Baukje Dijkstra

X-ray structure of bovine pancreatic phospholipase A2 at atomic resolution

Using synchrotron radiation and a CCD camera, X-ray data have been collected from wild-type bovine pancreatic phospholipase A(2) at 100 K to 0.97 A resolution allowing full anisotropic refinement. The final model has a conventional R factor of 9.44% for all reflections, with a mean standard uncertainty for the positional parameters of 0.031 A as calculated from inversion of the full positional least-squares matrix. At 0.97 A resolution, bovine pancreatic phospholipase A(2) reveals for the first time that its rigid scaffolding does not preclude flexibility, which probably plays an important role in the catalytic process. Functionally important regions (the interfacial binding site and calcium-binding loop) are located at the molecular surface, where conformational variability is more pronounced. A cluster of 2-methyl-2,4-pentanediol molecules is present at the entrance of the hydrophobic channel that leads to the catalytic site and mimics the fatty-acid chains of a substrate analogue. Bovine pancreatic phospholipase A(2) at atomic resolution is compared with previous crystallographic structures and with models derived from nuclear magnetic resonance studies. Given the high structural similarity among extracellular phospholipases A(2) observed so far at lower resolution, the results arising from this structural analysis are expected to be of general validity for this class of enzymes.

The Modified painDETECT Questionnaire for Patients with Hip or Knee Osteoarthritis: Translation into Dutch, Cross-Cultural Adaptation and Reliability Assessment

There is a growing amount of evidence that alteration in pain processing by the peripheral and central nervous system play a role in osteoarthritis pain, leading to neuropathic-like symptoms. It is essential to identify knee and hip osteoarthritis patients with a neuropathic pain profile in order to offer such patients education and additional treatment options besides conventional pain treatment. The painDETECT Questionnaire is a self-report questionnaire developed to discriminate between nociceptive and neuropathic pain. This questionnaire was modified to fit patients suffering from knee osteoarthritis. The aim of this study was to translate and cross-culturally adapt the modified painDETECT Questionnaire to the Dutch language and to provide a modified version to fit patients with hip osteoarthritis. Reliability for internal consistency, repeatability and floor and ceiling effects were subsequently assessed. A total of 278 patients were included in the reliability study and 123 patients in the repeatability analysis. The Dutch modified painDETECT Questionnaire shows good internal consistency and small relative measurement errors, represented by a good intraclass correlation coefficient. Absolute measurement error, represented by the Standard Error of Measurement, was acceptable. However, a measurement bias might be present when it comes to repeatability. To our knowledge, this study is the first to provide a Dutch modified painDETECT Questionnaire to fit hip and knee osteoarthritis patients and to assess internal consistency, reliability and agreement. International guidelines were followed in the translation process and this study has ample sample size with an adequate time interval for repeatability. Based on this study, the Dutch modified painDETECT Questionnaire seems to be fit as a discriminative tool to identify knee and hip osteoarthritis patients with a neuropathic pain profile. Whether it is also suitable as an evaluative tool to record changes over time or after an intervention remains open to further investigation.

Predicting Failure in Early Acute Prosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention: External Validation of the KLIC Score

BACKGROUND Debridement, antibiotics, and implant retention (DAIR) is a widely used treatment modality for early acute prosthetic joint infection (PJI). A preoperative risk score was previously designed for predicting DAIR failure, consisting of chronic renal failure (K), liver cirrhosis (L), index surgery (I), cemented prosthesis (C), and C-reactive protein >115 mg/L (KLIC). The aim of this study was to validate the KLIC score in an external cohort. METHODS We retrospectively evaluated patients with early acute PJI treated with DAIR between 2006 and 2016 in 3 Dutch hospitals. Early acute PJI was defined as <21 days of symptoms and DAIR performed within 90 days after index surgery. Failure was defined as the need for (1) second DAIR, (2) implant removal, (3) suppressive antimicrobial treatment, or (4) infection-related death within 60 days after debridement. RESULTS A total of 386 patients were included. Failure occurred in 148 patients (38.3%). Patients with KLIC scores of ≤2, 2.5-3.5, 4-5, 5.5-6.5, and ≥7 had failure rates of 27.9%, 37.1%, 49.3%, 54.5%, and 85.7%, respectively (P < .001). The receiver-operating characteristic curve showed an area under the curve of 0.64 (95% confidence interval 0.59-0.69). A KLIC score higher than 6 points showed a specificity of 97.9%. CONCLUSION The KLIC score is a relatively good preoperative risk score for DAIR failure in patients with early acute PJI and appears to be most useful in clinical practice for patients with low or high KLIC scores.

