Discovering Associations Between Acoustic Emission and Magnetic Resonance Imaging Biomarkers From 10 Osteoarthritic Knees.

OBJECTIVE: Acoustic emission (AE) sensed from knee joints during weight-bearing movements greatly increases with joint deterioration, but the relationship between AE patterns and specific anatomical damage, as seen for example in magnetic resonance imaging (MRI), is unknown. This knowledge is essential to validate AE biomarkers for the evaluation of knee joints, and forms the objective of this exploratory work to associate knee AE and MRI. METHODS: A novel processing framework is proposed to enable direct correlation between static 3D MRI of knees and their dynamic 1D AE during sit-stand-sit movements. It comprises a method to estimate articular cartilage thickness according to joint angle from knee MRI, and a method to derive statistically representative waveform features according to joint angle from movement and load-dependent knee AE. RESULTS: In 10 subjects diagnosed with knee osteoarthritis, age 55∼79 years and body mass index 25∼35 kg/m2, a strong inverse relationship between knee AE and cartilage thickness in the medial tibiofemoral compartment around the fully standing position was observed. Knees with thinner articular cartilage generated more AE with higher amplitude, greater energy, longer duration, and higher frequencies, in agreement with the assumption of more intense articulation friction under full body weight. CONCLUSION: AE provides promising quantitative biomarkers in knee joint disease. SIGNIFICANCE: These findings provide impetus for the further development of AE as a low-cost non-invasive biomarker modality to improve the management of knee joint disease.

Use of acoustic emission to identify novel candidate biomarkers for knee osteoarthritis (OA).

Our objective was to determine the efficacy and feasibility of a new approach for identifying candidate biomarkers for knee osteoarthritis (OA), based on selecting promising candidates from a range of high-frequency acoustic emission (AE) measurements generated during weight-bearing knee movement. Candidate AE biomarkers identified by this approach could then be validated in larger studies for use in future clinical trials and stratified medicine applications for this common health condition. A population cohort of participants with knee pain and a Kellgren-Lawrence (KL) score between 1-4 were recruited from local NHS primary and secondary care sites. Focusing on participants' self-identified worse knee, and using our established movement protocol, sources of variation in AE measurement and associations of AE markers with other markers were explored. Using this approach we identified 4 initial candidate AE biomarkers, of which "number of hits" showed the best reproducibility, in terms of within-session, day to day, week to week, between-practitioner, and between-machine variation, at 2 different machine upper frequency settings. "Number of hits" was higher in knees with KL scores of 2 than in KL1, and also showed significant associations with pain in the contralateral knee, and with body weight. "Hits" occurred predominantly in 2 of 4 defined movement quadrants. The protocol was feasible and acceptable to all participants and professionals involved. This study demonstrates how AE measurement during simple sit-stand-sit movements can be used to generate novel candidate knee OA biomarkers. AE measurements probably reflect a composite of structural changes and joint loading factors. Refinement of the method and increasing understanding of factors contributing to AE will enable this approach to be used to generate further candidate biomarkers for validation and potential use in clinical trials.

Acoustic emission and angular movement variations from early adulthood healthy knees to late adulthood osteoarthritic knees.

From sit-stand-sit movements performed by healthy and osteoarthritic knees in three different age bands, this paper presents the investigation of the relationship between joint angular movement measured using electro-goniometers and acoustic emission measured using piezoelectric sensors. By partitioning joint movement in each sit-stand-sit cycle into sub-movement phases based on ascending and descending as well as acceleration and deceleration, the statistical analysis reveals aged and osteoarthritic knees exhibiting increased asymmetry and more variable angular movement compared with young and age-matched healthy knees, particularly in the descending-deceleration phase. With further evidence of a clear difference in the number of acoustic emission events detected from different knee groups, the study suggests the descending-deceleration phase likely to be most informative for quantitative assessment of knee aging and condition.

The impact of ankylosing spondylitis/axial spondyloarthritis on work productivity.

Ankylosing spondylitis (AS) is a chronic inflammatory condition that has a significant impact on the quality of life and work productivity. New classification criteria have enabled earlier diagnosis of this condition. However, work productivity is an important issue that is still often overlooked during clinical assessments and consultations. This article focusses on the relationship between axial spondyloarthritis (axial SpA) and work productivity. It summarises the impact of this condition on work productivity, and it highlights the tools available to assess this. It also highlights the increasing role and potential of employers, health professionals and new treatments for enhancing work productivity for people with this condition.

Novel conserved group A streptococcal proteins identified by the antigenome technology as vaccine candidates for a non-M protein-based vaccine.

