Brief Report: A Phase IIb Trial of a Novel Extended‐Release Microsphere Formulation of Triamcinolone Acetonide for Intraarticular Injection in Knee Osteoarthritis

Objective: FX006 is a novel, microsphere‐based, extended‐release formulation of triamcinolone acetonide for intraarticular (IA) injection designed to maintain treatment concentration in the joint and provide prolonged analgesic benefits in patients with osteoarthritis (OA) of the knee. This study was undertaken to compare the analgesic benefits of 2 FX006 doses with saline placebo injection. Methods: In this phase IIb study, participants with knee OA (Kellgren/Lawrence grade 2–3) and average daily pain (ADP) intensity ≥5 to ≤9 (on a 0–10 Numerical Rating Scale) were randomized (1:1:1) to receive single IA injections of FX006 32 mg (n = 104) or 16 mg (n = 102) or saline placebo (n = 100). The primary end point was the least squares mean (LSM) change from baseline to week 12 in weekly mean ADP intensity scores for FX006 32 mg versus saline placebo. Results: The primary end point was not met (LSM change at week 12 −3.1 with FX006 32 mg versus −2.5 with saline placebo; LSM difference [95% confidence interval] −0.58 [−1.22, 0.07]) (P = 0.08). However, improvements in ADP intensity were significantly greater with FX006 32 mg than saline placebo at weeks 1–11 and week 13. Improvements in ADP intensity were significantly greater with FX006 16 mg versus saline placebo at weeks 1–9. A dose‐response effect in duration of maximal analgesic effect was evident (13 weeks with 32 mg versus 9 weeks with 16 mg), with FX006 32 mg providing increased therapeutic benefit relative to FX006 16 mg. All treatments were well tolerated. Conclusion: Although the primary end point was not met, our findings indicate a prolonged reduction in symptoms with FX006 with an evident dose response and a safety profile similar to saline placebo

Uses and misuses of the STROBE statement: bibliographic study

Objectives Appropriate reporting is central to the application of findings from research to clinical practice. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations consist of a checklist of 22 items that provide guidance on the reporting of cohort, case-control and cross-sectional studies, in order to facilitate critical appraisal and interpretation of results. STROBE was published in October 2007 in several journals including The Lancet, BMJ, Annals of Internal Medicine and PLoS Medicine. Within the framework of the revision of the STROBE recommendations, the authors examined the context and circumstances in which the STROBE statement was used in the past. Design The authors searched the Web of Science database in August 2010 for articles which cited STROBE and examined a random sample of 100 articles using a standardised, piloted data extraction form. The use of STROBE in observational studies and systematic reviews (including meta-analyses) was classified as appropriate or inappropriate. The use of STROBE to guide the reporting of observational studies was considered appropriate. Inappropriate uses included the use of STROBE as a tool to assess the methodological quality of studies or as a guideline on how to design and conduct studies. Results The authors identified 640 articles that cited STROBE. In the random sample of 100 articles, about half were observational studies (32%) or systematic reviews (19%). Comments, editorials and letters accounted for 15%, methodological articles for 8%, and recommendations and narrative reviews for 26% of articles. Of the 32 observational studies, 26 (81%) made appropriate use of STROBE, and three uses (10%) were considered inappropriate. Among 19 systematic reviews, 10 (53%) used STROBE inappropriately as a tool to assess study quality. Conclusions The STROBE reporting recommendations are frequently used inappropriately in systematic reviews and meta-analyses as an instrument to assess the methodological quality of observational studies

How to spot a statistical problem: advice for a non-statistical reviewer

Statistical analyses presented in general medical journals are becoming increasingly sophisticated. BMC Medicine relies on subject reviewers to indicate when a statistical review is required. We consider this policy and provide guidance on when to recommend a manuscript for statistical evaluation. Indicators for statistical review include insufficient detail in methods or results, some common statistical issues and interpretation not based on the presented evidence. Reviewers are required to ensure that the manuscript is methodologically sound and clearly written. Within that context, they are expected to provide constructive feedback and opinion on the statistical design, analysis, presentation and interpretation. If reviewers lack the appropriate background to positively confirm the appropriateness of any of the manuscript’s statistical aspects, they are encouraged to recommend it for expert statistical review

