A direct comparison in diagnostic performance of CDUS, FDG-PET/CT and MRI in patients suspected of giant cell arteritis.

OBJECTIVES: This study directly compares diagnostic performance of Colour Duplex Ultrasound (CDUS), Fluor-18-deoxyglucose Positron Emission Tomography Computed Tomography (FDG-PET/CT) and Magnetic Resonance Imaging (MRI) in patients suspected of giant cell arteritis (GCA). METHODS: Patients with suspected GCA were included in a nested-case control pilot study. CDUS, whole body FDG-PET/CT and cranial MRI were performed within 5 working days after initial clinical evaluation. Clinical diagnosis after six months follow-up by experienced rheumatologists in the field of GCA, blinded for imaging, was used as reference standard. Diagnostic performance of the imaging modalities was determined. Stratification for GCA subtype was performed and imaging results were evaluated in different risk stratification groups. RESULTS: In total, 23 patients with GCA and 19 patients suspected of but not diagnosed with GCA were included. Sensitivity was 69.6% (95%CI 50.4%-88.8%) for CDUS, 52.2% (95%CI 31.4%-73.0%) for FDG-PET/CT and 56.5% (95%CI 35.8%-77.2%) for MRI. Specificity was 100% for CDUS, FDG-PET/CT and MRI. FDG-PET/CT was negative for GCA in all isolated cranial GCA patients (n = 8), while MRI was negative in all isolated extracranial GCA patients (n = 4). In 4 GCA patients with false-negative (n = 2; intermediate and high risk) or inconclusive (n = 2; low and intermediate risk) CDUS results, further imaging confirmed diagnosis. CONCLUSIONS: Sensitivity of CDUS was highest, while specificity was excellent in all imaging modalities. Nevertheless, confidence intervals of all imaging modalities were overlapping. Following EULAR recommendations, CDUS can be used as a first test to diagnose GCA. With insufficient evidence for GCA, further testing considering GCA subtype is warranted.

Monitoring patients with celiac disease on gluten free diet: different outcomes comparing three tissue transglutaminase IgA assays.

OBJECTIVES: Tissue transglutaminase (tTG) IgA antibodies are a hallmark for celiac disease (CD). In CD patients on gluten free diet (GFD) these antibodies are transient. Few studies are available comparing the tTG-IgA assay characteristics for monitoring response to GFD. Since discrepant results were reported in patients on GFD after switching tTG-IgA assays, we conducted a retrospective observational study to monitor GFD response using three different tTG-IgA assays. METHODS: Diagnostic samples from 44 adults and 17 children with CD were included. Of most patients two follow-up samples after introduction of GFD were available. In all samples tTG-IgA were assessed using one fluorochrome-enzyme immuno-assay (FEIA) and two chemiluminescence immuno-assays (CLIA) and intestinal fatty acid binding protein (i-FABP) as surrogate marker for intestinal epithelial damage was measured. RESULTS: Using CLIA assays, normalization of antibody levels was delayed compared to FEIA (p<0.001). Of all samples taken after at least 6 months on GFD with elevated i-FABP indicating intestinal epithelial damage, 40 % had positive tTG-IgA according to the FEIA, 85 and 90 % according to the two CLIA. CONCLUSIONS: Normalization of tTG-IgA in patients on GFD depends on the assay used. Both CLIA appear to be more sensitive in detecting suboptimal treatment response in CD-indicated by elevated i-FABP - when applying the manufacturer's recommended cut-off for the diagnosis of CD.

Patterns of physical activity over time in older patients rehabilitating after hip fracture surgery: a preliminary observational study.

