Autologous Mesenchymal Stromal Cells Immobilized in Plasma-Based Hydrogel for the Repair of Articular Cartilage Defects in a Large Animal Model.

The treatment of cartilage defects in trauma injuries and degenerative diseases represents a challenge for orthopedists. Advanced mesenchymal stromal cell (MSC)-based therapies are currently of interest for the repair of damaged cartilage. However, an approved system for MSC delivery and maintenance in the defect is still missing. This study aimed to evaluate the effect of autologous porcine bone marrow MSCs anchored in a commercially available polyglycolic acid-hyaluronan scaffold (Chondrotissue®) using autologous blood plasma-based hydrogel in the repair of osteochondral defects in a large animal model. The osteochondral defects were induced in twenty-four minipigs with terminated skeletal growth. Eight animals were left untreated, eight were treated with Chondrotissue® and eight received Chondrotissue® loaded with MSCs. The animals were terminated 90 days after surgery. Macroscopically, the untreated defects were filled with newly formed tissue to a greater extent than in the other groups. The histological evaluations showed that the defects treated with Chondrotissue® and Chondrotissue® loaded with pBMSCs contained a higher amount of hyaline cartilage and a lower amount of connective tissue, while untreated defects contained a higher amount of connective tissue and a lower amount of hyaline cartilage. In addition, undifferentiated connective tissue was observed at the edges of defects receiving Chondrotissue® loaded with MSCs, which may indicate the extracellular matrix production by transplanted MSCs. The immunological analysis of the blood samples revealed no immune response activation by MSCs application. This study demonstrated the successful and safe immobilization of MSCs in commercially available scaffolds and defect sites for cartilage defect repair.

Experimental surgery as part of the development of degradable biomaterials for cardiovascular surgery

Introduction: Cardiovascular diseases are responsible for significant morbidity and mortality in the population. Artificial vascular grafts are often essential for surgical procedures in radical or palliative treatment. Many new biodegradable materials are currently under development. Preclinical testing of each new material is imperative, both in vitro and in vivo, and therefore animal experiments are still a necessary part of the testing process before any clinical use. The aim of this paper is to present the options of using various experimental animal models in the field of cardiovascular surgery including their extrapolation to clinical medicine. Methods: The authors present their general experience in the field of experimental surgery. They discuss the selection process of an optimal experimental animal model to test foreign materials for cardiovascular surgery and of an optimal region for implantation. Results: The authors present rat, rabbit and porcine models as optimal experimental animals for material hemocompatibility and degradability testing. Intraperitoneal implantation in the rat is a simple and feasible procedure, as well as aortic banding in the rabbit or pig. The carotid arteries can also be used, as well. Porcine pulmonary artery banding is slightly more difficult with potential complications. The banded vessels, explanted after a defined time period, are suitable for further mechanical testing using biomechanical analyses, for example, the inflation-extension test. Conclusion: An in vivo experiment cannot be avoided in the last phases of preclinical research of new materials. However, we try to strictly observe the 3R concept ­ Replacement, Reduction and Refinement; in line with this concept, the potential of each animal should be used as much as possible to reduce the number of animals.

Hyperbaric oxygen enhances collagen III formation in wound of ZDF rat.

Diabetic foot ulcer (DFU) is a serious complication of diabetes and hyperbaric oxygen therapy (HBOT) is also considered in comprehensive treatment. The evidence supporting the use of HBOT in DFU treatment is controversial. The aim of this work was to introduce a DFU model in ZDF rat by creating a wound on the back of an animal and to investigate the effect of HBOT on the defect by macroscopic evaluation, quantitative histological evaluation of collagen (types I and III), evaluation of angiogenesis and determination of interleukin 6 (IL6) levels in the plasma. The study included 10 rats in the control group (CONT) and 10 in the HBOT group, who underwent HBOT in standard clinical regimen. Histological evaluation was performed on the 18th day after induction of defect. The results show that HBOT did not affect the macroscopic size of the defect nor IL6 plasma levels. A volume fraction of type I collagen was slightly increased by HBOT without reaching statistical significance (1.35+/-0.49 and 1.94+/-0.67 %, CONT and HBOT, respectively). In contrast, the collagen type III volume fraction was ~120 % higher in HBOT wounds (1.41+/-0.81 %) than in CONT ones (0.63+/-0.37 %; p=0.046). In addition, the ratio of the volume fraction of both collagens in the wound ((I+III)w) to the volume fraction of both collagens in the adjacent healthy skin ((I+III)h) was ~65 % higher in rats subjected to HBOT (8.9+/-3.07 vs. 5.38+/-1.86 %, HBOT and CONT, respectively; p=0.028). Vessels density (number per 1 mm2) was found to be higher in CONT vs. HBOT (206.5+/-41.8 and 124+/-28.2, respectively, p<0.001). Our study suggests that HBOT promotes collagen III formation and decreases the number of newly formed vessels at the early phases of healing.

