A European-Japanese study on peach allergy: IgE to Pru p 7 associates with severity.

BACKGROUND: Pru p 3 and Pru p 7 have been implicated as risk factors for severe peach allergy. This study aimed to establish sensitization patterns to five peach components across Europe and in Japan, to explore their relation to pollen and foods and to predict symptom severity. METHODS: In twelve European (EuroPrevall project) and one Japanese outpatient clinic, a standardized clinical evaluation was conducted in 1231 patients who reported symptoms to peach and/or were sensitized to peach. Specific IgE against Pru p 1, 2, 3, 4 and 7 and against Cup s 7 was measured in 474 of them. Univariable and multivariable Lasso regression was applied to identify combinations of parameters predicting severity. RESULTS: Sensitization to Pru p 3 dominated in Southern Europe but was also quite common in Northern and Central Europe. Sensitization to Pru p 7 was low and variable in the European centers but very dominant in Japan. Severity could be predicted by a model combining age of onset of peach allergy, probable mugwort, Parietaria pollen and latex allergy, and sensitization to Japanese cedar pollen, Pru p 4 and Pru p 7 which resulted in an AUC of 0.73 (95% CI 0.73-0.74). Pru p 3 tended to be a risk factor in South Europe only. CONCLUSIONS: Pru p 7 was confirmed as a significant risk factor for severe peach allergy in Europe and Japan. Combining outcomes from clinical and demographic background with serology resulted in a model that could better predict severity than CRD alone.

Performance of knee image digital analysis of radiographs of patients with end-stage knee osteoarthritis.

OBJECTIVE: Knee Image Digital Analysis (KIDA) is standardized radiographic analysis software for measuring osteoarthritis (OA) characteristics. It was validated in mild OA, but used for severe OA as well. The current goal was to evaluate the performance of KIDA in severe OA. DESIGN: Of 103 patients, standardized radiographs were performed before and one and 2 years after treatment for severe OA. All radiographs were evaluated on subchondral bone density, joint space width (JSW), osteophytes, eminence height, and joint angle, twice within years by the same observer. Part of the radiographs were randomly selected for reevaluation twice within 1 month and evaluation by another observer. The intraclass correlation coefficient (ICC), smallest detectable difference (SDD) and coefficient of variation (CV) were calculated; the SDD and CV were compared to those in mild OA. The relation of severity with KIDA parameters and with observer differences was calculated with linear regression. RESULTS: Intra-observer ICCs were higher in the 98 severe radiographs reanalyzed within 1 month (all >0.8) than the 293 reanalyzed within years (all >0.5; most >0.8) and than inter-observer ICCs (all >0.7). SDDs and CVs were smaller when reanalyzed within a month and comparable to those in mild OA. Some parameters showed bias between readings. Severity showed significant relation with osteophytes and JSW parameters, and with the observer variation in these parameters (all P < 0.04). CONCLUSIONS: KIDA is a well-performing tool also for severe OA. In order to decrease variability and SDDs, images should be analyzed in a limited time frame and randomized order.

An automated workflow based on hip shape improves personalized risk prediction for hip osteoarthritis in the CHECK study.

OBJECTIVE: To design an automated workflow for hip radiographs focused on joint shape and tests its prognostic value for future hip osteoarthritis. DESIGN: We used baseline and 8-year follow-up data from 1,002 participants of the CHECK-study. The primary outcome was definite radiographic hip osteoarthritis (rHOA) (Kellgren-Lawrence grade ≥2 or joint replacement) at 8-year follow-up. We designed a method to automatically segment the hip joint from radiographs. Subsequently, we applied machine learning algorithms (elastic net with automated parameter optimization) to provide the Shape-Score, a single value describing the risk for future rHOA based solely on joint shape. We built and internally validated prediction models using baseline demographics, physical examination, and radiologists scores and tested the added prognostic value of the Shape-Score using Area-Under-the-Curve (AUC). Missing data was imputed by multiple imputation by chained equations. Only hips with pain in the corresponding leg were included. RESULTS: 84% were female, mean age was 56 (±5.1) years, mean BMI 26.3 (±4.2). Of 1,044 hips with pain at baseline and complete follow-up, 143 showed radiographic osteoarthritis and 42 were replaced. 91.5% of the hips had follow-up data available. The Shape-Score was a significant predictor of rHOA (odds ratio per decimal increase 5.21, 95%-CI (3.74-7.24)). The prediction model using demographics, physical examination, and radiologists scores demonstrated an AUC of 0.795, 95%-CI (0.757-0.834). After addition of the Shape-Score the AUC rose to 0.864, 95%-CI (0.833-0.895). CONCLUSIONS: Our Shape-Score, automatically derived from radiographs using a novel machine learning workflow, may strongly improve risk prediction in hip osteoarthritis.