BACKGROUND: To investigate patterns of continuously monitored physical activity in older patients rehabilitating after hip fracture surgery and the association with patient characteristics. METHODS: Physical activity of surgically treated hip fracture patients aged 70 years or older, who were rehabilitating at a skilled nursing home, was continuously monitored using a tri-axial accelerometer. The intensity of physical activity per day was calculated from the accelerometer signals to describe the daily physical activity levels of the enrolled patients. The patterns of three different aspects of physical activity were investigated: overall physical activity, overall variability, and day-to-day variability. Two experts in the geriatric rehabilitation field helped identifying unique physical activity patterns for each aspect based on visual analysis. Eighteen healthcare professionals independently classified each patient in one of the predefined patterns for each aspect. Differences between physical activity patterns and patient characteristics were assessed using a Kruskal-Wallis or Fisher's Exact Test. RESULTS: Physical activity data from 66 older patients were used in this preliminary study. A total of six unique patterns were identified for overall physical activity and overall variability, and five unique patterns for the day-to-day variability. The most common pattern found for the overall physical activity and day-to-day variability had a S-shape, which first slowly increased, then steeply increased, and subsequently flattened (n = 23, 34.8%). A N-shape pattern was found the most common pattern for overall variability, which first slowly increased, then steeply increased, then decreased and lastly increased (n = 14, 21.2%). The functionality at admission to rehabilitation, measured with the Barthel Index, and the duration of rehabilitation stay differed between the patterns of physical activity. CONCLUSIONS: Multiple patterns of physical activity among older patients during hip fracture rehabilitation were found in this preliminary study. The functionality at admission to rehabilitation and the duration of rehabilitation stay were associated with the different patterns found in this study. Results of this study highlight the importance of personalized hip fracture treatment.

Transparency in hip fracture recovery over institutional boundaries: The transmural monitoring pathway.

OBJECTIVES: To develop a transmural pathway for healthcare professionals across institutions to monitor the recovery of hip fracture patients. The secondary objectives were to evaluate the pathway's feasibility and initial outcomes. DESIGN: Prospective cohort study. METHOD: Stakeholders of the hospital and geriatric rehabilitation institutions implemented a transmural monitoring pathway in which different geriatric health domains were monitored during three phases: The in-hospital, inpatient rehabilitation, and outpatient follow-up phase. The outcomes for the first 291 patients and the feasibility of the pathway were evaluated. If the outcomes of the clinimetrics significantly improved over time, progress in functional recovery was assumed. Feasibility was assessed according to the rate of adherence to the clinimetric tests. RESULTS: During the in-hospital phase, patients showed a decline in functional level (the Katz index of independence in Activities of Daily Living (Katz-ADL) pre-fracture vs. discharge: 0 (0-2) vs. 4 (4-5), P < 0.001). Patients, in which 78.6% (n = 140) had cognitive impairment and 41.2% had malnutrition, showed the most progress (Katz-ADL 2 (1-3)) during the inpatient rehabilitation phase. In the outpatient follow-up phase, recovery remained ongoing, but most patients had not returned to their pre-fracture functional levels (Katz-ADL 1 (1-3)). The pathway feasibility during the first phase was excellent (>85%), whereas room for improvement existed during other phases (<85%). CONCLUSION: The transmural monitoring pathway provides insight into the entire recovery process for all involved healthcare professionals. Patients showed the most progress during the rehabilitation phase. The pathway feasibility was excellent during the in-hospital phase, but improvements could be made during other phases.

External validation of the giant cell arteritis probability score in the Netherlands.

OBJECTIVES: To prevent complications of giant cell arteritis (GCA), early and accurate diagnosis is essential. Recently, Laskou et al. (2019) developed the giant cell arteritis probability score (GCAPS) which allows physicians to assess the likelihood of GCA at an early stage. The aim of this study was to validate the GCAPS in a Dutch hospital. METHODS: A retrospective cohort of patients with suspected GCA between January 1st, 2017 and October 1st, 2019 was used. As the variable extracranial artery abnormality was not measured, a modified GCAPS was used (m-GCAPS). Clinical diagnosis of the rheumatologist after six months follow-up was used as reference. The m-GCAPS was assessed for discrimination and calibration. We applied risk stratification according to Sebastian et al. (2020) (low, intermediate and high-risk groups based on the median and 75th percentile). RESULTS: Our study included 209 suspected GCA patients. 135 patients had complete records. Of these patients, 40 had GCA. The m-GCAPS had an area under the curve of 0.83, a sensitivity of 80.0% and specificity of 75.8% at the optimal cut-off value >10.5. The Hosmer-Lemeshow test was non-significant. Using risk stratification, GCA prevalence was 12.5% in the low (score<9), 23.3% in the intermediate (9-12) and 78.6% in the high-risk group (>12). CONCLUSIONS: The m-GCAPS showed good discrimination and calibration in a Dutch retrospective cohort and can aid early recognition of GCA. Stratification into low, intermediate and high-risk is promising, but might need optimisation.

Improved outcomes in patients with diabetic foot ulcers despite of differences in baseline characteristics.