A new foam-based method for the (bio)degradation of hydrocarbons in contaminated vadose zone.

An innovative foam-based method for Fenton reagents (FR) and bacteria delivery was assessed for the in situ remediation of a petroleum hydrocarbon-contaminated unsaturated zone. The surfactant foam was first injected, then reagent solutions were delivered and propagated through the network of foam lamellae with a piston-like effect. Bench-scale experiments demonstrated the feasibility of the various treatments with hydrocarbon (HC) removal efficiencies as high as 96 %. Compared to the direct injection of FR solutions, the foam-based method led to larger radii of influence and more isotropic reagents delivery, whereas it did not show any detrimental effect regarding HC oxidation. Despite 25 % of HCs were expelled from the treated zone because of high foam viscosity, average degradation rates were increased by 20 %. At field-scale, foam and reagent solutions injections in soil were tracked both using visual observation and differential electric resistivity tomography. The latter demonstrated the controlled delivery of the reactive solutions using the foam-based method. Even if the foam-based method duration is about 5-times longer than the direct injection of amendment solutions, it provides important benefits, such as the confinement of harmful volatile hydrocarbons during Fenton treatments, the enhanced reagents delivery and the 30 % lower consumption of the latter.

Management of seasonal influenza by family physicians.

INTRODUCTION: Seasonal influenza is responsible for approximately 2.5 million consultations with the family physician (FP) per year in France. We performed this study with FPs to assess whether their practice complied with French guidelines. MATERIAL AND METHOD: Descriptive survey carried out from June to August 2018 using a questionnaire sent electronically to 1,140 Alsatian FPs. RESULTS: A total of 121 FPs responded to the questionnaire (10.6%). The main clinical symptoms that FPs believed to be the most reliable to diagnose influenza were fever (95%) and arthromyalgia (76.9%), well ahead of cough (27.3%). Overall, 23.1% of FPs declared that they occasionally used microbiological confirmation; 80.2% of FPs performed hand hygiene once per consultation but 95.9% did not wear surgical masks when managing patients with influenza and only 53.7% wore them when they themselves presented with influenza-like symptoms. Hand sanitizers, masks, or tissues were made available to patients in 35.5%, 19.8%, and 30.6%, respectively. Overall, 77.7% of participating physicians were vaccinated against influenza. Influenza vaccination was widely offered to high-risk patients, but some groups were insufficiently vaccinated: obese patients (32.2%) and pregnant women (47.9%). Overall, 48.8% of physicians never prescribed oseltamivir at a curative dose and 72.7% never prescribed it at a preventive dose; 86.8% of physicians prescribed at least one non-recommended symptomatic treatment including an NSAID (24.8%) or aspirin (12.4%). CONCLUSION: This study revealed several mismatches with guidelines and suggested potential corrective actions.

Effectiveness of a community-based health programme on the blood pressure control, adherence and knowledge of adults with hypertension: A PRECEDE-PROCEED model approach.

