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Background and Purpose: Diagnostics and treatment of developmental dysplasia of the hip (DDH) are highly variable in clinical practice. To obtain more uniform and evidence-based treatment pathways, we developed the 'Dutch guideline for DDH in children < 1 year'. This study describes recommendations for unstable and decentered hips., Materials and Methods: The Appraisal of Guidelines for Research and Evaluation criteria (AGREE II) were applied. A systematic literature review was performed for six predefined guideline questions. Recommendations were developed, based on literature findings, as well as harms/benefits, patient/parent preferences, and costs (GRADE)., Results: The systematic literature search resulted in 843 articles and 11 were included. Final guideline recommendations are (i) Pavlik harness is the preferred first step in the treatment of (sub) luxated hips; (ii) follow-up with ultrasound at 3-4 and 6-8 weeks; (iii) if no centered and stable hip after 6-8 weeks is present, closed reduction is indicated; (iv) if reduction is restricted by limited hip abduction, adductor tenotomy is indicated; (v) in case of open reduction, the anterior, anterolateral, or medial approach is advised, with the choice based on surgical preference and experience; (vi) after reduction (closed/open), a spica cast is advised for 12 weeks, followed by an abduction device in case of residual dysplasia., Interpretation: This study presents recommendations on the treatment of decentered DDH, based on the available literature and expert consensus, as Part 2 of the first official and national evidence-based 'Guideline for DDH in children < 1 year'. Part 1 describes the guideline sections on centered DDH in a separate article.

Despite the high incidence of developmental dysplasia of the hip (DDH), treatment is very diverse. Therefore, the Dutch Orthopedic Society developed a clinical practice guideline with recommendations for optimal and uniform treatment of DDH. This article summarizes the guideline on centered DDH (i.e. Graf types 2A-C). The guideline development followed the criteria of Appraisal of Guidelines for Research and Evaluation II. A systematic literature review was performed to identify randomized controlled trials and comparative cohort studies including children <1 year with centered DDH. Articles were included that compared (1) treatment with observation, (2) different abduction devices, (3) follow-up frequencies, and (4) discontinuation methods. Recommendations were based on Grading Recommendations Assessment, Development, and Evaluation, which included the literature, clinical experience and consensus, patient and parent comfort, and costs. Out of 430 potentially relevant articles, 5 comparative studies were included. Final guideline recommendations were (1) initially observe 3-month-old patients with centered DDH, start abduction treatment if the hip does not normalize after 6-12 weeks; (2) prescribe a Pavlik harness to children <6 months with persisting DDH on repeated ultrasonography, consider alternative abduction devices for children >6 months; (3) assess patients every 6 weeks; and (4) discontinue the abduction device when the hip has normalized or when the child is 12 months. This paper presents a summary of part 1 of the first evidence-based guideline for treatment of centered DDH in children <1 year. Part 2 presents the guideline on decentered DDH in a separate article.

Vaccination guidelines for patients treated for hematological diseases are typically conservative. Given their high risk for severe COVID-19, it is important to identify those patients that benefit from vaccination. We prospectively quantified serum immunoglobulin G (IgG) antibodies to spike subunit 1 (S1) antigens during and after 2-dose mRNA-1273 (Spikevax/Moderna) vaccination in hematology patients. Obtaining S1 IgG ≥ 300 binding antibody units (BAUs)/mL was considered adequate as it represents the lower level of S1 IgG concentration obtained in healthy individuals, and it correlates with potent virus neutralization. Selected patients (n = 723) were severely immunocompromised owing to their disease or treatment thereof. Nevertheless, >50% of patients obtained S1 IgG ≥ 300 BAUs/mL after 2-dose mRNA-1273. All patients with sickle cell disease or chronic myeloid leukemia obtained adequate antibody concentrations. Around 70% of patients with chronic graft-versus-host disease (cGVHD), multiple myeloma, or untreated chronic lymphocytic leukemia (CLL) obtained S1 IgG ≥ 300 BAUs/mL. Ruxolitinib or hypomethylating therapy but not high-dose chemotherapy blunted responses in myeloid malignancies. Responses in patients with lymphoma, patients with CLL on ibrutinib, and chimeric antigen receptor T-cell recipients were low. The minimal time interval after autologous hematopoietic cell transplantation (HCT) to reach adequate concentrations was <2 months for multiple myeloma, 8 months for lymphoma, and 4 to 6 months after allogeneic HCT. Serum IgG4, absolute B- and natural killer-cell number, and number of immunosuppressants predicted S1 IgG ≥ 300 BAUs/mL. Hematology patients on chemotherapy, shortly after HCT, or with cGVHD should not be precluded from vaccination. This trial was registered at Netherlands Trial Register as #NL9553., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients., Methods: Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC 0-12 h  -C min -C max ) and its intra- and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring., Results: Fifteen patients aged 40-74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (C min percentile (P)10-P90: 665-1404 ng/mL and 557-1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra- and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated., Conclusion: With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real-life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long-term effects on quality of life., Clinical Trial Registration: NTR5000 (Netherlands Trial Register, www.trialregister.nl)., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Objectives: To compare nilotinib concentrations obtained by venous blood sampling and dried blood spot (DBS) in patients with chronic myeloid leukaemia (CML). It was investigated how to predict nilotinib plasma levels on the basis of DBS., Methods: Forty duplicate DBS and venous blood samples were collected from 20 patients. Capillary blood was obtained by finger prick and spotted on DMPK-C Whatman sampling paper, simultaneously with venous blood sampling. Plasma concentrations were predicted from DBS concentrations using three methods: (1) individual and (2) mean haematocrit correction and (3) the bias between plasma and DBS concentrations. Results were compared using Deming regression and Bland-Altman analysis., Key Findings: Nilotinib plasma concentrations ranged from 376 to 2663 μg/l. DBS concentrations ranged from 144 to 1518 μg/l. The slope was 0.56 (95% CI, 0.51 to 0.61) with an intercept of -41.68 μg/l (95% CI, -93.78 to 10.42). Mean differences between calculated and measured plasma concentrations were -14.3% (method 1), -14.0% (method 2) and -0.6% (method 3); differences were within 20% of the mean in 73%, 85% and 80% of the samples, respectively. The slopes were respectively 0.96 (95% CI, 0.86 to 1.06), 0.95 (95% CI, 0.86 to 1.03) and 1.00 (95% CI, 0.91 to 1.09)., Conclusions: Plasma concentrations of nilotinib could be predicted on the basis of DBS. DBS sampling to assess nilotinib concentrations in CML patients seems a suitable alternative for venous sampling., (© 2017 Royal Pharmaceutical Society.)

