Showing papers by "Michael Hughes published in 2020"

The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements

Abstract: Summary Background Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. Methods Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. Findings Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. Interpretation Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. Funding An unrestricted grant from Boehringer Ingelheim International.

Raynaud phenomenon and digital ulcers in systemic sclerosis.

Abstract: Raynaud phenomenon is a symptom complex caused by impaired digital perfusion and can occur as a primary phenomenon or secondary to a wide range of underlying causes. Raynaud phenomenon occurs in virtually all patients with systemic sclerosis (SSc) and is often the earliest clinical manifestation to occur. Careful assessment is required in patients with Raynaud phenomenon to avoid missing secondary causes such as SSc. Digital ulcers are a painful and disabling visible manifestation of digital vascular injury in patients with SSc. Progress has been made in the classification and assessment of digital ulcers and in understanding ulcer pathogenesis, and there are a wide range of treatments available to both prevent and heal digital ulcers, some of which are also used in Raynaud phenomenon management. In this Review, the assessment of patients with Raynaud phenomenon is discussed, including 'red flags' that are suggestive of SSc. The pathogenesis, classification and assessment of SSc-associated digital ulcers are also covered, alongside an overview of management approaches for SSc-associated Raynaud phenomenon and digital ulcers. Finally, unmet needs are discussed and the concept of a unified vascular phenotype in which therapies that affect the vasculature to support disease modification strategies is introduced.

Learning Loss, a Potential Challenge for Transition to Undergraduate Study Following COVID19 School Disruption

Abstract: In a normal year approximately 3 months pass between students taking their final examinations in high school or college and beginning an undergraduate course in chemistry. In the months prior to those examinations, students will usually have undertaken an extensive period of revision and consolidation of the key concepts learned throughout their course. Some of this will be supported by their teachers and some will be independent study. The COVID19 pandemic resulted in the cancellation of these examinations in the UK and Ireland, potentially leaving students with a 6-month gap between their last formal study and beginning their undergraduate courses. Insights from the literature and from teachers of students in the 16–18 age range show that it is likely students beginning undergraduate courses in the autumn of 2020 will have weaknesses in subject knowledge compared to previous cohorts. This is likely to be more significant in the areas of synthetic transformations in organic chemistry and core physical chemistry topics. In this communication we present a brief analysis of the potential issues with subject knowledge in order that instructors in higher education may be better informed about the potential challenges in teaching and learning following the COVID19 disruption.

Multicenter Qualitative Study Exploring the Patient Experience of Digital Ulcers in Systemic Sclerosis.

Abstract: Objective Digital ulcers (DUs) are a major cause of disease-related morbidity and are a difficult-to-treat vascular complication of systemic sclerosis (SSc). Demonstrating treatment efficacy has traditionally focused on clinician assessment of DUs alone. No existing patient-reported outcome (PRO) instrument captures the multifaceted impact of SSc-DU. We report the findings of a multicenter qualitative research study exploring the patient experience of SSc-DU. Methods Patient focus groups were conducted across 3 scleroderma units, following a topic guide devised by SSc patients, experts, and experienced qualitative researchers. A purposive sampling framework ensured that the experiences of a diverse group of patients were captured. Focus groups were audio recorded, and information was transcribed, anonymized, and analyzed using inductive thematic analysis. We continued focus groups until thematic saturation was achieved. Results Twenty-nine SSc patients with a history of DU disease participated in 4 focus groups across the UK (Bath, Manchester, and London). Five major interrelated themes (and subthemes) were identified that encompass the patient experience of SSc-DU: disabling pain and hypersensitivity; deep and broad-ranging emotional impact; impairment of physical and social activity; factors aggravating occurrence, duration, and impact; and mitigating, managing, and adapting. Conclusion The patient experience of SSc-DU is multifaceted and comprises a complex interplay of experiences associated with significant pain and morbidity. Patient experiences of SSc-DU are not captured using existing SSc-DU outcomes. Our findings will inform the development of a novel PRO instrument to assess the severity and impact of SSc-DU for use in future SSc-DU clinical trials.

Recent advances steer the future of systemic sclerosis toward precision medicine.

