Showing papers by "Michael Hughes published in 2016"

BSR and BHPR guideline for the treatment of systemic sclerosis

Abstract: SCOPE AND PURPOSE: SSc is a complex, multi-organ disease that requires a comprehensive multidisciplinary guideline. This is a short summary of the guideline, which is available in full as supplementary material at Rheumatology Online. Each recommendation is graded for level of evidence (I-IV) and strength (A-D). ELIGIBILITY AND EXCLUSION CRITERIA: Patients are classified as having SSc based on current classification criteria (ACR/EULAR 2013 [1]). Other scleroderma spectrum diseases are not included in this document.

In-utero triple antiretroviral exposure associated with decreased growth among HIV-exposed uninfected infants in Botswana.

Abstract: Objective:To assess associations between in-utero triple antiretrovirals (cART) versus zidovudine (ZDV) monotherapy exposure and growth among HIV-uninfected children of HIV-infected women in Botswana.Design:Secondary retrospective data analysis from two randomized intervention trials of mother-to-ch

Calcium channel blockers for primary Raynaud's phenomenon

Abstract: Background Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. This is an update of the review first published in 2014. Objectives To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant-preference scores and physiological measurements. Search methods For this update the Cochrane Vascular Trial Search Co-ordinator searched the Specialised Register (last searched January 2016) and the Cochrane Register of Studies (CENTRAL) (2015, Issue 12). In addition the TSC searched clinical trials databases. Selection criteria Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon. Data collection and analysis Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data. Main results We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999) suggesting little effect on severity. Participant-preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): none of these trials found any statistically significant between-treatment group differences. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). Overall, the trials were classed as being at low or unclear risk of bias; and the quality of the evidence presented was moderate for number of attacks, very low for duration of attacks, high for severity scores and low for patient preference scores. Authors' conclusions The randomised controlled trials included in this review provide moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks and high-quality evidence that they have little effect on severity. We are unable to comment on duration of attacks or on patient preference due to the very low and low quality of evidence as a result of small sample sizes in the included studies and the variable data quality of outcome measures.

Line-scanning fiber bundle endomicroscopy with a virtual detector slit.

Abstract: Coherent fiber bundles can be used to relay the image plane from the distal tip of an endomicroscope to an external confocal microscopy system. The frame rate is therefore determined by the speed of the microscope’s laser scanning system which, at 10-20 Hz, may be undesirably low for in vivo clinical applications. Line-scanning allows an increase in the frame rate by an order of magnitude in exchange for some loss of optical sectioning, but the width of the detector slit cannot easily be adapted to suit different imaging conditions. The rolling shutter of a CMOS camera can be used as a virtual detector slit for a bench-top line-scanning confocal microscope, and here we extend this idea to endomicroscopy. By synchronizing the camera rolling shutter with a scanning laser line we achieve confocal imaging with an electronically variable detector slit. This architecture allows us to acquire every other frame with the detector slit offset by a known distance, and we show that subtracting this second image leads to improved optical sectioning.

Autonomous Scanning for Endomicroscopic Mosaicing and 3D Fusion

Abstract: Robotic-assisted Minimally Invasive Surgery (RMIS) can benefit from the automation of common, repetitive or well-defined but ergonomically difficult tasks. One such task is the scanning of a pick-up endomicroscopy probe over a complex, undulating tissue surface in order to enhance the effective field-of-view through video mosaicing. In this paper, the da Vinci surgical robot, through the dVRK framework, is used for autonomous scanning and 2D mosaicing over a user-defined region of interest. To achieve the level of precision required for high quality large-area mosaic generation, which relies on sufficient overlap between consecutive image frames, visual servoing is performed using a tracking marker attached to the probe. The resulting sub-millimetre accuracy of the probe motion allows for the generation of large endomicroscopy mo- saics with minimal intervention from the surgeon. It also allows the probe to be maintained in an orientation perpendicular to the local tissue surface, providing optimal imaging results. Images are streamed from the endomicroscope and overlaid live onto the surgeons view, while 2D mosaics are generated in real-time, and fused into a 3D stereo reconstruction of the surgical scene, thus providing intuitive visualisation and fusion of the multi-scale images. The system therefore offers significant potential to enhance surgical procedures, by providing the operator with cellular-scale information over a larger area than could typically be achieved by manual scanning.

