Exploring NICU nurses' views of a novel genetic point-of-care test identifying neonates at risk of antibiotic-induced ototoxicity: A qualitative study.

AIM: To explore the views of neonatal intensive care nursing staff on the deliverability of a novel genetic point-of-care test detecting a genetic variant associated with antibiotic-induced ototoxicity. DESIGN: An interpretive, descriptive, qualitative interview study. METHODS: Data were collected using semi-structured interviews undertaken between January and November 2020. Participants were neonatal intensive care nursing staff taking part in the Pharmacogenetics to Avoid Loss of Hearing trial. RESULTS: Thematic analysis resulted in four themes: perceived clinical utility; the golden hour; point-of-care device; training and support. Recommendations were made to streamline the protocol and ongoing training and support were considered key to incorporating the test into routine care. CONCLUSION: Exploring the views of nurses involved in the delivery of the point-of-care test was essential in its implementation. By the study endpoint, all participants could see the value of routine clinical introduction of the point-of care test. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses are in a key position to support the delivery of point-of-care genetic testing into mainstream settings. This study has implications for the successful integration of other genetic point-of-care tests in acute healthcare settings. IMPACT: The study will help to tailor the training and support required for routine deployment of the genetic point-of-care test. The study has relevance for nurses involved in the development and delivery of genetic point-of-care tests in other acute hospital settings. REPORTING METHOD: This qualitative study adheres to the Standards for Reporting Qualitative Research EQUATOR guidelines and utilizes COREQ and SRQR checklists. PATIENT OR PUBLIC CONTRIBUTION: All staff working on the participating neonatal intensive care units were trained to use the genetic point-of-care test. All inpatients on the participating units were eligible to have testing via the point-of-care test. The Pharmacogenetics to Avoid Loss of Hearing Patient and Public Involvement and Engagement group provided valuable feedback. TRIAL AND PROTOCOL REGISTRATION: Registered within the University of Manchester. Ethics approval reference numbers: IRAS: 253102 REC reference: 19/NW/0400. Also registered with the ISRCTN ref: ISRCTN13704894.

Non-reassuring results in agreement trial comparing glass and plastic capillary tubes for neonatal blood gas sampling.

AIM: To determine agreement between neonatal capillary blood gases taken with plastic and glass tubes. METHODS: An agreement study was carried out in a regional tertiary neonatal unit. Inpatient babies ≥1 kg were recruited to the study when parents gave consent. After taking the routine glass capillary tube sample, a plastic tube sample was taken and run if the heel continued to bleed. Successful sample pairs were recorded and analysed against pre-defined acceptable differences. Assessment was also made of differences in failure rates between tube types for each parameter. RESULTS: Twenty-eight babies provided 135 blood gas pairs, of which five pairs were excluded. Successful pairing of results was achieved for pH in 105 valid samples. There were more failed plastic samples than glass, reaching significance for almost all parameters. pH, pO2 and pCO2 showed poor agreement (<80%) between glass and plastic tubes. On limited analysis of one successful blood gas pair per neonate to minimise bias, results remained non-reassuring. CONCLUSION: The findings of this study do not advocate switching from glass to plastic capillary tubes in our Newborn Intensive Care Unit. Further studies are required to assess agreement of glass and plastic capillary tubes for neonatal blood gas sampling.

Impact of Physician-Defined Flares on Quality of Life and Work Impairment: An International Survey of 2238 Patients With Psoriatic Arthritis.