Measurement error in continuous endpoints in randomised trials: Problems and solutions.

In randomised trials, continuous endpoints are often measured with some degree of error. This study explores the impact of ignoring measurement error and proposes methods to improve statistical inference in the presence of measurement error. Three main types of measurement error in continuous endpoints are considered: classical, systematic, and differential. For each measurement error type, a corrected effect estimator is proposed. The corrected estimators and several methods for confidence interval estimation are tested in a simulation study. These methods combine information about error-prone and error-free measurements of the endpoint in individuals not included in the trial (external calibration sample). We show that, if measurement error in continuous endpoints is ignored, the treatment effect estimator is unbiased when measurement error is classical, while Type-II error is increased at a given sample size. Conversely, the estimator can be substantially biased when measurement error is systematic or differential. In those cases, bias can largely be prevented and inferences improved upon using information from an external calibration sample, of which the required sample size increases as the strength of the association between the error-prone and error-free endpoint decreases. Measurement error correction using already a small (external) calibration sample is shown to improve inferences and should be considered in trials with error-prone endpoints. Implementation of the proposed correction methods is accommodated by a new software package for R.

Effectiveness of Remission Induction Strategies for Early Rheumatoid Arthritis: a Systematic Literature Review.

PURPOSE OF REVIEW: To review the effectiveness of remission induction strategies compared to single csDMARD-initiating strategies according to current guidelines in early RA. RECENT FINDINGS: Twenty-nine studies, heterogeneous on, e.g., specific treatment strategy and remission outcome used, were identified. Using DAS28-remission over 12 months, 13 (76%) of 17 remission induction strategies showed significantly more patients achieving remission. Pooled relative "risk" was 1.73 [95%CI 1.59-1.88] for bDMARD-based remission induction strategies and 1.20 [95%CI 1.03-1.40] for combination csDMARD-based remission induction strategies compared to single csDMARD-initiating strategies. When additional glucocorticoid "bridging therapy" was used in single csDMARD-initiating strategies, the higher proportion patients achieving remission in remission induction strategies was no longer statistically significant (pooled RR 1.06 [95%CI 0.83-1.35]). For other remission outcomes, results were in line with above. Remission induction strategies are more effective in achieving remission compared to single csDMARD-initiating strategies, possibly more so in bDMARD-based induction strategies. However, compared to single csDMARD-initiating strategies with glucocorticoids, induction strategies may not be more effective.

Disease burden of knee osteoarthritis patients with a joint replacement compared to matched controls: a population-based analysis of a Dutch medical claims database.

OBJECTIVE: On a population level, the incidence of knee prostheses (KPs) has increased, but excess health care costs per patient, compared to matched controls without a KP, in the years surrounding these procedures and their determinants are largely unknown. We therefore aimed to provide estimates of age- and sex-specific incidence of KPs, revision KPs, and prosthesis complications in patients with knee osteoarthritis (OA) and to determine excess health care costs in the years surrounding surgery compared with matched controls. METHODS: All KPs in OA patients in the Achmea Health Database were identified as well as up to four controls. Incidence rates of KPs, revisions, and complications from 2006 to 2013 were determined. Annual health care cost and excess costs (over matched controls) preceding, during, and after surgery were calculated and their determinants were evaluated. RESULTS: The increased incidence of KPs, revisions, and complications was strongest in younger age categories and men. The average costs per patient were relatively stable between 2006 and 2012. KP patient's annual health care costs increased towards the year of surgery. After surgery, costs decreased, but remained higher as compared to costs prior to surgery. High post-surgery costs were mainly associated with subsequent revisions or additional KPs, but costs were also higher in females, lower age categories, and lower social economic status. CONCLUSION: These results underscore the increasing burden and medical need associated with end-stage OA, especially in younger age categories. Improvement of guidelines tailored to individual patient groups aimed at avoiding complications and revisions is required to counteract this increasing burden.

