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Eveline de Haan,1,2 Gert R Roukema,1 Veronique AJIM van Rijckevorsel,1 Tjallingius M Kuijper,3 Louis de Jong1 On behalf of Dutch Hip Fracture RegistryCollaboration1Surgery Department, Maasstad Hospital, Rotterdam, Zuid-Holland, the Netherlands; 2Surgery Department, Franciscus Hospital, Rotterdam, Zuid-Holland, the Netherlands; 3Science Board, Maasstad Hospital, Rotterdam, Zuid-Holland, the NetherlandsCorrespondence: Eveline de Haan, Email e.eveline.de.haan@gmail.comPurpose: The primary objective of this study was to identify new risk factors and to confirm previously reported risk factors associated with 30-day mortality after hip fracture surgery.Patients and methods: A prospective hip fracture database was used to obtain data. In total, 3523 patients who underwent hip fracture surgery between 2011 and 2021 were included. Univariable and multivariable logistic regression was used to screen and identify candidate risk factors. Twenty-seven baseline factors and 16 peri-operative factors were included in the univariable analysis and 28 of those factors were included in multivariable analysis.Results: 8.6% of the patients who underwent hip fracture surgery died within 30 days after surgery. Prognostic factors associated with 30-day mortality after hip fracture surgery were as follows: age 90– 100 years (OR = 4.7, 95% CI: 1.07– 19.98, p = 0.041) and above 100 years (OR = 11.3, 95% CI: 1.28– 100.26, p = 0.029), male gender (OR = 2.6, 95% CI: 1.97– 3.33, p < 0.001), American Society of Anesthesiologists (ASA) 3 and ASA 4 (OR = 2.1, 95% CI: 1.44– 3.14, p < 0.001), medical history of dementia (OR = 1.7, 95% CI: 1.25– 2.36, p = 0.001), decreased albumin level (OR = 0.94, 95% CI: 0.92– 0.97, p < 0.001), decreased glomerular filtration rate (GFR) (OR = 0.98, 95% CI: 0.98– 0.99, p < 0.001), residential status of nursing home (OR = 2.1, 95% CI: 1.44– 2.87, p < 0.001), higher Katz Index of Independence in Activities of Daily Living (KATZ-ADL) score (OR = 1.1, 95% CI: 1.01– 1.16, p=0.018) and postoperative pneumonia (OR = 2.4, 95% CI: 1.72– 3.38, p < 0.001).Conclusion: A high mortality rate in patients after acute hip fracture surgery is known. Factors that are associated with an increased mortality are age above 90 years, male gender, ASA 3 and ASA 4, medical history of dementia, decreased albumin, decreased GFR, residential status of nursing home, higher KATZ-ADL score and postoperative pneumonia.Keywords: hip fracture, mortality, independent risk factors, clinical outcomes

Veronique AJIM van Rijckevorsel,1 Gert R Roukema,1 Taco MAL Klem,2 Tjallingius M Kuijper,3 Louis de Jong2 On behalf of Dutch Hip Fracture Registry Collaboration1Surgery Department, Maasstad Hospital, DZ Rotterdam 3079, Netherlands; 2Surgery Department, Franciscus Hospital, PM Rotterdam 3045, Netherlands; 3Science Board, Maasstad Hospital, DZ Rotterdam 3079, NetherlandsCorrespondence: Veronique AJIM van Rijckevorsel Email veroniquevanrijckevorsel@gmail.comIntroduction: The Nottingham Hip Fracture Score (NHFS) was developed to predict 30-day mortality for patients with hip fracture. This study aimed to validate the NHFS in a cohort with sufficient statistical power.Methods: Data were extracted from a prospective hip-fracture database (FAMMI). Patients were included between January 1, 2018 and January 11, 2021. All consecutively admitted patients ≥ 18 years of age with a hip fracture (ie, femoral neck fracture, intertrochanteric fracture, and subtrochanteric fracture) were included. Mann–Whitney’s U values were calculated to find potential miscalibration of the NHFS formula. Discrimination evaluation was performed using the concordance statistic as an equivalent to area under the receiver-operating curve.Results: In total, 2,458 patients were included. Mean age was 80± 12 years, and 66% were women (n=1,631). Median NHFS was 5 (4– 6) and overall 30-day mortality 7.9% (n=195). Overall goodness of fit was tested with Pearson’s ?2 (11.8, df 10; P=0.297). No statistically significant signs of miscalibration were found (Mann–Whitney U, P=0.08). Discrimination was tested with area under the receiver- operating curve, which was 72.1% (95% CI 68.7%– 75.4%). However, observed 30-day mortality in our population of hip-fracture patients was slightly higher than the NHFS prediction.Conclusion: The NHFS seemed to predict 30-day mortality with reasonable accuracy for patients with a hip fracture in a population within the Netherlands.Keywords: 30-day mortality, hip fractures, NHFS, validation, prediction tool

Louis de Jong,1 Veronique AJIM van Rijckevorsel,1 Jelle W Raats,1 Taco MAL Klem,2 Tjallingius M Kuijper,3 Gert R Roukema11Surgery Department, Maasstad Hospital, 3079 DZ Rotterdam, the Netherlands; 2Surgery Department, Franciscus Hospital, 3045 PM Rotterdam, the Netherlands; 3Science Board, Maasstad Hospital, 3079 DZ Rotterdam, the NetherlandsBackground: The primary aim of the present study was to verify the potential risk factors for developing a delirium after hip fracture surgery. The secondary aim of this study was to examine the related clinical outcomes after a delirium developed post-hip fracture surgery.Patients and methods: Data were extracted from a prospective hip fracture database and completed by retrospective review of the hospital records. A total of 463 patients undergoing hip fracture (hip hemiarthroplasty) surgery in a level II trauma teaching hospital between January 2011 and May 2016 were included. Delirium was measured using the Delirium Observation Screening Scale, the confusion assessment method, and an observatory judgment by geriatric medicine specialists.Results: The results showed that 26% of the patients (n=121) developed a delirium during hospital stay with a median duration during admission of 5 days (IQR 3–7). The multivariable model showed that the development of delirium was significantly explained by dementia (OR 2.75, P=0.001), age (OR 1.06, P=0.005), and an infection during admission (pneumonia, deep surgical site infection, or urinary tract infection) (OR 1.23, P=0.046). After 1 year of follow-up, patients who developed delirium after hip fracture surgery were significantly more discharged to (semi-independent) nursing homes (P

ObjectiveMethodResultsConclusionCurrently, expedited by the coronavirus disease 2019 pandemic, there is high demand for allocating patients in a state of low disease activity to telehealth, ideally based on remote measurements. This cross-sectional study assesses the discriminative accuracy of the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire regarding high and low disease activity. Furthermore, we aimed to optimize this classification, developing a remote triage score based on RAID and other patient-reported outcome measures (PROMs).Data were acquired from an outpatient clinic cohort of chronic rheumatoid arthritis patients at a large trainee hospital in the Netherlands. Patients were divided into high and low disease categories, based on 28-joint Disease Activity Score–C-reactive protein. Least absolute shrinkage and selection operator logistic regression were performed, including RAID item scores and other PROMs. Receiver operating characteristics curves and areas under the curve (AUCs) were obtained, and cut-off scores were based on predefined criteria of 90% and 95% sensitivity.In total, 278 patients were analysed, of whom 77.2% were identified as having low disease activity. RAID results correlated with DAS28-CRP, showing good performance. The regression model included the RAID items pain and functional disability assessment, and the self-reported swollen joint count (SR-SJC). With an AUC of 0.88 (95% confidence interval 0.84–0.92), this model performed better than the RAID total score.A remote triage score based on a composite score of pain, functional disability assessment, and SR-SJC can detect a sufficient proportion of patients with low disease activity who can be allocated to remote consultations. [ABSTRACT FROM AUTHOR]