OBJECTIVE: To describe psoriatic arthritis (PsA) flares and their effect on patient-reported outcomes (PROs). METHODS: Cross-sectional surveys of rheumatologists/dermatologists and their patients with PsA were conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States, capturing data on physician-reported patient flare status, demographics, PsA severity, and clinical outcomes. Patient-completed surveys captured data on PROs: 5-level EuroQol 5-dimension, Work Productivity and Activity Impairment questionnaire, Health Assessment Questionnaire-Disability Index, and 12-item Psoriatic Arthritis Impact of Disease questionnaire. Patients were compared by flare status using parametric and nonparametric tests. Multivariate regression was used to identify flare associations. Multivariate logistic regression adjusted for patient demographics and physician specialty assessed the effect of flare status. RESULTS: Among 2238 patients (586 from the US, 1652 from Europe) managed by 572 physicians, physician-reported flare was present for 168 patients (7.5%), and self-reported flare was present for 95 patients (10% of available data). Mean (SD) flare count over 12 months was 2.2 (4.9), lasting on average 16.4 (16.2) days. Flare status was linked to worse PROs. Patients who had not flared in the last 12 months or had never flared had a higher quality of life, lower overall work impairment, and a lower degree of disability compared with patients who were currently experiencing a flare (all; P < 0.01). CONCLUSION: Actively experiencing a flare adversely affected QOL, disability, and work productivity. PsA flares should be routinely assessed and managed in clinical care.

Women With Psoriatic Arthritis Experience Higher Disease Burden Than Men: Findings From a Real-World Survey in the United States and Europe.

OBJECTIVE: Although psoriatic arthritis (PsA) is equally present in men and women, sex may influence clinical manifestations and the impact of disease on patients' lives. This study assessed differences in clinical characteristics, disability, quality of life (QOL), and work productivity by sex in real-world practice. METHODS: A cross-sectional survey of rheumatologists/dermatologists and their patients with PsA was conducted in France, Germany, Italy, Spain, the United Kingdom, and the United States between June and August 2018. Data collected included demographics, treatment use, clinical characteristics (tender joint count, swollen joint count, body surface area affected by psoriasis), QOL (EuroQoL 5-Dimension questionnaire [EQ-5D], Psoriatic Arthritis Impact of Disease [PsAID12]), disability (Health Assessment Questionnaire-Disability Index [HAQ-DI]), and work productivity (Work Productivity and Impairment Index [WPAI]). Outcomes were compared between men and women using parametric and nonparametric tests, as appropriate. RESULTS: Of 2270 patients (mean age 48.6 [SD 13.3] yrs, mean disease duration 4.9 [SD 6.0] yrs), 1047 (46.1%) were women. Disease duration, disease presentation, and biologic use (mean 54.2%) were comparable between women and men. Women reported worse QOL (EQ-5D: 0.80 [SD 0.2] vs 0.82 [SD 0.2]; P = 0.02), greater disability (HAQ-DI: 0.56 [SD 0.6] vs 0.41 [SD 0.5]; P < 0.01) and work activity impairment (WPAI: 27.9% [SD 22.0] vs 24.6% [SD 22.4]; P < 0.01) than men. However, women had a lower burden of comorbidities (Charlson Comorbidity Index: 1.10 [SD 0.5] vs 1.15 [SD 0.6]; P < 0.01). CONCLUSION: In patients with similar PsA disease activity and treatment, women experienced greater disease impact than men. This represents a significant consideration for the therapeutic management of PsA.

Impact of key manifestations of psoriatic arthritis on patient quality of life, functional status, and work productivity: Findings from a real-world study in the United States and Europe.