A Machine Learning Trainable Model to Assess the Accuracy of Probabilistic Record Linkage

Record linkage (RL) is the process of identifying and linking data that relates to the same physical entity across multiple heterogeneous data sources. Deterministic linkage methods rely on the presence of common uniquely identifying attributes across all sources while probabilistic approaches use non-unique attributes and calculates similarity indexes for pair wise comparisons. A key component of record linkage is accuracy assessment — the process of manually verifying and validating matched pairs to further refine linkage parameters and increase its overall effectiveness. This process however is time-consuming and impractical when applied to large administrative data sources where millions of records must be linked. Additionally, it is potentially biased as the gold standard used is often the reviewer’s intuition. In this paper, we present an approach for assessing and refining the accuracy of probabilistic linkage based on different supervised machine learning methods (decision trees, naïve Bayes, logistic regression, random forest, linear support vector machines and gradient boosted trees). We used data sets extracted from huge Brazilian socioeconomic and public health care data sources. These models were evaluated using receiver operating characteristic plots, sensitivity, specificity and positive predictive values collected from a 10-fold cross-validation method. Results show that logistic regression outperforms other classifiers and enables the creation of a generalized, very accurate model to validate linkage results

Differential expression of factor XIIIa and CD34 in cutaneous mesenchymal tumors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73629/1/j.1600-0560.1993.tb00233.x.pd

Catalyst-Controlled Chemoselective Arylation of 2-Aminobenzimidazoles

What N would you like? The chemoselective and complementary Pd- and Cu-catalyzed N-arylation of 2-aminobenzimidazoles is described. Selective N-arylation of the amino group was achieved with a Pd-catalyzed method, while selective N-arylation of azole nitrogen was achieved with a Cu-catalyzed procedure (see scheme).National Institutes of Health (U.S.) (GM58160

Evaluation of magnetic resonance imaging guidelines for differentiation between thoracolumbar intervertebral disk extrusions and intervertebral disk protrusions in dogs

Four MRI variables have recently been suggested to be independently associated with a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion. Midline intervertebral disk herniation, and partial intervertebral disk degeneration were associated with intervertebral disk protrusion, while presence of a single intervertebral disk herniation and disk material dispersed beyond the boundaries of the intervertebral disk space were associated with intervertebral disk extrusion. The aim of this retrospective, cross‐sectional study was to determine whether using these MRI variables improves differentiation between thoracolumbar intervertebral disk extrusions and protrusions. Eighty large breed dogs with surgically confirmed thoracolumbar intervertebral disk extrusions or protrusions were included. Randomized MRI studies were presented on two occasions to six blinded observers, which were divided into three experience categories. During the first assessment, observers made a presumptive diagnosis of thoracolumbar intervertebral disk extrusion or protrusion without guidelines. During the second assessment they were asked to make a presumptive diagnosis with the aid of guidelines. Agreement was evaluated by Kappa‐statistics. Diagnostic accuracy significantly improved from 70.8 to 79.6% and interobserver agreement for making a diagnosis of intervertebral disk extrusion or intervertebral disk protrusion improved from fair (κ = 0.27) to moderate (κ = 0.41) after using the proposed guidelines. Diagnostic accuracy was significantly influenced by degree of observer experience. Intraobserver agreement for the assessed variables ranged from fair to excellent and interobserver agreement ranged from fair to moderate. The results of this study suggest that the proposed imaging guidelines can aid in differentiating thoracolumbar intervertebral disk extrusions from protrusions

Validation of methods for converting the original Disease Activity Score (DAS) to the DAS28