To assess the cost–utility from healthcare and societal perspectives of the digital CaFaSpA referral strategy (CS) for axial spondyloarthritis (axSpA) in primary care patients with chronic low back pain (CLBP). A cluster randomized controlled trial was performed in the Netherlands. General practice units were randomized into CS or usual care (UC). Economic evaluation was performed from the healthcare and societal perspectives within a 12-month time horizon. Outcome measures encompassed disability [Roland–Morris Disability Questionnaire (RMDQ)] and health-related quality of life (EQ-5D-3L). Direct medical (iMTA Medical Consumption Questionnaire) and indirect costs (iMTA Productivity Cost Questionnaire), including productivity loss, were evaluated. Incremental cost–utility ratios (ICURs) were calculated. The study included 90 GP clusters with 563 patients (CS: n = 260; UC: n = 303) (mean ± sd age 36.3 ± 7.5 years; 66% female). After 12 months, no minimal important differences in outcomes were observed for RMDQ (−0.21, 95%CI −1.52 to 1.13) or EQ-5D (−0.02, 95%CI −0.08 to 0.05). However, total costs were significantly lower in the CS group owing to lower productivity loss costs. The ICUR for RMDQ was €18,059 per point decrease and €220,457 per quality-adjusted life year increase. Digital referral did not decrease the overall healthcare status of patients after 1 year of follow-up and appears to be more cost-effective than UC. Therefore, CS can be used as an appropriate primary care referral model for CLBP patients at risk for axSpA. This will accelerate timely provision of care by the right caregiver. [ABSTRACT FROM AUTHOR]

The quality of referrals is often criticized, and the effectiveness of improvement efforts remains uncertain. We assessed the impact of a rheumatologist triaging patients in primary care on the appropriateness of referrals to secondary care, healthcare utilization, and patient experience and outcomes. A cluster randomized controlled trial was conducted with patients experiencing musculoskeletal complaints. Intervention practices deployed an experienced rheumatologist triaging patients through in-person review. Usual care was performed in control practices, where practitioners referred patients based on their own judgement. The primary outcome was the proportion of inflammatory rheumatic diseases (IRDs) diagnosed by rheumatologists in referred patients. Healthcare utilization (iMTA Medical Consumption Questionnaire), quality of life (EuroQol 5 Dimensions), and experience of care (Consumer Quality Index) were determined after 3 months of follow-up. Data were analysed according to the intention-to-treat principle. In total, 544 participants were included [mean age 51.4 (range 18–87) years; 24% were men]. Of all referred patients, 51% had an IRD in the intervention group versus 21% in the control group (p = 0.035). After 3 months of follow-up, patients from the triage intervention showed lower healthcare utilization (p = 0.006) and higher quality of life (p = 0.011), without a decline in experienced quality of care (p = 0.712), compared to controls. Triage by a rheumatologist in primary care provides appropriate care and adequate experience of care, leading to a higher quality of life. Long-term evidence is needed to assess the value on cost-effectiveness before implementing this strategy nationwide. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether, apart from effects of patient- and disease-related factors, psychosocial factors have additional effects on disease activity; and which factors are most influential during the first year of treatment in early rheumatoid arthritis (RA).Method: The study assessed 15 month follow-up data from patients in tREACH, a randomized clinical trial comparing initial triple disease-modifying anti-rheumatic drug therapy to methotrexate monotherapy, with glucocorticoid bridging in both groups. Patients were evaluated every 3 months and treated to target. Associations between Disease Activity Score (DAS) at 3, 9, and 15 months and psychosocial factors (anxiety, depression, fatigue, and coping with pain) at the previous visit were assessed by multivariable linear regression correcting for demographic, clinical, and treatment-related factors.Results: At 3, 9, and 15 months of follow-up, 265, 251, and 162 patients, respectively, were available for analysis. Baseline anxiety and coping with pain were associated with DAS at 3 months; coping with pain at 6 months was associated with DAS at 9 months, and fatigue at 12 months with DAS at 15 months. Psychosocial factors were moderately correlated. Effects on DAS were mainly due to tender joint count and global health.Conclusion: Psychosocial factors have additional effects on DAS throughout the first year of treatment in early RA. A change was observed from anxiety and coping with pain at baseline being associated with subsequent DAS towards fatigue being associated with subsequent DAS at 12 months. Owing to the explorative nature of this study, more research is needed to confirm this pattern. [ABSTRACT FROM AUTHOR]

Introduction: The aim of our study was to validate the original Charlson Comorbidity Index (1987) (CCI) and adjusted CCI (2011) as a prediction model for 30-day and 1-year mortality after hip fracture surgery. The secondary aim of this study was to verify each variable of the CCI as a factor associated with 30-day and 1-year mortality., Methods: A prospective database of two-level II trauma teaching hospitals in the Netherlands was used. The original CCI from 1987 and the adjusted CCI were calculated based on medical history. To validate the original CCI and the adjusted CCI, the CCI was plotted against the observed 30-day and 1-year mortality, and the area under the curve (AUC) was calculated., Results: A total of 3523 patients were included in this cohort study. The mean of the original CCI in this cohort was 5.1 (SD ± 2.0) and 4.6 (SD ± 1.9) for the adjusted CCI. The AUCs of the prediction models were 0.674 and 0.696 for 30-day mortality for the original and adjusted CCIs, respectively. The AUCs for 1-year mortality were 0.705 and 0.717 for the original and adjusted CCIs, respectively., Conclusions: A higher original and adjusted CCI is associated with a higher mortality rate. The AUC was relatively low for 30-day and 1-year mortality for both the original and adjusted CCIs compared to other prediction models for hip fracture patients in our cohort. The CCI is not recommended for the prediction of 30-day and 1-year mortality in hip fracture patients., (© 2024. The Author(s).)