The incidence of diabetes is increasing worldwide with concomitant raising number of patients with diabetic foot disease. Diabetic foot disease treatment has received more attention in the past decades, culminating in the creation of multidisciplinary outpatient clinics, but at the same time, complexity of patients seems to have increased. The aim of this article is to study differences in patient characteristics and outcomes (ulcer healing and ulcer-free survival days) in patients with a diabetic foot ulcer in two prospective cohorts with 15 years in between. Prospective cohort study of all patients in one diabetic foot centre of expertise in 2003-2004 and 2014-2018. Clinical outcomes were determined after a follow-up period of 12 months. Outcomes were differences in baseline characteristics and comorbidities, and differences in ulcer-related outcomes between both cohorts. We included all consecutive diabetic foot ulcer patients from our centre for the period 2003-2004 (n = 79) and 2014-2018 (n = 271). Age (67.0 ± 14.3 vs. 71.6 ± 11.5, p = 0.003) and prevalence of end-stage renal disease (1.3% vs. 7.7%, p = 0.036) were significantly higher in the more recent population. The more recent population had higher healing rate (53.2% vs. 76.4%, p < 0.001), higher median ulcer-free survival days once an ulcer had healed [173 days (IQR 85.3-295.5) vs. 257.0 (IQR 157.0-318.0), p = 0.026], and fewer minor amputations (20.3% vs. 8.1%, p = 0.002). People with diabetic foot ulcers treated in 2014-2018 were older and more frequently diagnosed with ESRD, compared to this population in 2003-2004, while other characteristics were similar; ulcer-related outcomes were better.

Distribution and relevance of Dientamoeba fragilis and Blastocystis species in gastroenteritis: results from a case-control study.

The actual role of Dientamoeba fragilis and Blastocystis in patients with gastrointestinal symptoms is still under debate. A multicenter case-control study was performed in The Netherlands to elucidate the clinical relevance of molecular diagnostics results in gastroenteritis (GE). Samples from this case-control study were used to perform a detailed analysis on the presence of D. fragilis and Blastocystis in relation to gastrointestinal symptoms. In the present study, a real-time PCR for Blastocystis was performed on 1374 case samples and 1026 control samples from the multicenter gastroenteritis case-control study previously tested for D. fragilis. Prevalence of both micro-organisms was highest in children under 20 years of age and lowest in the oldest age group. A significantly lower overall detection of D. fragilis and Blastocystis was found in cases (both 25.8%) as compared to controls (37.6% and 40.0%, respectively). The difference for D. fragilis was statistically significant for subjects above 20 years of age. For Blastocystis, the difference was statistically significant in all age groups, except in children less than 5 years of age. A negative relation between D. fragilis-positive cases and diarrhea was found in this study population. More GE symptoms were reported in cases without D. fragilis or Blastocystis. In the present study, prevalence of both D. fragilis and Blastocystis is lower in cases with gastroenteritic symptoms than in controls. Besides, in cases with D. fragilis or Blastocystis, no association is shown between any of the GE symptoms. Interestingly, this suggests that the presence of these protozoans may be considered characteristic of a healthy intestinal microbiome.

Papillary Thyroid Cancers with Focal Tall Cell Change are as Aggressive as Tall Cell Variants and Should Not be Considered as Low-Risk Disease.

BACKGROUND: The tall cell variant of papillary thyroid carcinoma (PTC) is as an aggressive histological variant. The proportion of tall cells needed to influence prognosis is debated. METHODS: Patients with PTC and tall cells, defined as having a height-to-width ratio of ≥ 3:1, seen at a high-volume center between 2001 and 2015, were reviewed. Specimens were classified as (1) focal tall cell change, containing < 30% of tall cells; (2) tall cell variant, ≥ 30% of tall cells; and (3) control cases selected from infiltrative classical PTCs without adverse cytologic features. Univariate, sensitivity, and multivariate analyses were performed with persistent/recurrent disease as the primary outcome. RESULTS: We identified 96 PTCs with focal tall cell change, 35 with the tall cell variant and 104 control cases. Factors associated with poor clinical prognosis were significantly greater in those with focal tall cell change and tall cell variants. Regarding primary outcome, hazard ratios were 2.3 (95% confidence interval [CI] 1.0-5.7) for focal tall cell change, and 3.4 (95% CI 1.2-8.7) for tall cell variants compared with controls. Five-year disease-free survival was higher for the control group (92.7%, CI 87.4-98.0) compared with focal tall cell change (76.3%, CI 66.1-86.5) and the tall cell variant (62.2%, CI 43.2-81.2). When stratified in groups consisting of tall cell proportions (< 10%, 10-19%, 20-29% and ≥ 30%), identification of ≥ 10% tall cell change was associated with worse outcome (p = 0.002). CONCLUSIONS: PTCs with ≥ 10% tall cell change have worse prognosis than those without tall cells. Our data indicate that thyroid cancer management guidelines should consider PTCs with focal tall cell change outside of the low-risk classification.