Haemoglobinopathies and the rheumatologist

Abstract: The haemoglobinopathies are a relatively common, heterogeneous group of inherited conditions that are the result of either a quantitative abnormality (e.g. thalassaemia) or structural [e.g. sickle cell anaemia (SCA)] of the globin part of the haemoglobin molecule. Musculoskeletal (MSK) complications are common in patients with haemoglobinopathies and may affect the whole of the MSK system, in addition to bone, which is the primary site of the disease. Typical MSK complications include painful vaso-occlusive disease and osteomyelitis in SCA and reduced BMD in thalassaemia. Patients may also develop a number of related (e.g. gout) or unrelated rheumatic diseases (e.g. inflammatory arthritis and autoimmune CTDs). Treatment of MSK conditions in patients with haemoglobinopathies may be challenging (e.g. bone marrow suppression from disease-modifying agents) and in particular in SCA, steroid therapy (by any route) may precipitate potentially severe vaso-occlusive complications. Rheumatologists need to be aware of the range of MSK complications, treatment challenges and the need for such patients to be managed as part of a dedicated multidisciplinary team alongside haematology.

Thermographic Abnormalities are Associated with Future Digital Ulcers and Death in Patients with Systemic Sclerosis.

Abstract: Objective. Capillaroscopic abnormalities are predictive of future digital ulcers (DU). Our aim was to investigate whether functional digital vascular disease (thermographically assessed) is also associated with future DU. Methods. A retrospective case note review of patients with systemic sclerosis (SSc) undergoing thermography and who were followed for up to about 3 years. Results. There were 138 patients (equal mixture of normal/abnormal thermography). Patients with abnormal thermography were more likely to develop DU (clinician-observed and/or patient-reported, OR 2.84, p = 0.021), including multiple episodes, and more likely to die (OR 5.42, p = 0.050). Conclusion. Abnormal thermography is associated with DU and disease severity in patients with SSc.

Does the Clinical Context Improve the Reliability of Rheumatologists Grading Digital Ulcers in Systemic Sclerosis

Abstract: OBJECTIVES: Digital ulcers (DUs) are often a primary end point in systemic sclerosis (SSc) clinical trials, although the reliability of rheumatologists grading DUs is poor to moderate at best. DU assessment in recent trials has been based upon visual inspection alone, which potentially misses 'real-world' clinical contextual information. Our aim was to investigate whether this clinical information improves the reliability of rheumatologists grading DUs. A secondary aim was to assess agreement between patients and rheumatologists. METHOD: Eighty images of a range of digital lesions were collected from patients with SSc with the clinical context: pain (severity and temporal relationship), lesion duration and discharge (patient reported and clinician observed). Raters received all images either with or without the clinical context, and graded these images (using a custom-built interface) on an ordinal scale of severity: 'no ulcer', 'inactive ulcer' or 'active ulcer'. Patients also graded their lesion/s on the same scale. RESULTS: Fifty-one rheumatologists from 15 countries completed the study (26 without and 25 with context): 4590 (including 510 repeated) image gradings were obtained. Context did not significantly increase (without and with context) either intra- (0.64,0.71) or inter-rater (0.32,0.36) reliability. Pain (VAS and temporal relationship) and discharge (patient reported and clinician observed) were associated with increased lesion severity, and duration with reduced severity. Agreement between individual patients and rheumatologists was poor without and with context (0.19,0.28). CONCLUSION: The overall intra and inter-rater reliability of DU grading did not significantly improve with the clinical context. Agreement between patients and rheumatologists was poor. This article is protected by copyright. All rights reserved.

Novel Balloon Surface Scanning Device for Intraoperative Breast Endomicroscopy.

Abstract: Recent advances in fluorescence confocal endomicroscopy have allowed real-time identification of residual tumour cells on the walls of the cavity left by breast conserving surgery. However, it is difficult to systematically survey the surgical site because of the small imaging field-of-view of these probes, compounded by tissue deformation and inconsistent probe-tissue contact when operated manually. Therefore, a new robotized scanning device is required for controlled, large area scanning and mosaicing. This paper presents a robotic scanning probe with an inflatable balloon, providing stable cavity scanning over undulating surfaces. It has a compact design, with an outer diameter of 4 mm and a working channel of 2.2 mm, suitable for a leached flexible fibre bundle endomicroscope probe. With the probe inserted, the tip positioning accuracy measured to be 0.26 mm for bending and 0.17 mm for rotational motions. Large area scanning was achieved (25–35 mm2) and the experimental results demonstrate the potential clinical value of the device for intraoperative cavity tumour margin evaluation.

