Metabolic syndrome and psoriatic arthritis: the role of weight loss as a disease-modifying therapy.

Psoriatic arthritis (PsA) is an inflammatory joint and entheseal disease associated with significant personal and public health burden. PsA has a prevalence of up to 1%, affecting ~20% of people suffering with psoriasis. PsA is frequently accompanied by metabolic syndrome (MetS), and both conditions are characterised by a chronic pro-inflammatory state, with several key cytokines in PsA (interleukin (IL)-17 and IL-23) also elevated in those with MetS. This narrative review aims to provide an update on MetS in PsA, focusing on its prevalence, pathogenesis, prognosis, treatment interactions and future therapeutic options. MetS is particularly prevalent in PsA compared to other inflammatory arthritides. Cohort studies indicate a higher risk of PsA in individuals with obesity, while Mendelian randomization studies link childhood obesity, insulin resistance, and dyslipidaemia to PsA. Weight loss interventions have been shown to reduce disease activity in PsA. Additionally, MetS negatively impacts the efficacy of tumour necrosis factor inhibitor (TNFi) drugs in treating PsA. Drugs given for PsA may also affect the conditions constituting MetS. Leflunomide has been shown to reduce body weight but also increase blood pressure. TNFi drugs lead to weight gain but reduce cardiovascular risk. Janus kinase inhibitors increase lipid levels and cardiovascular risk among high-risk groups. Anti-IL-17 and anti-IL-12/IL-23 drugs may cause a short-term increase in cardiovascular risk, although the long-term effects have yet to be established. Weight loss represents an unexplored avenue for disease modification in PsA, alongside a plethora of general health benefits. Dietary and exercise modifications are the cornerstone of weight management but vary substantially across individuals. Novel therapies to treat weight loss, such as glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors, may prove useful alongside disease-modifying therapies for those with PsA and MetS and should be investigated as potential therapeutic adjuncts.

What effects do obesity and related health problems have on psoriatic arthritis? Psoriatic arthritis (PsA) is a condition that causes joint pain and swelling, which can lead to permanent damage to the joints over time. This condition affects 1 in 100 people and 1 in 5 people with psoriasis. Metabolic syndrome (MetS) is a condition where a person has a combination of high body fat, high blood pressure, high blood sugar and/or high cholesterol. MetS is more common in someone with PsA. If a person has MetS, they are more likely to get PsA. If a person with PsA has MetS, they have worse joint problems and their joint problems do not improve as much with certain treatments. Many of the drugs given for PsA can affect MetS. This can include increasing or decreasing body weight, increasing blood pressure and increasing or decreasing the risk of having a heart attack or stroke. Different medications affect these risks in different ways. Weight loss helps people with PsA improve their joint problems. However, some people find losing weight harder than others. Medications that can help people lose weight, could be useful to improve joint problems in PsA. Future studies should see if these medications can be useful in people with PsA and MetS.

Insomnia and short sleep duration, but not chronotype, is associated with chronic widespread pain: Mendelian randomization study.

OBJECTIVES: Sleep disturbance has been associated with chronic widespread pain (CWP), but their causal relationship remains unclear. We aimed to examine the causal relationship and direction between CWP and sleep traits, namely insomnia, sleep duration and chronotype, using Mendelian Randomization. METHOD: We used genetic association data from ~0.5 million individuals and up to 1.8 million controls from the UK Biobank (UKB). All traits were defined predominantly by self-report. Short sleep duration was defined as average ≤6 hours per 24 hours. Chronotype refers to the inclination to sleep at certain times where some wake and go to bed early ('morning' person), and others wake and go to sleep later ('evening' person). To permit use of the largest available genetic association data, we used the Causal Analysis Using Summary Effect estimates (CAUSE) method, which allows for sample overlap. RESULTS: Insomnia (OR 1.009, 95% credible interval 1.005, 1.014; p = 0.018 that the causal model is a better fit than non-causal model) and short sleep duration (OR 1.060, 95%CrI 1.038, 1.083; p = 0.040) were causally associated with increased risk of CWP, with limited evidence for reverse causation. There was no evidence in support of long sleep duration or chronotype being associated with CWP. CONCLUSIONS: This study suggest that insomnia and short sleep duration (≤6 hours) are associated with an increased risk of CWP. Improving short sleep duration and insomnia, rather than chronotype, may be effective in reducing the risk of CWP, although these results should be replicated in epidemiological and interventional studies.