Abstract: The term “precision medicine” has become increasingly popular by proposing a medical model which allows to choose a personalized treatment. Hippocrates, almost 2500 years ago, was himself a proponent of personalized medicine, in fact he advised “give different ones (liquid medicines) to different patients, for the sweet one do not benefit everyone, nor do the astringent ones, nor are all the patients able to drink the same things” [1]. The personalized approach has always been of fundamental importance in the relationship between the physician and the patient and still today continues to represent a significant central part of precision medicine. Previously, treatment choice was largely based only on signs and symptoms presented by patients. However, precision medicine includes an approach to patient with a wide array of individual data including clinical features, lifestyle, genetic, and biomarker information as well as disease symptoms and signs [2]. Hippocrates already suggested to evaluate factors like physical appearance, a person’s age, and the time of the year when prescribing medicines [3] to better target drug prescription to individual patients. Therefore, this medical approach may help to predict which is the best treatment in a specific group/s of patients. It is clear that the development of precision medicine has fundamentally changed the treatment approach to several diseases, in particular in neoplastic diseases, using genetic and molecular diagnostics with DNA evaluation. However, its role in every day healthcare is relatively limited to date. Recently, many significant efforts have been made to better understand the pathogenetic [4] and genetic mechanisms in a broad range of rheumatic diseases. This knowledge could allow to stratify patients and therefore potentially expand a precision medicine approach in the rheumatic diseases field. Systemic sclerosis (SSc) is a connective tissue disease characterized by autoimmune features, vasculopathy, and fibrosis [4, 5]. Skin fibrosis is a well-known distinctive trait of the disease and the severity of skin involvement has been reported to be predictive of disease mortality [6]. Usually, the disease is classified according to skin involvement extension in a limited and a diffuse subset, but today it is clearly evident that this subsetting does not express the practical reality of the disease [7, 8]. In fact, the disease is characterized by a wide variability in both the clinical phenotype and in progression. In daily practice, clinical parameters are used to attempt to identify homogeneous groups of patients, as the isolated diffusing capacity for carbon monoxide (DLco) reduction characterizing a particular subset of SSc ACA positive patients [9]. An association of muscle involvement and autoantibody profile was recently described suggesting that X-ray findingsmay identify a precise subgroup of SSc patients [10]. It is also suggested that racial differences can be associated with distinct subsets [11]. However, patients within the same subset may show substantial different disease evolution including organ involvement as well as a heterogeneous response to treatment [12, 13]. The current ACR/EULAR classification for SSc which was proposed in 2013 has significantly higher sensitivity and specificity compared with existing classification criteria [14]. Significant efforts have now been devoted in establishing the very early diagnosis of SSc [15]. To date, clinical trials to recruit homogeneous populations of SSc patients have selected (in general) patients with either early active diffuse SSc or those patients with single internal organ involvement, for example, pulmonary arterial hypertension (PAH) or interstitial lung disease (ILD) [16]. Furthermore, Gemma Lepri and Michael Hughes contributed equally to this work.

The emerging role of lung ultrasound in COVID-19 pneumonia.

Abstract: In the last decades lung ultrasound (LUS) has become of crucial importance in the evaluation and monitoring of a widely range of pulmonary diseases. One of the major benefits which favours this examination, is that this is a non-invasive, low-cost and radiation-free imaging modality which allows repeated imaging. LUS plays an important role in a wide range of pathologies, including cardiogenic oedema, acute respiratory distress syndrome and fibrosis. Specific LUS findings have proved useful and predictive of acute respiratory distress syndrome which is of particular relevance in the suspicion and monitoring of patients with lung disease. Furthermore, several studies have confirmed the role of LUS in the screening of interstitial lung diseases in connective tissue diseases. Given these data, LUS will likely play an important role in the management of COVID-19 patients from identification of specific abnormalities corresponding to definite pneumonia phases and CT scans findings. In addition, LUS could allow reduction in the exposure of health-care workers to potential infection. Herein, we provide a summary on emerging role of lung ultrasound in COVID-19 pneumonia.

Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease.

Abstract: Background. We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. Methods. We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. Results. From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive fter a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. Conclusions. The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.

A systematic review of internet-based information for individuals with Raynaud’s phenomenon and patients with systemic sclerosis

Abstract: The authors have identified an error in thier manuscript and have incorrectly referred to the overall DISCERN score for SSc and RP as 2.21 and 1.99, respectively, in the abstract and discussion. The correct DISCERN quality scores are listed in Table 2.

