Longitudinal determinants of employment status in people with relapsing-remitting multiple sclerosis.

Purpose: To investigate longitudinal relationships between employment status and disease-related, (neuro)psychological, and work-related factors in people with multiple sclerosis (MS). Methods: 170 employed people with MS underwent yearly neurological and neuropsychological examinations to assess MS-related disability and cognitive functioning. Additionally, they completed yearly questionnaires assessing depression, anxiety, fatigue, cognitive complaints, workplace support and coping. Multilevel models for change were fitted to examine progression of these factors over three years, and to assess possible relationships with change in employment status. Results: People with a deteriorated employment status after three years reported more depression (p=0.009), a higher impact of fatigue (p<0.001), more cognitive complaints (p<0.001) and less workplace support (p=0.001) at baseline than people with a stable employment status. There were no differences in progression over time of the examined variables between people with a stable or deteriorated employment status. Conclusion: More depression, a higher impact of fatigue, more cognitive complaints and less workplace support are predictive of a deteriorated employment status after three years in individuals with MS. How these factors progress over time is not different between those with a stable or deteriorated employment. MS-related disability, anxiety, objective cognition and coping were not related to a deterioration in employment status.

AI-support for the detection of intracranial large vessel occlusions: One-year prospective evaluation.

Purpose: Few studies have evaluated real-world performance of radiological AI-tools in clinical practice. Over one-year, we prospectively evaluated the use of AI software to support the detection of intracranial large vessel occlusions (LVO) on CT angiography (CTA). Method: Quantitative measures (user log-in attempts, AI standalone performance) and qualitative data (user surveys) were reviewed by a key-user group at three timepoints. A total of 491 CTA studies of 460 patients were included for analysis. Results: The overall accuracy of the AI-tool for LVO detection and localization was 87.6%, sensitivity 69.1% and specificity 91.2%. Out of 81 LVOs, 31 of 34 (91%) M1 occlusions were detected correctly, 19 of 38 (50%) M2 occlusions, and 6 of 9 (67%) ICA occlusions. The product was considered user-friendly. The diagnostic confidence of the users for LVO detection remained the same over the year. The last measured net promotor score was -56%. The use of the AI-tool fluctuated over the year with a declining trend. Conclusions: Our pragmatic approach of evaluating the AI-tool used in clinical practice, helped us to monitor the usage, to estimate the perceived added value by the users of the AI-tool, and to make an informed decision about the continuation of the use of the AI-tool.

How does hip osteoarthritis differ from knee osteoarthritis?

Hip and knee osteoarthritis (OA) are leading causes of global disability. Most research to date has focused on the knee, with results often extrapolated to the hip, and this extends to treatment recommendations in clinical guidelines. Extrapolating results from research on knee OA may limit our understanding of disease characteristics specific to hip OA, thereby constraining development and implementation of effective treatments. This review highlights differences between hip and knee OA with respect to prevalence, prognosis, epigenetics, pathophysiology, anatomical and biomechanical factors, clinical presentation, pain and non-surgical treatment recommendations and management.

Is a model of stratified exercise therapy by physical therapists in primary care feasible in patients with knee osteoarthritis? : a mixed methods study.

OBJECTIVES: To explore the feasibility of a newly developed model of stratified exercise therapy in primary care for patients with knee osteoarthritis (OA). DESIGN: Mixed method design (process, outcome and qualitative evaluation). SETTING: Six physical therapy practices in primary care around Amsterdam. PARTICIPANTS: Fifty eligible patients with knee OA, visiting one of the participating physical therapists (PTs). INTERVENTION: Patients were allocated to a subgroup based on a simple stratification tool and received subgroup-specific, protocolized, 4-month, exercise therapy. MAIN OUTCOME MEASURES: Feasibility of this model of stratified exercise therapy was explored by multiple process parameters, outcome measures (physical functioning and knee pain; at baseline and 4-months follow-up) and experiences from patients and PTs. RESULTS: From 97 potentially eligible patients, fifty patients were included and allocated to the 'high muscle strength subgroup' (n=17), 'depression subgroup' (n=4), 'obesity subgroup' (n=6) or 'low muscle strength subgroup' (n=23). Three patients dropped out during the study period. PTs provided relatively low numbers of sessions (on average 10 sessions), although exceedance of the recommended maximum number of sessions did occur frequently. We found clinically relevant improvements on physical functioning and knee pain (P<0.001 for both) for the total group. In general, the model of stratified exercise therapy was considered to be easily applicable and of added value for daily practice. CONCLUSIONS: Our model of stratified exercise therapy seems to be feasible in primary care, although a number of limitations were reported. Future research should determine the (cost-)effectiveness of an adapted model, compared to usual, non-stratified exercise therapy.

