patients were asked if they had missed an etanercept dose, at which date and for what reason. Non-adherence was defined as serum etanercept concentration <0.1 µg/mL and no valid reason to miss the prescribed etanercept dose. RESULTS: In total, 292 consecutive patients treated with etanercept were included. Most patients had a valid reason to miss their etanercept dose (25/37). In total 12 out of 292 patients (4.1%, 95% confidence interval 2.2-7.2) were non-adherent during the 3 year period. In a small percentage of patients (3.4%, 95% confidence interval 0.8-10.4) who failed to respond to etanercept therapy, according to their rheumatologist, this was associated with inadequate exposure to etanercept and thus non-adherence. CONCLUSION: In this study, adherence to etanercept therapy was measured using serum etanercept concentration. In most patients an absent etanercept concentration was due to a medical reason. Furthermore, the majority of patients were adherent to etanercept therapy and had adequate drug exposure. In total, only 12 out of 292 patients (4.1%) were non-adherent during 3 years of follow-up. These findings highlight that only a small minority of patients are non-adherent to etanercept treatment, especially compared to adherence rates of other drugs. However, physicians should be aware that in patients failing to respond to treatment, non-adherence is a possible cause.

Correction: Gas sensing performance at room temperature of nanogap interdigitated electrodes for detection of acetone at low concentration.

[This corrects the article DOI: 10.1039/C7RA09441H.].

Determination of the positions and orientations of concentrated rod-like colloids from 3D microscopy data.

Confocal microscopy in combination with real-space particle tracking has proven to be a powerful tool in scientific fields such as soft matter physics, materials science and cell biology. However, 3D tracking of anisotropic particles in concentrated phases remains not as optimized compared to algorithms for spherical particles. To address this problem, we developed a new particle-fitting algorithm that can extract the positions and orientations of fluorescent rod-like particles from three dimensional confocal microscopy data stacks. The algorithm is tailored to work even when the fluorescent signals of the particles overlap considerably and a threshold method and subsequent clusters analysis alone do not suffice. We demonstrate that our algorithm correctly identifies all five coordinates of uniaxial particles in both a concentrated disordered phase and a liquid-crystalline smectic-B phase. Apart from confocal microscopy images, we also demonstrate that the algorithm can be used to identify nanorods in 3D electron tomography reconstructions. Lastly, we determined the accuracy of the algorithm using both simulated and experimental confocal microscopy data-stacks of diffusing silica rods in a dilute suspension. This novel particle-fitting algorithm allows for the study of structure and dynamics in both dilute and dense liquid-crystalline phases (such as nematic, smectic and crystalline phases) as well as the study of the glass transition of rod-like particles in three dimensions on the single particle level.

Can forearm muscle activity be selectively recorded using conventional surface EMG-electrodes in transcranial magnetic stimulation? A feasibility study.

OBJECTIVES: This feasibility study evaluates the effect of varying the position of conventional surface EMG-electrodes on the forearm when using Transcranial Magnetic Stimulation (TMS). The aim was to find optimal bipolar electrode positions for forearm extensor muscles, which would be clinically relevant to predict motor recovery after stroke. METHODS: In a healthy female subject, three rings of surface EMG-electrodes were placed around the dominant forearm, leading to 200 different electrode pairs. Both peripheral electrical stimulation and TMS were applied at suprathreshold intensities. RESULTS: With electrical stimulation of the median and radial nerve, similar waveform morphology was found for all electrode pairs, covering both flexors and extensors. Also with TMS, remarkable similarities between all electrode pairs were found, suggesting minimal selectivity. In both peripheral electrical stimulation and TMS, the curves became more irregular with decreasing inter-electrode distances. CONCLUSION: Neither with peripheral electrical stimulation nor with TMS it was possible to selectively record extensor or flexor forearm muscle activity using conventional surface EMG-electrodes. SIGNIFICANCE: Despite this negative result, the important role of the forearm extensor muscles in the prognosis of motor recovery after stroke warrants further research into novel methods for selectively recording muscle activity in TMS other than by conventional surface EMG.

Self-assembly of a colloidal interstitial solid with tunable sublattice doping.