A sex-specific association between incident radiographic osteoarthritis of hip or knee and incident peripheral arterial calcifications: 8-year prospective data from Cohort Hip and Cohort Knee (CHECK).

OBJECTIVES: There is sparse evidence for a relationship between cardiovascular disease (CVD) and osteoarthritis (OA). We investigated the association between incidence of arterial calcifications and incidence of radiographic knee and/or hip OA. DESIGN: We used baseline and 8-year follow-up data of Cohort Hip and Cohort Knee (CHECK). Knees and hips were either Kellgren-Lawrence (KL) grade 0 or 1 at baseline. Arterial calcifications were scored on hip and knee radiographs using a four-grade scale. Scores were summed for patient-level analyses. To investigate incidence, participants with arterial calcifications at baseline or missing follow-up were excluded. Incident OA was defined per joint as KL ≥ 2 or prosthesis at year eight. The association between incidenct of arterial calcifications and incident OA was studied using mixed-effects logistic regression. RESULTS: Of 763 participants included, 623 (82%) were women. Mean (sd) age was 56 (5.1) years, mean (sd) body mass index (BMI) 26.2 (4.1) kg/m2. Arterial calcifications developed in 174 participants (283 joints). OA developed in 456 participants (778 joints). Sex modified the association between arterial calcification and OA. In women, incident arterial calcification around a joint was positively associated with incident OA in that joint (adjusted OR 2.51 (95% CI 1.57-4.03)). In men, no association was observed on joint-level, but at patient-level the arterial calcification sum score was negatively associated with incident OA (adjusted OR per point increase 0.70 (95% CI 0.54-0.90)) indicating a systemic effect. CONCLUSIONS: We observed sex-dependent associations between incident arterial calcification and incident radiographic knee and/or hip OA, which differs between joint- and patient-level.

Personalised treatment using serum drug levels of adalimumab in patients with rheumatoid arthritis: an evaluation of costs and effects.

OBJECTIVE: To evaluate the cost-effectiveness of personalised treatment for rheumatoid arthritis (RA) using clinical response and serum adalimumab levels. METHODS: A personalised treatment algorithm defined, based on clinical (European League Against Rheumatism) response and drug levels at 6 months, whether adalimumab treatment should be continued in a specific dose or discontinued and/or switched to a next biological. Outcomes were simulated using a patient level Markov model, with 3 months cycles, based on a cohort of 272 adalimumab-treated patients with RA for 3 years and data of patients from the Utrecht Rheumatoid Arthritis Cohort. Costs, clinical effectiveness and quality adjusted life years (QALYs) were compared with outcomes as observed in usual care and incremental cost-effectiveness ratios were calculated. Analyses were performed probabilistically. RESULTS: Clinical effectiveness was higher for the cohort simulated to receive personalised care compared with usual care; the average difference in QALYs was 3.84 (95 percentile range -8.39 to 16.20). Costs were saved on drugs: €2 314 354. Testing costs amounted to €10 872. Mean total savings were €2 561 648 (95 percentile range -3 252 529 to -1 898 087), resulting in an incremental cost-effectiveness ratio of €666 500 or €646 266 saved per QALY gained from a societal or healthcare perspective, respectively. In 72% of simulations personalised care saved costs and resulted in more QALYs, in 28% it was cost saving with lower QALYs. Scenario analyses showed cost saving along with QALYs gain or limited loss. CONCLUSIONS: Tailoring biological treatment to individual patients with RA starting adalimumab using drug levels and short-term outcome is cost-effective. Results underscore the potential merit of personalised biological treatment in RA.

Systemic biochemical markers of joint metabolism and inflammation in relation to radiographic parameters and pain of the knee: data from CHECK, a cohort of early-osteoarthritis subjects.

