Biosensors are ideally portable, low-cost tools for the rapid detection of pathogens, proteins, and other analytes. The global biosensor market is currently worth over 10 billion dollars annually and ...is a burgeoning field of interdisciplinary research that is hailed as a potential revolution in consumer, healthcare, and industrial testing. A key barrier to the widespread adoption of biosensors, however, is their cost. Although many systems have been validated in the laboratory setting and biosensors for a range of analytes are proven at the concept level, many have yet to make a strong commercial case for their acceptance. Though it is true with the development of cheaper electrodes, circuits, and components that there is a downward pressure on costs, there is also an emerging trend toward the development of multianalyte biosensors that is pushing in the other direction. One way to reduce the cost that is suitable for certain systems is to enable their reuse, thus reducing the cost per test. Regenerating biosensors is a technique that can often be used in conjunction with existing systems in order to reduce costs and accelerate the commercialization process. This article discusses the merits and drawbacks of regeneration schemes that have been proven in various biosensor systems and indicates parameters for successful regeneration based on a systematic review of the literature. It also outlines some of the difficulties encountered when considering the role of regeneration at the point of use. A brief meta-analysis has been included in this review to develop a working definition for biosensor regeneration, and using this analysis only ∼60% of the reported studies analyzed were deemed a success. This highlights the variation within the field and the need to normalize regeneration as a standard process across the field by establishing a consensus term.
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IJS, KILJ, NUK, PNG, UL, UM
Background
The management of total iliac artery occlusion is now undertaken routinely using percutaneous techniques but there are no controlled data to indicate whether either balloon angioplasty or ...stent placement is preferable. This was a multicentre randomized trial to assess whether stents confer any safety or efficacy advantage over balloon angioplasty for complete iliac artery occlusion.
Methods
Six participating centres recruited patients with symptoms of lower limb peripheral arterial disease due to iliac artery occlusion 8 cm or less in length. Patients were assigned randomly to either percutaneous transluminal angioplasty (PTA group) or primary stent placement (stent group) alone after the lesion had been traversed with a guidewire.
Results
There were 118 patients recruited to the study; six were excluded from the analysis owing to major protocol violations, leaving a total of 112 patients for analysis. Some 55 patients had PTA and 57 had a primary iliac stent. Technical success was achieved in 46 patients (84 per cent) in the PTA group and 56 (98 per cent) in the stent group (P = 0·007). There were 11 (20 per cent) major procedural complications after PTA compared with three (5 per cent) after primary stenting (P = 0·010). There were no significant differences in primary or secondary patency between the groups after 1 and 2 years.
Conclusion
Primary stent placement for iliac artery occlusion increased technical success and reduced major procedural complications (predominantly distal embolization) compared with balloon angioplasty. Registration number: ISRCTN 48145465 (http://www.controlled‐trials.com).
Stent safer
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract Purpose Although a number of osteoarthritis (OA) management guidelines exist, uptake has been suboptimal. Our aim was to review and critically evaluate existing OA management guidelines to ...better understand potential issues and barriers. Methods A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, 2 authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality using the AGREE II instrument; three generated summary recommendations based on the extracted guideline data. Results Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol (first line) and NSAIDs (topical or oral, second line). Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin. Conclusions The relative agreement on many OA management recommendations across organizations indicates a problem with dissemination and implementation rather than a lack of quality guidelines. Future efforts should focus on optimizing implementation in primary care settings, where the majority of OA care occurs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
Reduced ability to contract the quadriceps muscles is often found immediately following anterior cruciate ligament (ACL) surgery. This can lead to muscle atrophy and decreased function. ...Application of neuromuscular electrical stimulation (NMES) may be a useful adjunct intervention to ameliorate these deficits following ACL surgery. The purpose of this review was to determine whether NMES in addition to standard physical therapy is superior to standard physical therapy alone in improving quadriceps strength or physical function following ACL surgery.
Methods
A computer-assisted literature search was conducted utilizing PubMed, CINAHL, PEDro and Cochrane Library databases for randomized clinical trials where patients after ACL surgery received NMES with the outcome of muscle strength and/or physical function. Random effect models were used to pool summary estimates using standardized mean differences (SMD) for strength outcomes. Physical function outcomes were assessed qualitatively. Methodological quality was assessed from the Physiotherapy Evidence Database (PEDro)-score.
Results
Eleven studies met our inclusion criteria; results from six of these were pooled in the meta-analysis showing a statistically significant short-term effect of NMES (4–12 weeks) after surgery compared to standard physical therapy SMD = 0.73 (95% CI 0.29, 1.16). Physical function also improved significantly more in the NMES groups. PEDro scores ranged from 3/10 to 7/10 points.