Exploring the prognostic significance of arm-level copy number alterations in triple-negative breast cancer.

Somatic copy number alterations (SCNAs) are prevalent in cancer and play a significant role in both tumorigenesis and therapeutic resistance. While focal SCNAs have been extensively studied, the impact of larger arm-level SCNAs remains poorly understood. Here, we investigated the association between arm-level SCNAs and overall survival in triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer lacking targeted therapies. We identified frequent arm-level SCNAs, including 21q gain and 7p gain, which correlated with poor overall survival in TNBC patients. Further, we identified the expression of specific genes within these SCNAs associated with survival. Notably, we found that the expression of RIPK4, a gene located on 21q, exhibited a strong correlation with poor overall survival. In functional assays, we demonstrated that targeting Ripk4 in a murine lung metastatic TNBC model significantly reduced tumor burden, improved survival, and increased CD4+ and CD8+ T cell infiltration. RIPK4 enhanced the survival of triple-negative breast cancer cells at secondary sites, thereby facilitating the formation of metastatic lesions. Our findings highlight the significance of arm-level SCNAs in breast cancer progression and identify RIPK4 as a putative driver of TNBC metastasis and immunosuppression.

Comparison of clinical features between patients with anti-synthetase syndrome and dermatomyositis: Results from the MYONET registry.

OBJECTIVES: To compare clinical characteristics, including the frequency of cutaneous, extramuscular manifestations, and malignancy, between adults with anti-synthetase syndrome (ASyS) and dermatomyositis (DM). METHODS: Using data regarding adults from the MYONET registry, a cohort of DM patients with anti-Mi2/-TIF1É£/-NXP2/-SAE/-MDA5 autoantibodies, and a cohort of ASyS patients with anti-tRNA synthetase autoantibodies (anti-Jo1/-PL7/-PL12/-OJ/-EJ/-Zo/-KS) were identified. Patients with DM sine dermatitis or with discordant dual autoantibody specificities were excluded. Sub-cohorts of patients with ASyS with or without skin involvement were defined based on presence of DM-type rashes (heliotrope rash, Gottron's papules/sign, violaceous rash, shawl sign, V sign, erythroderma, and/or periorbital rash). RESULTS: In total 1,054 patients were included (DM, n = 405; ASyS, n = 649). In ASyS cohort, 31% (n = 203) had DM-type skin involvement (ASyS-DMskin). A higher frequency of extramuscular manifestations, including Mechanic's hands, Raynaud's phenomenon, arthritis, interstitial lung disease, and cardiac involvement differentiated ASyS-DMskin from DM (all p< 0.001), whereas higher frequency of any of four DM-type rashes: heliotrope rash (n = 248, 61% vs n = 90, 44%), violaceous rash (n = 166, 41% vs n = 57, 9%), V sign (n = 124, 31% vs n = 28, 4%), and shawl sign (n = 133, 33% vs n = 18, 3%) differentiated DM from ASyS-DMskin (all p< 0.005). Cancer-associated myositis (CAM) was more frequent in DM (n = 67, 17%) compared with ASyS (n = 21, 3%) and ASyS-DMskin (n = 7, 3%) cohorts (both p< 0.001). CONCLUSION: DM-type rashes are frequent in patients with ASyS; however, distinct clinical manifestations differentiate these patients from classical DM. Skin involvement in ASyS does not necessitate increased malignancy surveillance. These findings will inform future ASyS classification criteria and patient management.

Utility of Musculoskeletal Ultrasound in Psoriatic Arthritis.