Background: In our hospital a fast-track setting including a multimodal pain protocol is used for total hip arthroplasty (THA). Despite this multimodal pain protocol there is still a large range in reported postoperative pain between patients, which hinders mobilization and rehabilitation postoperatively. The goal of this study was to identify which patient-specific and surgical characteristics influence postoperative pain after THA in a fast-track setting., Methods: All 74 patients with osteoarthritis of the hip who underwent primary THA procedure by anterior supine intermuscular approach between November 2012 and January 2014 were included in this prospective cohort study. The protocol for pain medication was standardized. Postoperative pain determined with the Numeric Rating Score was collected at 17 standardized moments. Linear mixed models were used to examine potential patient-specific and surgical factors associated with increased postoperative pain., Results: Pain patterns differed substantially across individuals. Adjusted for other variables in the model, preoperative use of pain medication (regression coefficient 0.78 (95% CI 0.28-1.26); p = 0.005) and preoperative neuropathic pain scored by DN4 (regression coefficient 0.68 (95% CI 0.15-1.20); p = 0.02) were the only factors significantly associated with higher postoperative pain scores., Conclusions: The knowledge of which factors are associated with higher postoperative pain scores after THA in a fast-track setting may help optimizing perioperative postoperative pain management and preoperative education of these patients., Trial Registration: The study was retrospectively registered in the ISRCTN registry under identifier ISRCTN15422220 (date of registration: July 25, 2017).

There is still discussion about possible advantages and disadvantages of the less invasive anterior approach for total hip arthroplasty (THA). The purpose of our systematic review was to evaluate literature regarding the anterior approach in comparison to other approaches. Furthermore, we investigated if there is a description of a learning curve for the anterior approach.Data were obtained from EMBASE, Cochrane, PsycINFO, CINAHL, Web-of-Science, Scopus, Google scholar, and PubMed since their inception up to June 2015. 2 reviewers independently selected the studies and independently conducted the quality assessment. Because studies were considered heterogeneous regarding outcome measures, determinants studied, and methodological quality, we decided to perform a "best evidence synthesis". A total of 64 studies met the inclusion criteria.Strong evidence for no difference in component placement between the anterior approach and other approaches was found. Also, strong evidence for faster postoperative recovery and less need for assistive devices after the anterior approach were found. All other studied parameters only demonstrated conflicting evidence. Although the learning curve for the anterior approach is not yet clear, this learning curve should not to be neglected.In conclusion, the less invasive anterior approach provides benefits in the early postoperative period only, when compared to other approaches.

