Miniature gastrointestinal endoscopy: Now and the future

Since its original application, gastrointestinal (GI) endoscopy has undergone many innovative transformations aimed at expanding the scope, safety, accuracy, acceptability and cost-effectiveness of this area of clinical practice. One method of achieving this has been to reduce the caliber of endoscopic devices. We propose the collective term "Miniature GI Endoscopy". In this Opinion Review, the innovations in this field are explored and discussed. The progress and clinical use of the three main areas of miniature GI endoscopy (ultrathin endoscopy, wireless endoscopy and scanning fiber endoscopy) are described. The opportunities presented by these technologies are set out in a clinical context, as are their current limitations. Many of the positive aspects of miniature endoscopy are clear, in that smaller devices provide access to potentially all of the alimentary canal, while conferring high patient acceptability. This must be balanced with the costs of new technologies and recognition of device specific challenges. Perspectives on future application are also considered and the efforts being made to bring new innovations to a clinical platform are outlined. Current devices demonstrate that miniature GI endoscopy has a valuable place in investigation of symptoms, therapeutic intervention and screening. Newer technologies give promise that the potential for enhancing the investigation and management of GI complaints is significant

Quantitative bone marrow lesion size in osteoarthritic knees correlates with cartilage damage and predicts longitudinal cartilage loss

<p>Abstract</p> <p>Background</p> <p>Bone marrow lesions (BMLs), common osteoarthritis-related magnetic resonance imaging findings, are associated with osteoarthritis progression and pain. However, there are no articles describing the use of 3-dimensional quantitative assessments to explore the longitudinal relationship between BMLs and hyaline cartilage loss. The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume, and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage.</p> <p>Methods</p> <p>107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis. An 'index' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity. Subsequently, each knee was evaluated in four regions: index femur, index tibia, non-index femur, and non-index tibia. Approximate BML volume, the product of three linear measurements, was calculated for each BML within a region. Cartilage parameters in the index tibia and femur were measured based on manual segmentation.</p> <p>Results</p> <p>BML volume changes by region were: index femur (median [95% confidence interval of the median]) 0.1 cm³(-0.5 to 0.9 cm³), index tibia 0.5 cm³(-0.3 to 1.7 cm³), non-index femur 0.4 cm³(-0.2 to 1.6 cm³), and non-index tibia 0.2 cm³(-0.1 to 1.2 cm³). Among 44 knees with full thickness cartilage loss, baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area (<it>r </it>= 0.63, <it>p</it>< 0.002) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area (<it>r </it>= 0.48 <it>p</it>< 0.002).</p> <p>Conclusions</p> <p>Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes. Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss.</p

Effect of a natural extract of chicken combs with a high content of hyaluronic acid (Hyal-Joint®) on pain relief and quality of life in subjects with knee osteoarthritis: a pilot randomized double-blind placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Intra-articular hyaluronic acid represents a substantive addition to the therapeutic armamentarium in knee osteoarthritis. We examined the effect of dietary supplementation with a natural extract of chicken combs with a high content of hyaluronic acid (60%) (Hyal-Joint^®) (active test product, AP) on pain and quality of life in subjects with osteoarthritis of the knee.</p> <p>Methods</p> <p>Twenty subjects aged ≥40 years with knee osteoarthritis (pain for at least 15 days in the previous month, symptoms present for ≥6 months, Kellgren/Lawrence score ≥2) participated in a randomized double-blind controlled trial. Ten subjects received AP (80 mg/day) and 10 placebo for 8 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and quality of life by the Short Form-36 (SF-36v2) were administered at baseline and after 4 and 8 weeks of treatment.</p> <p>Results</p> <p>WOMAC pain (primary efficacy variable) was similar in both study groups (mean [SD]) with 6.6 (4.0) points in the AP group and 6.4 (2.7) in the placebo group (<it>P </it>= 0.943). As compared with baseline, subjects in both groups showed statistically significant improvements in WOMAC pain, stiffness, physical function subscales, and in the aggregate score, but the magnitude of changes was higher in the AP group for WOMAC physical function (-13.1 [12.0] vs. -10.1 [8.6], <it>P </it>= 0.575) and total symptoms (-18.6 [16.8] vs. -15.8 [11.4], <it>P </it>= 0.694). At 4 weeks, statistically significant mean changes compared with baseline were observed in the SF-36v2 scales of role-physical, bodily pain, social functioning and role-emotional among subjects in the AP group, and in physical functioning, bodily pain, and social functioning in the placebo group. At 8 weeks, changes were significant for role-physical, bodily pain, and physical component summary in the AP group, and for physical functioning and role-emotional in the placebo arm. Changes in bodily pain and social functioning were of greater magnitude in subjects given AP.</p> <p>Conclusion</p> <p>This pilot clinical trial showed that daily supplementation with oral hyaluronic acid from a natural extract of chicken combs (Hyal-Joint^®) was useful to enhance several markers of quality of life in adults with osteoarthritis of the knee. The results warrant further study in larger sample sizes.</p