Using textbook outcome as a measure of quality of care in oesophagogastric cancer surgery.

BACKGROUND: Textbook outcome is a multidimensional measure representing an ideal course after oesophagogastric cancer surgery. It comprises ten perioperative quality-of-care parameters and has been developed recently using population-based data. Its association with long-term outcome is unknown. The objectives of this study were to validate the clinical relevance of textbook outcome at a hospital level, and to assess its relation with long-term survival after treatment for oesophagogastric cancer. METHODS: All patients with oesophageal or gastric cancer scheduled for surgery with curative intent between January 2009 and June 2015 were selected from an institutional database. A Cox model was used to study the association between textbook outcome and survival. RESULTS: A textbook outcome was achieved in 58 of 144 patients (40·3 per cent) with oesophageal cancer and in 48 of 105 (45·7 per cent) with gastric cancer. Factors associated with not achieving a textbook outcome were failure to achieve a lymph node yield of at least 15 (after oesophagectomy) and postoperative complications of grade II or more. After oesophagectomy, median overall survival was longer for patients with a textbook outcome than for patients without (median not reached versus 33 months; P = 0·012). After gastrectomy, median survival was 54 versus 33 months respectively (P = 0·018). In multivariable analysis, textbook outcome was associated with overall survival after oesophagectomy (hazard ratio 2·38, 95 per cent c.i. 1·29 to 4·42) and gastrectomy (hazard ratio 2·58, 1·25 to 5·32). CONCLUSION: Textbook outcome is a clinically relevant measure in patients undergoing oesophagogastric cancer surgery as it can identify underperforming parameters in a hospital setting. Overall survival in patients with a textbook outcome is better than in patients without a textbook outcome.

Characterization of the Adsorption Mechanism of Manganese Phosphate Conversion Coating Derived Tribofilms.

Casing connections in the oil and gas industry are typically coated with zinc and/or manganese phosphate for corrosion protection during storage. The presence of phosphate coatings is also known to give beneficial tribological performance. The coating allows the system to run without problems long after it is worn off. This is because of two mechanisms. Glaze layer formation on the coated surface and, as will be shown, tribofilm formation on the uncoated counter-surface. An investigation into the mechanism behind this tribofilm formation is presented in this paper. The aim is to develop lubricants that exploit these mechanisms. A pin-on-disc set-up was used to investigate the interaction of a manganese phosphated disc and bare counter surface. Six base oils with different polarity and viscosity were used. The resulting tribofilms were analysed using optical microscopy, scanning electron microscopy, X-ray diffractometry, X-ray photoelectron spectroscopy, focused ion beam, and atomic force microscopy. The tribofilm is robust, amorphous, and only forms in the presence of a lubricant under sliding conditions and adsorbs on substrates with a large variation in chemical composition. It is concluded that the tribofilm consists of physisorbed manganese phosphate and formation is shear stress activated.

The pan phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) blocks survival, adhesion and proliferation of primary chronic lymphocytic leukemia cells.

The phosphoinositide 3-kinases (PI3Ks) are critical components of the B-cell receptor (BCR) pathway and have an important role in the pathobiology of chronic lymphocytic leukemia (CLL). Inhibitors of PI3Kδ block BCR-mediated cross-talk between CLL cells and the lymph node microenvironment and provide significant clinical benefit to CLL patients. However, the PI3Kδ inhibitors applied thus far have limited direct impact on leukemia cell survival and thus are unlikely to eradicate the disease. The use of inhibitors of multiple isoforms of PI3K might lead to deeper remissions. Here we demonstrate that the pan-PI3K/mammalian target of rapamycin inhibitor SAR245409 (voxtalisib/XL765) was more pro-apoptotic to CLL cells--irrespective of their ATM/p53 status--than PI3Kα or PI3Kδ isoform selective inhibitors. Furthermore, SAR245409 blocked CLL survival, adhesion and proliferation. Moreover, SAR245409 was a more potent inhibitor of T-cell-mediated production of cytokines, which support CLL survival. Taken together, our in vitro data provide a rationale for the evaluation of a pan-PI3K inhibitor in CLL patients.

Sclerosing Mesenteritis.