Insights in work rehabilitation after minimally invasive esophagectomy.

BACKGROUND: Little is known about work rehabilitation after totally minimally invasive esophagectomy. The goal of this study was to further objectify the postoperative work rehabilitation. Not only duration of sick leave, but also the extent of return to work will be assessed. METHODS: This retrospective multicenter study was conveyed between January 2009 and April 2014. Eighty-six preoperatively employed patients were included. Data regarding patients' preoperative occupation, actual job status, and postoperative duration until return to work were retrieved. Potential prognostic factors for work rehabilitation were analyzed. Complaints that could impede rehabilitation were questioned (based on EORTC QLQ-C30 and QLQ-OES18). Work activity, defined as either partially or fully resumed professional activity as compared to the preoperative status, was measured at 3, 6, 12, and 18 months postoperatively. RESULTS: At 6-month follow-up, 40.2% of patients reached partial and 14.6% had full professional recovery and after 12 months 28.2% and 40.8%, respectively. After 18 months, a stagnation was seen (19.0% partial; 43.1% full recovery). Median follow-up was 18 months (IQR 12-18). Self-employment was a significant predictor for full professional recovery (p = 0.005, OR 2.45 95% CI 1.32-4.56). The median time to full professional recovery was shorter for this group. The most common complaint among all patients was fatigue. This complaint did not significantly differ between working (fully and partially) and non-working groups (p = 0.727). CONCLUSIONS: Only approximately 40% of patients reached full professional recovery 1 year after totally minimally invasive esophagectomy. Barely any progression toward return to work was seen after 1 year postoperatively. Roughly 30% of patients never returned to work. Self-employed workers had a higher percentage of restoration to full professional activity, as well as shorter duration to return. These findings highlight the importance of adequate counseling of patients in order to prepare them for the impact of this procedure on professional activities.

Ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers: A prospective cohort study.

Healing rates may not give a complete indication of the effectiveness and management of diabetic foot ulcers because of high recurrence rates. The most important outcome for patients is remaining ulcer-free; however, this has hardly been investigated. The aim of our study was to prospectively investigate ulcer-free survival days and ulcer healing in patients with diabetic foot ulcers. This was a prospective cohort study of all referrals to our diabetic foot expertise centre from December 2014 to April 2017. Outcomes were determined after a minimum follow-up period of 12 months. Primary outcomes were ulcer-free survival days and 12-month healing percentages. Predictors for ulcer-free survival days and healing were investigated in multivariate analyses. A total of 158 patients were included. Median ulcer-free survival days in the healed group were 233 days (interquartile range [IQR] 121-312) and 131 days (IQR 0-298) in the overall population. The healing rate at 12-month follow up was 67% (106/158), and the recurrence rate was 31% (33/106). Independent predictors of ulcer-free survival days were duration of diabetes, peripheral artery disease (PAD), cardiovascular disease, end-stage renal disease (ESRD), and infection. Ulcer-free survival days are related to PAD and cardiovascular disease, and ulcer-free survival days should be the main outcome when comparing the effectiveness of management and prevention of the diabetic foot ulcers.

Totally minimally invasive esophagectomy after neoadjuvant chemoradiotherapy: Long-term oncologic outcomes.

