Patterns of risk of cancer in patients with metal-on-metal hip replacements versus other bearing surface types: a record linkage study between a prospective joint registry and general practice electronic health records in England.

BACKGROUND: There are concerns that metal-on-metal hip implants may cause cancer. The objective of this study was to evaluate patterns and timing of risk of cancer in patients with metal-on-metal total hip replacements (THR). METHODS: In a linkage study between the English National Joint Registry (NJR) and the Clinical Practice Research Datalink (CPRD), we selected all THR surgeries (NJR) between 2003 and 2010 (n = 11,540). THR patients were stratified by type of bearing surface. Patients were followed up for cancer and Poisson regression was used to derive adjusted relative rates (RR). RESULTS: The risk of cancer was similar in patients with hip resurfacing (RR 0.69; 95% Confidence Interval [CI] 0.39–1.22) or other types of bearing surfaces (RR 0.96; 95% CI 0.64–1.43) compared to individuals with stemmed metal-on-metal THR. The pattern of cancer risk over time did not support a detrimental effect of metal hip implants. There was substantial confounding: patients with metal-on-metal THRs used fewer drugs and had less comorbidity. CONCLUSIONS: Metal-on-metal THRs were not associated with an increased risk of cancer. There were substantial baseline differences between the different hip implants, indicating possibility of confounding in the comparisons between different types of THR implants

Severity of Diabetes Mellitus and Total Hip or Knee Replacement: A Population-Based Case-Control Study

Contains fulltext : 171491.pdf (publisher's version ) (Open Access)It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.A population-based case-control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78-0.94)) and THR (OR = 0.90 (95% CI = 0.82-0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes

Вплив глобалізації на модифікацію стратегії соціально-економічного розвитку Бразилії

У статті розкрито характер та напрями модифікації національної стратегії розвитку Бразилії, яка зазнала значних змін унаслідок посилення глобалізації світового господарства. Значну увагу приділено дослідженню особливостей і результатів економічних реформ, які були впроваджені Бразилією з метою побудови ефективної соціально-економічної системи.В статье раскрываются характер и направления модификации национальной стратегии развития Бразилии, которая претерпела значительные изменения вследствие усиления глобализации мирового хозяйства. Значительное внимание уделяется исследованию особенностей и результатов экономических реформ, которые были осуществлены Бразилией с целью построения эффективной социально-экономической системы.This article focuses on the nature and direction of modification of the national strategy of Brazil, which has undergone significant changes due to increasing globalization of world economy. Special attention is paid to analysis of peculiarities and results of economic reforms that were implemented in order to build effective social and economic systems of Brazil

Orthopedic surgery increases atherosclerotic lesions and necrotic core area in ApoE-/- mice

Background and aims Observational studies show a peak incidence of cardiovascular events after major surgery. For example, the risk of myocardial infarction increases 25-fold early after hip replacement. The acuteness of this increased risk suggests abrupt enhancement in plaque vulnerability, which may be related to intra-plaque inflammation, thinner fibrous cap and/or necrotic core expansion. We hypothesized that acute systemic inflammation following major orthopedic surgery induces such changes. Methods ApoE−/− mice were fed a western diet for 10 weeks. Thereafter, half the mice underwent mid-shaft femur osteotomy followed by realignment with an intramedullary K-wire, to mimic major orthopedic surgery. Mice were sacrificed 5 or 15 days post-surgery (n = 22) or post-saline injection (n = 13). Serum amyloid A (SAA) was measured as a marker of systemic inflammation. Paraffin embedded slides of the aortic root were stained to measure total plaque area and to quantify fibrosis, calcification, necrotic core, and inflammatory cells. Results Surgery mice showed a pronounced elevation of serum amyloid A (SAA) and developed increased plaque and necrotic core area already at 5 days, which reached significance at 15 days (p = 0.019; p = 0.004 for plaque and necrotic core, respectively). Macrophage and lymphocyte density significantly decreased in the surgery group compared to the control group at 15 days (p = 0.037; p = 0.024, respectively). The density of neutrophils and mast cells remained unchanged. Conclusions Major orthopedic surgery in ApoE−/− mice triggers a systemic inflammatory response. Atherosclerotic plaque area is enlarged after surgery mainly due to an increase of the necrotic core. The role of intra-plaque inflammation in this response to surgical injury remains to be fully elucidated. © 2016 Elsevier Ireland Lt

Busulfan exposure associated with event-free survival in children after allogeneic haematopoietic stem cell transplantation: A retrospective multicenter cohort study