PURPOSE: Psoriatic arthritis (PsA) is a chronic autoimmune disease that causes a variety of musculoskeletal abnormalities. Musculoskeletal ultrasound in PsA is becoming increasingly popular, both in clinical practice and research. This narrative reviews recent literature on the utility of ultrasound in PsA. METHODS: A search of PubMed was used to identify publications written in English, with titles containing the term psoriatic arthritis and either ultrasound, ultrasonography, or sonographic. A total of 178 publications were identified; those that were not relevant (n = 59), were not original research (n = 45), or that had small (<30) sample sizes (n = 34) were excluded, leaving 40 studies for review of the use of ultrasound in various aspects of PsA. Publications with similar findings were grouped into seven domains: (1) the use of ultrasound findings compared to clinical assessment; (2) the use of ultrasound in the assessment of enthesitis; (3) the use of ultrasound in the assessment of nails; (4) the use of ultrasound as a screening tool in patients with psoriasis at risk for PsA; (5) the use of ultrasound in differentiating PsA from other similar conditions; (6) the use of ultrasound as a measure of disease activity; and (7) the use of ultrasound compared to MRI. FINDINGS: In recent studies, ultrasound measures of inflammation tended to agree with objective clinical findings of disease, such as swollen joint counts, while being less influenced by subjective measures, such as pain. Ultrasound has utility in the assessment of enthesitis and psoriatic nail disease in PsA, and as an overall measure of disease activity. Ultrasound-based outcomes measures have been used in observational studies and in clinical trials involving PsA, and may have utility as a measure of treatment response. The findings from recent studies suggest that ultrasound may have utility in improving the accuracy and precision of screening programs designed to identify subclinical PsA in cohorts of patients with psoriasis; however, cost-efficacy remains to be determined. Beyond screening, ultrasound may have utility in the diagnosis of PsA in patients with suspected inflammatory arthritis, and ultrasound measures of inflammation agree with MRI measures of inflammation, meaning that incorporating ultrasound into clinical practice might help to overcome the barriers associated with MRI. IMPLICATIONS: As ultrasound technology continues to advance, and associated costs decrease, it is likely that ultrasound will become more integrated into the clinical journeys of patients with PsA.

SARS-CoV-2 vaccination and new-onset myasthenia gravis: A report of 7 cases and review of the literature.

Myasthenia gravis (MG) is an antibody-mediated immune disorder of the neuromuscular junction. SARS-CoV-2 is now recognised as a trigger factor for autoimmune diseases and to cause immune-mediated dysregulation, likely due to molecular mimicry induced by viral antigens. SARS-CoV-2 vaccination, similarly, results in exposure to viral antigen. Here we report 7 cases of new-onset myasthenia gravis in timely association with SARS-CoV-2 vaccination, including the first paediatric case identified to date. We also reviewed the literature for other new-onset MG cases reported within 4 weeks of SARS-CoV-2 vaccination and discuss our findings in the context of altered (auto)immunity following SARS-CoV-2 vaccination and/or infection.

Pregnancy outcomes of a joint obstetric and rheumatology clinic in a tertiary centre: a 2-year retrospective study of 98 pregnancies.

Objectives: The purpose of this study was to describe the maternal and fetal outcomes in patients with inflammatory rheumatic diseases attending a joint rheumatology and obstetric clinic in the UK. Methods: Electronic records of 98 patients attending the joint rheumatology and obstetric clinic between January 2018 and January 2020 were analysed. Data on patient demographics, characteristics (including age, ethnicity, diagnosis, and medications taken during pregnancy), pregnancy outcomes (miscarriage, stillbirth or live birth), maternal complications [infection, post-partum haemorrhage (PPH) or pre-eclampsia] and fetal complications (sepsis, congenital heart block, prematurity and low birth weight) were tabulated. Subgroups of patients based on maternal diagnosis, medications and Ro/La antibody status were described in a similar manner. Results: The cohort was found to be predominantly Caucasian women >30 years of age, diagnosed with a CTD. Of 98 pregnancies, 97% (n = 95) resulted in a live birth, with only 2% resulting in miscarriage (n = 2) and 1% in stillbirth (n = 1). The median duration of gestation was 38 (interquartile range 37-39) weeks, and the majority of patients had a normal vaginal delivery (35%, n = 34), whereas 30% had emergency Caesarean sections (n = 29). The median birth weight was 3120 (interquartile range 2690-3410) g. The most common maternal complications were PPH (56%, n = 54) and infection (22%, n = 21). The most common fetal complications were prematurity (23%, n = 22) and low birth weight (17%, n = 16). Conclusion: We report favourable outcomes from this service model, including a high live birth rate, a low miscarriage rate and a high median birth weight. With limited reported data of pregnancy outcomes from joint obstetric/rheumatology clinics, this service model might be beneficial in other centres.