BACKGROUND AND OBJECTIVES: Minimally invasive esophagectomy is emerging with comparable short-term outcomes as open esophagectomies. Neoadjuvant chemoradiotherapy followed by surgery is considered standard of care in the Netherlands for patients with esophageal cancer. The aim of this study was to analyze the long-term oncologic outcome after neoadjuvant chemoradiotherapy followed by totally minimally invasive esophagectomy. METHODS: Neoadjuvant carboplatin and paclitaxel based chemotherapy was concomitantly given with 41.4 Gy radiotherapy. Six weeks after neoadjuvant treatment, totally minimally invasive esophagectomy was performed. RESULTS: From December 2010 until December 2015 161 patients received this combination of treatment. In 128 male and 33 female patients with median age of 65 years (58-71), 88 minimally invasive esophagectomies with intrathoracic anastomosis and 73 minimally invasive esophagectomies with cervical anastomosis were carried out. Radical (R0) resection was confirmed in 156 patients (97%). In hospital mortality occurred in 6 patients (3.7%). Overall survival was 79% and 51% at 1 and 5 years, respectively, with a median follow-up of 24.5 months (13-38). Disease-free survival was, respectively, 76% and 55%. CONCLUSIONS: Totally minimally invasive esophagectomy after neoadjuvant chemoradiotherapy for esophageal cancer is a safe treatment with low postoperative mortality rates and favorable overall and disease-free survival.

Diagnostic delay in patients with giant cell arteritis: results of a fast-track clinic.

Giant cell arteritis (GCA) can lead to severe complications if left untreated. The aim of this study was to describe time from onset of symptoms to diagnosis and treatment in GCA suspected patients in a fast-track clinic (FTC), and secondarily to assess the influence of GCA symptoms on this time. A retrospective cohort consisting of suspected GCA patients who visited the FTC between January 2017 and October 2019 was used. Time between symptom onset, first general practitioner visit, FTC referral, first FTC visit, and treatment initiation was analysed. Furthermore, this was stratified for subtypes of GCA and GCA symptoms. Of 205 patients referred with suspected GCA, 61 patients received a final diagnosis of GCA (GCA+) and 144 patients had no GCA (GCA-). Median time after onset of symptoms to first FTC visit was 31.0 days (IQR 13.0-108.8) in all referred patients. Time between onset of symptoms and first GP visit was 10.5 (4.0-36.3) days, and time between first GP visit and FTC referral was 10.0 (1.0-47.5) days. Patients were generally seen at the FTC within 1 day after referral. For patients with isolated cranial GCA (n = 41), median delay from onset of symptoms to treatment initiation was 21.0 days (11.0-73.5), while this was 57.0 days (33.0-105.0) in patients with extracranial large-vessel involvement (n = 20) (p = 0.02). Our results indicate considerable delay between symptom onset and FTC referral in patients suspected of GCA. Suspected patients were examined and GCA+ patients were treated instantly after referral. Key Points • GCA can cause severe complications with delayed treatment, but non-specific symptoms make diagnosis challenging. • Diagnostic delay still occurs despite introducing a successful fast-track clinic resulting from delay between start of symptoms and FTC referral. • Patients who presented with constitutional symptoms had longer delay than patients who presented with isolated cranial symptoms.

Treating to the target of remission in early rheumatoid arthritis is cost-effective: results of the DREAM registry.

BACKGROUND: Where health economic studies are frequently performed using modelling, with input from randomized controlled trials and best guesses, we used real-life data to analyse the cost-effectiveness and cost-utility of a treatment strategy aiming to the target of remission compared to usual care in early rheumatoid arthritis (RA). METHODS: We used real-life data from comparable cohorts in the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry: the DREAM remission induction cohort (treat-to-target, T2T) and the Nijmegen early RA inception cohort (usual care, UC). Both cohorts were followed prospectively using the DREAM registry methodology. All patients fulfilled the American College of Rheumatology criteria for RA and were included in the cohort at the time of diagnosis. The T2T cohort was treated according to a protocolised strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6). The UC cohort was treated without DAS28-guided treatment decisions. EuroQol-5D utility scores were estimated from the Health Assessment Questionnaire. A health care perspective was adopted and direct medical costs were collected. The incremental cost effectiveness ratio (ICER) per patient in remission and incremental cost utility ratio (ICUR) per quality-adjusted life year (QALY) gained were calculated over two and three years of follow-up. RESULTS: Two year data were available for 261 T2T patients and 213 UC patients; an extended follow-up of three years was available for 127 and 180 patients, respectively. T2T produced higher remission percentages and a larger gain in QALYs than UC. The ICER was € 3,591 per patient in remission after two years and T2T was dominant after three years. The ICUR was € 19,410 per QALY after two years and T2T was dominant after three years. CONCLUSIONS: We can conclude that treating to the target of remission in early RA is cost-effective compared with UC. The data suggest that in the third year, T2T becomes cost-saving.

