FORMULATION AND CHARECTERISATION OF COLON TARGETED pH DEPENDENT MICROSPHERES OF CAPECITABINE FOR COLORECTAL CANCER

The aim of the present work was to prepare the colon-targeting microspheres of capecitabine (CPB) for the treatment of colorectal cancer to reduce dosing frequency and improve patient compliance. PH-sensitive polymer Eudragit L100, S100 separately and in combination (1:2) was used to formulate the microspheres by emulsion solvent diffusion technique using varying drug – polymer ratios (1:2 to 1:6). Microspheres were evaluated for particle size, shape, flow properties, surface morphology by scanning electron microscopy, yield, drug content, and in vitro drug release behavior and found to be significantly affected by polymer concentration. The formulated microspheres were discrete, spherical with relatively smooth surface, and with good flow properties. CPB-loaded microspheres demonstrated good entrapment efficiency (53.28 to 93.76%). The release study was done in simulated gastrointestinal fluids for 2 hrs in SGF (pH 1.2), for 3 hrs in SIF (pH 6.8) and up to 24 hrs in SCF (pH 7.4) and have shown that the drug was protected from being released in the physiological environment of the stomach and small intestine and efficiently released in colon (99.39%). Formulation ELS2 gave the best result among all formulations (1.59% release at end of 2 hrs, 19.24% at the end of 5 hr, and 99.39% at the end of the study). It is concluded from the present study that pH sensitive Eudragit microspheres are promising carriers for oral colon-targeted delivery of CPB for colorectal cancer. Key Words: Capecitabine, Eudragit L-100, Eudragit S-100, microspheres, pH sensitive, colon targeting, colorectal cancer

Configuration of anchorage holes affects fixation of the acetabular component in cemented total hip replacement - a finite element study

Our survey of current practice among UK orthopaedic surgeons shows wide variations in fixation techniques. The aim of this study is to investigate the effect of drilling different configurations of anchorage holes in the acetabulum on implant stability. To avoid variables that could incur during in-vitro testing, we used commercially-available COSMOS finite element analysis package to investigate the stress distributions, deformations, and strains on the cement mantle when drilling three large anchorage holes and six smaller ones, with straight and rounded cement pegs. The results, which are in line with our in-vitro studies on simulated reconstructed acetabulae, indicate better stability of the acetabular component when three larger holes than six smaller holes are drilled and when the necks of the anchorage holes are rounded. The longevity of total hip replacements could be improved by drilling three large anchorage holes, rather than many smaller ones, as initially proposed by Charnley

Dynamic in vitro measurement of patellar movement after total knee arthroplasty: an in vitro study

BACKGROUND: Changing the kinematic behaviour of patellar movement could be one of the reasons for anterior knee pain after implantation of a total knee arthroplasty (TKA). The aim of the current study was to measure the potential influence on patellar kinematics of patellar resurfacing during TKA. METHODS: Patellar movement before and after TKA with and without patellar resurfacing was measured under dynamic conditions in an in vitro cadaver simulation. Physiologic Musculus quadriceps forces were applied to five physiologic human knee specimens undergoing simulated isokinetic extension motions, patellar movement was measured using an ultrasonic measurement system. Thereafter, the Interax(® )I.S.A.-prosthesis system was implanted without and with resurfacing the patella, and patellar movement was again measured. RESULTS: The physiologic patella center moved on a semilunar path up to 6.4 mm (SD 6.4 mm) medially during extension. After TKA, the unresurfaced patella showed significantly less medial translation (p = 0.04) than the resurfaced patella. Subsequent resurfacing of the patella then resulted in a return to mediolateral positioning of the patella similar to the physiological case, whereas the resurfaced patella tilted up to twice as much as physiologic. CONCLUSION: The results of this study suggest that resurfacing of the patella during TKA can result in a restoration of the physiologic mediolateral shift of the patellofemoral joint while angulation of the patella remains unphysiologic

Clinical outcomes after anterior cruciate ligament injury: panther symposium ACL injury clinical outcomes consensus group

© 2020, The Author(s). Purpose: A stringent outcome assessment is a key aspect for establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. The aim of this consensus statement was to establish what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used and at what follow-up time those outcomes should be assessed. Methods: To establish a standardized approach to assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, PA; USA, in June 2019. The group reached consensus on nine statements by using a modified Delphi method. Results: In general, outcomes after ACL treatment can be divided into four robust categories—early adverse events, patient-reported outcomes, ACL graft failure/recurrent ligament disruption and clinical measures of knee function and structure. A comprehensive assessment following ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained re-injuries, validated knee-specific PROs and Health-Related Quality of Life questionnaires. In the mid- to long-term follow-up, the presence of osteoarthritis should be evaluated. Conclusion: This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment. Level of evidence: V