Only limited data are available regarding the infiltration of local anaesthetic for total hip arthroplasty (THA), and no studies were performed for THA using the anterior approach. In this prospective, randomised placebo-controlled study we investigated the effect of both standard and reverse infiltration of local anaesthetic in combination with the anterior approach for THA. The primary endpoint was the mean numeric rating score for pain four hours post-operatively. In addition, we recorded the length of hospital stay, the operating time, the destination of the patient at discharge, the use of pain medication, the occurrence of side effects and pain scores at various times post-operatively. Between November 2012 and January 2014, 75 patients were included in the study. They were randomised into three groups: standard infiltration of local anaesthetic, reversed infiltration of local anaesthetic, and placebo. There was no difference in mean numeric rating score for pain four hours post-operatively (p = 0.87). There were significantly more side effects at one and eight hours post-operatively in the placebo group (p = 0.02; p = 0.03), but this did not influence the mobilisation of the patients. There were no differences in all other outcomes between the groups. We found no clinically relevant effect when the infiltration of local anaesthetic with ropivacaine and epinephrine was used in a multimodal pain protocol for THA using the anterior approach., (©2015 The British Editorial Society of Bone & Joint Surgery.)

After implementation of a 'fast-track' rehabilitation protocol in our hospital, mean length of hospital stay for primary total hip arthroplasty decreased from 4.6 to 2.9 nights for unselected patients. However, despite this reduction there was still a wide range across the patients' hospital duration. The purpose of this study was to identify which specific patient characteristics influence length of stay after successful implementation of a 'fast-track' rehabilitation protocol. A total of 477 patients (317 female and 160 male, mean age 71.0 years; 39.3 to 92.6, mean BMI 27.0 kg/m(2);18.8 to 45.2) who underwent primary total hip arthroplasty between 1 February 2011 and 31 January 2013, were included in this retrospective cohort study. A length of stay greater than the median was considered as an increased duration. Logistic regression analyses were performed to identify potential factors associated with increased durations. Median length of stay was two nights (interquartile range 1), and the mean length of stay 2.9 nights (1 to 75). In all, 266 patients had a length of stay ≤ two nights. Age (odds ratio (OR) 2.46; 95% confidence intervals (CI) 1.72 to 3.51; p < 0.001), living situation (alone vs living together with cohabitants, OR 2.09; 95% CI 1.33 to 3.30; p = 0.002) and approach (anterior approach vs lateral, OR 0.29; 95% CI 0.19 to 0.46; p < 0.001) (posterolateral approach vs lateral, OR 0.24; 95% CI 0.10 to 0.55; p < 0.001) were factors that were significantly associated with increased length of stay in the multivariable logistic regression model., (©2015 The British Editorial Society of Bone & Joint Surgery.)

This study describes specific complications noticed during the first unselected cases operated by anterior approach for THA in our hospital and specific adjustments that were applied on the procedure to prevent these complications. We retrospectively analysed the differences between 202 patients who were operated by a standardised approach and 248 patients who were operated after adjustments were implemented with the procedure. Injury to the lateral femoral cutaneous nerve (LFCN), fractures of the greater trochanter and dislocation were specific complications that were noticed with the initial technique.Prevalence of injury to the LFCN decreased from 7.9% to 0.8% (p<0.001), fractures of the greater trochanter decreased from 5.4% to 0.8% (p = 0.004) and the incidence of dislocation decreased from 4.5% to 1.6% (p = 0.074).

Background and Purpose: Rapid recovery protocols after total hip arthroplasty (THA) have been introduced worldwide in the last few years and they have reduced the length of hospital stay. We show the results of the introduction of a rapid recovery protocol for primary THA for unselected patients in our large teaching hospital., Patients and Methods: In a retrospective cohort study, we included all 1,180 patients who underwent a primary THA between July 1, 2008 and June 30, 2012. These patients were divided into 3 groups: patients operated before, during, and after the introduction of the rapid recovery protocol. There were no exclusion criteria. All complications, re-admissions, and reoperations were registered and analyzed., Results: The mean length of hospital stay decreased from 4.6 to 2.9 nights after the introduction of the rapid recovery protocol. There were no statistically significant differences in the rate of complications, re-admissions, or reoperations between the 3 groups., Interpretation: In a large teaching hospital, the length of hospital stay decreased after introduction of our protocol for rapid recovery after THA in unselected patients, without any increase in complications, re-admissions, or reoperation rate.

One of the reasons for inadequate pain treatment in hospitalized patients is that nurses have insufficient knowledge about pain and pain management. To address this problem, a Pain Monitoring Program (PMP) for nurses was developed, implemented, and evaluated. The PMP consisted of two components: educating nurses about pain, pain assessment, and pain management, and implementing daily pain assessment by means of a numeric rating scale. The effects of the PMP were measured in a one-group pretest-post-test design. The results show that nurses have knowledge deficits and prejudices with regard to pain and pain management. Age and additional pain courses in pain partly predict nurses' pain knowledge. After nurses were educated, the average score on the Pain Knowledge Questionnaire increased from 69.1% (SD = 13.2) at pretest to 75.8% (SD = 11.5) at post-test (P < 0.001). Nurses' attitudes changed with regard to their level of knowledge and skills in relieving pain, willingness to assess pain on a daily basis, and attention to patients' pain complaints. It can be concluded that the PMP is effective in improving nurses' knowledge of pain management and focusing nurses' attention to patients' pain complaints.