Raynaud's phenomenon.

Abstract: Raynaud's phenomenon (RP) is a common vasospastic condition which affects ~5% of the general population. The majority of individuals have primary RP; however, Raynaud's can also occur secondary to a broad range of underlying medical conditions and drug therapies. RP is a cardinal feature in patients with systemic sclerosis and is often the earliest symptom of the disease. Unlike primary RP, patients with secondary RP can develop persistent digital ischaemia, including ulcers and gangrene. Patients require a comprehensive clinical assessment and investigation, in particular, the detection of autoantibodies and nailfold capillaroscopic abnormalities. Non-pharmacological management is indicated in all patients. There are a wide range of available drug therapies to treat RP, including when complicated by digital ulceration, and surgical intervention is sometimes required. Future research is needed to understand the complex pathogenesis of RP and to measure the impact and severity of RP to develop optimised approaches to management.

Digital ulcer debridement in systemic sclerosis: a systematic literature review

Abstract: Optimal wound care is an essential component in the management of systemic sclerosis (SSc) digital ulcers (DUs). DU debridement has been suggested to reduce ulcer-related pain and improve tissue healing. However, only a minority of rheumatologists perform DU debridement, and there is no standard of care/protocol. Our objectives were to (i) evaluate the current evidence for the use of debridement in DU management and (ii) assess whether there are any specific protocols. A systematic literature review was performed searching the PubMed database (between 01/01/1950-01/03/2019) in accordance with PRISMA guidelines. Two independent reviewers screened and extracted the abstracts/full manuscripts. Articles in English, which focussed on SSc-DU debridement/curettage, were included. Exclusion criteria included studies of juvenile/paediatric patients and basic/non-clinical research. Our search identified 1497 studies of which 4 studies were included in our final analysis. Three studies used scalpel debridement, and one study used this in combination with autolytic debridement. No studies specifically reported the effect on DU healing from debridement. Autolytic debridement with hyaluronate-based products was associated with significant ulcer pain and inflammation. Local anaesthetic significantly reduces pain both during and after debridement. Combined local and oral analgesia is often required for more severe or infected DUs. DU (scalpel and autolytic) debridement is being used by some clinicians in rheumatology; however, there are no standardised protocols. To improve wound care for SSc-DUs, future research should focus on developing a standardised protocol for SSc-DU debridement, with a view to facilitate randomised controlled trials to demonstrate safety and treatment efficacy.Key Points• Optimal wound care is an essential component in the management of systemic sclerosis-digital ulcers.• 'Sharp' debridement uses a scalpel, whereas 'autolytic' debridement uses dressings to optimize endogenous tissue lysis.• There is significant variation in the use of digital ulcer debridement in systemic sclerosis.• A standardized protocol and randomized controlled trials are needed to demonstrate debridement the safety and efficacy of digital ulcer debridement in systemic sclerosis.

Patient experiences of digital ulcer development and evolution in systemic sclerosis

Abstract: 1. Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, The University of Manchester, UK. 2. Department of Rheumatology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK. 3. Royal National Hospital for Rheumatic Diseases (at Royal United Hospitals), Bath, UK. 4. Department of Pharmacy and Pharmacology, University of Bath, Bath, UK. 5. Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, Bristol, UK. 6. Department of Rheumatology, Royal Free Hospital, University College London, London, UK. 7. University of Pittsburgh Medical Center, Pittsburgh, PA. 8. University of Utah and Salt Lake Veterans Affair Medical Center, Salt Lake City, USA. 9. Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester. 10. Scleroderma Program, University of Michigan, Ann Arbor, Michigan, USA. 11. Division of Rheumatology, University of Florence, Florence, Italy. 12. Patient representative. Contact via Professor Herrick, The University of Manchester. 13. Tulane University School of Medicine, New Orleans Scleroderma & Sarcoidosis Patient Care & Research Center, UMC Comprehensive Pulmonary Hypertension Center, New Orleans, LA, USA. 14. NIHR Bristol Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

Mother-to-Child HIV Transmission With In Utero Dolutegravir vs. Efavirenz in Botswana.