Group A streptococci (GAS) can cause a wide variety of human infections ranging from asymptomatic colonization to life-threatening invasive diseases. Although antibiotic treatment is very effective, when left untreated, Streptococcus pyogenes infections can lead to poststreptococcal sequelae and severe disease causing significant morbidity and mortality worldwide. To aid the development of a non-M protein-based prophylactic vaccine for the prevention of group A streptococcal infections, we identified novel immunogenic proteins using genomic surface display libraries and human serum antibodies from donors exposed to or infected by S. pyogenes. Vaccine candidate antigens were further selected based on animal protection in murine lethal-sepsis models with intranasal or intravenous challenge with two different M serotype strains. The nine protective antigens identified are highly conserved; eight of them show more than 97% sequence identity in 13 published genomes as well as in approximately 50 clinical isolates tested. Since the functions of the selected vaccine candidates are largely unknown, we generated deletion mutants for three of the protective antigens and observed that deletion of the gene encoding Spy1536 drastically reduced binding of GAS cells to host extracellular matrix proteins, due to reduced surface expression of GAS proteins such as Spy0269 and M protein. The protective, highly conserved antigens identified in this study are promising candidates for the development of an M-type-independent, protein-based vaccine to prevent infection by S. pyogenes.

Discovering differences in acoustic emission between healthy and osteoarthritic knees using a four-phase model of sit-stand-sit movements.

By performing repeated sit-stand-sit movements to create stress on knee joints, short transient bursts of high frequency acoustic emission (AE) released by the knee joints were acquired from two age matched groups consisting of healthy and osteoarthritic (OA) knees, and significant differences between these two groups were discovered from the signal analysis performed. The analysis is based on a four-phase model of sit-stand-sit movements and a two-feature descriptor of AE bursts. The four phases are derived from joint angle measurement during movement, and they consist of the ascending-acceleration and ascending-deceleration phases in the sit-to-stand movement, followed by the descending-acceleration and descending-deceleration phases in the stand-to-sit movement. The two features are extracted from AE measurement during movement, and they consist of the peak magnitude value and average signal level of each AE burst. The proposed analysis method is shown to provide a high sensitivity for differentiation of the two age matched healthy and OA groups, with the most significant difference found to come from the peak magnitude value in the ascending-deceleration phase, clear quantity and strength differences in the image based visual display of their AE feature profiles due to substantially more AE bursts from OA knee joints with higher peak magnitude values and higher average signal levels, and two well separated clusters in the space formed by the principal components. These results provide ample support for further development of AE as a novel tool to facilitate dynamic integrity assessment of knee joints in clinic and home settings.

The role of quality tools in assessing reliability of the internet for health information.

The Internet has made it possible for patients and their families to access vast quantities of information that previously would have been difficult for anyone but a physician or librarian to obtain. Health information websites, however, are recognised to differ widely in quality and reliability of their content. This has led to the development of various codes of conduct or quality rating tools to assess the quality of health websites. However, the validity and reliability of these quality tools and their applicability to different health websites also varies. In principle, rating tools should be available to consumers, require a limited number of elements to be assessed, be assessable in all elements, be readable and be able to gauge the readability and consistency of information provided from a patient's view point. This article reviews the literature on the trends of the Internet use for health and analyses various codes of conduct/ethics or 'quality tools' available to monitor the quality of health websites from a patient perspective.

The quality of information about kidney transplantation on the World Wide Web.

BACKGROUND: Websites on the Internet are used increasingly by patients and those caring for them as a source of medical information. This study investigated the nature and quality of the kidney transplant-related information currently available on the World Wide Web (WWW). METHODS: Four common search engines were used to explore the Internet using the keywords "kidney transplantation." Each website was assessed on the following categories: source, language, accessibility, presence of kitemarks, and quality/depth of information. Websites were scored independently by four transplant clinicians (two surgeons and two physicians), and a weighted Information Score (IS) was created to assess the overall clinical and educational value of the site. RESULTS: A total of 200 potential websites were identified of which 94 websites were suitable for scoring. The remaining 106 were repetitions or non-accessible links. The overall median weighted IS for the sites assessed was 21 (IQR 0-61). Median weighted IS of sites originating from Europe and USA were 47 (IQR = 21-61) and 45 (IQR = 15-61) respectively (p = 0.27). Websites belonging to academic institutions scored higher with a median weighted IS of 49 (IQR = 20-61) when compared with kitemarked websites (median 21, IQR = 5-45, p = 0.01). However, there was no statistically significant difference in weighted IS of kitemarked, professional (median 22, IQR = 2-53), commercial (median 20, IQR = 0-45), and individual websites (median 9, IQR 3-12). There was a good agreement between the observers who scored the websites with an intraclass correlation coefficient (ICC) of 0.79 and an associated 95% CI (0.73-0.90) for the four observers on the 94 websites. CONCLUSION: The educational material currently available on the WWW about kidney transplantation is often of poor quality and more input is required from transplant clinicians. Quality seals in the form of kitemarks may give a false sense of security. The gaps in validity and accuracy of the information available on complex topics such as kidney transplantation should be filled; otherwise poor quality information will continue to be the norm rather than the exception.