OBJECTIVE: To investigate associations of biochemical markers of joint metabolism and inflammation with minimum joint space width (JSW) and osteophyte area (OP area) of knees showing no or doubtful radiographic osteoarthritis (OA) and to investigate whether these differed between painful and non-painful knees. DESIGN: Serum (s-) and urinary (u-) levels of the cartilage markers uCTX-II, sCOMP, sPIIANP, and sCS846, bone markers uCTX-I, uNTX-I, sPINP, and sOC, synovial markers sPIIINP and sHA, and inflammation markers hsCRP and erythrocyte sedimentation rate (ESR) were assessed in subjects from CHECK (Cohort Hip and Cohort Knee) demonstrating Kellgren and Lawrence grade ≤1 OA on knee radiographs. Minimum JSW and OP area of these knees were quantified in detail using Knee Images Digital Analysis (KIDA). RESULTS: uCTX-II levels showed negative associations with minimum JSW and positive associations with OP area. sCOMP and sHA levels showed positive associations with OP area, but not with minimum JSW. uCTX-I and uNTX-I levels showed negative associations with minimum JSW and OP area. Associations of biochemical marker levels with minimum JSW were similar between painful and non-painful knees, associations of uCTX-II, sCOMP, and sHA with OP area were only observed in painful knees. CONCLUSIONS: In these subjects with no or doubtful radiographic knee OA, uCTX-II might not only reflect articular cartilage degradation but also endochondral ossification in osteophytes. Furthermore, sCOMP and sHA relate to osteophytes, maybe because synovitis drives osteophyte development. High bone turnover may aggravate articular cartilage loss. Metabolic activity in osteophytes and synovial tissue, but not in articular cartilage may be related to knee pain.

The ability of systemic biochemical markers to reflect presence, incidence, and progression of early-stage radiographic knee and hip osteoarthritis: data from CHECK.

OBJECTIVE: To relate systemic biochemical markers of joint metabolism to presence, incidence, and progression of early-stage radiographic knee and/or hip osteoarthritis (OA). METHOD: The cartilage markers uCTX-II, sCOMP, sPIIANP, and sCS846, bone markers uCTX-I, uNTX-I, sPINP, and sOC, and synovial markers sHA and sPIIINP were assessed by enzyme-linked immunosorbent assay or radioactive immunoassay in baseline samples of CHECK (Cohort Hip and Cohort Knee), a cohort study of early-stage symptomatic knee and/or hip OA. Knee and hip radiographs were obtained at baseline and 5-year follow-up. Presence of OA at baseline was defined as Kellgren and Lawrence (K&L) = 1 (maximum observed). Incidence of OA was defined as K&L = 0 at baseline and K&L ≥ 1 at 5-year follow-up. Progression of OA was defined as K&L = 1 at baseline and K&L ≥ 2 at 5-year follow-up. RESULTS: Data were available for 801 subjects at baseline and for 723 subjects at both baseline and 5-year follow-up. Multiple cartilage and synovial markers showed positive associations with presence and progression of knee and hip OA and with incidence of hip OA, except for negative associations of uCTX-II and sCOMP with incidence of knee OA. uCTX-II and sCOMP showed multiple interactions with other biomarkers in their associations with knee and hip OA. Bone markers were positively associated with presence of radiographic knee OA, but negatively associated with progression of radiographic hip OA. CONCLUSION: Especially metabolism in cartilage and synovial matrix appear to be of relevance in knee and hip OA. The role of bone metabolism appears to differ between knee and hip OA.

Anti-osteoporosis drug prescribing after hip fracture in the UK: 2000-2010.

UNLABELLED: The probability of initiating with anti-osteoporosis therapy increased from 7 % in 2000 to 46 % in 2010. This improvement was greater for patients over the age of 75 years. Men, those overweight, having dementia or exposed to antipsychotics, sedatives/hypnotics or opioid analgesics were significantly less likely to receive anti-osteoporosis drugs. INTRODUCTION: The objective of this study was to examine trends and determinants of anti-osteoporosis drug prescribing after hip fracture in the UK between 2000 and 2010. METHODS: Data were extracted from the UK Clinical Practice Research Datalink for patients ≥50 years who had a first hip fracture between 2000 and 2010 and who did not currently (≤6 months prior) receive anti-osteoporosis drugs (bisphosphonates, strontium ranelate, parathyroid hormone, calcitonin and raloxifene) (n = 27,542). The cumulative incidence probability of being prescribed anti-osteoporosis drugs within 1 year after hip fracture was estimated by Kaplan-Meier life-table analyses. Determinants for treatment initiation were estimated by Cox proportional hazards models. RESULTS: The probability of being prescribed any anti-osteoporosis drug after hip fracture increased from 7 % in 2000 to 46 % in 2010. This trend was more marked in patients ≥75 years. The increase in prescribing of anti-osteoporosis drugs was complemented by a similar increase in vitamin D/calcium provision. Cumulative incidence of receiving anti-osteoporosis therapy was greater at any given point in time in women (8 % in 2000, 51 % in 2010) compared to men (4 % in 2000, 34 % in 2010). In addition to male gender, multivariable Cox regression identified reduced likelihood of receiving anti-osteoporosis drugs for those being overweight, having dementia and exposed to psychotropic drugs (antipsychotics, sedatives/hypnotics) or opioid analgesics. CONCLUSION: Although the prescribing of anti-osteoporosis drugs after hip fracture has increased substantially since 2000, the overall rate remained inadequate, particularly in men. With the continuing increase in the absolute number of hip fractures, further research should be made into the barriers to optimise osteoporosis management.