Abstract: BACKGROUND A large-scale evaluation of mother-to-child transmission (MTCT) with dolutegravir (DTG)-based antiretroviral treatment (ART) has not been conducted previously. SETTING Botswana was the first African country to change from efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC) to DTG/TDF/FTC first-line ART. METHODS From April 2015 to July 2018, the Early Infant Treatment Study offered HIV DNA testing at <96 hours of life. Maternal ART regimen was available for screened infants who could be linked to the separate Tsepamo surveillance study database. We evaluated characteristics of HIV-positive infants, and compared MTCT rates by ART regimen for linked infants. RESULTS Of 10,622 HIV-exposed infants screened, 42 (0.40%) were HIV-positive. In total, 5064 screened infants could be linked to the surveillance database, including 1235 (24.4%) exposed to DTG/TDF/FTC and 2411 (47.6%) exposed to EFV/TDF/FTC. MTCT was rare when either regimen was started before conception: 0/213 [0.00%, 95% confidence interval (CI): 0.00% to 1.72%] on DTG, 1/1497 (0.07%, 95% CI: 0.00% to 0.37%) on EFV. MTCT was similar for women starting each ART regimen in pregnancy: 8/999 (0.80%, 95% CI: 0.35% to 1.57%) for DTG and 8/883 (0.91%, 95% CI: 0.39% to 1.78%) for EFV (risk difference 0.11%, 95% CI: -0.79% to 1.06%). Most MTCT events (4/8 with DTG, 6/9 with EFV) occurred when ART was started <90 days before delivery. Infants exposed to DTG in utero had lower baseline HIV RNA compared with other HIV-infected infants. CONCLUSION In utero MTCT in Botswana remains rare in the DTG era. No significant MTCT differences were observed between DTG/TDF/FTC and EFV/TDF/FTC. Risk was highest for both groups when ART was started in the third trimester.

Ultrasound findings in finger flexor tendons in systemic sclerosis: A cross-sectional pilot study

Abstract: Objective:Finger flexion contractures are an important cause of disability in patients with systemic sclerosis; however, their pathophysiology is poorly understood. Our aim was to assess the feasib...

Effect of Oral Oseltamivir on Virological Outcomes in Low-risk Adults With Influenza: A Randomized Clinical Trial

Abstract: Background Duration of viral shedding is a determinant of infectivity and transmissibility, but few data exist about oseltamivir's ability to alter viral shedding. Methods From January 2012 through October 2017, a randomized, double-blinded multicenter clinical trial was conducted in adults aged 18-64 years at 42 sites in Thailand, the United States, and Argentina. Participants with influenza A or B and without risk factors for complications of influenza were screened for the study. Eligible participants were randomized to receive oseltamivir 75 mg or placebo twice daily for 5 days. The primary endpoint was the percentage of participants with virus detectable by polymerase chain reaction in nasopharyngeal swab at day 3. Results Of 716 adults screened for the study, 558 were randomized, and 501 were confirmed to have influenza. Forty-six participants in the pilot study were excluded, and 449 of the 455 participants in the population for the primary analysis had day 3 viral shedding results. Ninety-nine (45.0%) of 220 participants in the oseltamivir arm had virus detected at day 3 compared with 131 (57.2%) of 229 participants in the placebo arm (absolute difference of -12.2% [-21.4%, -3.0%], P =; .010). The median time to alleviation of symptoms was 79.0 hours for the oseltamivir arm and 84.0 hours for the placebo arm (P =; .34) in those with confirmed influenza infection. Conclusions Oseltamivir decreased viral shedding in this low-risk population. However, in the population enrolled in this study, it did not significantly decrease the time to resolution of clinical symptoms. Clinical trials registration NCT01314911.

Further evidence that chilblains are a cutaneous manifestation of COVID-19 infection.

Abstract: A range of cutaneous conditions including chilblain‐like lesions have been reported in patients with Coronavirus 2019 (COVID‐19) due to severe acute respiratory Syndrome coronavirus 2 (SARS‐Cov‐2). Using clinical data and images, the authors of a recent nationwide Spanish survey identified 5 clinical patterns which were associated with different patient demographics, onset (timing), and prognosis.

Significant weight loss in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database.