AIMS AND OBJECTIVES: To determine the effectiveness of a community-based health programme grounded on the PRECEDE-PROCEED model, on the knowledge, adherence and blood pressure control of community-dwelling adults with hypertension. BACKGROUND: Hypertension has consistently been a leading cause of morbidity and mortality in different countries and has continuously increased in prevalence. Albeit manageable with lifestyle modification and anti-hypertensive medications, adequate knowledge and poor adherence to these treatment regimens are issues that have led to poor blood pressure control. DESIGN: Quasi-experimental, one-group pretest-post-test design. METHODS: The PRECEDE-PROCEED model was used to develop and evaluate the effectiveness of the community-based health programme. From August to October 2017, a total of 50 community-dwelling adults with hypertension participated in the programme which included blood pressure monitoring, targeted health educations, motivational interviews, individualised lifestyle modification plans and house-to-house visits. Knowledge, adherence and blood pressure were assessed at the start and at the end of the 2-month programme. Gathered data were analysed using descriptive statistics and RM-MANOVA. The TREND checklist was followed in reporting this study (See Appendix S1). RESULTS: After 2 months, the mean adherence, systolic blood pressure and diastolic blood pressure significantly improved, attributing more than 25% of the change. Although knowledge scores were significantly higher after the programme, it only accounted 9% of the improvement. CONCLUSION: This study provides evidence on the effectiveness of a community-based health programme grounded on the PRECEDE-PROCEED model on the knowledge, adherence and blood pressure control of community-dwelling adults with hypertension. RELEVANCE TO CLINICAL PRACTICE: The community-based health programme is beneficial to community-dwelling adults with hypertension in promoting knowledge and adherence to treatment regimen and improving BP control. This study also provides a framework for developing new or enhancing existing programmes on hypertension in the Philippines.

Analytical solution for bending vibration of a thin-walled cylinder rolling on a time-varying force.

This paper presents the analytical solution of radial vibration of a rolling cylinder submitted to a time-varying point force. In the simplest situation of simply supported edges and zero in-plane vibration, the cylinder is equivalent to an orthotropic pre-stressed plate resting on a visco-elastic foundation. We give the closed-form solution of vibration as a series of normal modes whose coefficients are explicitly calculated. Cases of both deterministic and random forces are examined. We analyse the effect of rolling speed on merging of vibrational energy induced by Doppler's effect for the example of rolling tyre.

[Biomechanical screening for injury prevention : The importance of 3D-motion analysis in high performance sports]. / Biomechanisches Screening zur Verletzungsprävention : Die Bedeutung der 3D-Bewegungsanalyse im Hochleistungssport.

Standardized clinical diagnostic procedures cannot assess the functionality of the anatomical structures in sport-specific movement. Biomechanical screening is able to detect deficits but is not sufficiently and objectively precise with the current clinical examination tools including conventional imaging techniques. The fields of use of functional testing methods are versatile and range from injury prevention analysis, screening during rehabilitation phases up to the return-to-play decision. Using simple musculoskeletal function analysis it is difficult to assess the risk of injuries. The main advantage of instrumented 3D-motion analysis is its potential to generate objective, reliable and reproducible data with exact joint angles, muscle activity, as well as loading inside the joints during movement. These marker-based motion analysis procedures are more time-consuming and more cost intensive and necessitate in particular biomechanical and medical knowledge to assess the analytical data in terms of clinical relevance. In the absence of scientific studies on biomechanical analyses in professional sports, this study shows preliminary approaches to this topic.

Veno-arterial extracorporeal membrane oxygenation in addition to primary PCI in patients presenting with ST-elevation myocardial infarction.

INTRODUCTION: Primary percutaneous coronary intervention (pPCI) in ST-elevation myocardial infarction (STEMI) can cause great haemodynamic instability. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) can provide haemodynamic support in patients with STEMI but data on outcome and complications are scarce. METHODS: An in-hospital registry was conducted enrolling all patients receiving VA-ECMO. Patients were analysed for medical history, mortality, neurological outcome, complications and coronary artery disease. RESULTS: Between 2011 and 2016, 12 patients underwent pPCI for STEMI and received VA-ECMO for haemodynamic support. The majority of the patients were male (10/12) with a median age of 63 (47-75) years and 4 of the 12 patients had a history of coronary artery disease. A cardiac arrest was witnessed in 11 patients. The left coronary artery was compromised in 8 patients and 4 had right coronary artery disease. All patients were in Killip class IV. Survival to discharge was 67% (8/12), 1­year survival was 42% (5/12), 2 patients have not yet reached the 1­year survival point but are still alive and 1 patient died within a year after discharge. All-cause mortality was 42% (5/12) of which mortality on ECMO was 33% (4/12). Patient-related complications occurred in 6 of the 12 patients: 1 patient suffered major neurological impairment, 2 patients suffered haemorrhage at the cannula site, 2 patients had limb ischaemia and 1 patient had a haemorrhage elsewhere. There were no VA-ECMO hardware malfunctions. CONCLUSION: VA-ECMO in pPCI for STEMI has a high survival rate and neurological outcome is good, even when the patient is admitted with a cardiac arrest.

