The Chikungunya virus: A reemerging cause of acute febrile illness in the high jungle of northern Peru.

BACKGROUND: The Chikungunya virus (CHIKV) is an emerging arthropod-borne virus (arbovirus) that causes undifferentiated acute febrile illness. Cases of CHIKV may be under-reported in Peru, given the various difficulties in diagnosing it, such as lack of diagnostic tests in remote areas, the passive nature of epidemiological surveillance, and co-circulation of other arthropod-borne pathogens. Therefore, a study was conducted in the high jungle of northern Peru to determine the prevalence of CHIKV among febrile patients and describe their clinical characteristics. METHODS: A cross-sectional study was conducted in the province of Jaen, Cajamarca, located in the high jungle of northern Peru. Patients attending primary healthcare centers within Cajamarca's Regional Health Directorate were enrolled. The study took place from June 2020 through June 2021. Patients were eligible if they sought outpatient healthcare for a clinical diagnosis of acute febrile illness (AFI). Serum samples were collected from all patients, and the diagnosis of CHIKV was determined using real-time RT-PCR, as well as the detection of IgM antibodies by ELISA. A logistic regression model was employed to identify the risk factors for CHIKV, and the odds ratios (ORs) were calculated, along with their corresponding 95% confidence intervals (95% CI). RESULTS: A total of 1 047 patients with AFI were included during the study period. CHIKV was identified in 130 patients of 1 047 (12.4%). Among the CHIKV positive cases, 84 of 130 (64.6%) were diagnosed by RT-PCR, 42 of 130 (32.3%) by IgM ELISA detection, and 4 of 130 (3.1%) by both assays. The majority of patients with CHIKV infection fell within the 18-39 years age group (50.0%), followed by the 40-59 years age group (23.9%) and those with 60 years or older (10.8%). The most common clinical symptoms observed in patients with CHIKV infection were headache (85.4%), myalgias (72.3%), and arthralgias (64.6%). The highest number of positive CHIKV cases occurred in May (23.1%), followed by March (20.0%) and February (13.8%) of 2021. CONCLUSION: The study reports a considerable frequency of CHIKV infections among patients with AFI from the high jungle of northern Peru. These findings highlight the importance of recognizing CHIKV as an ongoing pathogen with continuous transmission in various areas of Peru. It is crucial to enhance epidemiological surveillance by implementing reliable diagnostic techniques, as the clinical symptoms of CHIKV infection can be nonspecific.

Novel prognostic biomarkers in decompensated cirrhosis: a systematic review and meta-analysis.

BACKGROUND: Patients with decompensated cirrhosis experience high mortality rates. Current prognostic scores, including the model for end-stage liver disease (MELD), may underperform in settings other than in those they were initially developed. Novel biomarkers have been proposed to improve prognostication accuracy and even to predict development of complications. METHODS: We performed a systematic review and meta-analysis on novel urine and blood biomarkers and their ability to predict 90-day mortality in patients with decompensated cirrhosis. Secondary outcomes included 28-day and 1-year mortality, and development of acute-on-chronic liver failure, acute kidney injury and other complications. To overcome differences in units, temporal changes in assays and reporting heterogeneity, we used the ratio of means (RoM) as measure of association for assessing strength in predicting outcomes. An RoM>1 implies that the mean biomarker level is higher in those that develop the outcome than in those that do not. RESULTS: Of 6629 unique references, 103 were included, reporting on 29 different biomarkers, with a total of 31 362 biomarker patients. Most studies were prospective cohorts of hospitalised patients (median Child-Pugh-Turcotte score of 9 and MELD score of 18). The pooled 90-day mortality rate was 0.27 (95% CI 0.24 to 0.29). The RoM for predicting 90-day mortality was highest for interleukin 6 (IL-6) (2.56, 95% CI 2.39 to 2.74), followed by urinary neutrophil gelatinase-associated lipocalin (uNGAL) (2.42, 95% CI 2.20 to 2.66) and copeptin (2.33, 95% CI 2.17 to 2.50). These RoMs were all higher than for MELD (1.44, 95% CI 1.42 to 1.46). CONCLUSION: Novel biomarkers, including IL-6, uNGAL and copeptin, can probably improve prognostication of patients with decompensated cirrhosis compared with MELD alone.

Non-Selective Beta-Blockers and Risk of Sepsis in Patients with Cirrhosis and Ascites: Results from a Large Observational Study.