OBJECTIVES: To determine the individual impact of key manifestations of psoriatic arthritis (PsA) on quality of life (QoL), physical function, and work disability. METHODS: Data from the Adelphi 2018 PsA Disease-Specific Programme, a multinational, cross-sectional study of PsA patients, were used. PsA manifestations included peripheral arthritis (number of joints affected), psoriasis (body surface area [BSA]), axial involvement (inflammatory back pain [IBP] and sacroiliitis) enthesitis, and dactylitis. General, and disease-specific QoL, physical function, and work disability were measured with EQ-5D-5L, PsAID-12, HAQ-DI, and WPAI, respectively. Multivariate regression adjusting for potential confounders evaluated the independent effect of PsA manifestations on each outcome. RESULTS: Among the 2222 PsA patients analysed, 77.0% had active psoriasis and 64.4% had peripheral arthritis; 5.9%, 6.8%, 10.2%, and 3.6% had enthesitis, dactylitis, IBP, or sacroiliitis, respectively. Mean EQ VAS scores were significantly poorer in patients with vs. without enthesitis (59.9 vs. 75.6), dactylitis (63.6 vs. 75.4), and with greater peripheral joint involvement (none: 82.5; 1-2 affected joints: 74.1; 3-6 joints: 74.2; >6 joints: 65.0). Significantly worse mean PsAID-12 scores were associated with vs. without enthesitis (4.39 vs. 2.34) or dactylitis (4.30 vs. 2.32), and with greater peripheral joint involvement (none: 1.21; 1-2 joints: 2.36; 3-6 joints: 2.74; >6 joints: 3.92), and BSA (none: 1.49; >3-10%: 2.96; >10%: 3.43). Similar patterns were observed with HAQ-DI and WPAI scores. CONCLUSION: Most PsA manifestations were independently associated with worse general, and PsA-specific QoL, physical function, and work disability, highlighting the need for treatments targeting the full spectrum of PsA symptoms to lower the burden of disease.

Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO.

Although human naturally occurring regulatory T cells (Tregs) may express either CD45RA or CD45RO, we find in agreement with previous reports that the ( approximately 80%) majority of natural Tregs in adults are CD45RO(+). The proportion of CD45RA(+) Tregs decreases, whereas CD45RO(+) Tregs increase significantly with age. Nevertheless, a small proportion of CD45RA(+) Tregs are found even in old (>80 y) adults and a proportion of these express CD31, a marker for recent thymic emigrants. We found that CD45RO(+) Tregs were highly proliferative compared with their CD45RA(+) counterparts. This was due in part to the conversion of CD45RA Tregs to CD45RO expression after activation. Another difference between these two Treg populations was their preferential migration to different tissues in vivo. Whereas CD45RA(+) Tregs were preferentially located in the bone marrow, associated with increased CXCR4 expression, CD45RO(+) Tregs were preferentially located in the skin, and this was associated with their increased expression of CLA and CCR4. Our studies therefore show that proliferation features strongly in maintenance of the adult Treg pool in humans and that the thymus may make a minor contribution to the maintenance of the peripheral pool of these cells, even in older adults. Furthermore, the different tissue compartmentalization of these cells suggests that different Treg niches exist in vivo, which may have important roles for their maturation and function.

Effect of Fatigue on Health-Related Quality of Life and Work Productivity in Psoriatic Arthritis: Findings From a Real-World Survey.

OBJECTIVE: To evaluate fatigue frequency and severity among patients with psoriatic arthritis (PsA) and assess the effect of fatigue severity on patient-reported outcome measures (PROMs) assessing quality of life, function, and work productivity. METHODS: Data were derived from the Adelphi Disease Specific Programme, a cross-sectional survey conducted in 2018 in the United States and Europe. Patients had physician-confirmed PsA. Fatigue was collected as a binary variable and through its severity (0-10 scale, using the 12-item Psoriatic Arthritis Impact of Disease fatigue question) from patients; physicians also reported patient fatigue (yes/no). Other PROMs included the 5-level EuroQol 5-dimension questionnaire (EQ-5D-5L) for health-related quality of life (HRQOL), Health Assessment Questionnaire-Disability Index, and Work Productivity and Activity Impairment Questionnaire. Multivariate linear regression was used to evaluate the association between fatigue severity and other PROMs. RESULTS: Among the 831 included patients (mean age 47.5 yrs, mean disease duration 5.3 yrs, 46.9% female, 48.1% receiving a biologic), fatigue was reported by 78.3% of patients. Patients with greater fatigue severity had greater disease duration, PsA severity, pain levels, body surface area affected by psoriasis, and swollen and tender joint counts (all P < 0.05). In multivariate analyses, patients with greater fatigue severity experienced worse physical functioning, HRQOL, and work productivity (all P < 0.001). Presence of fatigue was underreported by physicians (reported in only 32% of patients who self-reported fatigue). CONCLUSION: Prevalence of patient-reported fatigue was high among patients with PsA and underrecognized by physicians. Fatigue severity was associated with altered physical functioning, work productivity, and HRQOL.