External validation of the 2022 ACR/EULAR classification criteria in patients with suspected giant cell arteritis in a Dutch fast-track clinic.

OBJECTIVE: Recently the Diagnostic and Classification Criteria in Vasculitis Study group developed and published new American College of Rheumatology/EULAR classification criteria for giant cell arteritis (GCA). To test robustness in a different clinical setting and inform clinicians on performance in clinical practice, we aim to externally validate them in patients with a suspicion of GCA referred to our GCA fast-track clinic. METHODS: Patients with suspected GCA from the Hospital Group Twente Early GCA in Twente prospective cohort were included. The clinical diagnosis of GCA verified after 6 months of follow-up made by the treating rheumatologist was used as a reference standard. A cut-off score of ≥6 was tested as described in the original article. Area under the receiver operating characteristics curve, sensitivity and specificity were calculated. RESULTS: In total, 133 patients with suspected GCA were included, of whom 53 were diagnosed with GCA and 80 patients were not diagnosed with GCA. The area under the curve (AUC) was 0.96 (95% CI 0.92 to 0.98). Using the proposed cut-off score of≥6, we found that sensitivity was 98.0% (95% CI 89.9% to 100%) and specificity was 57.5% (95% CI 45.9% to 68.5%). The majority of misclassified patients without GCA had classification scores of 6 and 7 as clinical and/or laboratory criteria were often present in our non-GCA population. CONCLUSION: Our results showed an excellent AUC and sensitivity with a moderate specificity for classification of GCA patients. Considering our relevant study population, we found that the new classification criteria might also be useful for diagnostic purposes, albeit with careful interpretation.

Evaluation of a workplace educational intervention on menopause: A quasi-experimental study.

OBJECTIVE: To evaluate the effects of a workplace educational intervention on menopause on self-efficacy regarding working during the climacteric. METHODS: Quasi-experimental design, with one intervention and one control group. Women aged 40 to 67, working in one of the two participating departments of a large municipality in the Netherlands, were recruited to participate in the study. The allocation of participants to intervention or control group was done at the departmental level. The main component of the multifaceted intervention consisted of educational workshops on menopause and work. The primary outcome was score on the Self-Efficacy to Manage Symptoms Scale. Secondary outcomes were scores on other self-efficacy scales, knowledge about the menopausal transition, menopausal symptoms, beliefs and behaviours and work-related variables. Differences between groups were analysed with Pearson's chi-square, Student's t-test or Mann-Whitney U. Analysis of covariance (ANCOVA) was used to correct for baseline and potential confounders. RESULTS: Data from 54 women were analysed, 25 in the intervention group and 29 in the control group. After 12 weeks of follow-up, the mean score on the Self-Efficacy to Manage Symptoms Scale was higher in the intervention group than in the control group: 6.52 (SD 1.45) versus 5.84 (SD 1.51), respectively, adjusted mean difference 0.75 (95 % CI 0.03-1.46, p = 0.040). The educational intervention increased self-reported knowledge (scored on the range 1-10) (adjusted mean difference 0.7, 95 % CI 0.26-1.15, p = 0.002) and resulted in a lower level of presenteeism (i.e., less impaired work performance) due to menopausal symptoms, measured by the Dutch Stanford Presenteeism Scale (adjusted mean difference 2.15, 95 % CI 0.13-4.18, p = 0.038), compared to the control group. CONCLUSIONS: This educational workplace intervention study shows promising positive effects on self-efficacy regarding working during the climacteric, knowledge about the menopausal transition and presenteeism due to menopausal symptoms. This is especially true for women already experiencing menopausal symptoms, while premenopausal women were harder to engage in the intervention. A larger study, with longer follow-up, preferably a randomized controlled trial, is needed to investigate the clinical relevance of these findings.

A tight control treatment strategy aiming for remission in early rheumatoid arthritis is more effective than usual care treatment in daily clinical practice: a study of two cohorts in the Dutch Rheumatoid Arthritis Monitoring registry.