Background and Aims: Previous studies have not been able to determine whether non-selective beta-blockers (NSBB) reduce the risk of sepsis in cirrhosis. We aimed to examine this question with data from 1198 patients with cirrhosis and ascites included in clinical studies of satavaptan, a vasopressin receptor antagonist with no effect on infection risk. Methods: Risk of sepsis was estimated for NSBB users vs nonusers. Patients were examined every four weeks, or in relation to hospitalization, for the one-year duration of the trials. We computed the cumulative risk of sepsis for patients who did vs did not use NSBB at baseline. We used Cox regression to compare hazard rates of sepsis between current users and nonusers, accounting for changes in NSBB use over time. We adjusted for patient sex and age, MELD-Na score, albumin, use of antibiotics, use of proton pump inhibitors, cirrhosis etiology, history of variceal bleeding or SBP, severity of ascites and HE, HCC, other cancers, and diabetes, while stratifying on geographical region. Results: Of the 1198 patients, 54% used NSBB at some time. There were 56 sepsis episodes. The 1-year risk of sepsis was reduced to 5.7% (95% confidence interval [CI] 2.8-8.6) in baseline NSBB users vs 11.6% (95% CI 7.0-15.9) in baseline nonusers. The hazard ratio of sepsis for current NSBB users vs current nonusers was reduced to 0.5 (95% CI 0.3-0.8) and after adjustment to 0.7 (95% CI 0.4-1.3). Conclusion: NSBB use may reduce the risk of sepsis in patients with cirrhosis and ascites, but the precision of the estimate was limited by the number of episodes of sepsis.

Determinants of Health-Related Quality of Life in Chronic Chikungunya Disease in Guadeloupe.

Chronic chikungunya disease is associated with a poor quality of life and a variety of symptoms, not restricted to the musculoskeletal system. Patients with chronic chikungunya disease in Guadeloupe were evaluated in order to identify the main factors determining the quality of life. Patients were followed up at a mean of 36 months after chikungunya infection, undergoing detailed clinical examination for musculoskeletal involvement, with assessment of subjective symptoms and the impact on mood, physical activity, and quality of life (SF12). Patients had extensive musculoskeletal involvement shown by tenderness in 9 ± 4 joints and stiffness in 5 ± 4 joints. SF12 physical and mental component scores showed a poor health-related quality of life. Measures of joint pain, stiffness, and inflammation contributed to impaired quality of life scores. In addition, fatigue and interrupted sleep appeared to be important predictors for physical aspects of quality of life. The emergence of anxiodepressive syndromes post-chikungunya infection was associated with both physical and mental component scores of SF12. These data confirm that musculoskeletal symptoms are not the only determinants of quality of life in chronic chikungunya disease. Follow-up of patients should include assessment and management of fatigue, poor sleep quality, and anxiodepressive syndromes.

Development and validation of the Cirrhotic Ascites Severity model-A patient-reported outcome-based model to predict 1-year mortality.

Ascites formation is a sign of decompensation of cirrhosis and heralds a poor prognosis. The widely used standard binary classification of ascites as diuretic-responsive or refractory does not cover the spectrum of ascites and has limited prognostic information. We developed the Cirrhotic Ascites Severity (CIRAS) model to predict 1-year mortality among 465 patients randomized to placebo in the satavaptan trials investigating treatment of cirrhotic ascites. We used multivariable logistic regression to derive the CIRAS model based on these variables: ascites discomfort score (≤50 or >50), plasma sodium (≥140, 133-139, 125-132, or <125 mmoL/L), and a composite of ascites accumulation and diuretic treatment. We validated the prediction model in 697 trial participants randomized to satavaptan treatment. The 1-year all-cause mortality was 19.6%. The area under the receiver operator curve was higher for the CIRAS model than for the standard ascites classification into refractory and diuretic-responsive in both the development cohort (0.68 [95% confidence interval (CI): 0.62-0.75] vs. 0.62 [0.57-0.68]), and the validation cohort (0.68 [0.64-0.72] vs. 0.55 [0.51-0.60]). The CIRAS model had similar discrimination to the Child-Pugh score and nearly as good as the Model for End-Stage Liver Disease (MELD), MELD-Na, and MELD 3.0. Conclusions: The CIRAS model based on simple ascites-relevant data is an easily applicable and patient-centered way to describe the severity and prognosis of all ascites grades. It carries more prognostic information than today's label of "refractory ascites" and forms the basis for earlier and better clinical decisions related to ascites management.

Effects and safety of natriuretic peptides as treatment of cirrhotic ascites: A systematic review and meta-analysis.