Hereditary haemochromatosis presenting to rheumatology clinic as inflammatory arthritis.

Hereditary haemochromatosis (HH) is the most commonly identified genetic disorder in Caucasians. HH has a wide variety of clinical manifestations. As such, the presenting complaint in new diagnoses of HH can be non-specific such as fatigue; however, joint symptoms such as arthralgia are also common. These joint symptoms closely mimic the features of other musculoskeletal diseases such as rheumatoid arthritis (RA). Early diagnosis of HH is key to prevent long-term irreversible complications such as liver damage, diabetes and degenerative joint disease. We present a case of HH which was initially suspected to be early RA, with ultrasound findings of active synovitis. High clinical suspicion, a raised serum ferritin followed by genetic testing for C282Y mutation confirmed the diagnosis of HH. The synovitis responded to corticosteroids and was suspected to be due to pseudogout a known complication of HH. Early diagnosis and treatment resulted in a favourable outcome.

Septic arthritis caused by Mycoplasma hominis in a patient with systemic lupus erythematosus.

Mycoplasma hominis is one of the most common commensal organisms of the genitourinary tract. Immunocompromised patients are susceptible to developing severe infections secondary to M. hominis, and rarely, septic arthritis. This case report describes the occurrence of septic arthritis secondary to M. hominis in a 27-year-old woman with systemic lupus erythematosus (SLE), who presented with a 2-week history of left elbow swelling and tenderness, elevated inflammatory markers and joint aspiration findings consistent with infection. Serial blood cultures were negative. She was treated with flucloxacillin; however, failed to respond and so doxycycline was added to cover for atypical organisms. Subsequently, PCR analysis from the joint aspirate found M. hominis on day 16. Fortunately, doxycycline was an effective treatment for this atypical organism. This case outlines the importance of considering atypical organisms such as M. hominis as a cause of septic arthritis in immunosuppressed patients especially those with SLE.

A Case of IgG4-Related Disease and Membranous Nephropathy Associated with Thrombospondin Type-1 Domain-Containing 7A.

Background: IgG4-related disease (IgG4-RD) is a systemic multi-organ inflammatory disorder which affects the kidney 20% of the time. Patients with intrinsic IgG4-related kidney disease (IgG4-RKD) often have tubulointerstitial nephritis (TIN) whereas glomerular lesions like membranous nephropathy (MN) are less common. Antibodies to thrombospondin type-1 domain-containing 7A (THSD7A) have been described in primary MN, but never in association with IgG4-RKD. Case Report: We report the first case of IgG4-MN associated with THSD7A antibodies in serum and positivity on glomerular staining, in a 57-year-old Caucasian male with IgG4-RD affecting the pancreas, liver, lacrimal glands, extraocular muscles, and kidneys. This patient presented initially with glomerular disease including significant proteinuria consistent with MN. Glomerular staining for THSD7A antigen and serum THSD7A antibody titres was positive. Treatment with corticosteroids and cyclophosphamide successfully induced remission with resolution of proteinuria, and improvement in renal function. However, despite maintenance azathioprine, the patient relapsed 39 months later. On relapse, there was minimal proteinuria but a significant rise in creatinine. Subsequent renal biopsy showed less glomerular disease and instead a TIN pattern. Subsequent treatment with Rituximab and corticosteroids successfully induced remission. Conclusion: The role of THSD7A autoantibodies in MN is emerging, and as both IgG4-MN and presence of THSD7A antibody are rare occurrences in themselves, we speculate that there may be an undiscovered association between THSD7A and IgG4-MN. Routine testing for THSD7A in IgG4-MN may help to identify the link.

Concurrent Chemoradiation With or Without Durvalumab in Elderly Patients With Unresectable Stage III NSCLC: Safety and Efficacy.

