Older patients with nonspecific complaints at the Emergency Department are at risk of adverse health outcomes.

OBJECTIVE: Older adults at the Emergency Department (ED) often present with nonspecific complaints (NSC) such as 'weakness' or 'feeling unwell'. Health care workers may underestimate illness in patients with NSC, leading to adverse health outcomes. This study compares characteristics and outcomes of NSC-patients versus specific complaints (SC) patients. METHODS: Cohort study in patients ≥ 70 years in two Dutch EDs. NSC was classified according to the BANC-study-framework based on the medical history in the ED letter, before additional diagnostics took place. A second classification was performed at the end of the ED visit/hospital admission. Primary outcomes were functional decline, institutionalization, and mortality at 30 days. RESULTS: 26% (n = 228) of a total of 888 included patients presented with NSC. Compared with SC-patients, NSC-patients were older, more frail, and more frequently female. NSC-patients had a higher risk of functional decline and institutionalization at 30 days (adjusted ORs 1.84, 95% CI 1.27 - 2.72, and 2.46, 95% CI 1.51-4.00, respectively), but not mortality (adjusted OR 1.26, 95% CI 0.58 - 2.73). Reclassification to a specific complaint after the ED visit or hospital admission occurred in 54% of NSC-patients. CONCLUSION: NSC occur especially in older, frail female patients and are associated with an increased risk of functional decline and institutionalization, even after adjustment for worse baseline status. In half of the patients, a specific complaint revealed during ED or hospital stay. Physicians at the ED should consider NSC as a red flag needing appropriate observation and evaluation of underlying serious conditions and needs of this vulnerable patient group.

In RA patients without prevalent CVD, incident CVD is mainly associated with traditional risk factors: A 20-year follow-up in the CARRÉ cohort study.

OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD. METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors). RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89). CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.

Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up.

OBJECTIVE: The aim of this study was to investigate early radiological and clinical outcome of autologous minced cartilage treatment as a single-step treatment option in patients with a chondral or osteochondral lesion (OCL) in the knee. DESIGN: Eighteen patients with an OCL in the knee were included. Cartilage from healthy-appearing loose bodies and/or the periphery of the defect were minced into small chips and sealed in the defect using fibrin glue. Preoperatively, and at 3 (n = 14) and 12 (n = 18) months follow-up, magnetic resonance imaging (MRI) was performed. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was used to assess the cartilage repair tissue on MRI at 12 months. The International Knee Documentation Score, Knee Injury and Osteoarthritis Outcome Score, EuroQoL-5D, and Visual Analogue Scale pain were collected preoperatively and 12 months after surgery. RESULTS: Three months postoperative, MRI showed complete defect filling in 11 out of 14 patients. Mean MOCART 2.0 score at 12 months was 65.0 ± 18.9 with higher scores for lateral femoral chondral lesions compared to medial femoral chondral lesions (75.8 ± 14.3, 52.5 ± 15.8 respectively, P = 0.02). Clinical and statistical significant improvements were observed in the patient-reported outcome measures at 12 months postoperatively compared to preoperatively. CONCLUSION: Treatment of OCLs using the autologous minced cartilage procedure resulted in good cartilage repair measured by MOCART 2.0. Clinically relevant improvements were observed in the clinical scores. This study suggests autologous minced cartilage as a promising, single-step treatment for OCLs.

The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis.

OBJECTIVE: Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. METHODS: A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. RESULTS: 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. CONCLUSION: DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. PROSPERO ID: CRD42020168337.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

OBJECTIVE: To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. DESIGN: Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. RESULTS: No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. CONCLUSIONS: Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis.

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1-1.8) vs. 0.7 (0.6-0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1-1.8) to 1.4 (1.1-1.7), p = 0.17] slightly improved and beta cell function [133% (115-151) to 118% (109-130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

Correction to: Paediatric intensive care admission blood pressure and risk of death in 30,334 children.

The authors of the article entitled "Paediatric Intensive Care admission blood pressure and risk of death in 30,334 children" inform that due to an error in their database extraction, the following corrections to the data published should be notified.

Knee adduction moments are not increased in obese knee osteoarthritis patients during stair negotiation.