Long-term persistence with anti-osteoporosis drugs after fracture.

UNLABELLED: Long-term persistence with anti-osteoporosis drugs and determinants for discontinuation among fracture patients were examined. Persistence was 75.0 and 45.3 % after 1 and 5 years, respectively. Those aged ≥80 years were at increased risk of early discontinuation. Within 1 year after discontinuation, 24.3 % restarted therapy, yet 47.0 % persisted for 1 year. INTRODUCTION: The risk of osteoporotic fracture can effectively be reduced with use of anti-osteoporosis drugs. However, little is known about persistence with these drugs after fracture where subsequent fracture risk is high. The aims were to determine long-term persistence with anti-osteoporosis drugs among fracture patients, including its determinants, and to describe restart and subsequent persistence. METHODS: A cohort study was conducted within the Dutch PHARMO Database Network. Patients aged ≥50 years (n = 961) who received anti-osteoporosis drugs within 1 year after fracture, but not in the preceding year, were included (2002-2011). Persistence (defined as the proportion on treatment) and the proportion restarting after discontinuation were estimated using Kaplan-Meier analyses. Time-dependent Cox regression was used to identify determinants of non-persistence including age, sex, initial dosage regime, fracture type, comorbidities, and drug use. RESULTS: Persistence with anti-osteoporosis drugs was 75.0 % (95 % confidence interval (CI) 72.0-77.7) and 45.3 % (95 % CI 40.4-50.0) after 1 and 5 years, respectively. A significant determinant of non-persistence was age ≥80 years (reference 50-59 years: adjusted hazard ratio [adj. HR] 1.65; 95 % CI 1.15-2.38). This effect was not constant over time (≤360 days following initiation: adj. HR 2.07; 95 % CI 1.27-3.37; >360 days: adj. HR 1.08; 95 % CI 0.62-1.88). Within 1 year after discontinuation, 24.3 % (95 % CI 20.1-29.2) restarted therapy, yet 47.0 % persisted for 1 year. CONCLUSIONS: This study identified suboptimal persistence with anti-osteoporosis drugs among fracture patients. Major target groups for measures aimed to improve persistence may be those aged >80 years and those restarting therapy.

Economic evaluation of a tight-control treatment strategy using an imaging device (handscan) for monitoring joint inflammation in early rheumatoid arthritis.

OBJECTIVES: To evaluate the cost-effectiveness of a tight-control treatment strategy using the handscan (TCHS) compared to using only clinical assessments (TC) and compared to a general non-tight-control treatment strategy (usual care; UC) in early rheumatoid arthritis (RA). METHODS: Data from 299 early RA patients from the CAMERA trial were used. Clinical outcomes were extrapolated to Quality Adjusted Life Years (QALYs) and costs using a Markov model. Costs and QALYs were compared between the TC and UC treatment strategy arm of the CAMERA trial and a simulated tight-control treatment strategy using the handscan (TCHS). Incremental Cost-Effectiveness Ratios (ICERs) were calculated and several scenario analyses performed. All analyses were performed probabilistically to obtain confidence intervals and costs-effectiveness planes and acceptability curves. RESULTS: In TCHS, €4,660 (95% CI -€11,516 to €2,045) was saved and 0.06 (95% CI 0.01 to 0.11) QALYs were gained when compared to UC, with an ICER of €77,670 saved per QALY gained. Ninety-one percent (91%) of simulations resulted in less costs and more QALYs. TCHS resulted in comparable costs or even limited savings €642 (95% CI -€6,903 to €5,601)) and comparable QALYs to TC. In all scenario analyses, TCHS and TC were found to be cost effective as compared to UC. CONCLUSIONS: A tight-control treatment strategy is highly cost-effective compared to a non-tight-control approach in early RA. Using the handscan as a monitoring device might facilitate implementation of tight-control treatment strategy at comparable costs and with comparable effects. This approach should be investigated further.