INTRODUCTION: The addition of durvalumab after chemoradiation therapy (CRT) in unresectable stage III NSCLC significantly improves survival. The benefit of this approach in elderly patients is controversial given the toxicity associated with CRT and, thus, may be underutilized. We sought to investigate the outcomes of elderly patients treated with CRT without or without durvalumab at our center. METHODS: We reviewed all stage III patients with NSCLC treated with CRT between 2018 and 2020. Patients were analyzed on the basis of age: less than 70 years and 70 years and older. The end points evaluated were treatment patterns, toxicity, progression-free survival, and overall survival. RESULTS: The baseline characteristics including Eastern Cooperative Oncology Group performance status and comorbidities were similar among the 115 patients (44 elderly, 71 young). Completion rates of CRT (100%, 97%) and chemotherapy dose intensity (97%, 97%) were high in elderly and young patients, respectively. There was a trend toward increased hospitalizations in elderly patients because of infections (27% versus 13%, p = 0.08). Of those who did not have primary progression after CRT, 78% of eldery and 81% of young patients received durvalumab. The incidence of grade 3 or higher immune-related adverse events was 9% in elderly and 6% in young patients (p = 0.67). The median progression-free survival was similar (15.6 versus 10.5 mo, p = 0.10), even after adjusting for comorbidities (hazard ratio = 0.6, p = 0.09). The 12-month overall survival rates were 78% in the elderly and 76% in young patients (p = 0.98). CONCLUSIONS: Well-selected elderly patients can be treated safely with CRT followed by durvalumab with similar survival benefits compared with their younger counterparts. We would advocate for the referral of all elderly patients for oncologic assessment to avoid undertreatment.

The financial impact of cancer care on renal cancer patients.

INTRODUCTION Advances in novel treatment options may render renal cell cancer (RCC) patients susceptible to the financial toxicity (FT) of cancer treatment, and the factors associated with FT are unknown. MATERIALS AND METHODS: Eligible patients were ≥ 18 years old and had a diagnosis of stage IV RCC for at least 3 months. Patients were recruited from Princess Margaret Cancer Centre and Sunnybrook Odette Cancer Centre (Toronto, Canada). FT was assessed using the validated Comprehensive Score for Financial Toxicity (COST) instrument, a 12-question survey scored from 0-44, with lower scores reflecting worse FT. Patient and treatment characteristics, out-of-pocket costs (OOP) and private insurance coverage (PIC) were collected. Factors associated with worse FT (COST score < 21) were determined. RESULTS: Sixty-five patients were approached and 80% agreed to participate (n = 52). The median age was 62 (44-88); 20% were female (n = 10); 43% were age ≥ 65 (n = 22); 63% were Caucasian (n = 31). Median COST score was 20.5 (3-44). Factors associated with worse FT were age < 65 (OR 9.5, p = 0.007), high OOP (OR 4.4, p = 0.04) and receiving treatment off clinical trial (in comparison to being on surveillance or on clinical trial) (OR 5.9, p = 0.03), when adjusting for other factors in multivariable logistic regression. However, there was no correlation between annual income or PIC and FT. CONCLUSION: Financial toxicity in the RCC population is more significant in younger patients and those on treatment outside of a clinical trial. Financial aid should be offered to these at-risk patients to optimize adherence to life prolonging RCC treatments.

Subtypes of EGFR- and HER2-Mutant Metastatic NSCLC Influence Response to Immune Checkpoint Inhibitors.