Objectives: The aim of this study was to assess whether the ratio of the mean infrarenal neck diameter to the suprarenal aortic diameter is a predictor for a durable proximal seal after endovascular aneurysm repair (EVAR)., Methods: A total of 439 patients who underwent elective EVAR between 2004 and 2018 in a single vascular referral center met our inclusion criteria. Ratios were calculated by dividing the mean infrarenal neck diameter by 4 different suprarenal aortic diameters. Patients who developed a late type 1A endoleak (n=20) or proximal neck dilatation mandating revision (n=8) were compared with the 411 patients without long-term proximal seal complications., Results: Patients who developed a late type 1A endoleak had more frequently hypertension, a shorter infrarenal neck length, and a larger mean infrarenal neck diameter. The ratio of the mean infrarenal neck diameter to all 4 suprarenal aortic diameters was higher in the late type 1A endoleak group compared with the group without a late type 1A endoleak. Least absolute shrinkage and selection operator (LASSO) logistic regression identified a combination of 6 variables as the best combination to predict a late type 1A endoleak: presence of hypertension, increased mean infrarenal neck diameter, decreased aneurysm neck length, larger ratio of the mean infrarenal neck diameter to the aortic diameter proximal to the superior mesenteric artery (SMA), larger ratio of the mean infrarenal neck diameter to the aortic diameter proximal to the upper renal artery, and increased β-angle. Of these, based on both the univariate area under the curve (AUC) and optimal LASSO model restricted to a single predictor, the ratio of the mean infrarenal neck diameter to the aortic diameter proximal to the SMA (AUC, 0.770; cutoff value, 0.997) was considered the best prognostic variable., Conclusion: The ratio of the mean infrarenal neck diameter to the aortic diameter proximal to the SMA is a good predictor for a late type 1A endoleak. Patients with mean infrarenal neck diameter larger than the diameter proximal to the SMA (ratio >1) are at risk for a late type 1A endoleak., Clinical Impact: In this single-center, retrospective cohort study, we found that the ratio of the mean infrarenal neck diameter to the aortic diameter proximal to the SMA is a good predictor for a late type 1A endoleak. We conclude that the suprarenal diameter must be taken into account before assessing endovascular aortic aneurysm repair eligibility. Patients with a ratio >1 may not be the best candidates for a durable result after EVAR and may be better off with fenestrated EVAR or open repair., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The primary aim of this study was to identify risk factors and validate earlier reported risk factors for Prosthetic Joint Infection (PJI) after hemiarthroplasty. The secondary aim was to assess peri‑operative clinical outcomes, adverse events and mortality rates in PJI patients after hemiarthroplasty., Methods: A prospective hip fracture database was used to obtain data for this observational cohort study. Patients who underwent hemiarthroplasty between 2011 and 2021 were included. A PJI was diagnosed by the Musculoskeletal Infection Society criteria. Univariable and multivariable analyses were performed to identify factors highly associated with a PJI., Results: In total, 2044 patients were analysed of which 72 patients (3.5 %) developed PJI. The multivariable analysis showed that Body Mass Index (BMI) >30 (OR2.84, P = 0.020), operating time of <45 min (OR=2.80, P = 0.002), occurrence of haematoma (OR=6.24, P<0.001), decreasing level of hemoglobin (OR=1.62, P = 0.001) and re-operation for luxation (OR=9.25, P<0.001) were significant independent prognostic risk factors for development of PJI after hemiarthroplasty. Diabetes Mellitus (OR=0.34, P = 0.018) and >20 hemiarthroplasties performed by the surgeon in the previous year (OR=0.33, P = 0.019) were prognostic protective factors. In patients with PJI, 40 % (n = 29) died within one year after surgery, compared with 27 % (n = 538) in patients without PJI (OR=1.80, P = 0.017)., Conclusion: Independent significant prognostic factors highly associated with PJI after hemiarthroplasty were BMI >30, operating time of <45, decreasing level of hemoglobin, occurrence of haematoma and re-operation for luxation. Diabetes Mellitus and >20 hemiarthroplasties performed by the surgeon in the previous year were prognostic protective factors for the development of PJI. PJI was associated with significantly higher 1-year all-cause mortality., Competing Interests: Declaration of competing interest No conflict of interest or competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To develop a color code and to investigate the validity of Laser Speckle Contrast Imaging (LSCI) for measuring burn wound healing potential (HP) in burn patients as compared to the reference standard Laser Doppler Imaging (LDI)., Method: A prospective, observational, cohort study was conducted in adult patients with acute burn wounds. The relationship between mean flux measured with LDI and mean perfusion units (PU) measured with LSCI was expressed in a regression formula. Measurements were performed between 2 and 5 days after the burn wound. The creation of a LSCI color code was done by mapping the clinically validated color code of the LDI to the corresponding values on the LSCI scale. To assess validity of the LSCI, the ability of the LSCI to discriminate between HP < 14 and ≥ 14 days and HP < 21 and original ≥ 21 days according to the LDI reference standard was evaluated, with calculation of receiver operating characteristics (ROC) curves., Results: A total of 50 patients were included with a median age of 40 years and total body surface area burned of 6%. LSCI values of 143 PU and 113 PU were derived as the cut-off values for the need of conservative treatment (HP < 14 and ≥ 14 days) resp. surgical closure (HP < 21 and ≥ 21 days). These LSCI cut off values showed a good discrimination between HP 14 days versus ≥ 14 days (Area Under Curve (AUC)= 0.89; sensitivity 85% and specificity = 82%) and a good discrimination between HP 21 days versus ≥ 21 days (AUC of 0.89, sensitivity 81% and specificity 88%)., Conclusion: This is the first study in which a color code for the LSCI in adult clinical burn patients has been developed. Our study reconfirms the good performance of the LSCI for prediction of burn wound healing potential. This provides additional evidence for the potential value of the LSCI in specialized burn care., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest. Perimed AB provided the Laser Speckle Contrast Imager for free. Perimed AB did not have any involvement in the study design, data collection and data analysis, nor in the writing process and submission of this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Protein malnutrition after bariatric surgery is a severe complication and leads to significant morbidity. Previous studies have shown that protein intake and physical activity are the most important factors in the preservation of fat-free mass during weight loss. Low protein intake is very common in patients undergoing bariatric surgery despite dietary counseling. Protein powder supplements might help patients to achieve the protein intake recommendations after bariatric surgery and could therefore contribute to preserve fat-free mass. This double-blind randomized placebo-controlled intervention study aims to assess the effect of a daily consumed clear protein powder shake during the first 6 months after bariatric surgery on fat-free mass loss in the first 12 months after laparoscopic Roux-en-Y gastric bypass (LRYGB)., Methods and Analysis: Inclusion will take place at the outpatient clinic of the bariatric expertise center for obesity of the Maasstad Hospital. Patients will be randomly assigned to either the intervention or control group before surgery. The intervention group will receive a clear protein powder shake of 200 ml containing 20 g of whey protein dissolved in water which should be taken daily during the first 6 months after LRYGB on top of their normal postoperative diet. The control group will receive an isocaloric, clear, placebo shake containing maltodextrine. Postoperative rehabilitation and physiotherapeutical guidance will be standardized and similar in both groups. Also, both groups will receive the same dietary advice from specialized dieticians. The main study parameter is the percentage of fat-free mass loss 6 months after surgery, assessed by multi-frequency bioelectrical impedance analysis (MF-BIA)., Ethics and Dissemination: The protocol, version 2 (February 20, 2022) has been approved by the Medical Research Ethics Committees United (MEC-U) (NL 80414.100.22). The results of this study will be submitted to peer-reviewed journals., Trial Registration: ClinicalTrials.gov NCT05570474. Registered on October 5, 2022., (© 2023. The Author(s).)

Objectives: Aortic diameters may differ significantly between patients with different gender and body size. The aim of this study was to relate absolute aortic diameters to age, sex, height, and weight of the patients and to correct for these factors by calculating the ratio between the infrarenal and the suprarenal aortic diameters., Methods: A total of 458 patients who underwent elective endovascular aneurysm repair (EVAR) between 2004 and 2018 were included. The aortic anatomy in this group of elective EVAR patients was compared with a control group of 75 patients without an abdominal aortic aneurysm (AAA). The aortic diameter was measured at 4 suprarenal points and 4 infrarenal points. Ratios were calculated by dividing the mean infrarenal neck diameter by 4 suprarenal measurements., Results: Patients in the aneurysm group had significantly larger suprarenal and infrarenal aortic diameters. The ratios between the mean infrarenal neck diameter and all 4 suprarenal measurements were larger in the AAA group than in the control group. In both groups, there was a significant correlation between the mean infrarenal neck diameter and sex, height, weight, and body surface area (BSA). However, in both groups, all 4 ratios between the mean infrarenal neck diameter and suprarenal aortic diameters were not correlated with age, sex, height, weight, or BSA, except for the ratio between the mean infrarenal neck diameter and the aortic diameter measurement proximal to the upper renal artery, which was correlated to weight and BSA in the control group., Conclusion: The mean infrarenal neck diameter is correlated with sex, height, weight, and BSA. However, when the suprarenal aortic diameter was used as an internal control for the mean infrarenal neck diameter, we were able to correct for these variations in aortic diameters due to sex and body size. The clinical relevance of this ratio in patients treated by EVAR has yet to be assessed in future research., Clinical Impact: In the assessment for EVAR suitability the absolute diameter of the aneurysm neck is taken into account. We believe that using absolute diameters is not the appropriate way to assess this suitability, but that patient characteristics such as age, gender and body size, should be factored into this assessment. In this paper, we show that suprarenal and infrarenal aortic diameters are both significantly increased in patients with an aneurysm compared with patients without an aneurysm. Besides, we found that mean infrarenal aortic diameter is correlated with sex, height, weight, and body surface area. Finally, we propose a new ratio system, using suprarenal diameters as an internal control, to correct for aortic diameter variations due to sex and body size., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Current guidelines recommend tapering biological disease-modifying antirheumatoid drugs (bDMARDs) in rheumatoid arthritis (RA) if the disease is under control. However, guidelines on tapering are lacking. Assessing cost-effectiveness of different tapering strategies might provide broader input for creating guidelines on how to taper bDMARDs in patients with RA. The aim of this study is to evaluate the long-term cost-effectiveness from a societal perspective of bDMARD tapering strategies in Dutch patients with RA, namely 50% dose reduction (tapering), discontinuation and a 50% dose reduction followed by discontinuation (de-escalation)., Methods: Using a societal perspective, a Markov model with a life-time horizon of 30 years was used to simulate 3-monthly transitions between Disease Activity 28 (DAS28)-defined health states of remission (<2.6), low disease activity (2.63.2). Transition probabilities were estimated through literature search and random effects pooling. Incremental costs, incremental quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits for each tapering strategy were compared with continuation. Deterministic, probabilistic sensitivity analyses and multiple scenario analyses were performed., Results: After 30 years, the ICERs were €115 157/QALY lost, €74 226/QALY lost and €67 137/QALY lost for tapering, de-escalation and discontinuation, respectively; mainly driven by bDMARD cost savings and a 72.8% probability of a loss in quality of life. This corresponds to a 76.1%, 64.3% and 60.1% probability of tapering, de-escalation and discontinuation being cost-effective, provided a willingness-to-accept threshold of €50 000/QALY lost., Conclusions: Based on these analyses, the 50% tapering approach saved the highest cost per QALY lost., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Whereas in the treatment of rheumatoid arthritis much evidence exists on the effects of current pharmacologic treatment on clinical outcomes, little is known about the effects on patient-reported outcomes. This systematic review aims to evaluate the effects of disease-modifying antirheumatic drugs (DMARDs) on the patient-relevant domains of pain, fatigue, activity limitation, overall emotional and physical health impact, and work/school/housework ability and productivity., Methods: A literature search was conducted to identify randomized controlled trials wherein registered DMARDs were compared with placebo or methotrexate and reported the effects on patient-reported outcomes included in the International Consortium of Health Outcomes Measurement standard set for inflammatory arthritis. Random effects meta-analyses using the standardized mean differences of change scores as the effect measure were performed for the domains of pain, fatigue, and activity limitation, comparing DMARDs with placebo and methotrexate. The other 2 domains were presented narratively., Results: Across the 5 domains, 69 records belonging to 52 studies were identified. All meta-analyses showed a decrease of burden when DMARDs were compared with placebo (standardized mean differences [95% confidence interval] in pain -0.80 [-0.99, -0.61], fatigue -0.48 [-0.64, -0.32], and activity limitation -0.56 [- 0.63, -0.49]) and when compared with methotrexate (-0.55 [-0.70, -0.41), -0.44 [-0.55, -0.33], and - 0.37 [-0.44, -0.30], respectively)., Conclusion: DMARDs decrease the burden in all the domains that are relevant to patients. Effect sizes may be influenced by DMARD type. Therefore, in the decision for rheumatoid arthritis treatment, patient-reported outcomes should be taken into account., (© 2022 American College of Rheumatology.)