Therapeutic targeting of cytokines.

Over recent years, with many advances in understanding the pathological processes that underlie many inflammatory conditions, it has become clear that targeting cytokines has proven to be highly effective therapeutically. The second International Cytokine symposium, held recently in Manchester UK, has provided an important forum for bringing basic and clinical scientists together to discuss many aspects of cytokine medicine from the laboratory to the clinic. In this article, we provide an overview of the main issues raised from this important conference and set the scene for more detailed reports that follow in subsequent articles in this journal.

Cytokine medicines in clinical practice: current issues.

Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field.

Second International Conference on Cytokine Medicines.

The Second International Conference on Cytokine Medicine was held in Manchester, UK and was organised by an international consortium comprising leading clinicians and researchers from healthcare organisations, universities and industry, all with cognate interests in this field. The conference attracted a diverse mix of delegates including clinicians from a wide range of specialities, biomedical scientists, and a barrister with particular expertise in the legal aspects of care provision in healthcare systems. This meeting uniquely focused on cytokine therapies across the spectrum of medical problems, from bench to bedside, including emerging applications for cytokine therapies, issues raised by the delivery of cytokine medicines in clinical practice, and future developments in this broad and exciting area.

Health sequelae of human cryptosporidiosis in immunocompetent patients.

BACKGROUND: There have been no systematic studies following up the longer term health effects of cases of cryptosporidiosis for which genotype data exist. METHODS: We report a follow-up study of cases of laboratory-confirmed cryptosporidiosis. Case patients were sent a postal questionnaire asking about a wide range of symptoms occurring within 2 months after their initial diagnosis, and control subjects were sent the questionnaire 2 months after they had been recruited to the original study. RESULTS: Completed questionnaires were received from 235 case patients and 232 control subjects. For 111 of the case patients, the species of the infecting strain was known; 61 of these strains were Cryptosporidium hominis (human genotype), and 50 were Cryptosporidium parvum (bovine genotype). Forty percent of the case patients reported recurrence of intestinal symptoms after resolution of the acute stage of illness, irrespective of whether infection was with C. hominis or C. parvum. Reports of joint pain (odds ratio [OR], 2.8), eye pains (OR, 2.44), recurrent headache (OR, 2.10), dizzy spells (OR, 1.69), and fatigue (OR, 3.0) were significantly more common in case patients than in control subjects, but only in people who had experienced C. hominis infection. Joint symptoms experienced by case patients were of longer duration than those experienced by control subjects. CONCLUSIONS: Our results confirm previous reports of a high rate of relapse of gastrointestinal symptoms following recovery from an acute episode of cryptosporidiosis and show that C. hominis but not C. parvum is associated with an increased risk of nonintestinal sequelae. This study demonstrates that the impact of cryptosporidiosis on public health extends beyond that of the acute diarrheal illness and can lead to significant health sequelae.

The prevalence of subclinical amyloidosis in Polish patients with rheumatoid arthritis.

The aims of this study were to determine the proportion of rheumatoid arthritis (RA) patients attending hospital in whom amyloid deposits were present in abdominal fat aspiration (AFA) samples, and to assess possible risk factors for amyloid development in RA. One -hundred and twenty-one patients (16 males, 105 females) with RA referred to the Department of Rheumatology in Wroclaw between 1996 and 2001 were studied regardless of RA duration or laboratory findings. Abdominal subcutaneous fine-needle aspiration was performed, and samples of adipose tissue stained with alkaline Congo red then examined by polarized light microscopy. The presence or absence of amyloid fat deposits (AFD) was determined according to whether typical apple-green birefringence was observed. Amyloid deposits were found in 35 (29%) patients. Amyloidosis was significantly more common in males and in patients with longer disease duration. Patients with AFD had previously undergone less treatment with disease-modifying antirheumatic drugs (DMARDs) than those without AFD, and significantly fewer patients with AFD had previously taken methotrexate than those without AFD (25% vs 45%; p<0.01). Renal involvement was found in 12 of 35 patients with AFD (34%). Using the AFA technique, amyloid deposits were found commonly in RA patients, particularly in males with longer disease duration and in patients not treated intensively with DMARDs, especially methotrexate. AFA has potential useful application as a method for detecting amyloidosis before the overt occurrence of renal or other pathology related to amyloid deposits.