Isotretinoin-induced skeletal hyperostosis

We describe a case of skeletal hyperostosis in a 29 year old man presenting with non-inflammatory back pain with a past history of isotretinoin therapy for acne. The development of skeletal hyperostosis, predominantly of the spine, has been reported in association with isotretinoin use and has a radiographic picture similar to diffuse idiopathic skeletal hyperostosis. The prevalence and severity of this condition appears to correlate with duration of therapy. Isotretinoin is a well-established treatment for severe acne. It is important for the rheumatologist be aware of this phenomenon when assessing young patients with musculoskeletal symptoms and evidence of radiological abnormalities.Scott W Graf, and Samuel L Whittl

Prioritization of clinical questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis

OnlinePublAim: Living guidelines aim to reduce delays in translating new knowledge into practice by updating individual recommendations as soon as relevant new evidence emerges. We surveyed members of the Australian Rheumatology Association (ARA) to develop a list of priority questions for the Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis (ALG) and to explore clinicians' use of clinical practice guidelines. Methods: An electronic survey of ARA members was performed in two phases. The first survey contained questions about current guideline use and beliefs and invited participants to submit at least three questions relevant to the management of rheumatoid arthritis (RA). In the second round, participants selected 10 questions they considered to be the highest priority from the collated list and ranked them in priority order. The sum of ranks was used to generate a final priority list. Results: There were 115 (21%) and 78 (14%) responses to the first and second survey rounds respectively. 87% of respondents use existing rheumatology guidelines in their usual practice, primarily EULAR guidelines. Most respondents favored the development of Australian rheumatology guidelines. In total, 34 potential recommendation topics were identified and ranked in order of priority. Conclusion: A list of 34 clinical questions about RA management, ranked in order of importance by clinicians, has informed the development of the ALG. Similar prioritization exercises in other contexts may permit guidelines to be tailored to the needs of guideline users in their specific context, which may facilitate international collaboration and promote efficient translation of evidence to practice.Samuel L. Whittle, Vanessa Glennon, Rachelle Buchbinde

Low-bias RNA sequencing of the HIV-2 genome from blood plasma

Accurate determination of the genetic diversity present in the HIV quasispecies is critical for the development of a preventative vaccine: in particular, little is known about viral genetic diversity for the second type of HIV, HIV-2. A better understanding of HIV-2 biology is relevant to the HIV vaccine field because a substantial proportion of infected people experience long-term viral control, and prior HIV-2 infection has been associated with slower HIV-1 disease progression in coinfected subjects. The majority of traditional and next-generation sequencing methods have relied on target amplification prior to sequencing, introducing biases that may obscure the true signals of diversity in the viral population. Additionally, target enrichment through PCR requires a priori sequence knowledge, which is lacking for HIV-2. Therefore, a target enrichment free method of library preparation would be valuable for the field. We applied an RNA shotgun sequencing (RNA-Seq) method without PCR amplification to cultured viral stocks and patient plasma samples from HIV-2-infected individuals. Libraries generated from total plasma RNA were analyzed with a two-step pipeline: (i) de novo genome assembly, followed by (ii) read remapping. By this approach, whole-genome sequences were generated with a 28× to 67× mean depth of coverage. Assembled reads showed a low level of GC bias, and comparison of the genome diversities at the intrahost level showed low diversity in the accessory gene vpx in all patients. Our study demonstrates that RNA-Seq is a feasible full-genome de novo sequencing method for blood plasma samples collected from HIV-2-infected individuals.IMPORTANCE An accurate picture of viral genetic diversity is critical for the development of a globally effective HIV vaccine. However, sequencing strategies are often complicated by target enrichment prior to sequencing, introducing biases that can distort variant frequencies, which are not easily corrected for in downstream analyses. Additionally, detailed a priori sequence knowledge is needed to inform robust primer design when employing PCR amplification, a factor that is often lacking when working with tropical diseases localized in developing countries. Previous work has demonstrated that direct RNA shotgun sequencing (RNA-Seq) can be used to circumvent these issues for hepatitis C virus (HCV) and norovirus. We applied RNA-Seq to total RNA extracted from HIV-2 blood plasma samples, demonstrating the applicability of this technique to HIV-2 and allowing us to generate a dynamic picture of genetic diversity over the whole genome of HIV-2 in the context of low-bias sequencing

Vaccination Rates, Perceptions, and Information Sources Used by People With Inflammatory Arthritis

Objective. To determine vaccination rates, perceptions, and information sources in people with inflammatory arthritis. Methods. Participants enrolled in the Australian Rheumatology Association Database were invited to participate in an online questionnaire, conducted in January 2020, prior to the COVID-19 pandemic. Included questions were about vaccination history, modified World Health Organization Vaccination Hesitancy Scale, views of the information sources consulted, the Beliefs About Medicines Questionnaire, education, and the Single-Item Health Literacy Screener. Results. Response rate was 994 of 1498 (66%). The median age of participants was 62 years, with 67% female. Self-reported adherence was 83% for the influenza vaccine. Participants generally expressed positive vaccination views, particularly regarding safety, efficacy, and access. However, only 43% knew which vaccines were recommended for them. Vaccine hesitancy was primarily attributable to uncertainty and a perceived lack of information about which vaccines were recommended. Participants consulted multiple vaccination information sources (median 3, interquartile range 2-7). General practitioners (89%) and rheumatologists (76%) were the most frequently used information sources and were most likely to yield positive views. Negative views of vaccination were most often from internet chatrooms, social media, and mainstream media. Factors of younger age, male gender, and having more concerns about the harms and overuse of medicines in general were associated with lower adherence and greater uncertainty about vaccinations, whereas education and self-reported literacy were not. Conclusion. Participants with inflammatory arthritis generally held positive views about vaccination, although there was considerable uncertainty as to which vaccinations were recommended for them. This study highlights the need for improved consumer information about vaccination recommendations for people with inflammatory arthritis.Andrea Lyon, Alannah Quinlivan, Susan Lester, Claire Barrett, Samuel L. Whittle, Debra Rowett, Rachel Black, Premarani Sinnathurai, Lyn March, Rachelle Buchbinder, and Catherine L. Hil