Evidence for Impaired CARD15 Signalling in Crohn's Disease without Disease Linked Variants

BACKGROUND:Sensing of muramyl dipeptide (MDP) is impaired in Crohn's disease (CD) patients with disease-linked variants of the CARD15 (caspase activation and recruitment domain 15) gene. Animal studies suggest that normal CARD15 signalling prevents inflammatory bowel disease, and may be important for disease development in CD. However, only a small fraction of CD patients carry the disease linked CARD15 variants. The aim of this study was thus to investigate if changes could be found in CARD15 signalling in patients without disease associated CARD15 variants. METHODOLOGY/PRINCIPAL FINDINGS:By mapping the response to MDP in peripheral monocytes obtained from CD patients in remission not receiving immunosuppresives, an impaired response to MDP was found in patients without disease linked CARD15 variants compared to control monocytes. This impairment was accompanied by a decreased activation of IkappaB kinase alpha/beta (IKKalpha/beta), the initial step in the nuclear factor kappaB (NFkappaB) pathway, whereas activation of mitogen-activated protein (MAP)-kinases was unaffected. MDP additionally stimulates the inflammasome which is of importance for processing of cytokines. The inflammasome was constitutively activated in CD, but unresponsive to MDP both in CD and control monocytes. CONCLUSIONS/SIGNIFICANCE:These results suggest that inhibited MDP-dependent pathways in CD patients not carrying the disease-associated CARD15 variants might be of importance for the pathogenesis of CD. The results reveal a dysfunctional immune response in CD patients, not able to sense relevant stimuli on the one hand, and on the other hand possessing constitutively active cytokine processing

Tai Chi for treating knee osteoarthritis: Designing a long-term follow up randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Knee Osteoarthritis (KOA) is a major cause of pain and functional impairment among elders. Currently, there are neither feasible preventive intervention strategies nor effective medical remedies for the management of KOA. Tai Chi, an ancient Chinese mind-body exercise that is reported to enhance muscle function, balance and flexibility, and to reduce pain, depression and anxiety, may safely and effectively be used to treat KOA. However, current evidence is inconclusive. Our study examines the effects of a 12-week Tai Chi program compared with an attention control (wellness education and stretching) on pain, functional capacity, psychosocial variables, joint proprioception and health status in elderly people with KOA. The study will be completed by July 2009.</p> <p>Methods/Design</p> <p>Forty eligible patients, age > 55 yr, BMI ≤ 40 kg/m²with tibiofemoral osteoarthritis (American College of Rheumatology criteria) are identified and randomly allocated to either Tai Chi (10 modified forms from classical Yang style Tai Chi) or attention control (wellness education and stretching). The 60-minute intervention sessions take place twice weekly for 12 weeks. The study is conducted at an urban tertiary medical center in Boston, Massachusetts. The primary outcome measure is the Western Ontario and McMaster Universities (WOMAC) pain subscale at 12 weeks. Secondary outcomes include weekly WOMAC pain, function and stiffness scores, patient and physician global assessments, lower-extremity function, knee proprioception, depression, self-efficacy, social support, health-related quality of life, adherence and occurrence of adverse events after 12, 24 and 48 weeks.</p> <p>Discussion</p> <p>In this article, we present the challenges of designing a randomized controlled trial with long-term follow up. The challenges encountered in this design are: strategies for recruitment, avoidance of selection bias, the actual practice of Tai Chi, and the maximization of adherence/follow-up while conducting the clinical trial for the evaluation of the effectiveness of Tai Chi on KOA.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT00362453</p