The risk of major and any (non-hip) fragility fracture after hip fracture in the United Kingdom: 2000-2010.

UNLABELLED: The risk of a subsequent major or any fracture after a hip fracture and secular trends herein were examined. Within 1 year, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years. Subsequent fracture rates increased during the study period both for major and any (non-hip) fracture. INTRODUCTION: Hip fractures are associated with subsequent fractures, particularly in the year following initial fracture. Age-adjusted hip fracture rates have stabilised in many developed countries, but secular trends in subsequent fracture remain poorly documented. We thus evaluated secular trends (2000-2010) and determinants for the risk of a subsequent major (humerus, vertebral, or forearm) and any (non-hip) fracture after hip fracture. METHODS: Patients ≥50 years with a hip fracture between 2000 and 2010 were extracted from the UK Clinical Practice Research Datalink (n = 30,516). Incidence rates, cumulative incidence probabilities, and adjusted hazard ratios (aHRs) were calculated. RESULTS: Within 1 year following hip fracture, 2.7 and 8.4% of patients sustained a major or any (non-hip) fracture, which increased to 14.7 and 32.5% after 5 years, respectively. The most important risk factors for a subsequent major fracture within 1 year were the female gender [aHR 1.90, 95% confidence interval (CI) 1.51-2.40] and a history of secondary osteoporosis (aHR 1.54, 95% CI 1.17-2.02). The annual risk increased during the study period for both subsequent major (2009-2010 vs. 2000-2002: aHR 1.44, 95% CI 1.12-1.83) and any (non-hip) facture (2009-2010 vs. 2000-2002: aHR 1.80, 95% CI 1.58-2.06). CONCLUSION: The risk of sustaining a major or any (non-hip) fracture after hip fracture is small in the first year. However, given the recent rise in secondary fracture rates and the substantial risk of subsequent fracture in the longer term, fracture prevention is clearly indicated for patients who have sustained a hip fracture.

The separate impact of tight control schemes and disease activity on quality of life in patients with early rheumatoid arthritis: results from the CAMERA trials.

OBJECTIVES: To examine in patients with early rheumatoid arthritis (RA) whether quality of life (QoL), independently of disease activity, is affected by tight control treatment strategy schemes. METHODS: In the Computer Assisted Management in Early RA (CAMERA) trials, patients with early RA, disease duration <1 year, no prior use of DMARDs) had been randomised to a methotrexate (MTX)-based tight control strategy or usual care (CAMERA study) or to 10 mg/d prednisone or placebo both added from start to a MTX-based tight control strategy (CAMERA-II study). In either study, randomisation to the more intensive strategy resulted in lower disease activity. To assess QoL, the 'Influence of Rheumatic Diseases on General Health and Lifestyle' questionnaire (IRGL) was used. Baseline and 1- and/or 2-year measurements were analysed with regression analyses with the IRGL (sub)scales as outcome variables and treatment strategy and disease activity assessing 28 joints (DAS28) as independent variables, correcting for baseline values of each scale and possible confounders (gender, age, rheumatoid factor status). RESULTS: There was no clear association between either of the treatment strategies and QoL, but a decrease in DAS28 was associated with improvement in the majority of QoL (sub)scales. CONCLUSIONS: No independent effect of the specific tight control strategies schemes on QoL was found, while there was a clear disease activity related effect. Thus frequent outpatient visits or the inclusion of prednisone in a tight control strategy did not negatively influence QoL.

The effect of subcutaneous and sublingual birch pollen immunotherapy on birch pollen-related food allergy: a systematic review.