INTRODUCTION: The efficacy of immune checkpoint inhibitors (ICIs) is low among EGFR-mutated non-small-cell lung cancer (NSCLC), although prolonged responses have occasionally been reported. We investigated the association between mutation subtypes and ICI outcomes among HER2- and EGFR-mutated NSCLC. PATIENTS AND METHODS: This retrospective single-center study analyzed patients with EGFR- and HER2-mutated advanced NSCLC who received at least 1 cycle of ICI between 2013 and 2019. Patient characteristics, mutation subtype, and ICI outcomes. RESULTS: Among 48 patients with advanced NSCLC, 14 (29%) had HER2 mutations and 34 (71%) had EGFR mutations. EGFR mutations included 16 (47%) exon 19 deletion, 7 (21%) L858R, 5 (15%) uncommon, and 6 (18%) exon 20 insertion. Compared to EGFR-sensitizing mutations (ESMs), HER2 and EGFR exon 20 mutations were associated with a trend toward better response (respectively, ESM, HER2, and EGFR exon 20: 11%, 29%, and 50%; P = .07) and significantly better disease control rates (respectively, 18%, 57%, and 67%; P = .008). Compared to ESM, HER2 mutations (adjusted hazard ratio, 0.35; P = .02) and EGFR exon 20 mutations (adjusted hazard ratio, 0.37; P = .10 trend) were also associated with improved PFS. Programmed death ligand 1 (PD-L1) expression remained an independent predictor of PFS (adjusted hazard ratio, 0.42; 95% confidence interval, 0.23-0.76; P = .004). The 6-month PFS rates were 29% (HER2), 33% (EGFR exon 20), and 4% (ESM). ICIs were generally well tolerated in this population. Importantly, no immune-related toxicity was observed in 10 patients who received a tyrosine kinase inhibitor (TKI) as the immediate next line treatment after ICI. CONCLUSION: HER2 and EGFR exon 20 mutations derive greater benefit from ICIs with comparable PFS to wild-type historical second/third-line unselected cohorts. ICIs remain a treatment option for this genomic subgroup, given the absence of approved targeted therapies for these rare mutations.

Treatment and compliance with virtual reality and anaglyph-based training programs for convergence insufficiency.

BACKGROUND: Convergence insufficiency may be treated by visual exercises designed to increase convergence while maintaining single, clear, binocular vision. However, compliance with treatment is problematic, as patients often cease treatment when symptoms start to improve and before treatment is complete. The purpose of the present study was to assess the feasibility of using gamification of vision training to: (a) treat convergence insufficiency; and (b) improve compliance to treatment in comparison to a conventional treatment over a six-week treatment period. METHODS: Two interventions, anaglyphs and a virtual reality game of Snakes, were evaluated for their effectiveness in treating adults with convergence insufficiency. The prescribed training regimen was 20 minutes, three times per week for six weeks. Vision was assessed before and after the treatment period. Participants also filled in the Core Elements of the Gaming Experience Questionnaire to gauge impact of game design on compliance. RESULTS: Eighteen participants (mean age 20.8 ± 1.8 years) met the inclusion criteria for convergence insufficiency and nine participants were randomly assigned to each intervention. Repeated measures analysis of variance showed a significant effect of visit for near point of convergence (F1,16 = 38.32, p < 0.0001), near positive fusional reserves break (F1,16 = 21.94, p < 0.0001) and recovery (F1,16 = 26.87, p < 0.0001), but not of intervention type. Total time played was significantly longer for the virtual reality Snake Game than the anaglyph intervention (p < 0.0001), which translated to mean compliance of 82 per cent and 51 per cent respectively. CONCLUSION: Gamification of vision training in a virtual reality environment is feasible and associated with increased compliance, hence may be a useful strategy to treat convergence insufficiency.

Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study.

