Plan quality assessment of modern radiosurgery technologies in the treatment of multiple brain metastases.

Stereotactic radiosurgery (SRS) of multiple brain metastases has evolved over the last 40 years allowing centres to treat an increasing number of brain metastases in a single treatment fraction. HyperArcTMplanning optimisation technique is one such development that streamlines the treatment of multiple metastases with a single isocentre. Several studies have investigated the plan quality of HyperArc compared to CyberKnife or Gamma Knife, however there are limited number of studies that include all three modalities. It is the aim of this study to provide an assessment of plan quality between the three SRS platforms across ten patients with multiple brain metastases ranging from three to eight metastases per patient. Strict planning workflows were established to avoid bias towards any particular treatment platform. Plan quality was assessed through dose to organs at risk, Paddick conformity index (PCI), gradient index (GI), global efficiency index (Gη) and dose to normal brain tissue. Results from this study found mean PCI observed across Gamma Knife plans was significantly lower than HyperArc and CyberKnife. HyperArc plans observed significantly shorter beam-on times which were 10 to 20 times faster than CyberKnife and Gamma Knife plans. Gamma Knife and CyberKnife were found to produce plans with significantly superior GI, global efficiency index and the volume of healthy brain receiving greater than 12 Gy (V12Gy) when compared to HyperArc plans. Lesion volume was seen to influence the relative difference in dose metrics between systems. The study revealed that all three treatment modalities produced high quality plans for the SRS treatment of multiple brain metastases, each with respective benefits and limitations.

Impact of mismatches in HbA1c vs glucose values on the diagnostic classification of diabetes and prediabetes.

AIMS: To determine whether HbA1c mismatches (HbA1c levels that are higher or lower than expected for the average glucose levels in different individuals) could lead to errors if diagnostic classification is based only on HbA1c levels. METHODS: In a cross-sectional study, 3106 participants without known diabetes underwent a 75-g oral glucose tolerance test (fasting glucose and 2-h glucose) and a 50-g glucose challenge test (1-h glucose) on separate days. They were classified by oral glucose tolerance test results as having: normal glucose metabolism; prediabetes; or diabetes. Predicted HbA1c was determined from the linear regression modelling the relationship between observed HbA1c and average glucose (mean of fasting glucose and 2-h glucose from the oral glucose tolerance test, and 1-h glucose from the glucose challenge test) within oral glucose tolerance test groups. The haemoglobin glycation index was calculated as [observed - predicted HbA1c ], and divided into low, intermediate and high haemoglobin glycation index mismatch tertiles. RESULTS: Those participants with higher mismatches were more likely to be black, to be men, to be older, and to have higher BMI (all P<0.001). Using oral glucose tolerance test criteria, the distribution of normal glucose metabolism, prediabetes and diabetes was similar across mismatch tertiles; however, using HbA1c criteria, the participants with low mismatches were classified as 97% normal glucose metabolism, 3% prediabetes and 0% diabetes, i.e. mostly normal, while those with high mismatches were classified as 13% normal glucose metabolism, 77% prediabetes and 10% diabetes, i.e. mostly abnormal (P<0.001). CONCLUSIONS: Measuring only HbA1c could lead to under-diagnosis in people with low mismatches and over-diagnosis in those with high mismatches. Additional oral glucose tolerance tests and/or fasting glucose testing to complement HbA1c in diagnostic classification should be performed in most individuals.

Determination of size distributions of non-spherical pores or particles from single x-ray phase contrast images.

Although x-ray tomography is commonly used to characterize the three-dimensional structure of materials, sometimes this is impractical due either to limited time for data collection (such as in rapidly-evolving systems) or the need to limit the radiation exposure of the sample. In such situations, it is desirable to extract as much information as possible from a more limited data set. In this paper, we describe how to extract the size distribution of non-spherical pores (or, equivalently, particles) from single x-ray phase contrast imaging (XPCI). Because the pores overlap in projection, interpreting the images and extracting quantitative information about the size distribution is non-trivial. In this paper we extend a previously-developed Fourier-based framework for interpreting the speckle pattern of XPCI images from materials with spherical pores to the more challenging case of non-spherical pores. We develop an analytical expression for the XPCI image from a distribution of randomly-oriented ellipsoidal pores, and show that we can use this expression to extract quantitative information about the size distribution from single images. We discuss three approaches to evaluating this expression, corresponding to different assumptions about the nature of the size distribution, and validate our results with simulated XPCI images and experimental data from Berea sandstone.