Australian recommendations on perioperative use of disease-modifying anti-rheumatic drugs in people with inflammatory arthritis undergoing elective surgery.

OnlinePublDisease-modifying antirheumatic drugs (DMARDs) are effective treatments for inflammatory arthritis but carry an increased risk of infection. For patients undergoing surgery there is a need to consider the trade-off between a theoretical increased risk of infection with continuation of DMARDs perioperatively versus an increased risk of disease flare if they are temporarily withheld. We used GRADE methodology to develop recommendations for perioperative use of DMARDs for people with inflammatory arthritis undergoing elective surgery. The recommendations form part of the NHMRC-endorsed Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis. Conditional recommendations were made against routinely discontinuing conventional synthetic (cs) and biologic (b) DMARDs in the perioperative period but to consider temporary discontinuation of bDMARDs in individuals with a high risk of infection or where the impact of infection would be severe. A conditional recommendation was made in favour of temporary discontinuation of targeted synthetic (ts) DMARDs in the perioperative period.Rachelle Buchbinder, Vanessa Glennon, Renea V. Johnston, Sue E. Brennan, Chris Fong, Suzie Edward May, Sean O, Neill, Peter Smitham, Lyndal Trevena, Glen Whittaker, Anita Wluka, and Samuel L. Whittl

Which clinical research questions are the most important? Development and preliminary validation of the Australia & New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network Research Question Importance Tool (ANZMUSC-RQIT).

Background and aims High quality clinical research that addresses important questions requires significant resources. In resource-constrained environments, projects will therefore need to be prioritized. The Australia and New Zealand Musculoskeletal (ANZMUSC) Clinical Trials Network aimed to develop a stakeholder-based, transparent, easily implementable tool that provides a score for the 'importance' of a research question which could be used to rank research projects in order of importance. Methods Using a mixed-methods, multi-stage approach that included a Delphi survey, consensus workshop, inter-rater reliability testing, validity testing and calibration using a discrete-choice methodology, the Research Question Importance Tool (ANZMUSC-RQIT) was developed. The tool incorporated broad stakeholder opinion, including consumers, at each stage and is designed for scoring by committee consensus. Results The ANZMUSC-RQIT tool consists of 5 dimensions (compared to 6 dimensions for an earlier version of RQIT): (1) extent of stakeholder consensus, (2) social burden of health condition, (3) patient burden of health condition, (4) anticipated effectiveness of proposed intervention, and (5) extent to which health equity is addressed by the research. Each dimension is assessed by defining ordered levels of a relevant attribute and by assigning a score to each level. The scores for the dimensions are then summed to obtain an overall ANZMUSC-RQIT score, which represents the importance of the research question. The result is a score on an interval scale with an arbitrary unit, ranging from 0 (minimal importance) to 1000. The ANZMUSC-RQIT dimensions can be reliably ordered by committee consensus (ICC 0.73-0.93) and the overall score is positively associated with citation count (standardised regression coefficient 0.33, p<0.001) and journal impact factor group (OR 6.78, 95% CI 3.17 to 14.50 for 3rd tertile compared to 1st tertile of ANZMUSC-RQIT scores) for 200 published musculoskeletal clinical trials. Conclusion We propose that the ANZMUSC-RQIT is a useful tool for prioritising the importance of a research question.William J. Taylor, Robin Willink, Denise A. O, Connor, Vinay Patel, Allison Bourne, Ian A. Harris, Samuel L. Whittle, Bethan Richards, Ornella Clavisi, Sally Green, Rana S. Hinman, Chris G. Maher, Ainslie Cahill, Annie McPherson, Charlotte Hewson, Suzie E. May, Bruce Walker, Philip C. Robinson, Davina Ghersi, Jane Fitzpatrick, Tania Winzenberg, Kieran Fallon, Paul Glasziou, Laurent Billot, Rachelle Buchbinde

Patients' experience of shoulder disorders

Objectives: To describe the experiences (including symptoms and perceived impacts on daily living) of people with a shoulder disorder. Methods: Systematic review of qualitative studies. We searched for eligible qualitative studies indexed in Ovid MEDLINE, Ovid Embase, CINAHL (EBSCO), SportDiscus (EBSCO) and Ovid PsycINFO up until November 2017. Two authors independently screened studies for inclusion, appraised their methodological quality using the Critical Appraisal Skills Programme checklist, used thematic synthesis methods to generate themes describing the experiences reported by participants and assessed the confidence in the findings using the Grading of Recommendations Assessment, Development and Evaluation Confidence in Evidence fro

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available