Reliability of maximal isometric knee strength testing with modified hand-held dynamometry in patients awaiting total knee arthroplasty: useful in research and individual patient settings? A reliability study

<p>Abstract</p> <p><b>Background</b></p> <p>Patients undergoing total knee arthroplasty (TKA) often experience strength deficits both pre- and post-operatively. As these deficits may have a direct impact on functional recovery, strength assessment should be performed in this patient population. For these assessments, reliable measurements should be used. This study aimed to determine the inter- and intrarater reliability of hand-held dynamometry (HHD) in measuring isometric knee strength in patients awaiting TKA.</p> <p><b>Methods</b></p> <p>To determine interrater reliability, 32 patients (81.3% female) were assessed by two examiners. Patients were assessed consecutively by both examiners on the same individual test dates. To determine intrarater reliability, a subgroup (n = 13) was again assessed by the examiners within four weeks of the initial testing procedure. Maximal isometric knee flexor and extensor strength were tested using a modified Citec hand-held dynamometer. Both the affected and unaffected knee were tested. Reliability was assessed using the Intraclass Correlation Coefficient (ICC). In addition, the Standard Error of Measurement (SEM) and the Smallest Detectable Difference (SDD) were used to determine reliability.</p> <p><b>Results</b></p> <p>In both the affected and unaffected knee, the inter- and intrarater reliability were good for knee flexors (ICC range 0.76-0.94) and excellent for knee extensors (ICC range 0.92-0.97). However, measurement error was high, displaying SDD ranges between 21.7% and 36.2% for interrater reliability and between 19.0% and 57.5% for intrarater reliability. Overall, measurement error was higher for the knee flexors than for the knee extensors.</p> <p><b>Conclusions</b></p> <p>Modified HHD appears to be a reliable strength measure, producing good to excellent ICC values for both inter- and intrarater reliability in a group of TKA patients. High SEM and SDD values, however, indicate high measurement error for individual measures. This study demonstrates that a modified HHD is appropriate to evaluate knee strength changes in TKA patient groups. However, it also demonstrates that modified HHD is not suitable to measure individual strength changes. The use of modified HHD is, therefore, not advised for use in a clinical setting.</p

Effects of ex-vivo and in-vivo treatment with probiotics on the inflammasome in dogs with chronic enteropathy

Inflammasomes coordinate the maturation of IL-1β and IL-18 in response to danger signals. They are vital for maintenance of intestinal homeostasis and have been linked to chronic intestinal inflammation in humans. Probiotics have been advocated as treatment in intestinal inflammation. So far, no study has investigated the role of the inflammasome in canine chronic enteropathy (CE). In this study the intestinal expression of inflammasome components was assessed in CE dogs compared to controls, when treated with probiotic Enterococcus faecium (EF) ex-vivo and in-vivo. RNA extraction from endoscopic biopsies and reverse-transcriptase quantitative PCR was performed for NLRP3, casp-1, IL-1β and IL-18. Immunohistochemistry was performed to investigate protein expression in tissues. Gene expression of casp-1 and NLRP3 was lower in CE samples than controls. Ex-vivo treatment with EF reduced NLRP3 expression in control samples. Treatment of CE dogs with EF alongside dietary intervention had no effect on gene expression. In contrast, IL-1β protein expression in CE decreased with dietary treatment (but not with probiotics). The results of this study suggest that the inflammasome or its components may be partially involved in the inflammatory process seen in CE, but distinct from intestinal inflammation in humans

Applying an extended theoretical framework for data collection mode to health services research