Combining online and in-person methods to evaluate the content validity of PROMIS fatigue short forms in rheumatoid arthritis.

PURPOSE: Fatigue is frequent and often severe and disabling in RA, and there is no consensus on how to measure it. We used online surveys and in-person interviews to evaluate PROMIS Fatigue 7a and 8a short forms (SFs) in people with RA. METHODS: We recruited people with RA from an online patient community (n = 200) and three academic medical centers (n = 84) in the US. Participants completed both SFs then rated the comprehensiveness and comprehensibility of the items to their fatigue experience. Cognitive debriefing of items was conducted in a subset of 32 clinic patients. Descriptive statistics were calculated, and associations were evaluated using Pearson and Spearman correlation coefficients. RESULTS: Mean SF scores were similar (p ≥ .61) among clinic patients reflecting mild fatigue (i.e., 54.5-55.9), but were significantly higher (p < .001) in online participants. SF Fatigue scores correlated highly (r ≥ 0.82; p < .000) and moderately with patient assessments of disease activity (r ≥ 0.62; p = .000). Most (70-92%) reported that the items "completely" or "mostly" reflected their experience. Almost all (≥ 94%) could distinguish general fatigue from RA fatigue. Most (≥ 85%) rated individual items questions as "somewhat" or "very relevant" to their fatigue experience, averaged their fatigue over the past 7 days (58%), and rated fatigue impact versus severity (72 vs. 19%). 99% rated fatigue as an important symptom they considered when deciding how well their current treatment was controlling their RA. CONCLUSIONS: Results suggest that items in the single-score PROMIS Fatigue SFs demonstrate content validity and can adequately capture the wide range of fatigue experiences of people with RA.

Distal longitudinal deformation of a Synergy stent by jailed Rotawire guidewire.

Recent advances in stent technology have led to the development of thin strut platforms with fewer connectors. This has improved delivery but compromised strength, as illustrated by recent cases of longitudinal compression. We present an unusual case of longitudinal shortening at the distal end of a Synergy stent.

2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis

OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis

"OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies."

2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis

OBJECTIVE: To develop a new evidence-based, pharmacologic treatment guideline for rheumatoid arthritis (RA). METHODS: We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. RESULTS: The guideline covers the use of traditional disease-modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat-to-target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. CONCLUSION: This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision-making process taking into account patients' values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Sub-Nyquist field trial using time frequency packed DP-QPSK super-channel within fixed ITU-T grid.

Sub-Nyquist time frequency packing technique was demonstrated for the first time in a super-channel field trial transmission over long-haul distances. The technique allows a limited spectral occupancy even with low order modulation formats. The transmission was successfully performed on a deployed Australian link between Sydney and Melbourne which included 995 km of uncompensated SMF with coexistent traffic. 40 and 100 Gb/s co-propagating channels were transmitted together with the super-channel in a 50 GHz ITU-T grid without additional penalty. The super-channel consisted of eight sub-channels with low-level modulation format, i.e. DP-QPSK, guaranteeing better OSNR robustness and reduced complexity with respect to higher order formats. At the receiver side, coherent detection was used together with iterative maximum-a-posteriori (MAP) detection and decoding. A 975 Gb/s DP-QPSK super-channel was successfully transmitted between Sydney and Melbourne within four 50GHz WSS channels (200 GHz). A maximum potential SE of 5.58 bit/s/Hz was achieved with an OSNR = 15.8 dB, comparable to the OSNR of the installed 100 Gb/s channels. The system reliability was proven through long term measurements. In addition, by closing the link in a loop back configuration, a potential SE∙d product of 9254 bit/s/Hz·km was achieved.