BACKGROUND: Faecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after HSCT. METHODS: We did a retrospective cohort study at the Royal Manchester Children's Hospital, Manchester, UK, of patients who had received their first allogeneic HSCT between Feb 1, 2003, and Sept 1, 2016, and adenovirus infection recorded in their medical records. We excluded patients who had received second or third transplants or autologous HSCT transplants. We obtained characteristics of patients and transplants, including mortality and adenoviral reactivation, from medical records and the hospital database. All patients had blood samples tested weekly for adenovirus by PCR until immunosuppression was stopped and CD3 T-cell count recovered to greater than 0·3 × 109/L. Faecal PCR was done before transplantation in all patients, and after transplantation in patients who had diarrhoea, at the onset of symptoms and weekly thereafter until diarrhoea resolved. We analysed all samples available before and after HSCT. We did subgroup analyses for patients undergoing HSCT for cancer versus non-malignant conditions. We also assessed whether 5 log10 copies per g faeces was a suitable predictive threshold for adenoviraemia. FINDINGS: We included 341 patients who had undergone a first allogeneic HSCT (median age 4·6 years, IQR 1·5-8·0, range 0-20·0). After HSCT, PCR was done in 4116 faecal samples from 293 (86%) patients who had diarrhoea and in 10 649 blood samples from 341 patients. Follow-up ended on July 14, 2017. 173 (59%) of 293 patients had adenovirus in faecal samples and 63 (18%) of 341 had adenovirus in blood samples. Maximum faecal viral load before adenoviraemia correlated significantly with maximum blood viral load (r=0·51, 95% CI 0·38-0·61, p<0·0001). Faecal adenoviral viral load greater than 5 log10 copies per g faeces was predictive of adenoviraemia (odds ratio 10·2, 95% CI 4·9-21·6, p<0·0001) with sensitivity 75·9% and specificity 74·8%. These values were increased further in patients with cancer, to 86·4% and 87·5%, respectively. Among the 28 patients who had positive faecal and blood samples and who had undergone serial faecal PCR monitoring after HSCT, the median time between reaching the faecal viral load threshold and onset of adenoviraemia was 8·0 days (IQR 2·3-21·8, 95% CI 4·0-16·0). Non-relapse mortality was not associated with adenovirus reactivation in faeces alone (9·2%, 95% CI 5·4-14·3 in patients without reactivation vs 7·8%, 3·8-13·7 in those with positive faeces only), but was significantly increased in patients who developed adenoviraemia (27·0%, 95% CI 16·7-38·4, p<0·0001). INTERPRETATION: We identified a threshold faecal viral load that can predict the risk of adenoviraemia. Our findings support proliferation of adenovirus in the gastrointestinal tract before viraemia develops. Faecal PCR is suitable for early detection of children and young adults at risk of adenoviraemia, and its use might help reduce non-relapse mortality in allogeneic HSCT recipients. FUNDING: None.

Normative values for a tablet computer-based application to assess chromatic contrast sensitivity.

Tablet computer displays are amenable for the development of vision tests in a portable form. Assessing color vision using an easily accessible and portable test may help in the self-monitoring of vision-related changes in ocular/systemic conditions and assist in the early detection of disease processes. Tablet computer-based games were developed with different levels of gamification as a more portable option to assess chromatic contrast sensitivity. Game 1 was designed as a clinical version with no gaming elements. Game 2 was a gamified version of game 1 (added fun elements: feedback, scores, and sounds) and game 3 was a complete game with vision task nested within. The current study aimed to determine the normative values and evaluate repeatability of the tablet computer-based games in comparison with an established test, the Cambridge Colour Test (CCT) Trivector test. Normally sighted individuals [N = 100, median (range) age 19.0 years (18-56 years)] had their chromatic contrast sensitivity evaluated binocularly using the three games and the CCT. Games 1 and 2 and the CCT showed similar absolute thresholds and tolerance intervals, and game 3 had significantly lower values than games 1, 2, and the CCT, due to visual task differences. With the exception of game 3 for blue-yellow, the CCT and tablet computer-based games showed similar repeatability with comparable 95% limits of agreement. The custom-designed games are portable, rapid, and may find application in routine clinical practice, especially for testing younger populations.

Impact of Gamification of Vision Tests on the User Experience.

OBJECTIVE: Gamification has been incorporated into vision tests and vision therapies in the expectation that it may increase the user experience and engagement with the task. The current study aimed to understand how gamification affects the user experience, specifically during the undertaking of psychophysical tasks designed to estimate vision thresholds (chromatic and achromatic contrast sensitivity). METHODS: Three tablet computer-based games were developed with three levels of gaming elements. Game 1 was designed to be a simple clinical test (no gaming elements), game 2 was similar to game 1 but with added gaming elements (i.e., feedback, scores, and sounds), and game 3 was a complete game. Participants (N = 144, age: 9.9-42 years) played three games in random order. The user experience for each game was assessed using a Short Feedback Questionnaire. RESULTS: The median (interquartile range) fun level for the three games was 2.5 (1.6), 3.9 (1.7), and 2.5 (2.8), respectively. Overall, participants reported greater fun level and higher preparedness to play the game again for game 2 than games 1 and 3 (P < 0.05). There were significant positive correlations observed between fun level and preparedness to play the game again for all the games (p < 0.05). Engagement (assessed as completion rates) did not differ between the games. CONCLUSION: Gamified version (game 2) was preferred to the other two versions. Over the short term, the careful application of gaming elements to vision tests was found to increase the fun level of users, without affecting engagement with the vision test.