Rapid Point-of-Care Genotyping to Avoid Aminoglycoside-Induced Ototoxicity in Neonatal Intensive Care.

Importance: Aminoglycosides are commonly prescribed antibiotics used for the treatment of neonatal sepsis. The MT-RNR1 m.1555A>G variant predisposes to profound aminoglycoside-induced ototoxicity (AIO). Current genotyping approaches take several days, which is unfeasible in acute settings. Objective: To develop a rapid point-of-care test (POCT) for the m.1555A>G variant before implementation of this technology in the acute neonatal setting to guide antibiotic prescribing and avoid AIO. Design, Setting, and Participants: This pragmatic prospective implementation trial recruited neonates admitted to 2 large neonatal intensive care units between January 6, 2020, and November 30, 2020, in the UK. Interventions: Neonates were tested for the m.1555A>G variant via the rapid POCT on admission to the neonatal intensive care unit. Main Outcomes and Measures: The primary outcome assessed the proportion of neonates successfully tested for the variant of all infants prescribed antibiotics. Secondary outcomes measured whether implementation was negatively associated with routine clinical practice and the performance of the system. The study was statistically powered to detect a significant difference between time to antibiotic administration before and after implementation of the MT-RNR1 POCT. Results: A total of 751 neonates were recruited and had a median (range) age of 2.5 (0-198) days. The MT-RNR1 POCT was able to genotype the m.1555A>G variant in 26 minutes. Preclinical validation demonstrated a 100% sensitivity (95% CI, 93.9%-100.0%) and specificity (95% CI, 98.5%-100.0%). Three participants with the m.1555A>G variant were identified, all of whom avoided aminoglycoside antibiotics. Overall, 424 infants (80.6%) receiving antibiotics were successfully tested for the variant, and the mean time to antibiotics was equivalent to previous practice. Conclusions and Relevance: The MT-RNR1 POCT was integrated without disrupting normal clinical practice, and genotype was used to guide antibiotic prescription and avoid AIO. This approach identified the m.1555A>G variant in a practice-changing time frame, and wide adoption could significantly reduce the burden of AIO.

Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications.

BACKGROUND: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. MATERIALS AND METHODS: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells. RESULTS: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers. CONCLUSION: We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.

The kinetics of CD4+Foxp3+ T cell accumulation during a human cutaneous antigen-specific memory response in vivo.

Naturally occurring CD4(+)CD25(hi)Foxp3(+) Tregs (nTregs) are highly proliferative in blood. However, the kinetics of their accumulation and proliferation during a localized antigen-specific T cell response is currently unknown. To explore this, we used a human experimental system whereby tuberculin purified protein derivative (PPD) was injected into the skin and the local T cell response analyzed over time. The numbers of both CD4(+)Foxp3(-) (memory) and CD4(+)Foxp3(+) (putative nTreg) T cells increased in parallel, with the 2 populations proliferating at the same relative rate. In contrast to CD4(+)Foxp3(-) T cell populations, skin CD4(+)Foxp3(+) T cells expressed typical Treg markers (i.e., they were CD25(hi), CD127(lo), CD27(+), and CD39(+)) and did not synthesize IL-2 or IFN-gamma after restimulation in vitro, indicating that they were not recently activated effector cells. To determine whether CD4(+)Foxp3(+) T cells in skin could be induced from memory CD4(+) T cells, we expanded skin-derived memory CD4(+) T cells in vitro and anergized them. These cells expressed high levels of CD25 and Foxp3 and suppressed the proliferation of skin-derived responder T cells to PPD challenge. Our data therefore demonstrate that memory and CD4(+) Treg populations are regulated in tandem during a secondary antigenic response. Furthermore, it is possible to isolate effector CD4(+) T cell populations from inflamed tissues and manipulate them to generate Tregs with the potential to suppress inflammatory responses.