BACKGROUND: A 55-year-old Caucasian man presented with weight loss, cramping abdominal pains, an increasing abdominal circumference and diarrhea. Physical examination showed no abnormalities besides a puffy abdomen. His past medical history included a recent subcutaneous swelling in the neck, histologically compatible to a benign solitary fibrous tumor. All blood results were within normal limits. Abdominal ultrasonography showed a tumor with diameter of 6.7 cm, probably originating from the pancreas, with ascites and retroperitoneal lymphadenopathy. This was followed by a CT scan. CT scan of the abdomen was repeated following therapy.

BTK inhibitors in chronic lymphocytic leukemia: a glimpse to the future.

The treatment of chronic lymphocytic leukemia (CLL) with inhibitors targeting B cell receptor signaling and other survival mechanisms holds great promise. Especially the early clinical success of Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK), has received widespread attention. In this review we will focus on the fundamental and clinical aspects of BTK inhibitors in CLL, with emphasis on Ibrutinib as the best studied of this class of drugs. Furthermore, we summarize recent laboratory as well as clinical findings relating to the first cases of Ibrutinib resistance. Finally, we address combination strategies with Ibrutinib, and attempt to extrapolate its current status to the near future in the clinic.

Reciprocal effects of stable and temporary components of neuroticism and affective disorders: results of a longitudinal cohort study.

BACKGROUND: Cross-sectional studies show that neuroticism is strongly associated with affective disorders. We investigated whether neuroticism and affective disorders mutually reinforce each other over time, setting off a potential downward spiral. METHOD: A total of 2981 adults aged 18-65 years, consisting of healthy controls, persons with a prior history of affective disorders and persons with a current affective disorder were assessed at baseline (T1) and 2 (T2) and 4 years (T3) later. At each wave, affective disorders according to DSM-IV criteria were assessed with the Composite Interview Diagnostic Instrument (CIDI) version 2.1 and neuroticism with the Neuroticism-Extraversion-Openness Five Factor Inventory (NEO-FFI). RESULTS: Using structural equation models the association of distress disorders (i.e. dysthymia, depressive disorder, generalized anxiety disorder) and fear disorders (i.e. social anxiety disorder, panic disorder, agoraphobia without panic) with neuroticism could be attributed to three components: (a) a strong correlation of the stable components of distress and fear disorders with the stable trait component of neuroticism; (b) a modest contemporaneous association of change in distress and fear disorders with change in neuroticism; (c) a small to modest delayed effect of change in distress and fear disorders on change in neuroticism. Moreover, neuroticism scores in participants newly affected at T2 but remitted at T3 did not differ from their pre-morbid scores at T1. CONCLUSIONS: Our results do not support a positive feedback cycle of changes in psychopathology and changes in neuroticism. In the context of a relative stability of neuroticism and affective disorders, only modest contemporaneous and small to modest delayed effects of psychopathology on neuroticism were observed.

Knee joint stabilization therapy in patients with osteoarthritis of the knee: a randomized, controlled trial.

OBJECTIVE: To investigate whether an exercise program, initially focusing on knee stabilization and subsequently on muscle strength and performance of daily activities is more effective than an exercise program focusing on muscle strength and performance of daily activities only, in reducing activity limitations in patients with knee osteoarthritis (OA) and instability of the knee joint. DESIGN: A single-blind, randomized, controlled trial involving 159 knee OA patients with self-reported and/or biomechanically assessed knee instability, randomly assigned to two treatment groups. Both groups received a supervised exercise program for 12 weeks, consisting of muscle strengthening exercises and training of daily activities, but only in the experimental group specific knee joint stabilization training was provided. Outcome measures included activity limitations (Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC physical function, primary outcome), pain, global perceived effect and knee stability. RESULTS: Both treatment groups demonstrated large (∼20-40%) and clinically relevant reductions in activity limitations, pain and knee instability, which were sustained 6 months post-treatment. No differences in effectiveness between experimental and control treatment were found on WOMAC physical function (B (95% confidence interval - CI) = -0.01 (-2.58 to 2.57)) or secondary outcome measures, except for a higher global perceived effect in the experimental group (P = 0.04). CONCLUSIONS: Both exercise programs were highly effective in reducing activity limitations and pain and restoring knee stability in knee OA patients with instability of the knee. In knee OA patients suffering from knee instability, specific knee joint stabilization training, in addition to muscle strengthening and functional exercises, does not seem to have any additional value. Dutch Trial Register (NTR) registration number: NTR1475.

Trajectories of social anxiety during adolescence and relations with cognition, social competence, and temperament.