Abstract: Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

Sample size estimation for stratified individual and cluster randomized trials with binary outcomes.

Abstract: Individual randomized trials (IRTs) and cluster randomized trials (CRTs) with binary outcomes arise in a variety of settings and are often analyzed by logistic regression (fitted using generalized estimating equations for CRTs). The effect of stratification on the required sample size is less well understood for trials with binary outcomes than for continuous outcomes. We propose easy-to-use methods for sample size estimation for stratified IRTs and CRTs and demonstrate the use of these methods for a tuberculosis prevention CRT currently being planned. For both IRTs and CRTs, we also identify the ratio of the sample size for a stratified trial vs a comparably powered unstratified trial, allowing investigators to evaluate how stratification will affect the required sample size when planning a trial. For CRTs, these can be used when the investigator has estimates of the within-stratum intracluster correlation coefficients (ICCs) or by assuming a common within-stratum ICC. Using these methods, we describe scenarios where stratification may have a practically important impact on the required sample size. We find that in the two-stratum case, for both IRTs and for CRTs with very small cluster sizes, there are unlikely to be plausible scenarios in which an important sample size reduction is achieved when the overall probability of a subject experiencing the event of interest is low. When the probability of events is not small, or when cluster sizes are large, however, there are scenarios where practically important reductions in sample size result from stratification.

Brief Report: Sex Differences in Outcomes for Individuals Presenting for Third-Line Antiretroviral Therapy

Abstract: Background: Sex differences in studies of antiretroviral (ART) drug exposure and treatment outcomes support the hypothesis that some ART combinations may not be well tolerated in women. We evaluated disparities in outcomes between men and women participating in ACTG A5288, an interventional strategy trial for individuals failing a protease inhibitor-based second-line ART regimen in low- and middle-income countries. Methods: Participants were assigned to one of 4 cohorts (A-D) based on resistance profiles and ART history. Cohort A had no lopinavir/ritonavir (LPV/r) resistance and stayed on their second-line regimen, and cohorts B, C, and D had increasing resistance and accessed novel ART regimens. In this secondary analysis, we evaluated sex differences in the primary endpoint, HIV-1 RNA ≤200 copies/mL at week 48; confirmed virologic failure ≥1000 copies/mL (VF); and clinical outcomes and adverse events (intent-to-treat). Results: Women made up 258/545 (47%) of the study population. More women than men were assigned to cohort A. Median follow-up was 72 weeks. Fewer women than men had HIV-1 RNA ≤200 copies/mL at week 48: 39% vs. 49% in cohort A and 83% vs. 89% in cohorts B, C, and D combined. More women experienced VF, grade ≥3 signs and symptoms, but similar grade ≥3 diagnoses or laboratory abnormalities. Conclusions: More women than men entered the study with a resistance profile suggesting that their second-line regimen could have been effective in maintaining virologic suppression. The more frequent occurrence of grade ≥3 signs and symptoms in women suggests that tolerability issues were under recognized in women on protease inhibitor-based therapy.

Typhoid Fever in the US Pediatric Population, 1999-2015: Opportunities for Improvement.

Abstract: BACKGROUND Typhoid fever in the United States is acquired primarily through international travel by unvaccinated travelers. There is currently no typhoid vaccine licensed in the United States for use in children <2 years. METHODS We reviewed Salmonella enterica serotype Typhi infections reported to the Centers for Disease Control and Prevention (CDC) and antimicrobial-resistance data on Typhi isolates in CDC's National Antimicrobial Resistance Monitoring System from 1999 through 2015. RESULTS 5131 cases of typhoid fever were diagnosed and 5004 Typhi isolates tested for antimicrobial susceptibility. Among 1992 pediatric typhoid fever patients, 1616 (81%) had traveled internationally within 30 days of illness onset, 1544 (81%) of 1906 were hospitalized (median duration, 6 days; range, 0-50), and none died. Forty percent (799) were <6 years old; 12% were <2 years old. Based on age and travel destination, 1435 (83%) of 1722 pediatric patients were vaccine-eligible; only 68 (5%) of 1361 were known to be vaccinated. Of 2003 isolates tested for antimicrobial susceptibility, 1216 (61%) were fluoroquinolone-nonsusceptible, of which 272 (22%) were also resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole (multidrug-resistant [MDR]). All were susceptible to ceftriaxone and azithromycin. MDR and fluoroquinolone-nonsusceptible isolates were more common in children than adults (16% vs 9%, P < .001, and 61% vs 54%, P < .001, respectively). Fluoroquinolone nonsusceptibility was more common among travel-associated than domestically acquired cases (70% vs 17%, P < .001). CONCLUSIONS Approximately 95% of currently vaccine-eligible pediatric travelers were unvaccinated, and antimicrobial-resistant infections were common. New public health strategies are needed to improve coverage with currently licensed vaccines. Introduction of an effective pretravel typhoid vaccine for children <2 years could reduce disease burden and prevent drug-resistant infections.

