The Dutch version of the knee injury and osteoarthritis outcome score: A validation study

BACKGROUND: The Knee Injury and Osteoarthritis Outcome Score (KOOS) was constructed in Sweden. This questionnaire has proved to be valid for several orthopedic interventions of the knee. It has been formally translated and validated in several languages, but not yet in Dutch. The purpose of the present study was to evaluate the clinimetric properties of the Dutch version of the KOOS questionnaire in knee patients with various stages of osteoarthritis (OA). METHODS: The Swedish version of the KOOS questionnaire was first translated into Dutch according to a standardized procedure and second tested for clinimetric quality. The study population consisted of patients with different stages of OA (mild, moderate and severe) and of patients after primary TKA, and after a revision of the TKA. All patients filled in the Dutch KOOS questionnaire, as well as the SF-36 and a Visual Analogue Scale for pain. The following analyses were performed to evaluate the clinimetric quality of the KOOS: Cronbach's alpha (internal consistency), principal component analyses (factor analysis), intraclass correlation coefficients (reliability), spearman's correlation coefficient (construct validity), and floor and ceiling effects. RESULTS: For all patients groups Cronbach's alpha was for all subscales above 0.70. The ICCs, assessed for the patient groups with mild and moderate OA and after revision of the TKA patients, were above 0.70 for all subscales. Of the predefined hypotheses 60% or more could be confirmed for the patients with mild and moderate OA and for the TKA patients. For the other patient groups less than 45% could be confirmed. Ceiling effects were present in the mild OA group for the subscales Pain, Symptoms and ADL and for the subscale Sport/Recreation in the severe OA group. Floor effects were found for the subscales Sport/Recreation and Qol in the severe OA and revision TKA groups. CONCLUSION: Based on these different clinimetric properties within the present study we conclude that the KOOS questionnaire seems to be suitable for patients with mild and moderate OA and for patients with a primary TKA. The Dutch version of the KOOS had a lower construct validity for patients with severe OA on a waiting list for TKA and patients after revision of a TKA. Further validation studies on the Dutch version of the KOOS should also include a knee specific questionnaire for assessing the construct validity

Functional capacity and actual daily activity do not contribute to patient satisfaction after total knee arthroplasty

<p>Abstract</p> <p>Background</p> <p>After total knee arthroplasty (TKA) only 75-89% of patients are satisfied. Because patient satisfaction is a prime goal of all orthopaedic procedures, optimization of patient satisfaction is of major importance. Factors related to patient satisfaction after TKA have been explored, but no studies have included two potentially relevant factors, i.e. the functional capacity of daily activities and actual daily activity. This present prospective study examines whether functional capacity and actual daily activity (in addition to an extensive set of potential factors) contribute to patient satisfaction six months after TKA.</p> <p>Methods</p> <p>A total of 44 patients were extensively examined preoperatively and six months post surgery. Functional capacity was measured with three capacity tests, focusing on walking, stair climbing, and chair rising. Actual daily activity was measured in the patient's home situation by means of a 48-hour measurement with an Activity Monitor. To establish which factors were related to patient satisfaction six months post surgery, logistic regression analyses were used to calculate odds ratios.</p> <p>Results</p> <p>Preoperative and postoperative functional capacity and actual daily activity had no relation with patient satisfaction. Preoperatively, only self-reported mental functioning was positively related to patient satisfaction. Postoperatively, based on multivariate analysis, only fulfilled expectations regarding pain and experienced pain six months post surgery were related to patient satisfaction.</p> <p>Conclusions</p> <p>Functional capacity and actual daily activity do not contribute to patient satisfaction after TKA. Patients with a better preoperative self-reported mental functioning, and patients who experienced less pain and had fulfilled expectations regarding pain postoperatively, were more often satisfied.</p

Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

Hybrid Equation/Agent-Based Model of Ischemia-Induced Hyperemia and Pressure Ulcer Formation Predicts Greater Propensity to Ulcerate in Subjects with Spinal Cord Injury

Pressure ulcers are costly and life-threatening complications for people with spinal cord injury (SCI). People with SCI also exhibit differential blood flow properties in non-ulcerated skin. We hypothesized that a computer simulation of the pressure ulcer formation process, informed by data regarding skin blood flow and reactive hyperemia in response to pressure, could provide insights into the pathogenesis and effective treatment of post-SCI pressure ulcers. Agent-Based Models (ABM) are useful in settings such as pressure ulcers, in which spatial realism is important. Ordinary Differential Equation-based (ODE) models are useful when modeling physiological phenomena such as reactive hyperemia. Accordingly, we constructed a hybrid model that combines ODEs related to blood flow along with an ABM of skin injury, inflammation, and ulcer formation. The relationship between pressure and the course of ulcer formation, as well as several other important characteristic patterns of pressure ulcer formation, was demonstrated in this model. The ODE portion of this model was calibrated to data related to blood flow following experimental pressure responses in non-injured human subjects or to data from people with SCI. This model predicted a higher propensity to form ulcers in response to pressure in people with SCI vs. non-injured control subjects, and thus may serve as novel diagnostic platform for post-SCI ulcer formation. © 2013 Solovyev et al

Half-metallic ferrimagnetism in the [Sc1−x_{1-x}Vx_x]C and [Sc1−x_{1-x} Vx_x]Si alloys adopting the zinc-blende and wurtzite structures from first-principles