Oral Mycostatin as a possible alternative treatment for intractable Ménière's disease: preliminary cohort study.

Background: The potential efficacy of antifungal agents (e.g. Mycostatin) in treating acute attacks of Ménière's disease was first suggested in 1983 but few data have been published. Oral Mycostatin has been used as second-line medical treatment for intractable Ménière's disease at our institution for many years. Objective: This preliminary cohort study investigated the role of oral Mycostatin in intractable Ménière's disease. Methods: A retrospective review of patients with intractable Ménière's disease who started oral Mycostatin treatment between 2010 and 2012 was conducted. Results: Of 256 patients presenting with vertiginous disorders, 26 had definite Ménière's disease and had not responded to standard first-line treatment. Following oral Mycostatin treatment, improvements were reported for vertigo (n = 8), aural fullness (n = 7), tinnitus (n = 3) and subjective hearing loss (n = 3). Half of those with symptom improvement persisted with oral Mycostatin for two years and continued to remain asymptomatic. Conclusion: The use of oral Mycostatin to alleviate symptoms of intractable Ménière's disease showed promising results in this case series. Mycostatin may offer a safe and useful alternative for the management of Ménière's disease for patients with chronic unremitting symptoms in whom first-line treatment options have failed.

A survey of training in pediatric flexible bronchoscopy.

OBJECTIVE: There is currently no evidence-based method for defining competency in pediatric flexible bronchoscopy (FB). Based on expert opinion, guidelines using numbers of procedures have been published in defining competency for pediatric FB. The purpose of this study was to formally survey the opinion of USA pediatric pulmonology training directors about the assessment of competency and training experiences in pediatric FB in their programs. METHODS: An Internet-based Survey Monkey™ of the Pediatric Pulmonary Training Directors Association (PEPTDA) was administered 10/12/10 through 11/1/10 with a supplemental survey 6/1/11-6/30/11. RESULTS: This survey of US pediatric pulmonology training directors about competency and training in pediatric FB showed that a majority (86%) felt there was a minimum threshold of procedures for developing competency that could be defined, with a median of 50 and an average of 56.4 (SD = 33.0). The actual number of FBs performed by fellows during their 3-year fellowship averaged 89.4 (SD = 45.3) with a range of 10-200. The survey also revealed a variety of teaching techniques used for FB, including simulation technology. Finally many differences were reported in skill assessment, locations for performance of FB, and the range of underlying indications and patient populations. The apprenticeship model is the predominant method of learning FB in the surveyed programs. CONCLUSIONS: A majority of US pediatric pulmonology training directors felt that a minimum number of procedures could be defined for developing competency in pediatric FB. There was variability in the numbers of procedures performed, training techniques and assessment, and application of FB. This survey represents an initial step in assessing training and defining competency in pediatric FB.

A simple method to prevent the obstruction of post-tympanoplasty ventilation tubes.

The simultaneous insertion of a ventilation tube or grommet during tympanoplasty is a well-recognised practice among otologists. It is used to reverse atelectasis and to repneumatise the middle ear. A troublesome problem which can occur is post-operative, intraluminal grommet obstruction by blood or viscous mucoid secretions. Routine post-operative use of eardrops may help prevent grommet obstruction but cannot be administered after tympanoplasty when the ear canal is packed with dressings for up to three weeks post-operatively. In this article, we describe a simple method to prevent post-tympanoplasty grommet obstruction.

Sudden bilateral sensorineural hearing loss associated with urticarial vasculitis.

BACKGROUND: Bilateral sensorineural hearing loss associated with recurrent urticarial skin lesions may be signs of underlying Muckle-Wells syndrome. Previous reports have described the hearing loss to be progressive in nature. METHOD: To our knowledge, this paper presents the first published case of sudden onset, bilateral sensorineural hearing loss associated with urticarial vasculitis due to underlying Muckle-Wells syndrome. RESULTS: The patient underwent a cochlear implantation with a modest outcome. CONCLUSION: Cochlear implantation may help to rehabilitate sudden hearing loss associated with this condition, but early diagnosis may allow treatment with interleukin-1ß inhibitors such as anakinra.