Background: Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory diseases that often affect the wrist and, when affected, can lead to impaired wrist function and progressive joint destruction if inadequately treated. Standard care consists primarily of disease-modifying anti-rheumatic drugs (DMARDs), often supported by systemic corticosteroids or intra-articular corticosteroid injections (IACSI). IACSI, despite their use worldwide, show poor response in a substantial group of patients. Arthroscopic synovectomy of the wrist is the surgical removal of synovitis with the goal to relieve pain and improve wrist function. The primary objective of this study is to evaluate wrist function following arthroscopic synovectomy compared to IACSI in therapy-resistant patients with rheumatoid or psoriatic arthritis. Secondary objectives include radiologic progress, disease activity, health-related quality of life, work participation and cost-effectiveness during a 1-year follow-up., Methods: This protocol describes a prospective, randomized controlled trial. RA and PsA patients are eligible with prominent wrist synovitis objectified by a rheumatologist, not responding to at least 3 months of conventional DMARDs and naïve to biological DMARDs. For 90% power, an expected loss to follow-up of 5%, an expected difference in mean Patient-Rated Wrist Evaluation score (PRWE, range 0-100) of 11 and α = 0.05, a total sample size of 80 patients will be sufficient to detect an effect size. Patients are randomized in a 1:1 ratio for arthroscopic synovectomy with deposition of corticosteroids or for IACSI. Removed synovial tissue will be stored for an ancillary study on disease profiling. The primary outcome is wrist function, measured with the PRWE score after 3 months. Secondary outcomes include wrist mobility and grip strength, pain scores, DAS28, EQ-5D-5L, disease progression on ultrasound and radiographs, complications and secondary treatment. Additionally, a cost-effectiveness analysis will be performed, based on healthcare costs (iMCQ questionnaire) and productivity loss (iPCQ questionnaire). Follow-up will be scheduled at 3, 6 and 12 months. Patient burden is minimized by combining study visits with regular follow-ups., Discussion: Persistent wrist arthritis continues to be a problem for patients with rheumatic joint disease leading to disability. This is the first randomized controlled trial to evaluate the effect, safety and feasibility of arthroscopic synovectomy of the wrist in these patients compared to IACSI., Trial Registration: Dutch trial registry (CCMO), NL74744.100.20. Registered on 30 November 2020., Clinicaltrials: gov NCT04755127. Registered after the start of inclusion on 15 February 2021., (© 2023. The Author(s).)

Objective: Laser-based tissue perfusion monitoring techniques have been increasingly used in animal and human research to assess blood flow. However, these techniques use arbitrary units, and knowledge about their comparability is scarce. This study aimed to model the relationship between laser speckle contrast imaging (LSCI) and laser Doppler perfusion imaging (LDPI), for measuring tissue perfusion over a wide range of blood flux values., Methods: Fifteen healthy volunteers (53% female, median age 29 [IQR 22-40] years) were enrolled in this study. We performed iontophoresis with sodium nitroprusside on the forearm to induce regional vasodilation to increase skin blood flux. Besides, a stepwise vascular occlusion was applied on the contralateral upper arm to reduce blood flux. Both techniques were compared using a linear mixed model analysis., Results: Baseline blood flux values measured by LSCI were 33 ± 6.5 arbitrary unit (AU) (Coefficient of variation [CV] = 20%) and by LDPI 60 ± 11.5 AU (CV = 19%). At the end of the iontophoresis protocol, the regional blood flux increased to 724 ± 412% and 259 ± 87% of baseline measured by LDPI and LSCI, respectively. On the other hand, during the stepwise vascular occlusion test, the blood flux reduced to 212 ± 40% and 412 ± 177% of its baseline at LDPI and LSCI, respectively. A strong correlation was found between the LSCI and LDPI instruments at increased blood flux with respect to baseline skin blood flux; however, the correlation was weak at reduced blood flux with respect to baseline., Discussion: LSCI and LDPI instruments are highly linear for blood flux higher than baseline skin blood flux; however, the correlation decreased for blood flux lower than baseline. This study's findings could be a basis for using LSCI in specific patient populations, such as burn care., (© 2022 The Authors. Microcirculation published by John Wiley & Sons Ltd.)

Introduction: Inadequate pain management remains a problem in the emergency department (ED) and might increase the risk of chronic pain. Previous studies suggested that pain intensity is associated with pain chronification in specific patient groups. This study aims to study the association between pain intensity {[verbal] numeric rating scale ([V]NRS) ≥ 7} at discharge from the ED and pain chronification in the general population., Objective: To assess whether a high pain score at discharge from the ED increases the risk of chronic pain development., Methods: Adults who visited the ED with pain as their main complaint, and who were not hospitalized, were eligible for inclusion. Chronic pain was defined as pain with an (V)NRS score ≥1 90 days after the ED visit and with a similar location to the acute pain., Results: We included 1906 patients, of whom 825 participants completed 90 days of follow-up. Approximately 34.1% left the ED with an (V)NRS score ≥7, and 67.8% reported an (V)NRS score of ≥1 90 at days. Of all patients leaving the ED with an (V)NRS score ≥7, 76.5% developed chronic pain vs 63.2% of patients with (V)NRS score <7 ( P < 0.01). After correction, this difference was borderline statistically significant with an odds ratio of 1.45 (95% confidence interval: 0.99-2.13, P = 0.054). Various sensitivity analyses using a different (V)NRS at discharge and different definitions of chronic pain at 90 days showed a significant difference in the chronification of pain., Conclusion: This study suggests that pain intensity at discharge from the ED, regardless of the localization or cause of pain, increased the risk of developing chronic pain. By distinguishing patients at risk and providing an effective treatment, chronic pain and the associated burden of disease might be preventable., Competing Interests: The authors have no conflict of interest to declare.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)

Objective: To determine the diagnostic performance and clinical utility of the Rotterdam Early Arthritis Cohort (REACH) and the Clinical Arthritis Rule (CARE) referral rules in an independent population of unselected patients from primary care., Methods: This study consisted of adults who were suspected of the need for referral to a rheumatologist by their general practitioner. Diagnostic accuracy measures and a net benefit approach were used to compare both rules to usual care for recognizing inflammatory arthritis and inflammatory rheumatic diseases (IRDs). Using the least absolute shrinkage and selection operator method and cross-validation we created an optimal prediction rule for IRD., Results: This study consisted of 250 patients, of whom 42 (17%) were diagnosed with inflammatory arthritis and 55 (22%) with an IRD 3 months after referral. Considering inflammatory arthritis, the area under the receiver operating characteristic curve (AUC) was 0.72 (95% confidence interval [95% CI] 0.64-0.80) for REACH and 0.82 (95% CI 0.75-0.88) for CARE. Considering IRD, the AUC was 0.66 (95% CI 0.58-0.74) for REACH and 0.76 (95% CI 0.69-0.83) for CARE. CARE was of highest clinical value when compared to usual care. The composite referral rule for IRD of 10 parameters included sex, age, joint features, acute onset of symptoms, physical limitations, and duration of symptoms (AUC 0.82 [95% CI 0.75-0.88])., Conclusion: Both validated rules have a net benefit in recognizing inflammatory arthritis as well as IRD compared to usual care, but CARE shows superiority over REACH. Although the composite referral rule indicates a greater diagnostic performance, external validation is needed., (© 2021 American College of Rheumatology.)