BACKGROUND: Negotiating stairs is an important activity of daily living that is also associated with large loads on the knee joint. In medial compartment knee osteoarthritis, the knee adduction moment during level walking is considered a marker for disease severity. It could be argued that the discriminative capability of this parameter is even better if tested in a strenuous stair negotiation task. RESEARCH QUESTION: What is the relation with knee osteoarthritis on the knee adduction moment during the stance phase of both stair ascent and descent in patients with and without obesity? METHODS: This case control study included 22 lean controls, 16 lean knee osteoarthritis patients, and 14 obese knee osteoarthritis patients. All subjects ascended and descended a two-step staircase at a self-selected, comfortable speed. Three-dimensional motion analysis was performed to evaluate the knee adduction moment during stair negotiation. RESULTS: Obese knee osteoarthritis patients show a prolonged stance time together with a more flattened knee adduction moment curve during stair ascent. Normalized knee adduction moment impulse, as well as the first and second peaks were not different between groups. During stair descent, a similar increase in stance time was found for both osteoarthritis groups. SIGNIFICANCE: The absence of a significant effect of groups on the normalized knee adduction moment during stair negotiation may be explained by a lower ambulatory speed in the obese knee osteoarthritis group, that effectively lowers vertical ground reaction force. Decreasing ambulatory speed may be an effective strategy to lower knee adduction moment during stair negotiation.

Prescription patterns of lipid lowering agents among older patients in general practice: an analysis from a national database in the Netherlands.

BACKGROUND: Dutch cardiovascular risk management guidelines state almost every older adult (≥70 years) is eligible for a lipid lowering drug (LLD). However, life expectancy, frailty or comorbidities may influence this treatment decision. OBJECTIVE: investigate how many older adults, according to age, frailty (Drubbel-frailty index) and comorbidities were prescribed LLDs. METHODS: data of 244,328 adults ≥70 years from electronic health records of 415 Dutch general practices from 2011-15 were used. Number of LLD prescriptions in patients with (n = 55,309) and without (n = 189,019) cardiovascular disease (CVD) was evaluated according to age, frailty and comorbidities. RESULTS: about 69% of adults ≥70 years with CVD and 36% without CVD were prescribed a LLD. LLD prescriptions decreased with age; with CVD: 78% aged 70-74 years and 29% aged ≥90 years were prescribed a LLD, without CVD: 37% aged 70-74 years and 12% aged ≥90 years. In patients with CVD and within each age group, percentage of LLD prescriptions was 20% point(pp) higher in frail compared with non-frail. In patients without CVD, percentage of LLD prescriptions in frail patients was 11pp higher in adults aged 70-74 years and 40pp higher in adults aged ≥90 years compared to non-frail. Similar trends were seen in the analyses with number of comorbidities. CONCLUSION: in an older population, LLD prescriptions decreased with age but-contrary to our expectations-LLD prescriptions increased with higher frailty levels.

The effects of golimumab treatment on systolic and diastolic left ventricular function in ankylosing spondylitis.

BACKGROUND: Diastolic left ventricular (LV) dysfunction appears more prevalent in ankylosing spondylitis (AS). The effects of tumor necrosis factor alpha (TNF-α) blocking therapy, a strong and effective anti-inflammatory drug, on diastolic LV function in AS are unknown. The objective of the study was to find the effects of 1-year treatment with golimumab 50 mg subcutaneously once per month on systolic and diastolic LV dysfunction in AS patients. METHODS: Forty consecutive AS patients were treated with TNF-α blocking therapy for 1 year. Transthoracic echocardiography was performed in all patients at baseline and after 1 year of treatment. RESULTS: Diastolic LV function improved after treatment in four out of six (67%) AS patients who completed follow-up (P=0.125), and did not develop or worsen in any of the other patients. Treatment with TNF-α blocking therapy had no effect on systolic LV function. CONCLUSION: These findings give support to the hypothesis that diastolic LV dysfunction improves during treatment with TNF-α blocking therapy.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

Full blood count parameters for the detection of asthma inflammatory phenotypes.