© The Author(s) 2018.The Disease Activity Score (DAS) is integral in tailoring the clinical management of rheumatoid arthritis (RA) patients and is an important measure in clinical research. Different versions have been developed over the years to improve reliability and ease of use. Combining the original DAS and the newer DAS28 data in both contemporary and historical studies is important for both primary and secondary data analyses. As such, a methodologically robust means of converting the old DAS to the new DAS28 measure would be invaluable. Using data from The Early RA Study (ERAS), a sub-sample of patients with both DAS and DAS28 data were used to develop new regression imputation formulas using the total DAS score (univariate), and using the separate components of the DAS score (multivariate). DAS were transformed to DAS28 using an existing formula quoted in the literature, and the newly developed formulas. Bland and Altman plots were used to compare the transformed DAS with the recorded DAS28 to ascertain levels of agreement. The current transformation formula tended to overestimate the true DAS28 score, particularly at the higher end of the scale. A formula which uses all separate components of the DAS was found to estimate the scores with a higher level of precision. A new formula is proposed that can be used by other early RA cohorts to convert the original DAS to DAS28.Peer reviewedFinal Published versio

The Diabetes Manual trial protocol – a cluster randomized controlled trial of a self-management intervention for type 2 diabetes [ISRCTN06315411]

Background The Diabetes Manual is a type 2 diabetes self-management programme based upon the clinically effective 'Heart Manual'. The 12 week programme is a complex intervention theoretically underpinned by self-efficacy theory. It is a one to one intervention meeting United Kingdom requirements for structured diabetes-education and is delivered within routine primary care. Methods/design In a two-group cluster randomized controlled trial, GP practices are allocated by computer minimisation to an intervention group or a six-month deferred intervention group. We aim to recruit 250 participants from 50 practices across central England. Eligibility criteria are adults able to undertake the programme with type 2 diabetes, not taking insulin, with HbA1c over 8% (first 12 months) and following an agreed protocol change over 7% (months 13 to 18). Following randomisation, intervention nurses receive two-day training and delivered the Diabetes Manual programme to participants. Deferred intervention nurses receive the training following six-month follow-up. Primary outcome is HbA1c with total and HDL cholesterol; blood pressure, body mass index; self-efficacy and quality of life as additional outcomes. Primary analysis is between-group HbA1c differences at 6 months powered to give 80% power to detect a difference in HbA1c of 0.6%. A 12 month cohort analysis will assess maintenance of effect and assess relationship between self-efficacy and outcomes, and a qualitative study is running alongside. Discussion This trial incorporates educational and psychological diabetes interventions into a single programme and assesses both clinical and psychosocial outcomes. The trial will increase our understanding of intervention transferability between conditions, those diabetes related health behaviours that are more or less susceptible to change through efficacy enhancing mechanisms and how this impacts on clinical outcomes

Validation of a digital photographic method for assessment of dietary quality of school lunch sandwiches brought from home.

Background: It is a challenge to assess children's dietary intake. The digital photographic method (DPM) may be an objective method that can overcome some of these challenges. Objective: The aim of this study was to evaluate the validity and reliability of a DPM to assess the quality of dietary intake from school lunch sandwiches brought from home among children aged 7–13 years. Design: School lunch sandwiches (n=191) were prepared to represent randomly selected school lunch sandwiches from a large database. All components were weighed to provide an objective measure of the composition. The lunches were photographed using a standardised DPM. From the digital images, the dietary components were estimated by a trained image analyst using weights or household measures and the dietary quality was assessed using a validated Meal Index of Dietary Quality (Meal IQ). The dietary components and the Meal IQ obtained from the digital images were validated against the objective weighed foods of the school lunch sandwiches. To determine interrater reliability, the digital images were evaluated by a second image analyst. Results: Correlation coefficients between the DPM and the weighed foods ranged from 0.89 to 0.97. The proportion of meals classified in the same or an adjacent quartile ranged from 98% (starch) to 100% (fruits, vegetables, fish, whole grain, and Meal IQ). There was no statistical difference between fish, fat, starch, whole grains, and Meal IQ using the two methods. Differences were found for fruits and vegetables; Bland–Altman analyses showed a tendency to underestimate high amounts of these variables using the DPM. For interrater reliability, kappa statistics ranged from 0.59 to 0.82 across the dietary components and Meal IQ. Conclusions: The standardised DPM is a valid and reliable method for assessing the dietary quality of school lunch sandwiches brought from home