Multinodular thyroid goitre causing obstructive sleep apnoea syndrome.

BACKGROUND: Obstructive sleep apnoea syndrome has been linked to obesity, nasal obstruction and adenotonsillar hypertrophy, but rarely to large thyroid goitres. OBJECTIVE: To study the possible association between multinodular retrolaryngo-pharyngeal or retrosternal goitres and obstructive sleep apnoea syndrome. SUBJECTS AND METHODS: Retrospective case series at a tertiary referral centre (2000-2010). Study parameters included body mass index, Epworth sleep score and polysomnographic index. RESULTS: Five patients were diagnosed with obstructive sleep apnoea syndrome and managed with nasal continuous positive airway pressure ventilation. Computed tomography showed a retrolaryngo-pharyngeal or retrosternal goitre with significant tracheal compression, displacement and laryngeal oedema. After total thyroidectomy, obstructive sleep apnoea resolved in all patients. CONCLUSION: Large, multinodular goitres with retrolaryngo-pharyngeal extension can cause obstructive sleep apnoea syndrome due to laryngeal compression and oedema. In such cases, total thyroidectomy enables resolution of symptoms. Patients with obstructive sleep apnoea syndrome should be screened for thyroid goitre.

Lymphoproliferative disorder of nasopharynx after long-standing cyclosporin therapy for psoriatic arthritis.

BACKGROUND: The increased risk of developing lymphoproliferative disorders, mainly linked with Epstein-Barr virus infection, is well documented in patients with cyclosporin-induced immunosuppression following organ transplantation. Lymphoproliferative disease is extremely rare in the non-transplant setting. METHODS: We present the first published case of non-Epstein-Barr virus associated lymphoproliferative disease in a patient receiving long-standing cyclosporin therapy for psoriatic arthritis, which presented as a recurrent nasopharyngeal mass. RESULTS: Histological examination showed lymphoid hyperplasia in repeated biopsies. Macroscopic clearance was persistently followed by aggressive recurrence. Spontaneous regression occurred upon cyclosporin withdrawal. CONCLUSION: This rare complication of cyclosporin therapy in non-transplant patients is highlighted from an otolaryngological perspective, as the sole presentation may be a recurrent nasopharyngeal mass. Repeated biopsies showing lymphoid hyperplasia, together with aggressive recurrence, should prompt immediate drug withdrawal to reduce immunosuppression and promote spontaneous regression.

Vaginal repair with mesh versus colporrhaphy for prolapse: a randomised controlled trial.

OBJECTIVE: To compare vaginal repair augmented by mesh with traditional colporrhaphy for the treatment of pelvic organ prolapse. DESIGN: Prospective randomised controlled trial. SETTING: Tertiary teaching hospital. POPULATION: One hundred and thirty-nine women with stage >or=2 prolapse according to the pelvic organ prolapse quantification (POP-Q) system requiring both anterior and posterior compartment repair. METHODS: Subjects were randomised to anterior and posterior vaginal repair with mesh augmentation (mesh group, n = 69) or traditional anterior and posterior colporrhaphy (no mesh group, n = 70). MAIN OUTCOME MEASURES: The primary outcome was the absence of POP-Q stage >or=2 prolapse at 12 months. Secondary outcomes were symptoms, quality-of-life outcomes and satisfaction with surgery. Complications were also reported. RESULTS: For subjects attending the 12-month review, success in the mesh group was 81.0% (51 of 63 subjects) compared with 65.6% (40/61) in the no mesh group and was not significantly different (P-value = 0.07). A high level of satisfaction with surgery and improvements in symptoms and quality-of-life data were observed at 12 months compared to baseline in both groups, but there was no significant difference in these outcomes between the two groups. Vaginal mesh exposure occurred in four women in the mesh group (5.6%). De novo dyspareunia was reported by five of 30 (16.7%) sexually active women in the mesh group and five of 33 (15.2%) in the no mesh group at 12 months. CONCLUSION: In this study, vaginal surgery augmented by mesh did not result in significantly less recurrent prolapse than traditional colporrhaphy 12 months following surgery.