Background: Tranexamic acid (TXA) has shown to significantly reduce perioperative blood loss in elective orthopedic joint replacement surgery but is yet not implemented in acute hip fracture surgery for elderly patients who are particularly vulnerable to perioperative blood loss and postoperative anemia. Aim of this study is to answer the following questions: 1. Does TXA reduce bleeding associated complications in elderly patients? 2. Does TXA induce thromboembolic complications in elderly patients?, Hypothesis: TXA reduces perioperative blood loss and associated complications in acute hip fracture surgery in geriatric patients., Patients and Methods: In this observational cohort study with prospectively enrolled patients over 65 years of age who received an acute hip hemiarthroplasty, the primary outcome was blood loss, also described as Δ hemoglobin. Secondary outcomes were bleeding associated complications as hematomas. Also, the occurrence of thromboembolic events and mortality were examined., Results: In total 864 geriatric patients were included of which 235 received TXA and 629 did not. Multivariable analysis showed reduced Δ hemoglobin loss [-0.24 (-0.39; -0.09), p=0.002] and hematomas (OR 0.44 (0.21; 0.91), p=0.026). Pulmonary embolism were diagnosed more frequently after administration of TXA (2% versus 0.3%, p=0.008), without an association with increased 30-day mortality rate (6% versus 8%, p=0.3)., Discussion: TXA reduced perioperative blood loss and associated complications. However, adverse effects of TXA as pulmonary embolisms were found more frequently without effecting postoperative mortality rates. More research is needed to assess adverse effects of intravenous TXA and topical TXA as an alternative for systemic TXA to prevent systemic adverse effects., Level of Evidence: III, Observational cohort study., (Copyright © 2022. Published by Elsevier Masson SAS.)

Objectives: Patients on chronic lithium therapy sometimes develop chronic kidney disease. For clinical decision-making, it is important to know whether discontinuation of lithium can lead to improvement of renal function. We studied the trajectory of renal function in a population previously on chronic lithium therapy., Methods: From a large database of patients on chronic lithium therapy, we selected a group of patients who stopped using lithium and whose creatinine values at least half a year after lithium withdrawal were available. We measured the slope of renal function (eGFR) before and after discontinuation of lithium. We compared the subgroup of patients with improvement of the renal function with those who showed further deterioration of the eGFR., Results: eGFR slope significantly improved after discontinuation of lithium. Of patients with chronic kidney disease stage 3 or more (eGFR<60 ml/min), the vast majority showed an increase of eGFR or a decrease in the rate of decline after lithium withdrawal. The group of patients with further deterioration of the renal function had a mean eGFR of 32 ml/min, which was significantly lower than the patients with an improvement of the kidney function., Conclusions: Discontinuation of lithium leads in the majority of patients to improvement in renal function or at least less rapid deterioration., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: The aim of the present study was to compare the long-term survival of patients with a stable aneurysm sac vs those with aneurysm sac regression after endovascular aneurysm repair (EVAR) and to identify the independent risk factors for aneurysm sac regression and mortality after EVAR., Methods: We reviewed all the patients who had undergone EVAR from 2005 to 2018 with computed tomography angiography available at 1 year of follow-up. Aneurysm sac regression was defined as a diameter decrease of >10%. We used multivariable regression to identify the independent risk factors for sac regression. Kaplan-Meier analysis and Cox regression were performed to test the differences in 5-year mortality between a stable sac diameter and sac regression., Results: The inclusion criteria were met by 325 patients, with 185 in the sac regression group and 140 in the stable sac group. Multivariable logistic regression analysis showed that treatment of a ruptured aneurysm was an independent risk factor for aneurysm sac regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.96). Age (HR, 1.05; 95% CI, 1.01-1.09), ischemic heart disease (HR, 1.94; 95% CI, 1.13-3.31), neck thrombus (HR, 2.72; 95% CI, 1.07-6.95), and a type II endoleak (HR, 19.21; 95% CI, 7.32-50.40) were independent risk factors for a stable aneurysm sac diameter. Multivariable Cox regression showed a significantly increased risk of mortality for patients with a stable aneurysm sac after EVAR (odds ratio, 2.25; 95% CI, 1.36-3.72). No significant differences were found in cause of death between the two groups., Conclusions: A stable aneurysm sac after EVAR was associated with increased mortality. Age, ischemic heart disease, neck thrombus, and a type II endoleak were independent risk factors for a stable aneurysm sac. However, a well-founded explanation for this finding is still lacking. Future research should focus on aggressive treatment of type II endoleaks and inflammatory processes as potential pathophysiologic mechanisms., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Many of the anaesthetic drugs used for electroconvulsive therapy have anticonvulsant properties and may influence efficacy of electroconvulsive therapy. With this study we aim to provide more information on the effect of etomidate and methohexital on seizure duration. We explore the relationship between induction drug, motor and electroencephalography seizure duration. Moreover, we study the relationship of seizure duration and number of therapies., Methods: In this retrospective study we collected data from patient records from 2005 until 2016. Inclusion criteria were the use of etomidate and/or methohexital and documentation of dosage, electroconvulsive therapy dosage and seizure duration. Exclusion criteria were missing data on either induction drug, dosage or seizure duration., Results: Thirty seven patients were analysed. The mean age was 52 years and seventy six percent were female. Most patients were suffering from affective disorders (81%). Motor and electroencephalography seizure duration were analysed in 679 and 551 electroconvulsive therapies, respectively. Compared to methohexital, motor and electroencephalography seizures under etomidate were 7 and 13 s longer, respectively. Furthermore, there was a negative association between seizure duration and number of treatment and a negative association between seizure duration and electroconvulsive therapy dosage., Conclusions: This study demonstrates significant longer motor and electroencephalography seizure duration using etomidate compared to methohexital. Etomidate might therefore increase the effectiveness of electroconvulsive therapy. Moreover, we observed a negative association between seizure duration, number of treatment and electroconvulsive therapy dosage. With this study we contribute to the available literature comparing methohexital and etomidate as induction agents for electroconvulsive therapy., (© 2022. The Author(s).)

Morbid obesity is associated with a chronic state of low-grade inflammation, which may lead to accelerated differentiation of T and B cells. These differentiated immune cells are strongly cytotoxic and have an increased pro-inflammatory cytokine producing capacity. Furthermore, the anti-inflammatory function of the T and B cells decreases. The aim of this study was to evaluate the effect of morbid obesity on the subset profile and cytokine producing capacity of T and B cells. Subsequently, we assessed whether bariatric surgery affected the subset profile and cytokine producing capacity of these cells. We determined the proportion of T and B cell subsets and their cytokine producing capacity in peripheral blood collected from 23 morbidly obese patients before and three months after bariatric surgery using flow-cytometry. We compared this with the results of 25 lean controls. Both CD4+ and CD8+ T cells showed a more differentiated subset profile in morbidly obese patients as compared to lean controls, which was not recovered three months after bariatric surgery. The B cell composition of morbidly obese patients after bariatric surgery adjusted towards the profile of lean controls. However, the IL-2 and IFN-γ producing capacity of CD8+ T cells and the IL-2, IFN-γ, TNF-α and IL-10 producing capacity of B cells was not restored three months after bariatric surgery. In conclusion, the data suggest that the immune system has the capacity to recover from the detrimental effects of morbid obesity within three months after bariatric surgery in terms of cell composition; however, this was not seen in terms of cytokine producing capacity. The full restoration of the immune system after bariatric surgery may thus take longer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wijngaarden, Taselaar, Nuijten, Harst, Klaassen, Kuijper, Jongbloed, Ambagtsheer, Klepper, IJzermans, de Bruin and Litjens.)