What narrative devices do people with systemic sclerosis use to describe the experience of pain from digital ulcers: a multicentre focus group study at UK scleroderma centres.

Abstract: Objectives Digital ulcers (DUs) are a common complication in systemic sclerosis (SSc). No existing studies have specifically reported on the qualitative patient experience of DU pain, and our current patient-reported outcome measure (PROM) does not capture the multifaceted painful experience of SSc-DU. Our aim was to examine the patient experience of SSc-DU pain. Design Focus groups with people diagnosed with SSc who had experienced DUs were conducted using a topic guide developed by people with SSc, experts in SSc and experienced qualitative researchers. Focus groups were continued until data saturation had been reached. The focus groups were audio recorded, transcribed verbatim, anonymised and analysed using inductive thematic analysis. Our current study is an integration of the data from these focus groups to specifically examine the patient experience of DU pain. Setting Three specialist scleroderma units across the UK (Bath, Manchester and London). Participants Four focus groups were undertaken; 29 adults (20 women, 9 men) with SSc and a spectrum of historical DUs participated. We included participants with a diverse demographic (including ethnic) background and disease-related characteristics. Results Five narrative devices were identified, which encompass how people describe the pain from SSc-DUs: ‘Words to express DU-associated pain’, ‘Descriptions of physical and psychological reactions to pain’, ‘Comparisons with other painful events’, ‘Descriptions of factors that exacerbate pain’ and ‘Descriptions of strategies for coping with the pain’. Conclusion The experience of SSc-DU pain leads to the use of graphic language and rich description by participants in the focus group setting. Existing SSc-DU outcomes do not adequately capture the patient experiences of SSc-DU pain. Our findings further highlight the multifaceted nature of SSc-DUs and will hopefully support the development of a novel PROM to assess the severity and impact of SSc-DUs.

Digital ulcers: should debridement be a standard of care in systemic sclerosis?

Abstract: Summary Digital ulcers are a serious, recurrent complication in patients with systemic sclerosis. They are often slow to heal and exquisitely painful. Local wound care, such as debridement of the wound bed, is an essential component in the management of digital ulcers in systemic sclerosis. However, digital ulcer debridement is not a standard of care, and there is substantial international variation in the use of this approach. In this Viewpoint, we discuss the assessment of the wound bed and different methods of debridement using the model of tissue management, infection and inflammation, moisture control, and wound edge or epidermal advancement, known as TIME. We highlight the challenges in standard practice and the need for research into local wound care for this type of ulceration, before suggesting a potential roadmap to develop a standardised approach to support ulcer debridement in systemic sclerosis. Debridement might be the missing component in optimising the management of digital ulcers and we propose that the approach should be rigorously investigated as a standard of care in this common complication of systemic sclerosis.

A systematic review of internet‐based information on dermatomyositis and polymyositis

Abstract: Aim Patients with rheumatic diseases are increasingly using internet-based information to inform healthcare utilization and make treatment decisions. Our aim was to assess the readability and quality of internet-based information on dermatomyositis (DM) and polymyositis (PM). Method Key words "Dermatomyositis" and "Polymyositis" were searched on 3 commonly used search engines (Google, Yahoo and Bing). The first 3 pages (~30) of search results were examined from each search engine. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman-Liau index). Quality of information was assessed using the DISCERN tool, Journal of The American Medical Association (JAMA) benchmark criteria and Health on The Net Code (HoN code). We also examined Google Trends® data to determine if there were obvious temporal search patterns. Results Thirty-two websites were included in the study after duplicates were removed and exclusion criteria were applied. The overall quality was low including DISCERN with a median overall score of 38/80 (interquartile range 12.25), only 4/32 (13%) websites fulfilled all 4 JAMA benchmark criteria, and 9/32 (28%) had HoN code. Readability of information was assessed using 4 readability formulae (Flesch Reading Ease Score, Flesch-Kincaid Grade Level, the Simplified Measure of Gobbledygook index, the Coleman-Liau index. There was no obvious temporal trend in searches on analysis of Google Trends® data. Conclusion The overall quality and readability of internet-based information relating to DM and PM is poor. Patients require appropriate information of high quality and readability throughout the course of their disease in order to make informed decisions on their condition including treatment.