Cell-cell spread of human immunodeficiency virus type 1 overcomes tetherin/BST-2-mediated restriction in T cells.

Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism of viral dissemination. Tetherin (BST-2/CD317) is an interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether tetherin also restricts cell-cell spread is unclear. We performed quantitative cell-to-cell transfer analysis of wild-type (WT) or Vpu-defective HIV-1 in Jurkat and primary CD4(+) T cells, both of which express endogenous levels of tetherin. We found that Vpu-defective HIV-1 appeared to disseminate more efficiently by cell-to-cell contact between Jurkat cells under conditions where tetherin restricted cell-free virion release. In T cells infected with Vpu-defective HIV-1, tetherin was enriched at the VS, and VS formation was increased compared to the WT, correlating with an accumulation of virus envelope proteins on the cell surface. Increasing tetherin expression with type I interferon had only minor effects on cell-to-cell transmission. Furthermore, small interfering RNA (siRNA)-mediated depletion of tetherin decreased VS formation and cell-to-cell transmission of both Vpu-defective and WT HIV-1. Taken together, these data demonstrate that tetherin does not restrict VS-mediated T cell-to-T cell transfer of Vpu-defective HIV-1 and suggest that under some circumstances tetherin might promote cell-to-cell transfer, either by mediating the accumulation of virions on the cell surface or by regulating integrity of the VS. If so, inhibition of tetherin activity by Vpu may balance requirements for efficient cell-free virion production and cell-to-cell transfer of HIV-1 in the face of antiviral immune responses.

Comparing symptoms, treatment patterns, and quality of life of ankylosing spondylitis and non-radiographic axial spondyloarthritis patients in the USA: findings from a patient and rheumatologist Survey.

OBJECTIVES: The aim of this study was to compare the symptoms, treatment patterns, and quality of life (QoL) of ankylosing spondylitis (AS) patients to non-radiographic axial spondyloarthritis (nr-axSpA) patients in the USA. METHOD: A cross-sectional survey was conducted with rheumatologists and their consulting patients in the USA from June through August 2018. Patients who had a rheumatologist confirmed diagnosis of AS and nr-axSpA were eligible to participate. Patient demographics, symptoms, and medication use were reported by the rheumatologist, while work disability and QoL measures were reported by the patient. Patient demographics, symptoms, QoL and treatment patterns of AS and nr-axSpA patients were compared using parametric tests and non-parametric tests when appropriate. RESULTS: A total of 515 AS patients and 495 nr-axSpA patients were included in this analysis. A higher proportion of AS patients were male (p < 0.001), older (p = 0.014), and more likely to be prescribed a biologic (p < 0.0001). On average, AS patients experienced slightly more symptoms at diagnosis (p = 0.023); however, nr-axSpA patients were more likely to experience enthesitis (p = 0.048) and synovitis (p = 0.003). Patient reported outcomes such as the ASAS Health Index (p = 0.171), ASQoL (p = 0.296), BASDAI (p = 0.124), and WPAI (p = 0.183) were similar between AS and nr-axSpA patients after adjusting for confounding variables such as medication use. CONCLUSIONS: AS and nr-axSpA patients share the same clinical features. The burden of the disease, as assessed by QoL measurements, is also similar in AS and nr-axSpA patients; however, despite these similarities, patients with nr-axSpA are less likely to be treated with a biologic. KEY POINTS: • Ankylosing spondylitis and non • radiographic axial spondyloarthritis patients share similar clinical features and burden of disease. • Quality of life is similar among ankylosing spondylitis and non • radiographic axial spondyloarthritis after adjusting for current treatment patterns.

Cross-walk of the Assessment of Spondyloarthritis International Society Health Index and Ankylosing Spondylitis Quality of Life Scores in Ankylosing Spondylitis and Non-radiographic Axial Spondyloarthritis Patients.