Background: Birch pollen-related food allergy (BPFA) is the most common type of food allergy in birch-endemic areas such as Western and Central Europe. Currently, there is no treatment available for BPFA. Due to the cross-reactivity between birch pollen and a range of implicated plant foods, birch pollen allergen immunotherapy (AIT) may be effective in the treatment of BPFA. In this study, we systematically evaluate the effectiveness of birch pollen-specific subcutaneous or sublingual immunotherapy in treating BPFA. Methods: A search was performed in the PubMed, Embase, and Cochrane libraries. Studies were independently screened by two reviewers against predefined eligibility criteria. The outcomes of interest were changes in (1) severity of symptoms during food challenge, (2) eliciting dose (ED), and (3) food allergy quality of life (FA-QoL). The validity of the selected articles was assessed using the revised Cochrane risk of bias tool. We focused on studies with the lowest risk of bias and considered studies with a high risk of bias as supportive. Data were descriptively summarized. Results: Ten studies were selected that included 475 patients in total. Seven studies were categorized into "high risk of bias" and three into "moderate risk of bias." The three moderate risk of bias studies, with a total of 98 patients, reported on severity of symptoms during challenge and on the ED. All three studies had a control group. Compared to the control group, improvement in severity of symptoms was observed during challenge in two out of the three studies and on the eliciting dose in one out of three. Only one study investigated the effect of birch pollen AIT on FA-QoL, showing that there was no significant difference between patients receiving subcutaneous immunotherapy or a placebo. Of the seven supportive studies, four had a control group and of those, three showed improvement on both severity of symptoms and ED. None of the supportive studies investigated the effect of the therapy on FA-QoL. Conclusion: This systematic review shows that there is not enough evidence to draw firm conclusions about the effect of AIT on BPFA. Future research is warranted that uses robust clinical studies that include long-term effects, QoL, and multiple BPFA-related foods.

Skin pentosidine in very early hip/knee osteoarthritis (CHECK) is not a strong independent predictor of radiographic progression over 5 years follow-up.

OBJECTIVES: Age-related changes in articular cartilage are likely to play a role in the etiology of osteoarthritis (OA). One of the major age-related changes in cartilage is the accumulation of advanced glycation end products (AGEs). The present study evaluates whether pentosidine can predict radiographic progression and/or burden over 5 years follow-up in a cohort of early knee and/or hip OA. DESIGN: The 5 years follow-up data of 300 patients from cohort hip & cohort knee (CHECK) were used. Radiographic progression and burden were assessed by X-rays of both knees and hips (Kellgren and Lawrence (K&L) and Altman scores). Baseline pentosidine levels (and urinary CTXII as a comparator) were measured by high-performance-liquid-chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA). Univariable and multivariable associations including baseline radiographic damage, age, gender, body mass index (BMI) and kidney function were performed. RESULTS: Both pentosidine and urinary C-terminal telopeptide of type II collagen (uCTXII) correlated with radiographic progression and burden. In general pentosidine did not have an added predictive value to uCTXII for progression nor burden of the disease. The best prediction was obtained for burden of radiographic damage (R(2) = 0.60-0.88), bus this was predominantly determined by baseline radiographic damage (without this parameter R(2) = 0.07-0.17). Interestingly, pentosidine significantly added to prediction of osteophyte formation, whereas uCTXII significantly added to prediction of JSN in multivariable analysis. CONCLUSION: Pentosidine adds to prediction of radiographic progression and burden of osteophyte formation and uCTXII to radiographic progression and burden of JSN, but overall skin pentosidine did not perform better that uCTXII in predicting radiographic progression or burden. Burden of damage over 5 years is mainly determined by radiographic joint damage at baseline.

Are changes in bone mineral density different between groups of early rheumatoid arthritis patients treated according to a tight control strategy with or without prednisone if osteoporosis prophylaxis is applied?

UNLABELLED: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early rheumatoid arthritis (RA) patients receiving preventive treatment for osteoporosis. A small increase in lumbar bone mineral density (BMD) during the first year of treatment was recorded, regardless of use of glucocorticoids. INTRODUCTION: This study aims to describe effects on BMD of treatment according to EULAR guidelines with a methotrexate-based tight control strategy including 10 mg prednisone daily versus the same strategy without prednisone in early RA patients who received preventive therapy for osteoporosis. METHODS: Early RA patients were included in the CAMERA-II trial: a randomized, placebo-controlled, double-blind 2-year trial, in which effects of addition of 10 mg prednisone daily to a methotrexate-based tight control strategy were studied. All patients received calcium, vitamin D and bisphosphonates. Disease activity was assessed every 4 weeks. Radiographs of hands and feet and dual-energy X-ray absorptiometry of lumbar spine and left hip were performed at baseline and after 1 and 2 years of treatment. RESULTS: BMD increased significantly over time in both treatment groups at the lumbar spine with a mean of 2.6% during the first year (p<0.001), but not at the hip; at none of the time points did BMD differ significantly between the prednisone and placebo group. Higher age and lower weight at baseline and higher disease activity scores during the trial, but not glucocorticoid therapy, were associated with lower BMD at both the lumbar spine and the hip in mixed-model analyses. CONCLUSION: Addition of 10 mg prednisone daily to a methotrexate-based tight control strategy does not lead to bone loss in early RA patients on bisphosphonates. A small increase in lumbar BMD during the first year of treatment was found, regardless of use of glucocorticoids.