Validity of the Dutch modified painDETECT questionnaire for patients with hip or knee osteoarthritis

Abstract Background: The modified painDETECT questionnaire (PDQ) is a self-reported questionnaire to discriminate between nociceptive and neuropathic-like pain in patients with knee/hip osteoarthritis (OA). This study aims to assess the structural and construct validity of this questionnaire. Methods: Confirmatory factor analysis and hypothesis-testing was used. For 168 patients, predefined hypotheses were formulated on the correlation between the modified painDETECT and several other questionnaires, and in a subsample of 46 with pain pressure thresholds (PPTs). Results: Two principal components were confirmed. The pain pattern item did not load on any component. Eighty per cent of the hypotheses on the correlation between modified PDQ and the questionnaires were met, as were 50% concerning PPTs measurements. Conclusions: This study is the first to assess structural and construct validity of the modified PDQ knee/hip by using factor analysis and hypothesis-testing. This questionnaire seems to reflect neuropathic-like pain symptoms experienced by hip/knee OA-patients with adequate validity. The item on pain pattern might not reflect the construct. More than 75% of the predefined hypotheses regarding the modified PDQ and the other questionnaires were met. Only 50% of the hypotheses on PPTs measurements were met, probably due to heterogeneity and limited size of this subsample. Implications for rehabilitation Pain in osteoarthritis (OA) is partly caused by modification of pain transmission in the peripheral and central nervous system, leading to sensitisation. This process seems particularly significant in a subgroup of OA patients. Sensitisation in OA is associated with more disability in daily life, lower quality of life and more widespread pain, as well as poorer outcome of total joint surgery. Screening for sensitisation can help to identify the subgroup of patients who could benefit from multidisciplinary treatment options focussing on desensitisation, cognitive- and behavioural therapy and reducing chronification of widespread pain. Therefore, being particularly important in the field of rehabilitation. The Dutch modified PainDETECT-questionnaire is very useful for rehabilitation professionals as it is one of the first questionnaires specifically validated to assess neuropathic-like symptoms (indicating sensitisation) in patients with knee or hip osteoarthritis.

Neuropathic-like symptoms and the association with joint-specific function and quality of life in patients with hip and knee osteoarthritis

Objective There is an association between osteoarthritis-related pain severity and function, yet clear evidence about the sole influence of neuropathic-like symptoms on joint function and health-related quality of life (HRQoL) is lacking. Previous studies among knee OA patients show an association between neuropathic-like symptoms, lower functional status and lower quality of life, however analyses were unadjusted or had limited adjustment for influential covariates like pain intensity. The aim of this study was therefore to determine the influence of neuropathic-like symptoms—adjusted for multiple influential covariates—on joint-specific function and HRQoL in hip and knee OA patients. Methods In this observational study 255 patients (117 with hip OA and 138 with knee OA) completed the modified painDETECT questionnaire (mPDQ) to identify subjects with neuropathic-like symptoms (mPDQ score>12, possible neuropathic pain [NP] phenotype). The WOMAC and the RAND-36 were used to asses respectively function and HRQoL. Results were adjusted stepwise for age, sex and BMI (Model 1); back disorder, painful body regions, comorbidities and previous surgery (Model 2); and pain intensity and analgesic usage (Model 3). Results A possible NP phenotype was experienced by 37% of hip and 46% of knee OA patients. Final model 3 analysis revealed that hip OA patients with neuropathic-like symptoms scored significantly lower on pain-related aspects of HRQoL (ΔRAND-36 bodily pain: 6.8 points, p = 0.047) compared to patients with the unlikely NP phenotype. In knee OA patients, a possible NP phenotype was associated with diminished joint function (ΔWOMAC domains ranging 7.1 to 10.5 points, p<0.05) and more deficits on the physical functional aspect of HRQoL (ΔRAND-36 physical functioning: 6.8 points, p = 0.016). Conclusion Neuropathic-like symptoms deteriorate the subjective rating of pain-related quality of life in hip OA patients and significantly influence function in knee OA patients.

Feasibility and patient experience of a home-based rehabilitation program driven by a tablet application and mobility monitoring for patients after a total hip arthroplasty (Preprint)

Background Recent developments in technology are promising for providing home-based exercise programs. Objective The objective of this study was to evaluate the feasibility and patient experience of a home-based rehabilitation program after total hip arthroplasty (THA) delivered using videos on a tablet personal computer (PC) and a necklace-worn motion sensor to continuously monitor mobility-related activities. Methods We enrolled 30 independently living patients aged 18-75 years who had undergone THA as a treatment for primary or secondary osteoarthritis (OA) between December 2015 and February 2017. Patients followed a 12-week exercise program with video instructions on a tablet PC and daily physical activity registration through a motion sensor. Patients were asked to do strengthening and walking exercises at least 5 days a week. There was weekly phone contact with a physiotherapist. Adherence and technical problems were recorded during the intervention. User evaluation was done in week 4 (T1) and at the end of the program (T2). Results Overall, 26 patients completed the program. Average adherence for exercising 5 times a week was 92%. Reasons mentioned most often for nonadherence were vacation or a day or weekend off 25% (33/134) and work 15% (20/134). The total number of technical issues was 8. The average score on the user evaluation questionnaire (range 0-5) was 4.6 at T1 and 4.5 at T2. The highest score was for the subscale “coaching” and the lowest for the subscale “sensor.” Conclusions A home-based rehabilitation program driven by a tablet app and mobility monitoring seems feasible for THA patients. Adherence was good and patient experience was positive. The novel technology was well accepted. When the home-based rehabilitation program proves to be effective, it could be used as an alternative to formal physiotherapy. However, further research on its effectiveness is needed.