Purpose: The routine use of surgical drains in elective hip arthroplasty has been abandoned. Also in acute hip arthroplasty for femoral neck fractures drain use reduces. Question is, whether this is justified in geriatric patients, where the incidence of anticoagulation use is high. Therefore, the aim of this study is to compare the clinical outcomes in patients with and without the use of a wound drain after hip hemiarthroplasty., Methods: Data were extracted from a prospective hip fracture database and completed by retrospective review of the hospital records at two level II trauma centers between January 1st 2010 and May 16th 2016. Patients with a femoral neck fracture requiring hip hemiarthroplasty were included in the study., Results: This study cohort included 900 patients (68% female), with a median age of 83.5 (IQR 78-88), of which 544 (60%) had a wound drain. Patients with a wound drain needed more days to be ready for discharged (10.0 days (SD ± 43.3), P =  < 0.001) compared to patients without a drain (5.3 days (SD ± 4.2). With a drain more hemoglobin loss was found, 2.66 g/dL versus 2.4 g/dL (P = 0.008) and also more packed cells were supplemented, 0.29 versus 0.13 (P = 0.0016). Wound drain placement showed a statistically significant inverse relation with post-operative hematoma; odds ratio (OR 0.61, 95% CI 0.39; 0.94, P = 0.024), but no reduced risk of post-operative deep surgical site infection, (OR 1.09, 95% CI 0.43; 2.72, P = 0.862)., Conclusion: Surgical drain placement was not associated with a reduced risk of post-operative deep surgical site infections, nor one-year mortality. However, a decreased risk of post-operative wound hematoma was observed. Furthermore, patients with a drain needed more days to be ready for discharge, show more hemoglobin loss and need more packed cell supplementation during admission., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Rheumatoid arthritis (RA) of the wrist can lead to loss of wrist function and progressive joint destruction if inadequately treated. Arthroscopic synovectomy of the wrist may prove a valuable treatment for local inflammation., Objective: The aim of this study was to perform a systematic review evaluating functional outcomes and pain following arthroscopic synovectomy of the wrist in RA patients., Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines. MEDLINE, EMBASE, The Cochrane Library, Web of Science, and Google Scholar were searched for studies describing pain or functional outcomes following arthroscopic synovectomy of the wrist in RA patients (CRD42021270846). Risk of bias was assessed using the Methodological Index for Non-Randomized Studies. Data collection included patient characteristics, pain scores, wrist function questionnaires, secondary surgery, and complications., Results: Six noncomparative cohort studies were included, with a total of 153 arthroscopic synovectomies. Disease duration of RA ranged from 32 to 89 months, and radiographic progression was mild to moderate. The Methodological Index for Non-Randomized Studies scores ranged from 8 to 10 out of 16. Mean follow-up ranged from 21 to 95 months. Improvements were seen in pooled mean visual analog scale pain score (from 7.7 to 2.2, p < 0.05), pooled mean Modified Mayo Wrist Score (from 43.3 to 70.4, p < 0.05), and the Disability of the Arm, Shoulder, and Hand (from 67.5 to 36.5, p < 0.05). Two complications occurred, and 5 patients required secondary surgery., Conclusions: There is limited evidence suggesting that arthroscopic synovectomy of the wrist improves wrist function and pain in patients with RA, with few complications. In centers with arthroscopic expertise, it can be considered as a treatment option., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: For patients who are discharged to go home after a hospitalisation, timely and adequately informing their general practitioner is important for continuity of care, especially at the end of life. We studied the quality of the hospital discharge letter for patients who were hospitalised in their last year of life., Methods: A retrospective medical record review was performed. Included patients had been admitted to the hospital during the period 1 January to 1 July 2017 and had died within a year after discharge., Results: Data were collected from records of 108 patients with cancer or other diseases. For 57 patients (53%), the discharge letter included information that related to their limited life expectancy (e.g., agreements about treatment limitations), whereas the patient's limited life expectancy was addressed in the medical record in 76 cases (70%). We found related information in discharge letters for 36 patients (66%) who died <3 months compared to 21 patients (40%) who died 3-12 months after hospitalisation (p < 0.01)., Conclusion: For patients with a limited life expectancy going home after a hospitalisation, one out of two hospital discharge letters lacked any information addressing their limited life expectancy. Specific guidelines for medical information exchange between care settings are needed., (© 2021 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

Introduction: Geriatric hip fracture patients are characterized by frailty due to multiple comorbidities, such as cardiovascular disease, in which the use of antithrombotics is frequent. The aim of this study is to assess the effect of antithrombotics on perioperative care and patient outcomes after hip hemiarthroplasty following current guidelines., Materials and Methods: This observational cohort study included all consecutively admitted patients with a femoral neck fracture requiring hip hemiarthroplasty between January 1 st 2010, and May 16 th 2016, in two level II trauma teaching hospitals. Patients with multiple trauma injuries were excluded., Results: In total, n = 907 patients (68% female (n = 615), median age 84 years) were included of which n = 142 used a vitamin K antagonist (VKA) and n = 213 used antiplatelet (AP) therapy. Both were associated with more packed cell supplementation (.4 ± 1.1 units and .3 ± .8 units vs .2 ± .6 units, P < .001 and P = .03, respectively). VKA was associated with more hematomas compared no antithrombotics (23% vs 11%, P = .001). VKA had a longer time to surgery compared to no antithrombotics and AP (24 hours vs 19 and 20 hours, P < .001 and P < .001, respectively) and longer admission duration (9 days vs 7 days P < .001. There were no differences in 30 day mortality nor in 1-year mortality rates., Discussion: All modifiable causes for deep SSI, such as hematomas, should be prevented in acute hip fracture surgery. Since antithrombotics are associated with hematomas, an optimal handling in perioperative setting is necessary., Conclusion: VKA was associated with longer time to surgery, more hematomas, and longer admission duration. VKA and AP were associated with more packed cell supplementation., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Morbid obesity is characterized by chronic, low-grade inflammation, which is associated with 'inflamm-aging'. The presence of metabolic syndrome (MetS) might accelerate this phenomenon of metaflammation. In this study, we assessed the effects of morbid obesity and MetS on the composition of a broad spectrum of immune cells present within the circulation. A total of 117 morbidly obese patients (MOP) without MetS (MetS-), 127 MOP with MetS (MetS+) and 55 lean controls (LC) were included in this study. Absolute numbers of T cell, B cell, NK cell and monocyte subsets were assessed within peripheral blood using flow cytometry. Both absolute cell numbers and proportion of cells were evaluated correcting for covariates age, body mass index and cytomegalovirus serostatus. Although the absolute number of circulating CD4+ T cells was increased in the MetS+ group, the CD4+ T cell composition was not influenced by MetS. The CD8+ T cell and B cell compartment contained more differentiated cells in the MOP, but was not affected by MetS. Even though the absolute numbers of NK cells and monocytes were increased in the MOP as compared to LC, there was no difference in proportions of NK and monocyte subsets between the three study groups. In conclusion, although absolute numbers of CD4+ and CD8+ T cells, B cells, NK cells and monocytes are increased in MOP, obesity-induced effects of the composition of the immune system are confined to a more differentiated phenotype of CD8+ T cells and B cells. These results were not affected by MetS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wijngaarden, van der Harst, Klaassen, Dunkelgrun, Kuijper, Klepper, Ambagtsheer, IJzermans, de Bruin and Litjens.)