UNLABELLED: There is strong evidence from clinical trials that a 'treat to target' strategy is effective in reaching remission in rheumatoid arthritis (RA). However, the question is whether these results can be translated into daily clinical practice and clinical remission is a reachable target indeed. OBJECTIVE: The study aims to investigate whether in early RA a treatment strategy aiming at Disease Activity Score (DAS) 28 <2.6 is more effective than 'usual care' treatment for reaching clinical remission after 1 year. METHODS: Two early RA inception cohorts from two different regions including patients who fulfilled the American College of Rheumatology criteria for RA were compared. Patients in the tight-control cohort (n=126) were treated according to a DAS28-driven step-up treatment strategy starting with methotrexate, addition of sulphasalazine (SSZ) and exchange of SSZ by anti-tumour necrosis factor in case of failure. Patients in the usual-care cohort (n=126) were treated with methotrexate or SSZ, without DAS28-guided treatment decisions. The primary outcome was the percentage remission (DAS28<2.6) at 1 year. Time to first remission and change in DAS28 were secondary outcomes. RESULTS: After 1 year, 55% of tight-control patients had a DAS28<2.6 versus 30% of usual care patients (OR 3.1, 95% CI 1.8 to 5.2). The median time to first remission was 25 weeks for tight control and more than 52 weeks for usual care (p<0.0001). The DAS28 decreased with -2.5 in tight control and -1.5 in usual care (p<0.0001). CONCLUSION: In early RA, a tight control treatment strategy aiming for remission leads to more rapid DAS28 remission and higher percentages of remission after 1 year than does a usual care treatment.

The provisional ACR/EULAR definition of remission in RA: a comment on the patient global assessment criterion.

OBJECTIVES: The provisional ACR/European League Against Rheumatism (EULAR) definition of remission in RA requires a score of ≤1 on the patient global assessment (PGA, 0-10 scale). We explored the relation between the PGA criterion and the patient's clinical disease state in an observational dataset. METHODS: Data of 512 newly diagnosed RA patients of the Dutch Rheumatoid Arthritis Monitoring (DREAM) remission induction cohort were analysed. Both 28-joint counts and more comprehensive joint counts (tender joint count-53, swollen joint count-44) were used. RESULTS: ACR/EULAR remission was present in 20.1% of the patients when using 28-joint counts and in 17.4% of the patients when applying more comprehensive joint counts. In 108 patients, the PGA score was >1 despite fulfilment of the remaining criteria (TJC28, SJC28 and CRP in mg/dl ≤1). Residual disease activity was observed in 31.5% (34/108) and median (interquartile range) scores on PGA, pain and fatigue were 2.4 (1.8-4.0), 2.0 (1.1-3.0) and 2.7 (1.3-5.0), respectively. Applying more comprehensive joint counts showed comparable results. In 19.5% (100/512) of patients, disease activity was absent (TJC53 = 0, SJC44 = 0, and CRP ≤1). In 41% (n = 41) of these patients, the PGA score was >1. Receiver operating characteristic analysis showed moderate accuracy of the PGA to discriminate between fulfilment and no fulfilment of all remaining criteria. CONCLUSION: Frequently, patients did not meet the PGA criterion despite a good clinical disease state. Apparently the PGA is not solely influenced by RA disease activity. In patients with marked divergence between the PGA and objective clinical measurements, caution should be taken when applying the provisional ACR/EULAR definition of remission.

Implementation of a treat-to-target strategy in very early rheumatoid arthritis: results of the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study.

OBJECTIVE: Clinical remission is the ultimate therapeutic goal in rheumatoid arthritis (RA). Although clinical trials have proven this to be a realistic goal, the concept of targeting at remission has not yet been implemented. The objective of this study was to develop, implement, and evaluate a treat-to-target strategy aimed at achieving remission in very early RA in daily clinical practice. METHODS: Five hundred thirty-four patients with a clinical diagnosis of very early RA were included in the Dutch Rheumatoid Arthritis Monitoring remission induction cohort study. Treatment adjustments were based on the Disease Activity Score in 28 joints (DAS28), aiming at a DAS28 of <2.6 (methotrexate, followed by the addition of sulfasalazine, and exchange of sulfasalazine with biologic agents in case of persistent disease activity). The primary outcome was disease activity after 6 months and 12 months of followup, according to the DAS28, the European League Against Rheumatism (EULAR) response criteria, and the modified American College of Rheumatology (ACR) remission criteria. Secondary outcomes were time to first DAS28 remission and outcome of radiography. RESULTS: Six-month and 12-month followup data were available for 491 and 389 patients, respectively. At 6 months, 47.0% of patients achieved DAS28 remission, 57.6% had a good EULAR response, and 32.0% satisfied the ACR remission criteria. At 12 months, 58.1% of patients achieved DAS28 remission, 67.9% had a good EULAR response, and 46.4% achieved ACR remission. The median time to first remission was 25.3 weeks (interquartile range 13.0-52.0). The majority of patients did not have clinically relevant radiographic progression after 1 year. CONCLUSION: The successful implementation of this treat-to-target strategy aiming at remission demonstrated that achieving remission in daily clinical practice is a realistic goal.