We determine the phase diagram of a binary mixture of small and large hard spheres with a size ratio of 0.3 using free-energy calculations in Monte Carlo simulations. We find a stable binary fluid phase, a pure face-centered-cubic (fcc) crystal phase of the small spheres, and binary crystal structures with LS and LS(6) stoichiometries. Surprisingly, we demonstrate theoretically and experimentally the stability of a novel interstitial solid solution in binary hard-sphere mixtures, which is constructed by filling the octahedral holes of an fcc crystal of large spheres with small spheres. We find that the fraction of octahedral holes filled with a small sphere can be completely tuned from 0 to 1. Additionally, we study the hopping of the small spheres between neighboring octahedral holes, and interestingly, we find that the diffusion increases upon increasing the density of small spheres.

TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade.

OBJECTIVE: To investigate the expression of tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) in the inflamed synovium of patients with arthritis, as TWEAK blockade has been observed to have a beneficial effect in an animal model of rheumatoid arthritis (RA). METHODS: Synovial tissue (ST) biopsies were obtained from 6 early, methotrexate-naive patients with RA as well as 13 patients with RA and 16 patients with psoriatic arthritis (PsA) who were matched for treatment and disease duration. Serial ST samples were obtained from a separate cohort of 13 patients with RA before and after infliximab treatment. TWEAK and Fn14 expression was evaluated by immunohistochemistry and digital image analysis. RESULTS: TWEAK and Fn14 were clearly expressed in ST of patients with RA and PsA. TWEAK expression was significantly higher in RA (sub)lining samples compared to PsA (p = 0.005 and p = 0.014, respectively), but Fn14 expression was comparable. Double immunofluorescence showed TWEAK and Fn14 expression on fibroblast-like synoviocytes and macrophages, but not T cells. Of interest, persistent TWEAK and Fn14 expression was found after anti-TNF therapy. CONCLUSIONS: TWEAK and Fn14 are abundantly expressed in the inflamed synovium of patients with RA and PsA. This raises the possibility that blocking TWEAK/Fn14 signalling could be of therapeutic benefit in inflammatory arthritis.

Fabrication of large binary colloidal crystals with a NaCl structure.

Binary colloidal crystals offer great potential for tuning material properties for applications in, for example, photonics, semiconductors and spintronics, because they allow the positioning of particles with quite different characteristics on one lattice. For micrometer-sized colloids, it is believed that gravity and slow crystallization rates hinder the formation of high-quality binary crystals. Here, we present methods for growing binary colloidal crystals with a NaCl structure from relatively heavy, hard-sphere-like, micrometer-sized silica particles by exploring the following external fields: electric, gravitational, and dielectrophoretic fields and a structured surface (colloidal epitaxy). Our simulations show that the free-energy difference between the NaCl and NiAs structures, which differ in their stacking of the hexagonal planes of the larger spheres, is very small (approximately 0.002 k(B)T). However, we demonstrate that the fcc stacking of the large spheres, which is crucial for obtaining the pure NaCl structure, can be favored by using a combination of the above-mentioned external fields. In this way, we have successfully fabricated large, 3D, oriented single crystals having a NaCl structure without stacking disorder.

A prospective, randomised, placebo-controlled study to identify biomarkers associated with active treatment in psoriatic arthritis: effects of adalimumab treatment on synovial tissue.

OBJECTIVE: To determine which of the changes in synovial tissue correlates best with clinical response associated with effective therapy (adalimumab) to facilitate the planning of future studies with therapeutic agents for psoriatic arthritis (PsA). METHODS: A total of 24 patients with active PsA were randomised to receive adalimumab (n = 12) or placebo (n = 12) for 4 weeks. Synovial biopsies were obtained before and after 4 weeks of treatment. Immunohistochemical analysis was performed to characterise the cell infiltrate, expression of cytokines and matrix metalloproteinases (MMPs) and vascularity. Sections were analysed by digital image analysis. Statistical analysis was performed using covariance analysis. RESULTS: The mean Disease Activity Score in 28 joints (DAS28) after 4 weeks was 1.92 units lower (95% confidence interval (CI) 1.07 to 2.77) after adalimumab therapy compared with placebo. Paired pretreatment and post-treatment synovial samples were available from 19 patients. Many cell types were reduced after adalimumab treatment compared to placebo. After applying a ranked analysis of covariance (ANCOVA) model to correct for baseline imbalances, a significant effect of treatment was observed on CD3-positive cells: there was a median reduction of 248 cells/mm(2) after adalimumab versus placebo treatment (p = 0.035). In addition, the expression of MMP13 was significantly reduced after active treatment: the integrated optical density (IOD)/mm(2) was 18 190 lower after adalimumab treatment as compared to placebo (p = 0.033). CONCLUSION: Adalimumab therapy in PsA is associated with a marked reduction in T cell infiltration and MMP13 expression in synovial tissue, suggesting that these parameters could be used as biomarkers that are sensitive to change after active treatment in small proof of concept studies in PsA.