INTRODUCTION: Axial spondyloarthritis (axSpA) is a chronic rheumatic disease affecting the spine and sacroiliac joints, encompassing both ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA) patients. Patient quality of life (QoL) is assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) (disease-specific measure) and the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) (disease-specific measure). Both ASQoL and ASAS HI have similar parameters and scoring ranges, however, their performance relative to each other is unknown. We conducted a cross-walk analysis of the ASAS HI to the ASQoL in AS and nr-axSpA patients. METHODS: A cross-sectional survey using the Adelphi axSpA Disease Specific Programme™, conducted with rheumatologists and their consulting AS and nr-axSpA patients in the United States, was undertaken between Jun and Aug 2018. Rheumatologists provided confirmed diagnoses of AS and nr-axSpA alongside patients' demographic and clinical characteristics. Patients reported quality-of-life measures using the validated ASAS HI and ASQoL questionnaires. Model performance was assessed by comparing root-mean squared error (RMSE) from tenfold cross-validation to determine the best mapping from ASAS HI to ASQoL, and vice versa. RMSE was calculated overall, and for lower, middle and upper thirds of the predicted scale. RESULTS: Data from 283 AS and 274 nr-axSpA patients were analyzed. Predicting ASAS HI using ASQoL values, the best model was non-parametric local linear regression, with overall RMSE of 1.851. Predicting ASQoL using ASAS HI values, the best model also used non-parametric local-linear regression, with overall RMSE of 2.254. In predicting ASAS HI and ASQoL, models performed better in predicting lower values in the predicted scale (RMSE 1.597, 1.871, 2.871 across thirds for ASAS HI; and 1.719, 2.577, 3.140 for ASQoL). CONCLUSIONS: Results present a scoring algorithm for cross-walking the ASAS HI to the ASQoL and vice versa, with the approach enabling comparisons to be made across studies.

Real world effectiveness and satisfaction with secukinumab in the treatment of patients with psoriatic arthritis: a population survey in five European countries.

OBJECTIVES: To describe the effectiveness of secukinumab in the treatment of psoriatic arthritis (PsA) and associated physician satisfaction with secukinumab treatment, in routine clinical practice across five European countries. METHODS: A retrospective analysis of PsA patients receiving secukinumab for ≥4 months in France, Germany, Italy, Spain and the UK from March to December 2018. Data based on physician-completed questionnaires at initiation of treatment and at the data collection consultation were collected and used to assess effectiveness. RESULTS: 572 PsA patients with a mean age of 47.9 years, 57.0% were male, with 5.6% of patients with mild, 55.2% with moderate and 38.1% severe PsA prior to treatment initiation were included. 33.0% of patients received a dosage of 150 mg and 67.0% a dosage of 300 mg secukinumab. Around 84% of patients received secukinumab for 6 months or longer. Symptoms seen at current assessment in over 20% of patients were tender or swollen joints or psoriatic skin lesions. Between initiation of treatment and the current consultation, improvements in skin, joint and overall severity were reported. Physician satisfaction with secukinumab's ability to control disease was very high during the study period, greater than 90%, and was seen irrespective of disease severity at initiation, prior biologic use, treatment duration, time since diagnosis or onset of symptoms, treatment history, and BMI. CONCLUSION: Physicians were satisfied with the ability of secukinumab to control disease and it was effective in the treatment of PsA patients in routine clinical settings.

Pharmacogenetics to Avoid Loss of Hearing (PALOH) trial: a protocol for a prospective observational implementation trial.

INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss. METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice. ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study. TRIAL REGISTRATION NUMBER: ISRCTN13704894. PROTOCOL VERSION: V 1.3.

Use and Switching of Biologic Therapy in Patients with Non-Radiographic Axial Spondyloarthritis: A Patient and Provider Survey in the United States.