Employing first-principles calculations we study the structural, electronic and magnetic properties of the [Sc$_{1-x}$V$_x$]C and [Sc$_{1-x}$V$_x$]Si alloys. In their equilibrium rocksalt structure all alloys are non-magnetic. The zincblende and wurtzite structures are degenerated with respect to the total energy. For all concentrations the alloys in these lattice structures are half-metallic with the gap located in the spin-down band. The total spin moment follows the Slater-Pauling behavior varying linearly between the -1 $\mu_B$ of the perfect ScC and ScSi alloys and the +1 $\mu_B$ of the perfect VC and VSi alloys. For the intermediate concentrations V and Sc atoms have antiparallel spin magnetic moments and the compounds are half-metallic ferrimagnets. At the critical concentration, both [Sc$_{0.5}$V$_{0.5}$]C and [Sc$_{0.5}$V$_{0.5}$]Si alloys present zero total spin-magnetic moment but the C-based alloy shows a semiconducting behavior contrary to the Si-based alloys which is a half-metallic antiferromagnet

Neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal cancer:a feasibility and safety study

BACKGROUND: Standard treatment for colorectal peritoneal carcinomatosis typically involves cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and if possible, postoperative adjuvant chemotherapy. However, a substantial percentage of patients never receive adjuvant chemotherapy because of postoperative complications. Neoadjuvant chemotherapy could be beneficial in this setting, so we assessed its feasibility and safety when used before cytoreductive surgery and HIPEC. METHODS: In this non-randomized, single-center, observational feasibility study, patients were scheduled to receive six cycles of capecitabine and oxaliplatin before cytoreductive surgery and HIPEC. Computed tomography was performed after the third and sixth chemotherapy cycles to evaluate tumor response, and patients underwent cytoreductive surgery and HIPEC if there were no pulmonary and/or hepatic metastases. Postoperative complications, graded according to the Clavien-Dindo classification, were compared with those of a historic control group that received postoperative adjuvant chemotherapy. RESULTS: Of the 14 patients included in the study, 4 and 3 had to terminate neoadjuvant chemotherapy early because of toxicity and tumor progression, respectively. Cytoreductive surgery and HIPEC were performed in eight patients, and the timing and severity of complications were comparable to those of patients in the historic control group treated without neoadjuvant chemotherapy. CONCLUSION: Patients with peritoneal metastases due to colorectal carcinoma can be treated safely with neoadjuvant chemotherapy before definitive therapy with cytoreductive surgery and HIPEC. TRIAL REGISTRATION NUMBER: NTR 3905, registered on 20th march, 2013, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=3905

The intellectual influence of economic journals: quality versus quantity

The evaluation of scientific output has a key role in the allocation of research funds and academic positions. Decisions are often based on quality indicators for academic journals, and over the years, a handful of scoring methods have been proposed for this purpose. Discussing the most prominent methods (de facto standards) we show that they do not distinguish quality from quantity at article level. The systematic bias we find is analytically tractable and implies that the methods are manipulable. We introduce modified methods that correct for this bias, and use them to provide rankings of economic journals. Our methodology is transparent; our results are replicable

In silico assessment of potential druggable pockets on the surface of α1-Antitrypsin conformers

The search for druggable pockets on the surface of a protein is often performed on a single conformer, treated as a rigid body. Transient druggable pockets may be missed in this approach. Here, we describe a methodology for systematic in silico analysis of surface clefts across multiple conformers of the metastable protein α1-antitrypsin (A1AT). Pathological mutations disturb the conformational landscape of A1AT, triggering polymerisation that leads to emphysema and hepatic cirrhosis. Computational screens for small molecule inhibitors of polymerisation have generally focused on one major druggable site visible in all crystal structures of native A1AT. In an alternative approach, we scan all surface clefts observed in crystal structures of A1AT and in 100 computationally produced conformers, mimicking the native solution ensemble. We assess the persistence, variability and druggability of these pockets. Finally, we employ molecular docking using publicly available libraries of small molecules to explore scaffold preferences for each site. Our approach identifies a number of novel target sites for drug design. In particular one transient site shows favourable characteristics for druggability due to high enclosure and hydrophobicity. Hits against this and other druggable sites achieve docking scores corresponding to a Kd in the µM–nM range, comparing favourably with a recently identified promising lead. Preliminary ThermoFluor studies support the docking predictions. In conclusion, our strategy shows considerable promise compared with the conventional single pocket/single conformer approach to in silico screening. Our best-scoring ligands warrant further experimental investigation

RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design

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Effect of corticosteroid injection for trochanter pain syndrome: design of a randomised clinical trial in general practice

Background. Regional pain in the hip in adults is a common cause of a general practitioner visit. A considerable part of patients suffer from (greater) trochanteric pain syndrome or trochanteric bursitis. Local corticosteroid injections is one of the treatment options. Although clear evidence is lacking, small observational studies suggest that this treatment is effective in the short-term follow-up. So far, there are no randomised controlled trials available evaluating the efficacy of injection therapy. This study will investigate the efficacy of local corticosteroid injections in the trochanter syndrome in the general practice, using a randomised controlled trial design. The cost effectiveness of the corticosteroid injectio