[Arthritis psoriatica]. / Arthritis psoriatica.

The symptoms ofpsoriatic arthritis vary from arthralgia and enthesitis to chronic erosive and mutilating arthritis, and are seen in 6-39% of all psoriasis patients. Because of increasing awareness of the clinical signs of psoriatic arthritis among both dermatologists and rheumatologists, the diagnosis ofpsoriatic arthritis is made more often; this is important since earlier diagnosis and treatment can avoid irreversible joint destruction. The overlap between the immunological mechanisms in the pathogenesis ofpsoriasis and psoriatic arthritis has led to the identification of common therapeutic targets, of which tumour-necrosis factor (TNF) is the most important. The successful treatment of psoriasis patients with TNF-a-blocking agents has not only brought about a marked improvement in the quality of life of many patients but has also improved the insight into the pathogenesis, for example by demonstrating that the role of acquired immunity is much more important than was previously thought. The Dutch Society of Dermatology and Venereology and the Dutch Society of Rheumatology have drawn up guidelines for the treatment of patients with psoriasis and psoriatic arthritis using these so-called biologics.

Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment.

BACKGROUND: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis (PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets. OBJECTIVE: To investigate extensively the features of cell infiltration and expression of mediators of inflammation and joint destruction in the synovium of patients with PsA compared with patients with rheumatoid arthritis matched for disease duration and use of drugs. METHODS: Multiple synovial tissue biopsy specimens were obtained by arthroscopy from an inflamed joint in 19 patients with PsA (eight oligoarthritis, 11 polyarthritis) and 24 patients with rheumatoid arthritis. Biopsy specimens were analysed by immunohistochemistry to detect T cells, plasma cells, fibroblast-like synoviocytes, macrophages, proinflammatory cytokines, matrix metalloproteinases and tissue inhibitor metalloproteinase-1, adhesion molecules and vascular markers. Stained sections were evaluated by digital image analysis. RESULTS: The synovial infiltrate of patients with PsA and rheumatoid arthritis was comparable with regard to numbers of fibroblast-like synoviocytes and macrophages. T cell numbers were considerably lower in the synovium of patients with PsA. The number of plasma cells also tended to be lower in PsA. The expression of tumour necrosis factor alpha (TNFalpha), interleukin (IL) 1beta, IL6 and IL18 was as high in PsA as in rheumatoid arthritis. The expression of matrix metalloproteinases, adhesion molecules and vascular markers was comparable for PsA and rheumatoid arthritis. CONCLUSION: These data show increased proinflammatory cytokine expression in PsA synovium, comparable to results obtained for rheumatoid arthritis, and support the notion that, in addition to TNFalpha blockade, there may be a rationale for treatments directed at IL1beta, IL6 and IL18.

A randomised, double blind, placebo controlled, multicentre trial of combination therapy with methotrexate plus ciclosporin in patients with active psoriatic arthritis.

OBJECTIVES: To evaluate the safety and efficacy of adding ciclosporin A (CSA) to the treatment of patients with psoriatic arthritis (PsA) demonstrating an incomplete response to methotrexate (MTX) monotherapy. METHODS: In a 12 month, randomised, double blind, placebo controlled trial at five centres in three countries, 72 patients with active PsA with an incomplete response to MTX were randomised to receive either CSA (n = 38) or placebo (n = 34). Patients underwent full clinical and radiological assessment and, in addition, high resolution ultrasound (HRUS) was performed at one centre. An intention to treat (last observation carried forward) analysis was employed. RESULTS: Some significant improvements were noted at 12 months in both groups. However, in the active but not the placebo arm there were significant improvements in swollen joint count, mean (SD), from 11.7 (9.7) to 6.7 (6.5) (p<0.001) and C reactive protein, from 17.4 (14.5) to 12.7 (14.3) mg/l (p<0.05) as compared with baseline. The Psoriasis Area and Severity Index (PASI) score improved in the active group (2 (2.3) to 0.8 (1.3)) as compared with placebo (2.2 (2.7) to 1.9 (2.8)), p<0.001, and synovitis detected by HRUS (33 patients, 285 joints) was reduced by 33% in the active group compared with 6% in the placebo group (p<0.05). No improvement in Health Assessment Questionnaire or pain scores was detected. CONCLUSIONS: Synovitis detected by HRUS was significantly reduced. Combining CSA and MTX treatment in patients with active PsA, and a partial response to MTX, significantly improves the signs of inflammation but not pain or quality of life.