Conclusion
NMES in addition to standard physical therapy appears to significantly improve quadriceps strength and physical function in the early post-operative period compared to standard physical therapy alone.
Level of evidence
I.
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EMUNI, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Surgery for hip femoroacetabular impingement/acetabular labral tear (FAI/ALT) is exponentially increasing despite lacking investigation of the accuracy of various diagnostic measures. Useful clinical ...utility of these measures is necessary to support diagnostic imaging and subsequent surgical decision-making.
Summarise/evaluate the current diagnostic accuracy of various clinical tests germane to hip FAI/ALT pathology.
A computer-assisted literature search of MEDLINE, CINAHL and EMBASE databases using keywords related to diagnostic accuracy of the hip joint, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the search and reporting phases of the study. Quality assessment of bias and applicability was conducted using the Quality of Diagnostic Accuracy Studies-2 (QUADAS-2). Random effects models were used to summarise sensitivities (SN), specificities (SP), diagnostic odds ratio (DOR) and respective confidence intervals (CI).
The employed search strategy revealed 21 potential articles, with one demonstrating high quality. Nine articles qualified for meta-analysis. The meta-analysis demonstrated that flexion-adduction-internal rotation (pooled SN ranging from 0.94 (95% CI 0.90 to 0.97) to 0.99 (95% CI 0.98 to 1.00); DOR 5.71 (95% CI 0.84 to 38.86) to 7.82 (95% CI 1.06 to 57.84)) and flexion-internal rotation (pooled SN 0.96 (95% CI 0.81 to 0.99); DOR 8.36 (95% CI 0.41 to 171.3) tests possess only screening accuracy.
Few hip physical examination tests for diagnosing FAI/ALT have been investigated in enough studies of substantial quality to direct clinical decision-making. Further high-quality studies across a wider spectrum of hip pathology patients are recommended to discern the confirmed clinical utility of these tests.
PROSPERO Registration # CRD42014010144.
To compare the effectiveness of physical therapy (PT, evidence-based approach) and internet-based exercise training (IBET), each vs a wait list (WL) control, among individuals with knee ...osteoarthritis (OA).
Randomized controlled trial of 350 participants with symptomatic knee OA, allocated to standard PT, IBET and WL control in a 2:2:1 ratio, respectively. The PT group received up to eight individual visits within 4 months. The IBET program provided tailored exercises, video demonstrations, and guidance on progression. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC, range 0 no problems–96 extreme problems), assessed at baseline, 4 months (primary time point) and 12 months. General linear mixed effects modeling compared changes in WOMAC among study groups, with superiority hypotheses testing differences between each intervention group and WL and non-inferiority hypotheses comparing IBET with PT.
At 4-months, improvements in WOMAC score did not differ significantly for either the IBET or PT group compared with WL (IBET: −2.70, 95% Confidence Interval (CI) = −6.24, 0.85, P = 0.14; PT: −3.36, 95% (CI) = −6.84, 0.12, P = 0.06). Similarly, at 12-months mean differences compared to WL were not statistically significant for either group (IBET: −2.63, 95% CI = −6.37, 1.11, P = 0.17; PT: −1.59, 95% CI = −5.26, 2.08, P = 0.39). IBET was non-inferior to PT at both time points.
Improvements in WOMAC score following IBET and PT did not differ significantly from the WL group. Additional research is needed to examine strategies for maximizing benefits of exercise-based interventions for patients with knee OA.
NCT02312713.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background Numerous scientific organisations have developed evidence-based recommendations aiming to optimise the management of osteoarthritis (OA). Uptake, however, has been suboptimal. The ...purpose of this exercise was to harmonize the recent recommendations and develop a user-friendly treatment algorithm to facilitate translation of evidence into practice. Methods We updated a previous systematic review on clinical practice guidelines (CPGs) for OA management. The guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation for quality and the standards for developing trustworthy CPGs as established by the National Academy of Medicine (NAM). Four case scenarios and algorithms were developed by consensus of a multidisciplinary panel. Results Sixteen guidelines were included in the systematic review. Most recommendations were directed toward physicians and allied health professionals, and most had multi-disciplinary input. Analysis for trustworthiness suggests that many guidelines still present a lack of transparency. A treatment algorithm was developed for each case scenario advised by recommendations from guidelines and based on panel consensus. Conclusion Strategies to facilitate the implementation of guidelines in clinical practice are necessary. The algorithms proposed are examples of how to apply recommendations in the clinical context, helping the clinician to visualise the patient flow and timing of different treatment modalities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To assess the in vivo relationship between the mechanical response of intervertebral discs (IVDs) to dynamic activity and IVD biochemical composition assessed via T1rho relaxation imaging.