Objective: The aim of the current study was to evaluate the 2-year cost-utility ratio between tapering conventional synthetic disease-modifying antirheumatic drugs (csDMARD) first followed by the tumour necrosis factor (TNF)-inhibitor, or vice versa, in patients with rheumatoid arthritis (RA)., Methods: Two-year data of the Tapering strategies in Rheumatoid Arthritis trial were used. Patients with RA, who used both a csDMARD and a TNF-inhibitor and had a well-controlled disease (disease activity score ≤2.4 and swollen joint count≤1) for at least 3 months, were randomised into gradual tapering the csDMARD first followed by the TNF-inhibitor, or vice versa. Quality-adjusted life years (QALYs) were derived from the European Quality of life questionnaire with 5 dimensions. Healthcare and productivity costs were calculated with data from patient records and questionnaires. The incremental cost-effectiveness ratio and the incremental net monetary benefit were used to assess cost effectiveness between both tapering strategies., Results: 94 patients started tapering their TNF-inhibitor first, while the other 95 tapered their csDMARD first. QALYs (SD) were, respectively, 1.64 (0.22) and 1.65 (0.22). Medication costs were significantly lower in the patients who tapered the TNF-inhibitor first, while indirect cost were higher due to more productivity loss (p=0.10). Therefore, total costs (SD) were €38 833 (€39 616) for tapering csDMARDs first, and €39 442 (€47 271) for tapering the TNF-inhibitor (p=0.88). For willingness-to-pay (WTP) levels <€83 800 tapering, the csDMARD first has the highest probability of being cost effective, while for WTP levels >€83 800 tapering the TNF-inhibitor first has the highest probability., Conclusion: Our economic evaluation shows that costs are similar for both tapering strategies. Regardless of the WTP, tapering either the TNF-inhibitor or the csDMARD first is equally cost effective., Trial Registration Number: NTR2754., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the impact of a disease flare on patient reported outcome measures (PROMs) in rheumatoid arthritis (RA) patients, who are tapering treatment., Methods: Data were used from the TARA trial; a multicenter, randomized controlled trial in which RA patients, with a well-controlled disease (DAS≤2.4 and SJC≤1) for at least 6 months, gradually tapered their DMARDs. PROMs of patients with a flare (DAS>2.4 and/or SJC>1) were compared every three months before and after a flare with their own norm values. Linear Mixed Models were used to investigate whether a disease flare influenced functional ability (HAQ-DI), fatigue (BRAF-MDQ), quality of life (EQ-5D and SF36), anxiety and depression (HADS), morning stiffness, general health (GH) and worker productivity, and if so, the duration was determined. For unemployment and sick leave we used descriptive statistics., Results: A flare negatively influenced GH, morning stiffness, HAQ-DI, EQ-5D, BRAF-MDQ, and the SF36 physical component scale and this effect lasted >3 months. Except for the HAQ-DI, effect sizes exceeded the minimum clinically important differences (MCIDs). For the physical outcomes effects lasted >6 months. Worker productivity was not significantly affected by a flare., Conclusion: A disease flare influenced patients' lives, the largest effect was seen in the physical outcomes, and lasted 6 months. Although on a group level effect sizes for the separate PROMs were not always significant or larger than specific MCIDs, a disease flare can still be of great importance for individual patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to evaluate the effectiveness of two tapering strategies after achieving controlled disease in patients with rheumatoid arthritis (RA), during 1 year of follow-up., Methods: In this multicentre single-blinded (research nurses) randomised controlled trial, patients with RA were included who achieved controlled disease, defined as a Disease Activity Score (DAS) ≤ 2.4 and a Swollen Joint Count (SJC) ≤ 1, treated with both a conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and a TNF inhibitor. Eligible patients were randomised into gradual tapering csDMARDs or TNF inhibitors. Medication was tapered if the RA was still under control, by cutting the dosage into half, a quarter and thereafter it was stopped. Primary outcome was proportion of patients with a disease flare, defined as DAS > 2.4 and/or SJC > 1. Secondary outcomes were DAS, European Quality of Life-5 Dimensions (EQ5D) and functional ability (Health Assessment Questionnaire Disability Index [HAQ-DI]) after 1 year and over time., Results: A total of 189 patients were randomly assigned to tapering csDMARDs (n = 94) or tapering anti-TNF (n = 95). The cumulative flare rates in the csDMARD and anti-TNF tapering group were, respectively, 33 % (95% CI,24% to 43 %) and 43 % (95% CI, 33% to 53 % (p = 0.17). Mean DAS, HAQ-DI and EQ-5D did not differ between tapering groups after 1 year and over time., Conclusion: Up to 9 months, flare rates of tapering csDMARDs or TNF inhibitors were similar. After 1 year, a non-significant difference was found of 10 % favouring csDMARD tapering. Tapering TNF inhibitors was, therefore, not superior to tapering csDMARDs. From a societal perspective, it would be sensible to taper the TNF inhibitor first, because of possible cost reductions and less long-term side effects., Trial Registration Number: NTR2754., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The Nottingham Hip Fracture Score (NHFS) was developed to predict 30-day mortality following a fracture of the hip. While the NHFS has been validated in three hip fracture populations within Great Britain, these studies make no distinction between the type of fracture and surgery. Literature 'however' shows an increased risk for mortality after a hemi-arthroplasty following an intra-capsular hip fracture. To verify whether the mortality after an intra-capsular hip fracture is higher compared to the predicted mortality score according to the NHFS, a validation of the NHFS in patients with a hemi-arthroplasty after an intra-capsular hip fracture was performed., Methods: The NHFS was calculated for consecutive patients presenting with an intra-capsular fracture of the hip in two level II trauma teaching hospitals between 1 January 2011 and 1 May 2016. The observed 30-day mortality was compared with that predicted by the NHFS using several validation statistics., Results: A total of 901 patients were included in the present study. Mean age in the patients was 83 years (SD 8) and 623 (68%) of the patients were female. Almost 60% of the patients had an ASA-score (American Society of Anaesthesiologists [ASA]) of≥3 and overall 30-day mortality was 9.5% (n=86). The median NHFS was 5, and there was no significant change in median NHFS over the past 5 years. The mortality rate in the studied population of hemi-arthroplasty patients was significantly higher than mortality rates predicted by the NHFS (p=0.022, Pearson's Chi-squared test)., Conclusions: Findings suggest that for a patient with a hemi-arthroplasty following an intra-capsular hip fracture, there could be an underestimation for the 30-day mortality rate following the NHFS prediction model., Level of Evidence: Prognostic Level III, retrospective cohort study., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Fatigue has a large impact on quality of life and is still unmanageable for many patients. Study aims were describe (1) the prevalence and pattern of fatigue over time in patients with early rheumatoid arthritis under a treat-to-target strategy and (2) identify predictive factors for worsening and recovering of fatigue over time. Data from the tREACH study were used, comparing different treatment strategies with fatigue as secondary objective. Patient outcomes on fatigue, quality of life, depression, and coping were obtained every 6 months and clinically assessed every 3 months. Prediction of fatigue at 12 months was investigated with an ROC curve. Analysis was stratified into non-fatigue and fatigue at baseline. Logistic regression was used for the evolution of fatigue in relation with the covariates over time. Almost half of all patients (n = 246) had high fatigue levels at baseline, decreasing slightly over time. At 12 months, 43% of patients were fatigued; while 23% of the initially fatigued patients showed lower levels of fatigue, the fatigue level had increased in 15% of the initially non-fatigued patients. The strongest predictor of fatigue was the previous fatigue levels (AUC 0.89). Higher score on the depression scale and coping with limitations was associated with developing fatigue over time in the initially non-fatigued group. Despite a strict treat-to-target strategy, fatigue remained an overall problem during the first year of treatment, and was mainly predicted by its baseline status. In subgroups, a small additional effect of depression was seen. Monitoring fatigue and depression may be important in managing fatigue.

Purpose: The minimally invasive (MI) anterolateral approach is a relatively new approach for the treatment of femoral neck fractures with a hemiarthroplasty (HA). There is limited research available presenting clinical outcomes after an HA using the MI approach. Therefore the aim of the present study was to compare clinical outcomes of the MI and traditional anterolateral approaches in patients after HA., Methods: Data were extracted from a prospective hip fracture database and completed by retrospective review of the electronic medical records. Patients undergoing HA in a level II trauma teaching hospital between 1 January 2011 and 1 May 2016 were enrolled., Results: A total of 463 patients (67% female), 223 in the MI group (mean age, 82 ± 7) and 240 (mean age, 81 ± 8) in the traditional anterolateral group were enrolled. No significant difference was found in baseline characteristics. The surgeons experience measured by the operations performed per year was in favour of the MI anterolateral group (26 vs 18, p < 0.001). The median operating time for an MI approach was shorter (53 vs 69 min, p < 0.001). No significant differences were found in mortality rates (p = 0.131) and post-operative complications: haematomas (p = 0.63), dislocations (p = 0.63), deep surgical site infections (p = 0.66) and re-operations., Conclusions: Our findings show the MI anterolateral approach has a minimally shorter operation time with no difference in post-operative complications and clinical outcomes. We, therefore, conclude that the MI anterolateral approach is a safe alternative for the traditional anterolateral approach with an improved operation time, a smaller incision and less surrounding tissue damage., Level of Evidence: Prognostic level III retrospective cohort study.