BACKGROUND: In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a more accessible method is needed for clinical practice. OBJECTIVE: To investigate whether white blood cell counts and/or their derived ratios can predict sputum eosinophils or neutrophils in uncontrolled asthma. METHODS: This cross-sectional study evaluated 164 treated but uncontrolled asthmatic patients with sputum induction and blood collection. Receiver-operating characteristic (ROC) curves were used to assess the relationship between blood and sputum parameters. RESULTS: There was a significant positive relationship between blood eosinophil parameters and the percentage of sputum eosinophil count. A weak but significant correlation was found between sputum neutrophil percentage and blood neutrophil percentage (r = 0.219, P = 0.005). ROC curve analysis identified that blood eosinophil percentage count was the best predictor for eosinophilic asthma, with an area under the curve (AUC) of 0.907 (P < 0.001). The optimum cut-point for blood eosinophil percentage was 2.7%, and this yielded a sensitivity of 92.2% and a specificity of 75.8%. The absolute blood eosinophil count was also highly predictive with an AUC of 0.898 (P < 0.0001) at a blood eosinophil cut-off of 0.26 × 10(9) /L. The blood eosinophil/lymphocyte ratio (ELR) and eosinophil/neutrophil ratio (ENR) were increased in eosinophilic asthma, and the neutrophil/lymphocyte ratio (NLR) was increased in neutrophilic asthma. Neutrophilic asthma could also be detected by blood neutrophil percentages and NLR, but with less accuracy. CONCLUSIONS AND CLINICAL RELEVANCE: Blood eosinophil counts and derived ratios (ELR and ENR) can accurately predict eosinophilic asthma in patients with persistent uncontrolled asthma despite treatment. Blood neutrophil parameters are poor surrogates for the proportion of sputum neutrophils. Blood counts may be a useful aid in the monitoring of uncontrolled asthma.

Outcomes of an Australian testing programme for epidermal growth factor receptor mutations in non-small cell lung cancer.

BACKGROUND: Molecular characterisation of non-squamous non-small-cell lung cancer (NSCLC) is required to direct optimal treatment. Treatment of NSCLC with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase (EGFR-TKI) should be guided by the presence of activating mutations of the EGFR gene. AIM: To gain insight into the rate of testing, the range of tissues samples, test utility and outcome when cost of testing as a barrier to access is removed in the Australian setting. METHODS: In October 2010, a sponsored programme was commenced to gather data on EGFR gene mutation testing in Australia. Partnering laboratories were funded for provision of de-identified results. For participating patients, the programme supported the test charge. Mutation testing was performed using Sanger sequencing of exons 18-21 of the EGFR. RESULTS: Samples 2013 were submitted from 2012 patients. Full sequencing was achieved in 1717 (85%). Failure of full sequencing was more likely in samples derived from fine needle aspiration(FNA) biopsy than tissue biopsy or pleural/pericardial fluid cell blocks OR 3.1 (95% CI 1.9-5.2). There were 359 mutations seen in 337 patients. 14.5% of cases had a classical mutation conferring sensitivity to EGFR-TKI. In addition there was a range of less common mutations - some predicting responses and others of uncertain significance. 1.4% of cases had mutations associated with non-responsiveness to EGFR-TKI. CONCLUSIONS: EGFR gene mutation testing is feasible on local and interstate lung cancer samples. The rate of valid test outcomes is high, but FNA samples are associated with more frequent test failure.

Increased progression of carotid intima media thickness in thyroid peroxidase antibodies-positive rheumatoid arthritis patients.

OBJECTIVE: Autoimmune diseases such as rheumatoid arthritis (RA) and hypothyroidism tend to cluster, and this coexistence amplifies the elevated cardiovascular risk in RA. Whether thyroid peroxidase antibodies (TPOabs) are associated with increased cardiovascular disease (CVD) risk has not been studied extensively. Therefore, this study determined firstly the prevalence of TPOabs in RA and secondly whether TPOabs were associated with CVD. Moreover, this study explored whether TPOabs were related to RA characteristics. DESIGN AND METHODS: Data from the CARRÉ Study, an ongoing study investigating CVDs and its risk factors in RA (n=322), was used to ascertain the prevalence of TPOabs in RA patients. In addition, cardiovascular and RA disease characteristics were compared between TPOabs-positive and -negative patients at baseline and at a second visit after 3 years. RESULTS: TPOabs were present in 47/322 (15%) RA patients and TSH levels were higher in TPOabs-positive patients (1.40 mU/l) compared with TPOabs-negative patients (1.26 mU/l, P=0.048). At baseline and after 3 years no association was observed between TPOabs and (risk factors for) CVD. Regression analyses revealed a significantly larger progression of carotid intima media thickness (cIMT; ß=0.13 mm) in TPOabs-positive compared with TPOabs-negative patients independent of risk factors for cIMT progression. RA disease activity scores (DAS28) were higher in TPOabs-positive compared with TPOabs-negative patients (4.4 vs 3.8 P=0.018). CONCLUSIONS: TPOabs were associated with increased cIMT progression. Moreover, an association between TPOabs and DAS28 was observed. Hence, TPOabs seems to have a role in the amplified cardiovascular risk in RA patients.