The last frontier: transcatheter devices for percutaneous or minimally invasive treatment of chronic heart failure.

Heart failure has a high prevalence in the general population. Morbidity and mortality of heart failure patients remain high, despite improvements in drug therapy, implantable cardioverter-defibrillators and cardiac resynchronisation therapy. New transcatheter implantable devices have been developed to improve the treatment of heart failure. There has been a rapid development of minimally invasive or transcatheter devices used in the treatment of heart failure associated with aortic and mitral valve disease and these devices are being incorporated into routine clinical practice at a fast rate. Several other new transcatheter structural heart interventions for chronic heart failure aimed at a variety of pathophysiologic approaches are currently being developed. In this review, we focus on devices used in the treatment of chronic heart failure by means of left ventricular remodelling, left atrial pressure reduction, tricuspid regurgitation reduction and neuromodulation. The clinical evaluations of these devices are early-stage evaluations of initial feasibility and safety studies and additional clinical evidence needs to be gathered in appropriately designed clinical trials.

Perioperative management of antiplatelet treatment in patients undergoing isolated coronary artery bypass grafting in Dutch cardiothoracic centres.

BACKGROUND: International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG). METHODS: A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014. RESULTS: Eleven centres responded to the survey. Acetylsalicylic acid monotherapy was discontinued before surgery in 6 centres. In patients with an acute coronary syndrome receiving dual antiplatelet therapy (DAPT), most centres discontinued the P2Y12 inhibitor preoperatively. DAPT was restarted after surgery in 4 centres. However, 6 centres continued DAPT in patients who had undergone coronary stenting within one month of surgery. In patients with coronary stents, variation in the management of antiplatelet therapy increased in proportion to the interval between stenting and surgery. A total of 70 patients were included in the registry. Acetylsalicylic acid monotherapy was discontinued in 51% of patients and restarted in all patients. P2Y12 inhibitor treatment was discontinued before surgery in 70% of patients and re-initiated after CABG in 29%. CONCLUSIONS: Major differences were observed in the preoperative and postoperative management of antiplatelet treatment between different Dutch cardiothoracic centres and within a single centre. Part of this variation is probably due to lack of evidence and differences between the current guidelines; however, many of the strategies were not in accordance with any of these guidelines.

PABPN1 gene therapy for oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment.

Qigong in cancer care: a systematic review and construct analysis of effective Qigong therapy.

PURPOSE: This review (a) assesses the strength of evidence addressing Qigong therapy in supportive cancer care and (b) provides insights for definition of effective Qigong therapy in supportive cancer care. METHODS: This mixed-methods study includes (a) a systematic review of randomized clinical trials (RCTs) following PRISMA guidelines and (b) a constant-comparative qualitative analysis of effective intervention protocols. RESULTS: Eleven published randomized clinical trials were reviewed. A total of 831 individuals were studied. Geographic settings include the USA, Australia, China, Hong Kong, and Malaysia. Qigong therapy was found to have positive effects on the cancer-specific QOL, fatigue, immune function, and cortisol levels of individuals with cancer. Qigong therapy protocols varied supporting a plurality of styles. Qualitative analyses identified common programming constructs. Content constructs included exercise (gentle, integrated, repetitious, flowing, weight-bearing movements), breath regulation, mindfulness and meditation, energy cultivation including self-massage, and emphasis on relaxation. Logistic constructs included delivery by qualified instructors, home practice, and accommodation for impaired activity tolerance. CONCLUSIONS: There is global interest and a growing body of research providing evidence of therapeutic effect of Qigong therapy in supportive cancer care. While Qigong therapy protocols vary in style, construct commonalities do exist. Knowledge of the common constructs among effective programs revealed in this research may be used to guide future research intervention protocol and community programming design and development.

A Diabetes-specific Oral Nutritional Supplement Improves Glycaemic Control in Type 2 Diabetes Patients.