Evaluation of separate quantitative radiographic features adds to the prediction of incident radiographic osteoarthritis in individuals with recent onset of knee pain: 5-year follow-up in the CHECK cohort.

OBJECTIVE: Detailed radiographic evaluation might enable the identification of osteoarthritis (OA) earlier in the disease. This study evaluated whether and which separate quantitative features on knee radiographs of individuals with recent onset knee pain are associated with incidence of radiographic OA and persistence and/or progression of clinical OA during 5-year follow-up. METHOD: From the Cohort Hip & Cohort Knee study participants with knee pain at baseline were evaluated. Radiographic OA development was defined as Kellgren & Lawrence (K&L) grade ≥ II at 5-year follow-up. Clinical OA was defined as persistent knee pain and as progression of Westen Ontario & McMaster Universities Osteoarthritis index (WOMAC) pain and function score during follow-up. At baseline radiographic damage was determined by quantitative measurement of separate features using Knee Images Digital Analysis, and by K&L-grading. RESULTS: Measuring osteophyte area [odds ratio (OR) =7.0] and minimum joint space width (OR=0.7), in addition to demographic and clinical characteristics, improved the prediction of radiographic OA 5 years later [area under curve receiver operating characteristic=0.74 vs 0.64 without radiographic features]. When the predictive score (based on multivariate regression coefficients) was larger than the cut-off for optimal specificity, the chance of incident radiographic OA was 54% instead of the prior probability of 19%. Evaluating separate quantitative features performed slightly better than K&L-grading (AUC=0.70). Radiographic characteristics hardly added to prediction of clinical OA. CONCLUSION: In individuals with onset knee pain, radiographic characteristics added to the prediction of radiographic OA development 5 years later. Quantitative radiographic evaluation in individuals with suspected OA is worthwhile when determining treatment strategies and designing clinical trials.

Cross-sectional and predictive associations between plasma adipokines and radiographic signs of early-stage knee osteoarthritis: data from CHECK.

OBJECTIVE: To investigate cross-sectional and predictive associations of plasma adipokines with biochemical markers of systemic joint metabolism and radiographic signs of early-stage knee osteoarthritis (OA). DESIGN: The adipokines pLeptin, pAdiponectin, and pResistin, the cartilage markers C-terminal telopeptide of type II collagen (uCTX-II), N-terminal propeptide of type IIA procollagen (sPIIANP), chondroitin sulfate 846 (sCS846), and cartilage oligomeric matrix protein (sCOMP), and the synovial markers hyaluronic acid (sHA) and N-terminal propeptide of type III procollagen (sPIIINP) were assessed by enzyme-linked immunosorbent assay or radioactive immunoassay in baseline samples of Cohort Hip and Cohort Knee (CHECK), a cohort of 1002 subjects with early-stage symptomatic knee and/or hip OA. Knee radiographs were obtained at baseline and after 2 and 5 years and scored according to Kellgren & Lawrence. RESULTS: pLeptin showed positive associations with uCTX-II, sCOMP, sPIIANP, sHA, and sPIIINP, and with presence and progression of radiographic knee OA. Associations expectedly disappeared after adjustment for body mass index. pResistin showed positive associations with sPIIINP and present and incident radiographic knee OA that were largely independent of BMI. pAdiponectin showed positive associations with uCTX-II and sCOMP. Furthermore, pAdiponectin did not show associations with radiographic knee OA on itself, but associations of pResistin with present radiographic knee OA were stronger in higher pAdiponectin tertiles (P = 0.024 for interaction between pAdiponectin and pResistin). Although statistically significant, all associations were weak. CONCLUSIONS: Adipokines may have aggravating, although may be minor, structural effects in early-stage knee OA.