Impact of Preanalytical Factors on Calprotectin Concentration in Stool: A Multiassay Comparison.

BACKGROUND: Measuring calprotectin concentration in stool is increasingly important in monitoring disease activity and treatment response in inflammatory bowel disease. This study evaluates the impact of preanalytical storage conditions on reliability of calprotectin testing using 5 different calprotectin immunoassays. METHODS: Aliquots of homogenized fresh fecal samples in untreated or extracted form were stored at room temperature or 4°C. Calprotectin concentration was measured day 0 to 4 and 8. Five different immunoassays and accompanying extraction buffers were used (CALiaGold, Phadia EliA, Bühlmann fCal turbo, ELISA Bühlmann, Inova Quanta Flash). Repeated measurements of change from baseline calprotectin levels over time were analyzed using a mixed model analysis. RESULTS: Calprotectin concentrations declined over time under all preanalytical conditions with all assays, except for extracted feces stored at 4°C. The rate of decline was greatest in untreated stool kept at room temperature, reaching significant difference from baseline already after 1 day (P < 0.001). In extracted feces kept at room temperature, significant difference from baseline was reached after 2 days, and in untreated feces at 4°C, after 4 days. However, the results differed significantly between assays. After 4 days of storage at room temperature, the mean calprotectin decline from baseline differed between 30% and 60%, dependent on the assay used. CONCLUSIONS: Fecal calprotectin concentration in stool samples declines over time, and the rate of decline is greater at higher temperatures. In extracted feces stored at 4°C, calprotectin is most stable. It is assay-dependent how long extracted feces stored at 4°C give reliable test results.

Early Predictors for Discharge to Geriatric Rehabilitation after Hip Fracture Treatment of Older Patients.

OBJECTIVE: To investigate early predictors for discharge to a geriatric rehabilitation department at a skilled nursing home in older patients after hospitalization for hip fracture surgery. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data from 21,176 patients with hip fracture aged ≥70 years, who were registered in the Dutch Hip Fracture Audit database between January 1, 2017, and December 31, 2019, were included. METHODS: Patients were categorized into 3 discharge groups: home (n=7326), rehabilitation (n=11,738), and nursing home (n=2112). Age, gender, Pre-Fracture Mobility Score (PFMS), premorbid Katz index of independence in Activities of Daily Living (Katz-ADL), history of dementia, American Society of Anesthesiologists physical status classification (ASA score), type of anesthesia, fracture type, surgical treatment, and cotreatment by a geriatrician were gathered. Multinomial regression analysis was used to assess for early predictors. RESULTS: Higher age, poor premorbid mobility, lower premorbid Katz-ADL, no history of dementia, ASA score 3-5, general anesthesia, intramedullary implant, and cotreatment by a geriatrician were independent predictors for discharge to geriatric rehabilitation vs discharge home. Identical predictors were found for discharge to a nursing home vs discharge home. History of dementia and premorbid Katz-ADL were distinguishing factors; a higher premorbid Katz-ADL and a history of dementia were associated with a higher risk of discharge to a nursing home vs discharge home. The multinomial regression model correctly predicted 86%, 38.6%, and 2.4% of the patients in the rehabilitation group, home group, and nursing home group, respectively. CONCLUSIONS AND IMPLICATIONS: This study showed that age, PFMS, premorbid Katz-ADL, surgical treatment, ASA score, type of anesthesia, history of dementia, and cotreatment by a geriatrician were independent early predictors for discharge to geriatric rehabilitation vs discharge home in older patients after hip fracture surgery. Identical predictors were found as predictors for discharge to a nursing home vs discharge home, except for history of dementia and premorbid Katz-ADL.