Nonnucleoside Reverse-transcriptase Inhibitor- vs Ritonavir-boosted Protease Inhibitor-based Regimens for Initial Treatment of HIV Infection: A Systematic Review and Metaanalysis of Randomized Trials.

Abstract: Background Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. Methods We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. Results We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). Conclusions We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

Hyperlipidaemia in HIV-infected patients on lopinavir/ritonavir monotherapy in resource-limited settings.

Abstract: BackgroundCardiovascular disease (CVD) is an emerging concern for HIV-infected patients. Hyperlipidaemia is a risk factor for CVD and a complication of protease-inhibitor-based antiretroviral thera...

Do Negative Changes in Worldview Mediate Links Between Mass Trauma and Reckless Behavior? A Longitudinal Exploratory Study

Abstract: Trauma exposure heightens the risk of reckless behavior and is now included in DSM-5 posttraumatic stress disorder symptomatology. Individuals exposed to trauma may be likely to engage in reckless behavior because of negative changes in their worldview (referred to as disrupted worldview). The current study investigates the relationship between DSM-IV posttraumatic stress symptoms, disrupted worldview, and increased reckless behavior among 1145 students exposed to mass violence. Total posttraumatic stress symptomatology was associated with increased and persistent reckless behavior, supporting DSM-5 diagnostic inclusion. Although posttraumatic stress symptomatology predicted reckless behavior among those with varying levels of posttraumatic symptomatology, individuals with high symptomatology reported significantly higher recklessness. Disrupted worldview mediated the relationship between posttraumatic symptomatology and reckless behavior among individuals with high symptomatology, while only partially mediating the relationship among those with low symptomatology. These findings provide support for worldview disruptions as a mechanism by which prolonged reckless behavior may be manifested.

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

Abstract: Background: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression.Methods: Participants were the 911 HIV-infected antiretroviral-naive adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks).Results: During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compar...

Evaluating predictors of competing risk outcomes when censoring depends on time-dependent covariates, with application to safety and efficacy of HIV treatment

Abstract: We propose a prediction model for the cumulative incidence functions of competing risks, based on a logit link. Because of a concern about censoring potentially depending on time-varying covariates in our motivating human immunodeficiency virus (HIV) application, we describe an approach for estimating the parameters in the prediction models using inverse probability of censoring weighting under a missingness at random assumption. We then illustrate the application of this methodology to identify predictors of the competing outcomes of virologic failure, an efficacy outcome, and treatment limiting adverse event, a safety outcome, among human immunodeficiency virus-infected patients first starting antiretroviral treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Method for modeling radiative transport in luminescent particulate media.

Abstract: Modeling radiative transport in luminescent particulate media is important to a variety of applications, from biomedical imaging to solar power harvesting. When absorption and scattering from individual particles must be considered, the description of radiative transport is not straightforward. For large particles and interparticle spacing, geometrical optics can be employed. However, this approach requires accurate knowledge of several particle properties, such as index of refraction and absorption coefficient, along with particle geometry and positioning. Because the determination of these variables is often nontrivial, we developed an approach for modeling radiative transport in such media, which combines two simple experiments with Monte Carlo simulations to determine the particle extinction coefficient (Γ) and the probability of absorption of light by a particle (PA). The method is validated on samples consisting of luminescent phosphor powder dispersed in a silicone matrix.

Coexistent digital gouty and infective flexor tenosynovitis

Abstract: Flexor tenosynovitis of the hand is often caused by trauma or infection. Gouty tenosynovitis is an uncommon presentation of the condition and is usually misdiagnosed as infection with the patient undergoing surgery. The coexistence of infection and gout causing flexor tenosynovitis has never been described before in the literature; we report the first ever case and emphasise the importance of its awareness for optimal treatment. A 54-year-old man was initially diagnosed and treated as having infective flexor tenosynovitis and, later, due to a lack of improvement in his symptoms, was discovered to also have gout. We review the literature and suggest management strategy for use in daily clinical practice, including an algorithm, for this presentation.