INTRODUCTION: The Food and Drug Administration (FDA) approved certolizumab-pegol, the first biologic for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA), for use in the United States (US) in March of 2019. The objective of this study was to investigate biologic use and reasons for switching therapy among patients with nr-axSpA in the US. METHODS: This was a real-world, cross-sectional study of rheumatologists conducted in the US. Data were collected from June to August of 2018 via rheumatologist-completed patient record forms. Data from patients who had a rheumatologist-confirmed diagnosis of nr-axSpA were included in the study. Rheumatologists provided information on current medication use and reasons for switching biologics. RESULTS: Eighty-eight rheumatologists collected data on 495 nr-axSpA patients. Over half of nr-axSpA patients were male (53.3%), with a mean age of 44.2 years, and 69.8% of patients reported working full-time. Of the 495 nr-axSpA patients, 48.1% were receiving a biologic and no conventional synthetic disease-modifying anti-rheumatic drug (csDMARD), 18.4% csDMARD (no biologic), 18.2% non-steroidal anti-inflammatory drug (NSAIDs)/COX-2 (no biologic or csDMARD), 11.5% a biologic and a csDMARD, 2.0% were receiving no therapy, and 1.8% other therapy (no biologic, csDMARD, or NSAID/COX-2). Of 295 patients receiving a biologic, 77.8% were receiving their first, 13.8% their second, and 8.3% their third or more biologic. Of 74 nr-axSpA patients who switched from a previous biologic to their current biologic, rheumatologists reported that 51.4% switched due to condition worsening, 48.6% had a loss of response over time, 27.0% switched due to a lack of pain alleviation, and 25.7% of patients switched because remission was not induced. CONCLUSIONS: This study suggests that around 60% of nr-axSpA patients were receiving biologic therapy prior to the approval of certolizumab pegol. Switching of biologics is frequent in nr-axSpA patients and is usually due to lack of efficacy, loss or response, and effort to accomplish remission.

Impact of Enthesitis on Psoriatic Arthritis Patient-Reported Outcomes and Physician Satisfaction with Treatment: Data from a Multinational Patient and Physician Survey.

INTRODUCTION: Enthesitis is a core outcome domain assessed in psoriatic arthritis (PsA) clinical trials. Limited evidence describes the impact of enthesitis on patient-reported outcomes (PROs) and physician satisfaction with current treatment options. The objective of this analysis is to characterize the impact of enthesitis on PROs and physician satisfaction with currently available treatment in clinical practice settings. METHODS: Cross-sectional survey of rheumatologists, dermatologists, and their consulting patients with PsA in Australia, Canada, European Union (EU5), and the USA conducted in 2018. Physicians assessed current presence and severity of enthesitis, overall disease severity, other symptoms experienced, and their satisfaction with the current treatment. PsA participant self-reported data included current pain level, EQ5D, Psoriatic Arthritis Impact of Disease (PsAID12), Health Assessment Questionnaire Disability Index (HAQ-DI), and Work Productivity and Activity Impairment Index (WPAI-SHP). Bivariate descriptive analyses were conducted to describe features and outcomes in participants with and without enthesitis. RESULTS: Rheumatologists (454) and dermatologists (238) provided information for 3157 participants with PsA. Mean participant age was 49.2 years, and 45.9% were female. Enthesitis was present currently in 6.5% (205) of participants with PsA. Those with enthesitis had worse overall disease severity compared to those without enthesitis (12.2% vs 2.2% severe) and had more extraarticular manifestations, including nail psoriasis, dactylitis, and sacroiliitis. Enthesitis was associated with more pain, worse quality of life (QoL), increased disability, and a negative impact on work. Participants with enthesitis had higher NSAIDs and opioid pain medication use but similar biologic use. Physicians were significantly less satisfied with current PsA treatment in participants with enthesitis versus without enthesitis. CONCLUSIONS: Participants with psoriatic arthritis with enthesitis experienced significantly higher disease burden than those without enthesitis but were not more likely to receive advanced therapies. Physicians were significantly more dissatisfied with treatment in patients with enthesitis than in those without it.

Disease Characteristics and the Burden of Joint and Skin Involvement Amongst People With Psoriatic Arthritis: A Population Survey.