This cohort-sequential study examined developmental trajectories of social anxiety in a nonclinical sample (N = 331, 161 girls) aged 9 to 17 years at initial and 12 to 21 years at final assessment. We tested whether variables assessing cognition, social competence, and temperament discriminated between the trajectories. Variables were collected from different sources: participants, independent observers, parents, and teachers. Using Latent Class Growth Modeling (LCGM) we identified three distinct social anxiety trajectory groups: i) high and changing; ii) moderate and decreasing; and iii) low and decreasing. Multinomial regression analyses showed that the cognition variables, negative interpretations of ambiguous social situations and self-focused attention, differentiated between all three trajectories. A lack of social skills and having social problems at school were specifically related to the chance of following the high trajectory versus the moderate trajectory. Neuroticism differentiated between the low and moderate trajectories. Findings indicate that adolescents at risk of belonging to a high social anxiety trajectory can be discriminated from peers belonging to a less anxious trajectory using both cognition and social competence variables.

Physiotherapy in hip and knee osteoarthritis: development of a practice guideline concerning initial assessment, treatment and evaluation.

BACKGROUND: An update of a Dutch physiotherapy practice guideline in Hip and Knee Osteoarthritis (HKOA) was made, based on current evidence and best practice. METHODS: A guideline steering committee, comprising 10 expert physiotherapists, selected topics concerning the guideline chapters: initial assessment, treatment and evaluation. With respect to treatment a systematic literature search was performed using various databases, and the evidence was graded (1-4). For the initial assessment and evaluation mainly review papers and textbooks were used. Based on evidence and expert opinion, recommendations were formulated. A first draft of the guideline was reviewed by 17 experts from different professional backgrounds. A second draft was field-tested by 45 physiotherapists. RESULTS: In total 11 topics were selected. For the initial assessment, three recommendations were formulated, pertaining to history taking, red flags, and formulating treatment goals. Concerning treatment, 7 recommendations were formulated; (supervised) exercise therapy, education and self management interventions, a combination of exercise and manual therapy, postoperative exercise therapy and taping of the patella were recommended. Balneotherapy and hydrotherapy in HKOA, and thermotherapy, TENS, and Continuous Passive Motion in knee OA were neither recommended nor discouraged. Massage therapy, ultrasound, electrotherapy, electromagnetic field, Low Level Laser Therapy, preoperative physiotherapy and education could not be recommended. For the evaluation of treatment goals the following measurement instruments were recommended: Lequesne index, Western Ontario and McMaster Universities osteoarthritis index, Hip disability and Osteoarthritis Outcome Score and Knee injury and Osteoarthritis Outcome Score, 6-minute walktest, Timed Up and Go test, Patient Specific Complaint list, Visual Analoge Scale for pain, Intermittent and Constant OsteoArthritis Pain Questionnaire, goniometry, Medical Research Council for strength, handheld dynamometer. CONCLUSIONS: This update of a Dutch physiotherapy practice guideline on HKOA included 11 recommendations on the initial assessment, treatment and evaluation. The implementation of the guideline in clinical practice needs further evaluation.

Dynamic volume change measurements of cereal materials by environmental scanning electron microscopy and videomicroscopy.

Moisture migration induced volume change in cereal materials was studied by environmental scanning electron microscopy, videomicroscopy and stereoscopy. It is shown that the in situ volume change can be monitored by the changes of projection area with the assumption of isotropic swelling/shrinkage. The projection area change from videomicroscopy matches well with the volume change by stereoscopy after dimensional normalization. The arbitrary volume values in between two relative humidity levels are available by interpolating the equilibrium volumes at beginning and ending. The sorption/desorption curves were fitted by the 'parallel exponential kinetics' model, which described two independent, parallel processes as 'slow' and 'fast'. In the low relative humidity range, sorption curves match well with the 'parallel exponential kinetics' model and the two parallel processes tend to be identical when relative humidity increases. The diffusivity of water moisture in a cracker, which was estimated by the half-equilibrium principle, has a strong dependence on relative humidity.

Insurance problems among inflammatory bowel disease patients: results of a Dutch population based study.