Less Anterior Knee Pain with a Mobile-bearing Prosthesis Compared with a Fixed-bearing Prosthesis

Anterior knee pain is one of the major short-term complaints after TKA. Since the introduction of the mobile-bearing TKA, numerous studies have attempted to confirm the theoretical advantages of a mobile-bearing TKA over a fixed-bearing TKA but most show little or no actual benefits. The concept of self-alignment for the mobile bearing suggests the posterior-stabilized mobile-bearing TKA would provide a lower incidence of anterior knee pain compared with a fixed-bearing TKA. We therefore asked whether the posterior-stabilized mobile-bearing knee would in fact reduce anterior knee pain. We randomized 103 patients scheduled for cemented three-component TKA for osteoarthrosis in a prospective, double-blind clinical trial. With a 1-year followup, more patients experienced persistent anterior knee pain in the posterior-stabilized fixed-bearing group (10 of 53, 18.9%) than in the posterior-stabilized mobile-bearing group (two of 47, 4.3%). No differences were observed for range of motion, visual analog scale for pain, Oxford 12-item questionnaire, SF-36, or the American Knee Society score. The posterior-stabilized mobile-bearing knee therefore seems to provide a short-term advantage compared with the posterior-stabilized fixed-bearing knee

Theoretical framework and methodological development of common subjective health outcome measures in osteoarthritis: a critical review

Subjective measures involving clinician ratings or patient self-assessments have become recognised as an important tool for the assessment of health outcome. The value of a health outcome measure is usually assessed by a psychometric evaluation of its reliability, validity and responsiveness. However, psychometric testing involves an accumulation of evidence and has recognised limitations. It has been suggested that an evaluation of how well a measure has been developed would be a useful additional criteria in assessing the value of a measure. This paper explored the theoretical background and methodological development of subjective health status measures commonly used in osteoarthritis research. Fourteen subjective health outcome measures commonly used in osteoarthritis research were examined. Each measure was explored on the basis of their i) theoretical framework (was there a definition of what was being assessed and was it part of a theoretical model?) and ii) methodological development (what was the scaling strategy, how were the items generated and reduced, what was the response format and what was the scoring method?). Only the AIMS, SF-36 and WHOQOL defined what they were assessing (i.e. the construct of interest) and no measure assessed was part of a theoretical model. None of the clinician report measures appeared to have implemented a scaling procedure or described the rationale for the items selected or scoring system. Of the patient self-report measures, the AIMS, MPQ, OXFORD, SF-36, WHOQOL and WOMAC appeared to follow a standard psychometric scaling method. The DRP and EuroQol used alternative scaling methods. The review highlighted the general lack of theoretical framework for both clinician report and patient self-report measures. This review also drew attention to the wide variation in the methodological development of commonly used measures in OA. While, in general the patient self-report measures had good methodological development, the clinician report measures appeared less well developed. It would be of value if new measures defined the construct of interest and, that the construct, be part of theoretical model. By ensuring measures are both theoretically and empirically valid then improvements in subjective health outcome measures should be possible

Influence of surgical approach on component positioning in primary total hip arthroplasty

Background: Minimal invasive surgery (MIS) has gained growing popularity in total hip arthroplasty (THA) but concerns exist regarding component malpositioning. The aim of the present study was to evaluate femoral and acetabular component positioning in primary cementless THA comparing a lateral to a MIS anterolateral approach. Methods: We evaluated 6 week postoperative radiographs of 52 hips with a minimal invasive anterolateral approach compared to 54 hips with a standard lateral approach. All hips had received the same type of implant for primary cementless unilateral THA and had a healthy hip contralaterally. Results: Hip offset was equally restored comparing both approaches. No influence of the approach was observed with regard to reconstruction of acetabular offset, femoral offset, vertical placement of the center of rotation, stem alignment and leg length discrepancy. However, with the MIS approach, a significantly higher percentage of cups (38.5 %) was malpositioned compared to the standard approach (16.7 %) (p = 0.022). Conclusions: The MIS anterolateral approach allows for comparable reconstruction of stem position, offset and center of rotation compared to the lateral approach. However, surgeons must be aware of a higher risk of cup malpositioning for inclination and anteversion using the MIS anterolateral approach