Large vessel disease as a potentially treatable cause of devastating critical digital ischaemia in systemic sclerosis.

Abstract: A 60-year-old lady with known limited cutaneous SSc (anti-centromere antibody positive) and a history of severe digital vascular disease presented with progressive digital vascular ischaemia. Her history included bilateral (periarterial) sympathectomy and digital amputation. She had no modifiable cardiovascular risk factors and was taking sildenafil for SSc-digital vasculopathy. At presentation, there was ulceration of tip of the left index finger and thumb, with progressive necrosis (a) (Fig. 1). She was in significant pain and received a 5day course of intravenous iloprost. Despite this, she developed very tender swelling of her left wrist and forearm with absent radial and brachial pulses. A more proximal cause for compromised flow was suspected, and therefore, an urgently requested arterial Duplex scan demonstrated an occluded radial artery, with reversed flow in the ulnar artery. Flow in the brachial artery was noted to be severely damped. Therefore, computerised tomography angiography (CTA) was performed with a view to therapeutic intervention. CTA demonstrated a short occlusion of the left subclavian artery (b), which was confirmed by a catheter angiogram (c), performed prior to placement of a stent (d) to successfully relieve the obstruction. Subsequently, her clinical condition improved with reduced pain and limitation of ischaemic tissue loss. Critical digital ischaemia in SSc is a medical emergency because early recognition of proximal (large) vessel disease can potentially be amenable to tissue-saving revascularisation [1–3]. An increased risk of macrovascular disease has been reported in SSc, in particular, in those with limited disease and positive anti-centromere antibodies (like our patient) [1–3]. Other potential causes include (but are not limited to) inflammation (e.g. vasculitis), infection and embolism [3]. Clinicians must maintain a high index of suspicion and always actively consider large vessel disease in SSc-related critical digital ischaemia.

Hand Osteomyelitis in Patients With Secondary Raynaud Phenomenon.

Abstract: 6 S. aureus, E. cloacae Co-amoxiclav Swab 7 Coagulase-negative staphylococcus, E. cloacae, C. freundii, K. ascorbata Doxycycline, trimethoprim Bone R aynaud phenomenon (RP) is a common vasospastic disorder characterized by episodic color change and often intrusive neurosensory symptoms. The majority (80%–90%) of patients have primary (“idiopathic”) RP. However, the disorder can also occur secondary to a wide range of medical and drug causes. Important rheumatological causes include autoimmune connective tissue diseases and can complicate systemic vasculitis. To date, secondary RP (SRP) has been best studied in patients with systemic sclerosis (SSc). The majority (>96%) of patients with SSc develop RP, and this is often the first symptom of the disease. In patients with SSc, episodic vasospasm is complicated by progressive structural changes (“vasculopathy”), and this can result in persistent digital ischemia, namely, ulceration and gangrene. Digital ulcers are often infected, in particular, by Staphylococcus aureus and not uncommonly by enteric organisms, which highlights the need for meticulous wound care and hand hygiene. However, there is a paucity of data to inform the management of osteomyelitis (OM) in SSc, especially complicating digital ulcers and ischemia. Therefore, our existing treatment recommendations are largely based upon other diseases (eg, diabetes and atherosclerosis) and expert opinion. Against this background, our aim was to describe the clinical course of patients with hand OM including investigations, microbiology, management, and outcomes of patients with SRP referred to plastic surgery at a tertiary referral center.

Diverse Human Immunodeficiency Virus-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings.

Abstract: Background: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC). Methods: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated. Results: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients. Conclusions: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.