Busulfan exposure associated with event-free survival in children after allogeneic haematopoietic stem cell transplantation: A retrospective multicenter cohort study OBJECTIVE To determine the relationship between busulfan cumulative area under the curve (AUC] and event-free survival lEFS] in children undergoing allogeneic haematopoietic stem cell transplantation (alloHCT). DESIGN Retrospective, multicenter cohort study. METHODS Children who underwent alloHCT in 15 different centres worldwide were included in this study (2000-20131. Participants had to be on intravenous busulfan and pharmacokinetic samples had to be available. Exposure of interest was the cumulative AUC of busulfan, and primary outcome was EFS (time to graft failure, relapse or all-cause mortality). Cox regression models were used to derive relative risks (RR), and the optimal busulfan AUC level was estimated using propensity adjusted Weibull models. RESULTS A total of 674 subjects (41[%] malignant, 59[%] non- malignant) with a median age of 4.5 years (interquartile range 1.4-10.7 years) were included in the analysis. We observed a significant U-shaped relationship between busulfan cumulative AUC and EFS (P = 0.011). The optimal target was estimated at 90 mgh/L (78-101 mgh/L), and was independent of any of the investigated patient characteristics. An AUC below the target increased the risk of graft failure and relapse (relative risk 1.75, P = 0.004), while transplant-related mortality was more pronounced when the AUC was too high (relative risk 2.99, P <0.0011. CONCLUSION This is the largest study on the relationship between busulfan and clinical outcomes in children undergoing alloHCT. Our results strongly advocate the use of therapeutic drug monitoring of busulfan, using 90 mg-h/L (78-101 mg h/L) as a target

Severity of Diabetes Mellitus and Total Hip or Knee Replacement

Permissions RESEARCH ARTICLE: OBSERVATIONAL STUDY Severity of Diabetes Mellitus and Total Hip or Knee Replacement A Population-Based Case–Control Study Nielen, Johannes T.H. MSc; Emans, Pieter J. PhD; Dagnelie, Pieter C. PhD; Boonen, Annelies PhD; Lalmohamed, Arief PhD; de Boer, Anthonius PhD; van den Bemt, Bart J.F. PhD; de Vries, Frank PhD Editor(s): Roever., Leonardo Author Information Medicine 95(20):p e3739, May 2016. | DOI: 10.1097/MD.0000000000003739 OPEN SDC Metrics Abstract It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality. To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity. A population-based case–control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity. Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78–0.94)) and THR (OR = 0.90 (95% CI = 0.82–0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c. This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes

Melting of 2D liquid crystal colloidal structure

Using video microscopy, we investigated melting of a two-dimensional colloidal system, formed by glycerol droplets at the free surface of a nematic liquid crystalline layer. Analyzing different structure correlation functions, we conclude that melting occurs through an intermediate hexatic phase, as predicted by the Kosterlitz-Thouless-Halperin-Nelson-Young(KTHNY) theory. However, the temperature range of the intermediate phase is rather narrow, <1°C, and the characteristic critical power law decays of the correlation functions are not fully developed. We conclude that the melting of our 2D systems qualitatively occurs according to KTHNY, although quantitative details of the transition scenario may partly depend on the details of interparticle interaction

Use of glitazones and the risk of elective HIP or knee replacement: A population based case-control study

Background: Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, to date, no disease modifying drug exists for this disease. In vivo studies have shown that glitazones may be used as anti-arthritic drugs. (Kobayashi, 2005; Boileau, 2007). Objectives: To determine the risk of total joint replacement (TJR) with the use of glitazones. Methods: A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n=94,609) were defined as patients >18 years of age who had undergone TJR surgery between 2000 and 2012. Controls were matched by age, gender and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) associated with use of glitazones. We additionally evaluated risk of TJR in current glitazone users compared to DM patients using other antidiabetic drugs (ADs). In order to determine a dose effect relationship, we also stratified glitazone users by total number of prescriptions prior to surgery. Results: There is no difference in risk of TKR (OR=1.11 (95% CI=0.95-1.29)) or THR (OR=0.87 (95% CI=0.74-1.02)) between glitazone users and patients not using glitazones. Furthermore, there is no difference in risk of TKR (OR=1.03 (95% CI=0.88-1.22)) and THR (OR=0.90 (95% CI=0.75-1.08)) when glitazones users are compared to other AD users. Finally, we did not find a dose response effect with increasing number of prescriptions. Conclusions: This study did not find any evidence for an anti-arthritic effect of glitazones