Neurogenic heterotopic ossification in spinal cord injury.

Neurogenic heterotopic ossification (NHO) is a frequent complication in spinal cord injury (SCI) that is often difficult to treat. This review emphasizes the incidence, risk factors and clinical signs of NHO in SCI patients. Although the exact pathophysiology underlying NHO in neurologic patients is not yet understood, different pathogenic mechanisms have been proposed in the literature. A selection of the most important theories will be given and discussed. Moreover the different diagnostic, therapeutic, and preventive methods currently used in NHO management after SCI will be reviewed.

Treatment of upper extremity spasticity in stroke patients by focal neuronal or neuromuscular blockade: a systematic review of the literature.

Studies published from January 1966 until October 2000 on the clinical effects of focal neuronal and neuromuscular blockade in post stroke upper limb spasticity were identified. Twelve studies were included and evaluated on 13 methodological criteria. Ten studies on Botulinum toxin type A (BTX-A) treatment were found (of which 4 were randomised controlled trials (RCTs) and 6 were uncontrolled observational studies) as well as one uncontrolled observational study on phenol blockade of the subscapular muscle and one on alcohol blockade of the musculocutaneus nerve. The homogeneity of the patient groups with regard to diagnosis and their comparability with regard to functional prognosis and other sources of bias were generally unsatisfactory. Only two RCTs met predetermined criteria of minimal validity. There is evidence of effectiveness of BTX-A treatment on reducing muscle tone (varying between 0.8 and 2.0 points on the modified Ashworth scale) and improving passive range of motion at all arm-hand levels in chronic stroke patients for approximately 3-4 months. There is also preliminary evidence of a synergistic effect of concomitant electrostimulation. Taking into account a critical maximum dose of 100 MU Botox" (300-500 MU Dysport) for preserving active finger flexion, BTX-A treatment seems to be a safe focal spasmolytic treatment. Effectiveness of BTX-A treatment on improving functional abilities could not be convincingly demonstrated, although two subgroups may be identified that might specifically benefit at a functional level: (1) patients with mild spasticity and a potential for voluntary extensor activity and (2) patients with severe spasticity suffering from problems with positioning and taking care of the affected arm and hand. Larger controlled studies are needed to compare the effectiveness of BTX-A with other focal spasmolytic techniques paying special attention to individual goal assessment, the (duration of) functional benefits, co-treatment and aftercare, side-effects and cost-effectiveness.

Urinary incontinence in stroke patients after admission to a postacute inpatient rehabilitation program.

OBJECTIVE: To determine the incidence of poststroke urinary incontinence in stroke patients admitted for a postacute inpatient rehabilitation program and its association with discharge destination. DESIGN: Cohort study of first-time stroke patients admitted for a postacute inpatient rehabilitation program from August 1994 to August 1997. SETTING: Rehabilitation center in the Netherlands. PARTICIPANTS: Consecutive first-time stroke patients (n = 143). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Incidence rates calculated with observation time at risk in the denominator. Measures for outcome include the Modified Barthel Index (MBI) and the discharge destination. RESULTS: The incidence rate of urinary incontinence was 29/1000 persons per month (95% confidence interval [CI], 18-48/1000 persons monthly). For incontinent patients, the mean initial MBI score +/- standard deviation was 6.0 +/- 2.3 (range, 2-12); for continent patients, it was 11.5 +/- 9.8 (range, 2-18). This difference was statistically significant (t(139) = 2.12; p = .036; 95% CI for difference of the means, .379-10.84). Patients continent at time of discharge were more often discharged to their own homes than were incontinent patients (Fisher's exact test, p = .0006). CONCLUSIONS: In this select cohort, the incidence of urinary incontinence was lower than that reported in the literature. An association was found between urinary incontinence and discharge destination and between urinary incontinence and functional ability on admission.

Osteonecrosis after treatment for heterotopic ossification in spinal cord injury with the combination of surgery, irradiation, and an NSAID.

STUDY DESIGN: Case report. OBJECTIVE: Heterotopic ossification (HO) is a frequent complication in spinal cord injury (SCI) that is often difficult to treat. Although surgery may become necessary, operative resection has been associated with complications and poor outcome due to a high recurrence rate. Additional methods of treatment to reduce the recurrence rate have been developed, including post operative irradiation and NSAIDs. This article presents three patients, who developed an osteonecrosis of the femoral head after the combined treatment for HO of surgery, irradiation, and an NSAID.