BACKGROUND AND AIMS: The majority of patients with inflammatory bowel disease (IBD) have a normal life expectancy and therefore should not be weighted when applying for life assurance. There is scant literature on this topic. In this study our aim was to document and compare the incidence of difficulties in application for life and medical insurance in a population based cohort of IBD patients and matched population controls. METHODS: A population based case control study of 1126 IBD patients and 1723 controls. Based on a detailed questionnaire, the frequency and type of difficulties encountered when applying for life and medical insurance in matched IBD and control populations were appraised. RESULTS: In comparison with controls, IBD patients had an 87-fold increased risk of encountering difficulties when applying for life assurance (odds ratio (OR) 87 (95% confidence interval (CI) 31-246)), with a heavily weighted premium being the most common problem. Patients of high educational status, with continuous disease activity, and who smoked had the highest odds of encountering such problems. Medical insurance difficulties were fivefold more common in IBD patients compared with controls (OR 5.4 (95% CI 2.3-13)) although no specific disease or patient characteristics were identified as associated with such difficulties. CONCLUSIONS: This is the first detailed case control study that has investigated insurance difficulties among IBD patients. Acquiring life and medical insurance constituted a major problem for IBD patients in this study. These results are likely to be more widely representative given that most insurance companies use international guidelines for risk assessment. In view of the recent advances in therapy and promising survival data on IBD patients, evidence based guidelines for risk assessment of IBD patients by insurance companies should be drawn up to prevent possible discriminatory practices.

The development of postthrombotic syndrome in relationship to venous reflux and calf muscle pump dysfunction at 2 years after the onset of deep venous thrombosis.

OBJECTIVE: Postthrombotic syndrome (PTS) develops in 40% to 60% of patients with deep venous thrombosis. Factors that are important in the development of PTS include venous reflux, deep vein obstruction, and calf muscle pump dysfunction (CMD). METHODS: Reflux and CMD in relationship to the severity of PTS were evaluated in a 2-year follow-up study of patients with acute deep venous thrombosis. Duplex scanning was used to measure reflux. The supine venous pump function test (SVPT) measures CMD with strain-gauge plethysmography. The base-line examination was performed within 1 to 5 days after diagnosis. The next examinations were scheduled at 3, 6, 12, and 24 months. RESULTS: The study included 86 legs, and the 2-year follow-up period was completed for 70 legs. Significantly more reflux was found in previously thrombosed vein segments, with an odds ratio of 1.8 after 3 months, of 2.1 after 6 months, of 2.5 after 12 months, and of 3.2 after 24 months. Multiple regression results showed that the most important risk factor for early clinical signs of PTS was superficial reflux in months 3, 6, and 12 (P < or =.02). Deep reflux did not have a synergistic relationship with superficial reflux in correlation with the clinical signs of PTS. The SVPT was not able to predict the development of PTS. CONCLUSION: More reflux develops in previously thrombosed vein segments. As early as after the third month, patients with superficial reflux have an increased risk of development of the first clinical signs of PTS. Within 2 years, the SVPT shows no relationship with clinical signs of PTS.

Multicentre, randomised controlled trial of four-layer bandaging versus short-stretch bandaging in the treatment of venous leg ulcers.

BACKGROUND: Aim of the study was to compare the healing rates of venous ulcers obtained with four-layer bandages (4LB) versus short stretch bandages (SSB). DESIGN: Multicentre, randomised controlled trial performed in 5 centres of the Netherlands and in 2 centres in Austria ("PADS-study" = Profore Austrian Dutch Study). PATIENTS AND METHODS: 112 patients (53 treated with 4LB and 59 treated with SSB) completed at least one post-treatment follow-up, 90 completed the study. Bandaging and ulcer assessment was performed at weekly intervals. Randomisation was carried out for each centre and was stratified according to the size (more or less than 10 cm2) of the ulcerated area. Local therapy consisted of plain absorbing, non-adherent dressings. Time to complete healing was recorded up to a maximum of 16 weeks. The two treatment-groups were comparable regarding their baseline-characteristics. RESULTS: In total 33/53 (62%) of ulcer-patients were healed in the 4LB group, compared with 43/59 (73%) in the SSB group (difference 11%, 95% CI -28% to 7%). 77% of the ulcers with an initial area less than 5 cm2 healed as compared with 33% of the larger ulcers. The different healing rates in the centres could be explained by the different sizes of the treated ulcers. Based on Kaplan-Meier estimates the median healing time was 57 days for the 4LB (95% CI 47-85 days) and 63 days for the SSB (95% CI 43-70 days). CONCLUSION: The ulcer healing rate and the median healing time did not differ among the two types of bandages. The main discriminant criterion for healing was the initial ulcer size. In centres who are experienced users of short-stretch bandages, no statistically significant different healing rates of venous ulcers could be found after 4LB or SSB.