Actual and perceived nursing workload and the complexity of patients with total hip arthroplasty

BACKGROUND Little is known about the relation between patient complexity and nursing care of total hip arthroplasty (THA) patients. To improve patient care and hospital logistics, the aim of this study is to gain insight into the relation between patient complexity and the nursing staffs actual and perceived workload at an orthopedic ward during admission for a THA. DESIGN Prospective cohort study of 45 THA patients in the year 2014. Duration and type of nursing care activities were recorded during the first postoperative morning. A questionnaire was used to analyze the perceived workload of the nursing staff. Both actual and perceived workload were analyzed for their relation with patient complexity, expressed in the American Society of Anesthesiologists (ASA) score, Charlson comorbidity index (CCI), Katz Activities of Daily Life score (Katz-ADL) and Body Mass Index (BMI). RESULTS No relation was found between actual workload and measures for patient complexity. The perceived workload of the nursing staff was related to two complexity measures: ASA (r=0.71; p<0.001) and CCI (r=0.65; p=0.002). CONCLUSION Patient comorbidity is related to the perceived workload of the nursing staff during admission for a THA. Patient complexity is not related to actual workload. This study gives a first insight into the relation between patient comorbidity and nursing staff workload, to try to improve staffing numbers at the ward as well as patient care in the process.

VALIDITY OF THE DUTCH MODIFIED PAINDETECT QUESTIONNAIRE (MPDQ-NL) FOR PATIENTS WITH HIP OR KNEE OSTEOARTHRITIS

The etiology of pain in osteoarthritis (OA) is complex and multifactorial. A growing number of studies suggest that modification of pain-transmission in the peripheral and central nervous system, leading to sensitization, plays a role in OA pain. Sensitization seems to be associated with neuropathic pain-like symptoms and assessment of these symptoms can help to identify patients who could benefit from additional treatment options. Several questionnaires are available to distinguish neuropathic from nociceptive pain symptoms.

Duloxetine in OsteoArthritis (DOA) study: study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty

Introduction Residual pain is a major factor in patient dissatisfaction following total hip arthroplasty or total knee arthroplasty (THA/TKA). The proportion of patients with unfavourable long-term residual pain is high, ranging from 7% to 34%. There are studies indicating that a preoperative degree of central sensitisation (CS) is associated with poorer postoperative outcomes and residual pain. It is thus hypothesised that preoperative treatment of CS could enhance postoperative outcomes. Duloxetine has been shown to be effective for several chronic pain syndromes, including knee osteoarthritis (OA), in which CS is most likely one of the underlying pain mechanisms. This study aims to evaluate the postoperative effects of preoperative screening and targeted duloxetine treatment of CS on residual pain compared with care-as-usual. Methods and analysis This multicentre, pragmatic, prospective, open-label, randomised controlled trial includes patients with idiopathic hip/knee OA who are on a waiting list for primary THA/TKA. Patients at risk for CS will be randomly allocated to the preoperative duloxetine treatment programme group or the care-as-usual control group. The primary end point is the degree of postoperative pain 6 months after THA/TKA. Secondary end points at multiple time points up to 12 months postoperatively are: pain, neuropathic pain-like symptoms, (pain) sensitisation, pain catastrophising, joint-associated problems, physical activity, health-related quality of life, depressive and anxiety symptoms, and perceived improvement. Data will be analysed on an intention-to-treat basis. Ethics and dissemination The study is approved by the local Medical Ethics Committee (METc 2014/087) and will be conducted according to the principles of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard (GCP), and in compliance with the Medical Research Involving Human Subjects Act (WMO). Trial registration number 2013-004313-41; Pre-results.

Escherichia coli MltA: MAD phasing and refinement of a tetartohedrally twinned protein crystal structure. Addendum and erratum

Crystals were grown of a mutant form of the bacterial cell-wall maintenance protein MltA that diffracted to 2.15 A resolution. When phasing with molecular replacement using the native structure failed, selenium MAD was used to obtain initial phases. However, after MAD phasing the crystals were found to be tetartohedrally twinned, hampering correct space-group determination and refinement. A refinement protocol was designed to take tetartohedral twinning into account and was successfully applied to refine the structure. The refinement protocol is described and the reasons for the failure of molecular replacement and the success of MAD are discussed in terms of the effects of the tetartohedral twinning.