INTRODUCTION: Psoriatic arthritis (PsA) is a chronic, systemic, inflammatory disease where disease burden and quality of life (QoL) are affected by both joint and skin manifestations. METHODS: Patient and physician reported data were collected about 3200 patients in a cross-sectional survey of patients from nine countries. Patient-reported outcomes (PROs) included perceptions of symptom importance, EuroQol questionnaire (EQ-5D), Psoriatic Arthritis Impact of Disease (PsAID12), and Work Productivity and Activity Impairment (WPAI) Index. Outcomes were compared in patients with 'joint-only' and 'joint and skin' disease symptoms. RESULTS: Of the 3200 patients, 2703 had complete information for 'joint-only' or 'joint and skin' involvement and were included in the analysis. Patients had a mean age of 49.2 years, 45.2% were female, and 64.5% had 'joint and skin' involvement. Patients with 'joint and skin' involvement had higher mean tender and swollen joint counts (5.2 and 4.8) than patients who were 'joint-only' (2.0 and 1.5). Significantly more patients with active 'joint and skin' symptoms experienced a flare (currently or within the last 12 months) compared with 'joint-only' patients (34.9 vs. 23.2%, p < 0.001). When asked to prioritize the burden of symptoms, 61.6% of patients prioritized joints, 38.4% prioritized skin. Anxiety/depression was experienced by 41.4% of patients, 62.4% of whom indicated that both joint and skin symptoms were the cause. Patients with 'joint and skin' involvement reported significantly worse QoL, work productivity and activity impairment than 'joint-only' patients (EQ-5D index 0.79 vs. 0.85, p < 0.001; EQ-5D VAS 71.98 vs. 77.68, p < 0.001; PsAID12 2.91 vs. 1.66, p < 0.001; WPAI overall work impairment 25.61 vs. 16.32, p < 0.001). CONCLUSIONS: PsA patients who experience 'joint and skin' symptoms had significantly worse clinical outcomes, health-related QoL, and work productivity compared with patients with 'joint-only' symptoms.

Developing sustainable nursing and allied health professional research capacity.

BACKGROUND: Research provides the evidence on which to base effective, safe clinical services. Engaging healthcare staff in research improves healthcare. However, clinical staff may not want to leave clinical practice to develop their research experience. Gaining postdoctoral research experience is a difficult step to make and opportunities are limited. AIM: To describe an approach to developing sustainable research capacity by supporting nurses and allied health professionals to develop their postdoctoral research skills while remaining in clinical practice. DISCUSSION: An approach to developing nursing, midwifery and allied health professionals (NMAHPs)'s postdoctoral research skills was devised and implemented in an acute NHS hospital in England. This collaborative approach involved negotiating strategic support from senior managers and incorporated an action-learning framework to develop and fund a research project addressing a clinical priority. CONCLUSION: A 'whole organisation' approach is needed to develop postdoctoral nurse and NMAHP researchers that requires a reflexive model with strategic, organisational and individual support encompassing action learning and corporate buy-in from senior managers. IMPLICATIONS FOR PRACTICE: Taking such an approach can enable nurses to remain in practice while developing NMAHP-led research. This shows its usefulness to senior managers and enables nurses to have the knowledge and confidence to support others to develop their research skills.

Diagnosing and Preventing Hearing Loss in the Genomic Age.

Over the past two decades, significant technological advances have facilitated the identification of hundreds of genes associated with hearing loss. Variants in many of these genes result in severe congenital hearing loss with profound implications for the affected individual and their family. This review collates these advances, summarizing the current state of genomic knowledge in childhood hearing loss. We consider how current and emerging genetic technologies have the potential to alter our approach to the management and diagnosis of hearing loss. We review approaches being taken to ensure that these discoveries are used in clinical practice to detect genetic hearing loss as soon as possible to reduce unnecessary investigations, provide information about reproductive risks, and facilitate regular follow-up and early treatment. We also highlight how rapid sequencing technology has the potential to identify children susceptible to antibiotic-induced hearing loss and how this adverse reaction can be avoided.