Objectives: Patients with autoantibody-positive rheumatoid arthritis (RA) are less likely to experience pregnancy-induced improvement of RA disease activity (DAS28-C reactive protein (CRP)) compared with patients with autoantibody-negative RA. Anti-citrullinated protein antibodies (ACPAs) are the most specific autoantibodies for RA. We previously demonstrated that disease improvement is associated with changes in total IgG glycosylation, which regulate antibody effector function. Therefore, we sought to analyse the ACPA-IgG glycosylation profile during pregnancy with the aim to understand the lower change of pregnancy-induced improvement of the disease in patients with autoantibody-positive RA., Methods: ACPA-IgGs were purified from ACPA-positive patient sera (n=112) of the Pregnancy-induced Amelioration of Rheumatoid Arthritis cohort, a prospective study designed to investigate pregnancy-associated improvement of RA. The fragment crystallisable (Fc)glycosylation profile of ACPA-IgGs was characterised by mass spectrometry and compared with that of total IgG derived from the same patients or from ACPA-negative patients., Results: All ACPA-IgG subclasses display significant changes in the level of galactosylation and sialylation during pregnancy, although less pronounced than in total IgG. The pregnancy-induced increase in ACPA-IgG galactosylation, but not sialylation, associates with lower DAS28-CRP. In ACPA-positive patients, no such association was found with changes in the galactosylation of total IgG, whereas in ACPA-negative patients changes in disease activity correlated well with changes in the galactosylation of total IgG., Conclusions: In ACPA-positive RA, the pregnancy-induced change in galactosylation of ACPA-IgG, and not that of total IgG, associates with changes in disease activity. These data may indicate that in ACPA-positive patients the galactosylation of ACPA-IgG is of more pathogenic relevance than that of total IgG., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: The health-related quality of life (HRQOL) of people with HIV is lower than in the general population, but it is unknown how it compares with that of persons with other chronic medical conditions. We compared HRQOL in HIV with HRQOL in diabetes mellitus type 1, diabetes mellitus type 2 and rheumatoid arthritis (RA). In addition, we investigated factors associated with HRQOL in HIV., Design: Cross-sectional study., Methods: HRQOL was measured with the Medical Outcomes Study Short Form 36-item Health Survey in a nationwide sample of people with HIV in care in the Netherlands and on combination antiretroviral therapy for at least 6 months. We added data from studies in diabetes mellitus types 1 and 2, and RA. Logistic regression analysis was used to examine: the association between disease group and a poor HRQOL, and patient factors associated with poor HRQOL in HIV., Results: The odds of a poor physical HRQOL in the HIV group were comparable with the odds in diabetes mellitus types 1 and 2, but lower than in RA patients. The odds of a poor mental HRQOL in HIV were higher than in the other groups. In HIV, a history of AIDS, longer duration of combination antiretroviral therapy and severe comorbidity were associated with a poor physical HRQOL. Sub-Saharan African descent and CD4 cell count of less than 350 cells/μl were associated with poor mental HRQOL., Conclusion: People with HIV were more likely to have a poor mental HRQOL than patients with other chronic conditions. Addressing mental health should be an integral part of outpatient HIV care.

Objectives: Although RA patients achieve clinical remission, risk of flare still exists. Given the association between US synovitis and increased risk of flare, it is of clinical interest whether these patients report a different health status. Therefore, our aim was to evaluate the frequency of US remission in RA patients in clinical remission and to compare the health status of RA patients in clinical remission with those who were also in US remission., Methods: In a prospective study, we included 89 RA patients (aged >17 years) treated with a synthetic DMARD and a TNF inhibitor who were in remission (DAS in 44 joints ⩽2.4 and swollen joint count ⩽1). Demographic characteristics, swollen and tender joints, laboratory variables, US (MCP2-5, PIP2-5, wrists and MTP2-5) and patient-reported outcomes (general health, functional ability, fatigue, depression and anxiety, pain and morning stiffness) were recorded at two consecutive visits (3 months apart). US remission was defined as grey scale grade ⩽1 and power Doppler = 0., Results: At visit 1, 39% of patients were in US remission. At visit 2, 32% of patients were in US remission. At visit 1, functional ability (HAQ) was scored lower by patients in US remission (P = 0.029). At visit 2, HAQ scores were similar (P = 0.928). At visit 2, Hospital Anxiety and Depression Scale anxiety score and visual analog scale pain were significantly higher in patients in US remission. Similar levels were found for the other patient-reported outcomes., Conclusion: One-third of RA patients in clinical remission were in US remission. In our study population, we could not find a clear association between health status of RA patients and being in US remission., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Aims: Surgical site infection can be a devastating complication of hemiarthroplasty of the hip, when performed in elderly patients with a displaced fracture of the femoral neck. It results in a prolonged stay in hospital, a poor outcome and increased costs. Many studies have identified risk and prognostic factors for deep infection. However, most have combined the rates of infection following total hip arthroplasty and internal fixation as well as hemiarthroplasty, despite the fact that they are different entities. The aim of this study was to clarify the risk and prognostic factors causing deep infection after hemiarthroplasty alone., Patients and Methods: Data were extracted from a prospective hip fracture database and completed by retrospective review of the hospital records. A total of 916 patients undergoing a hemiarthroplasty in two level II trauma teaching hospitals between 01 January 2011 and 01 May 2016 were included. We analysed the potential peri-operative risk factors with univariable and multivariable logistic regression analysis., Results: A total of 92 patients (10%) had a surgical site infection, and 44 (4.9%) developed a deep infection. After univariable analyses, the multivariable model showed that the level of experience of the surgeon measured by the number of hemiarthroplasties performed per year was a significant prognostic factor (odds ratio (OR) 0.93, p = 0.042) for the development of an infection. Secondly, the development of a haematoma (OR 9.6, p < 0.001), a re-operation (OR 4.7, p = 0.004) and an operating time of < 45 mins (OR 5.1, p = 0.002) or > 90 mins (OR 2.7, p = 0.034) were also significant factors., Conclusion: There was a significant association between the experience of the surgeon and the rate of deep infection. Secondly, a haematoma, a re-operation and both shorter and longer operating times were associated with an increased risk of deep infection after hemiarthroplasty. No association was found between deep infection and the anatomical approach, the time when surgery was undertaken and the use of a drain. Cite this article: Bone Joint J 2017;99-B:1088-94., (©2017 The British Editorial Society of Bone & Joint Surgery.)

Background: The Fc glycosylation of immunoglobulin G (IgG) is well known to associate with rheumatoid arthritis (RA) disease activity. The same may be true for other classes of Igs. In the present study, we sought to determine whether the glycosylation of IgA was different between healthy subjects and patients with RA, as well as whether it was associated with RA disease activity, in particular with the pregnancy-associated improvement thereof or the flare after delivery., Methods: A recently developed high-throughput method for glycoprofiling of IgA1 was applied to affinity-captured IgA from sera of patients with RA (n = 252) and healthy control subjects (n = 32) collected before, during and after pregnancy., Results: IgA1 O-glycans bore more sialic acids in patients with RA than in control subjects. In addition, levels of bisecting N-acetylglucosamine of the N-glycans at asparagine 144 were higher in the patients with RA. The levels of several N-glycosylation traits were shown to change with pregnancy, similar to what has been shown before for IgG. However, the changes in IgA glycosylation were not associated with improvement or a flare of disease activity., Conclusions: The glycosylation of IgA differs between patients with RA and healthy control subjects. However, our data suggest only a minor, if any, association of IgA glycosylation with RA disease activity.

Background: Current guidelines suggest reduction of DMARDs can be considered in RA patients in remission. Objectives were (1) to estimate the relative importance of patient characteristics rheumatologists consider in their decision to de-escalate (2) to assess whether heterogeneity exists among rheumatologists with respect to de-escalation and (3) to identify the preferred de-escalation strategy., Methods: A discrete choice experiment (DCE) was conducted. All rheumatologists and trainees in The Netherlands were invited to participate. A conditional logit model was estimated to assess overall preference for de-escalation and its determinants. Heterogeneity was estimated by latent class analysis., Results: The DCE questionnaire was completed by 156 doctors. This questionnaire was constructed using the results of semi-structured interviews with 12 rheumatologists that identified five patient characteristics relevant for de-escalation: number of swollen joints (SJC), presence of DAS remission/low disease activity (LDA), patient history, duration of remission/LDA and patient willingness to de-escalate DMARDs. Overall SJC and patient history were most important. Latent class analysis revealed five subgroups of doctors, showing differences regarding willingness to de-escalate and relative importance of patient characteristics. De-escalation of the TNF inhibitor rather than methotrexate first was the most preferred strategy., Conclusions: Rheumatologists are not uniform in their decision on whom to de-escalate. Differences emerged in which characteristics they traded off resulting in five subgroups: those that taper (1) always, (2) in absence of swollen joints, (3) in absence of swollen joints and presence of favorable patient history, (4) in DAS remission and favorable patient history, and (5) taking into account all factors.