<p>Abstract</p> <p>Background</p> <p>Over the last 30 years options for collecting self-reported data in health surveys and questionnaires have increased with technological advances. However, mode of data collection such as face-to-face interview or telephone interview can affect how individuals respond to questionnaires. This paper adapts a framework for understanding mode effects on response quality and applies it to a health research context.</p> <p>Discussion</p> <p>Data collection modes are distinguished by key features (whether the survey is self- or interviewer-administered, whether or not it is conducted by telephone, whether or not it is computerised, whether it is presented visually or aurally). Psychological appraisal of the survey request will initially entail factors such as the cognitive burden upon the respondent as well as more general considerations about participation. Subsequent psychological response processes will further determine how features of the data collection mode impact upon the quality of response provided. Additional antecedent factors which may further interact with the response generation process are also discussed. These include features of the construct being measured such as sensitivity, and of the respondent themselves (e.g. their socio-demographic characteristics). How features of this framework relate to health research is illustrated by example.</p> <p>Summary</p> <p>Mode features can affect response quality. Much existing evidence has a broad social sciences research base but is of importance to health research. Approaches to managing mode feature effects are discussed. Greater consideration must be given to how features of different data collection approaches affect response from participants in studies. Study reports should better clarify such features rather than rely upon global descriptions of data collection mode.</p

Strength Training for Arthritis Trial (START): design and rationale

Background Muscle loss and fat gain contribute to the disability, pain, and morbidity associated with knee osteoarthritis (OA), and thigh muscle weakness is an independent and modifiable risk factor for it. However, while all published treatment guidelines recommend muscle strengthening exercise to combat loss of muscle mass and strength in knee OA patients, previous strength training studies either used intensities or loads below recommended levels for healthy adults or were generally short, lasting only 6 to 24 weeks. The efficacy of high-intensity strength training in improving OA symptoms, slowing progression, and affecting the underlying mechanisms has not been examined due to the unsubstantiated belief that it might exacerbate symptoms. We hypothesize that in addition to short-term clinical benefits, combining greater duration with high-intensity strength training will alter thigh composition sufficiently to attain long-term reductions in knee-joint forces, lower pain levels, decrease inflammatory cytokines, and slow OA progression. Methods/Design This is an assessor-blind, randomized controlled trial. The study population consists of 372 older (age ≥ 55 yrs) ambulatory, community-dwelling persons with: (1) mild-to-moderate medial tibiofemoral OA (Kellgren-Lawrence (KL) = 2 or 3); (2) knee neutral or varus aligned knee ( -2° valgus ≤ angle ≤ 10° varus); (3) 20 kg.m-2 ≥ BMI ≤ 45 kg.m-2; and (3) no participation in a formal strength-training program for more than 30 minutes per week within the past 6 months. Participants are randomized to one of 3 groups: high-intensity strength training (75-90% 1Repetition Maximum (1RM)); low-intensity strength training (30-40%1RM); or healthy living education. The primary clinical aim is to compare the interventions’ effects on knee pain, and the primary mechanistic aim is to compare their effects on knee-joint compressive forces during walking, a mechanism that affects the OA disease pathway. Secondary aims will compare the interventions’ effects on additional clinical measures of disease severity (e.g., function, mobility); disease progression measured by x-ray; thigh muscle and fat volume, measured by computed tomography (CT); components of thigh muscle function, including hip abductor strength and quadriceps strength, and power; additional measures of knee-joint loading; inflammatory and OA biomarkers; and health-related quality of life. Discussion Test-retest reliability for the thigh CT scan was: total thigh volume, intra-class correlation coefficients (ICC) = 0.99; total fat volume, ICC = 0.99, and total muscle volume, ICC = 0.99. ICC for both isokinetic concentric knee flexion and extension strength was 0.93, and for hip-abductor concentric strength was 0.99. The reliability of our 1RM testing was: leg press, ICC = 0.95; leg curl, ICC = 0.99; and leg extension, ICC = 0.98. Results of this trial will provide critically needed guidance for clinicians in a variety of health professions who prescribe and oversee treatment and prevention of OA-related complications. Given the prevalence and impact of OA and the widespread availability of this intervention, assessing the efficacy of optimal strength training has the potential for immediate and vital clinical impact