AIMS: Reducing the intake of low molecular weight carbohydrates with artificial nutrition may lower glycaemic response in patients with diabetes. We evaluated effects of a diabetes-specific carbohydrate modified oral nutritional supplement (ONS) during 12 weeks administration in 40 elderly type 2 normal weight patients with diabetes with previous involuntary weight loss. METHODS: Prospective, randomised, double-blind, controlled trial. Patients ingested 2×200 ml/day diabetes-specific or isocaloric standard ONS (control) in addition to their regular diet. Parameters of glucose and lipid metabolism, functional and nutritional status were assessed at baseline, weeks 6 and 12. RESULTS: Postprandial glucose incremental area under the curve (iAUC0-240 min) was comparable between treatment groups on day 1 (467.9±268.4 vs. 505.1±206.1 mmol/l*min, n.s. - arithmetic means±standard deviation) and was significantly lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (355.2±115.8 vs. 634.9±205.9 and 364.9±153.1 vs. 743.4±202.7; both P<0.0001). Postprandial peak glucose was significantly lower with the diabetes-specific ONS vs. controls in weeks 6 and 12 (P<0.0001) and the decrease in HbA1c, (baseline to week 12) was markedly pronounced (P=0.028). There were no differences between groups in insulin, HOMA-IR, lipid parameters, nutritional and performance status. Body weight and body mass index (BMI) increased significantly over time in both groups. CONCLUSIONS: Administration of a diabetes-specific ONS for 12 weeks reduced postprandial glycaemia after ingestion of the study treatment and improved long-term glycaemic control in elderly patients with type 2 diabetes and involuntary weight loss, thereby reducing their risk for diabetes-associated long-term complications.

[Asylum seekers and the healthcare situation]. / Asylbewerber und ihre Versorgungssituation.

Medical healthcare for refugees is strictly regulated by law in Germany but the great regional variation in the implementation is currently a huge challenge for healthcare providers. Providers are often not familiar with the specific local regulations and especially in emergencies it is often not possible to clarify open questions before treating patients. The high influx of refugees in the summer and fall of 2015 led to a situation that could only be managed with the voluntary and pragmatic help of all healthcare personnel involved. This article explains the most relevant regulations covering medical healthcare for refugees and asylum seekers. In addition, the procedure for the approval of asylum status in itself can have a direct or indirect impact on the health status of these individuals; therefore, some comments are made regarding this aspect.

NMR crystallography of monovalent cations in inorganic matrixes: Li(+) siting and the local structure of Li(+) sites in ferrierites.

(7)Li-(7)Li correlation MAS NMR spectroscopy, interpreted using periodic DFT including molecular dynamics conformational sampling of Li(+) sites, is employed to obtain the siting of Li(+) at exchangeable positions of ferrierites and the local structure of these Li(+) sites. The former is controlled by the Al siting in the zeolite framework.

The incidence of hepatocellular carcinoma is reduced in patients with chronic hepatitis B on long-term nucleos(t)ide analogue therapy.

BACKGROUND: North American data are lacking on the effect of nucleos(t)ide analogues (NA) in preventing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). AIM: To determine the incidence of HCC in NA-treated patients and compare this risk with that predicted without treatment based on the REACH-B model. METHODS: In this retrospective study, the incidence of HCC was determined in CHB patients initiated on NA from 1999 to 2012. Pre-treatment data utilised in the REACH-B model were used to predict the annual HCC risk. The standardised incidence ratio (SIR) for HCC was calculated by comparing the observed to expected number of cases, and HCC risk factors determined by Cox proportional hazards regression. RESULTS: Five hundred and forty nine initiated NA (14% lamivudine, 5% adefovir, 1.5% telbivudine, 39% entecavir, 41% tenofovir). Over a median follow-up of 3.2 years (IQR 1.9-4.6), 11 (3.2%) were diagnosed with HCC. Among 322 with data to calculate the REACH-B model, the median age at treatment initiation was 46 years (IQR 38-55), 65% were male, 32% HBeAg positive and 20% had cirrhosis. The median pre-treatment ALT was 71 U/L (IQR 41-127) and HBV DNA was 6.48 log10 copies/mL (4.95-8.04). The observed annual HCC incidence (0.9%; 95% CI 0.5-1.7) was significantly lower than predicted without treatment by the REACH-B model (SIR 0.46; 95% CI 0.23-0.82); this risk was reduced after 4 years of therapy (SIR 0.49; 95% CI 0.2-1.00). CONCLUSIONS: In this Canadian study of nucleos(t)ide analogues-treated patients with chronic hepatitis B, the incidence of HCC was lower than expected, suggesting that NA reduce the risk of chronic hepatitis B-related HCC.