Eighteen ...asymptomatic participants with no history of low back pain (LBP), injury, or surgery underwent magnetic resonance (MR) imaging of their lumbar spine prior to and immediately following a treadmill walking “stress test.” Anatomic (SPACE, FLASH) MR images were obtained pre- and post-exercise and utilized to measure IVD mechanical deformation. Quantitative (T1rho) imaging was performed pre-exercise to reflect IVD composition. Pre-exercise anatomic images were also utilized to assess IVD degenerative status based on the modified Pfirrmann scale. To quantify mechanical response, 3D surface models of the L1-L2–L5-S1 IVDs were created from manual segmentations of pre- and post-exercise anatomic images and utilized to assess changes in IVD height. IVD strain (%) was defined as change in IVD height normalized to pre-activity height. Linear mixed models were used to assess the relationships between IVD mechanical deformation (strain), composition (T1rho relaxation time), and degenerative status (Pfirrmann grade).
Increased compressive IVD strain was associated with lower T1rho relaxation times in the nucleus pulposus (NP) of the disc (βT1rho=5.07,CI:1.52,7.77,Rmarg2=0.52,p=0.005). Thus, an inverse relationship between IVD strain and NP T1rho relaxation time was observed.
The in vivo mechanical response of the IVD to the “stress test” was sensitive to differences in NP composition. The results of this study suggest that quantification of in vivo IVD mechanical function and composition may provide insight into IVD health.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine differences in biomarker levels between radiographic phenotypes of facet joint osteoarthritis (FOA) only, spine OA only ((disc space narrowing (DSN) and vertebral osteophytes (OST)) or ...the combination of FOA and spine OA.
A cross-sectional analysis of data from 555 participants in the Johnston County Osteoarthritis Project was performed. Lumbar spine levels were graded by severity (OST and DSN) and presence (FOA) of degeneration. Biomarkers included hyaluronan (HA) and type II collagen (CTX-II). Adjusted risk ratios (aRRR) were estimated using multinomial regression, with adjustment for age, race, sex, body mass index (BMI), and radiographic OA (knee, hip, hand). Interactions were tested between sex, race and low back symptoms.
FOA only was present in 22.4%, 14.5% had spine OA only, and 34.6% had the combination of FOA and spine OA. Compared to the reference group of neither FOA or spine OA, a one unit higher ln HA level was associated with 31% higher relative risk ratio (RRR = 1.31 (95% 1.03, 1.67)) of having FOA only, while, a one unit higher lnuCTX-II level was associated with 84% higher relative risk ratio (RRR = 1.84 (95% CI 1.19, 2.84)) of having spine OA only. No significant interactions were identified.
Interestingly, OA affecting the synovial facet joint was associated with a marker of inflammation (HA). Spine OA, affecting intervertebral discs that contain collagen type II, was associated with a marker reflecting collagen type II degradation (CTX-II). These findings suggest that biomarkers may reflect the different pathophysiologic processes of lumbar spine OA phenotypes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Nanobodies have been used on impedimetric immunosensors to detect rabbit IgG.•Unmodified nanobody sensors displayed a decrease in resistance upon analyte recognition.•Nanobodies were modified with a ...peptide spacer, effectively reversing this phenomena.•The use of a spacer also increased the sensitivity of the immunosensor.
Biosensors are increasingly heralded for their potential to create inexpensive diagnostic devices which are sensitive, selective and easy to use. One of the key categories of biosensor are immunosensors, which have historically used antibodies as bioreceptors. Though widely used, antibodies bring inherent limitations such as variability, limited stability and their reliance on animal sources.
This has led to the development of alternative immuno-reagents such as non-antibody binding proteins (NABPs). These are low molecular weight proteins which largely avoid the aforementioned advantages of antibodies. They are commonly produced by bacteria enabling the use of DNA technology to manipulate bioreceptors at the molecular level.
Single chain VHHs (commonly known as nanobodies) are an antibody derived NABP adapted from camelid heavy chain antibodies which are the isolated binding domain. Whilst nanobodies have been used for diagnostic and therapeutic applications, they have limited demonstration in biosensors.
In this study, both antibodies and nanobodies were used to construct a biosensor. In addition nanobody performance was optimised by introducing a novel peptide spacer. The role of nanobody orientation and spacing was thus investigated and spacer length was optimised, leading to an increase in the sensitivity of the biosensor.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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