Multispecies biofilm in an artificial wound bed--A novel model for in vitro assessment of solid antimicrobial dressings.

Wound infections represent a major problem, particularly in patients with chronic wounds. Bacteria in the wound exist mainly in the form of biofilms and are thus resistant to most antibiotics and antimicrobials. A simple and cost-effective in vitro model of chronic wound biofilms applied for testing treatments and solid devices, especially wound dressings, is presented in this work. The method is based on the well-established Lubbock chronic wound biofilm transferred onto an artificial agar wound bed. The biofilm formed by four bacterial species (Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and Pseudomonas aeruginosa) was stable for up to 48h post-transplant. The applicability of the model was evaluated by testing two common iodine wound treatments. These observations indicate that this method enables assessing the effects of treatments on established resilient wound biofilms and is clinically highly relevant.

Subchronic treatment with phencyclidine in adolescence leads to impaired exploratory behavior in adult rats without altering social interaction or N-methyl-D-aspartate receptor binding levels.

Although both the onset of schizophrenia and human phencyclidine (PCP) abuse typically present within the interval from adolescence to early adulthood, the majority of preclinical research employing the PCP model of schizophrenia has been conducted on neonatal or adult animals. The present study was designed to evaluate the behavioral and neurochemical sequelae of subchronic exposure to PCP in adolescence. Male 35-42-day-old Sprague Dawley rats were subcutaneously administered either saline (10 ml · kg(-1) ) or PCP hydrochloride (10 mg · kg(-1) ) once daily for a period of 14 days (n = 6/group). The animals were allowed to withdraw from treatment for 2 weeks, and their social and exploratory behaviors were subsequently assessed in adulthood by using the social interaction test. To examine the effects of adolescent PCP administration on the regulation of N-methyl-D-aspartate receptors (NMDARs), quantitative autoradiography was performed on brain sections of adult, control and PCP-withdrawn rats by using 20 nM (3) H-MK-801. Prior subchronic exposure to PCP in adolescence had no enduring effects on the reciprocal contact and noncontact social behavior of adult rats. Spontaneous rearing in response to the novel testing arena and time spent investigating its walls and floor were reduced in PCP-withdrawn animals compared with control. The long-term behavioral effects of PCP occurred in the absence of persistent deficits in spontaneous locomotion or self-grooming activity and were not mediated by altered NMDAR density. Our results document differential effects of adolescent PCP administration on the social and exploratory behaviors of adult rats, suggesting that distinct neurobiological mechanisms are involved in mediating these behaviors.

COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy.

BACKGROUND: This prospective study evaluated the relationship between arthralgia and compliance during the first year of adjuvant anastrozole therapy in postmenopausal women with hormone receptor-positive early breast cancer. PATIENTS AND METHODS: COMPliance and Arthralgia in Clinical Therapy (COMPACT) was an open-label, multicenter, noninterventional study conducted in Germany. Patients had started adjuvant anastrozole 3-6 months before the study start. The primary end points were arthralgia, compliance, and the relationship between compliance and arthralgia, assessed at specific time points. RESULTS: Overall, 1916 patients received upfront anastrozole. Mean arthralgia scores were increased from baseline at each visit up to 9 months. Compliance with anastrozole therapy gradually decreased over time from baseline to 9 months (P<0.001). At 9 months, investigators estimated that >95% of patients were compliant versus patient reports of <70%. There was a significant association between arthralgia mean scores and noncompliance at 6 months (P<0.0001), 9 months (P<0.0001), and overall (P<0.0001). Over time, new events or impairment of existing arthralgias were reported in 14% (3 months), 11% (6 months), and 9% (9 months) of patients. CONCLUSION: Arthralgia is important in the clinical management of women with early breast cancer and may contribute to noncompliance and clinical outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT00857012.