BACKGROUND: Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis, counterbalancing vasoconstriction and anti-natriuretic factors. The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies, and definitive results are lacking. AIM: To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites. METHODS: We searched MEDLINE, Web of Science, Scopus, Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites. Inclusion was not limited by treatment duration or dose, or by follow-up duration. Both randomised controlled trials and non-randomised studies were eligible for inclusion. The primary outcome was change in renal sodium excretion. Secondary outcomes included safety measures and changes in renal water excretion, plasma aldosterone concentration, and plasma renin activity. RESULTS: Twenty-two studies were included. Atrial natriuretic peptide (ANP) was the only intensively studied treatment. Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of > 30 ng/kg/min were administered compared with ≤ 30 ng/kg/min (P < 0.01). Moreover, natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites (P < 0.01). ANP infusions increased renal water excretion, although without reaching a statistically significant dose-response gradient. Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders (P < 0.01). Blood pressure decreases occurred less frequently when ANP doses ≤ 30 ng/kg/min were applied. The quality of evidence for a natriuretic response to ANP was low, mainly due to small sample sizes and considerable between-study heterogeneity. Data were sparse for the other natriuretic peptides; B-type natriuretic peptide and urodilatin. CONCLUSION: Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites. Continuous infusion rates > 30 ng/kg/min are the most effective. However, safety increases with infusion rates ≤ 30 ng/kg/min.

Household clustering supports a novel chemoprophylaxis trial design for a mosquito-borne viral disease.

Infections because of chikungunya and other mosquito-borne viruses, such as dengue and Zika, represent an area of significant unmet medical need. There are currently no approved medicines for prophylaxis or treatment of these diseases, and the development and implementation of vaccines against these viruses have proved problematic. Although antiviral molecules with treatment and prophylactic potential against the chikungunya virus have been identified, no successful field trials have been reported. Chemoprophylaxis may be attractive for unvaccinated at-risk populations; however, performing a successful chemoprophylaxis trial during a chikungunya outbreak will require a clearly identifiable at-risk population. We propose the application of a household transmission model as used in testing drugs against respiratory viruses. Current evidence on household clustering of chikungunya and other Aedes mosquito-borne viral infections is supportive. We suggest that this model may improve prophylaxis trial feasibility and focus research and future treatment on a population likely to benefit.

Spontaneous bacterial peritonitis has no effect on the long-term prognosis of cirrhosis patients with ascites.

INTRODUCTION AND OBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a frequent complication to cirrhosis with an unclear long-term prognosis. We aimed to examine its effect on mortality in two independent patient cohorts. PATIENTS AND METHODS: We used Danish healthcare data on cirrhosis patients with a first-time paracentesis in 2000-2014 and data from three randomized controlled trials on satavaptan treatment of ascites conducted in 2006-2008. We used the Kaplan-Meier method to estimate cumulative mortality, and Cox regression to compare the confounder-adjusted mortality hazard for patients with vs. without SBP. RESULTS: In the Danish Healthcare Cohort, we included 1.282 patients of whom 133 (10.4%) had SBP. The SBP patients' cumulative 4-month mortality was 51.2% (95% CI: 43.0-59.9%) vs. 34.7% (95% CI: 32.0-37.6) in those without SBP. The SBP patients' confounder-adjusted mortality hazard was 1.54-fold higher (95% CI: 1.18-2.00) in the four months after paracentesis, but was not increased thereafter (confounder-adjusted mortality hazard 1.02, 95% 0.72-1.46). In the satavaptan trial data of 1,198 cirrhosis patients with ascites, the 93 patients with SBP had a cumulative 4-month mortality of 38.6% (95% CI: 29.3-49.7) compared with 11.4% (95% CI: 8.5-15.2) in those without. The SBP patients' confounder-adjusted mortality hazard ratio was 3.86 (95% CI: 2.44-6.12) during the first four months, and was 1.23 (95% CI: 0.54-2.83) thereafter. CONCLUSIONS: In both cohorts of patients with cirrhosis, an SBP episode had a high short-term mortality compared to patients without SBP, and had no lasting effect on the long-term mortality.

Therapeutic and prophylactic treatment with a virus-specific antibody is highly effective in rodent models of Chikungunya infection and disease.

Chikungunya virus (CHIKV) has re-emerged as a significant human pathogen in the 21st century, causing periodic, and sometimes widespread, outbreaks over the past 15 years. Although mortality is very rare, a debilitating arthralgia is very common and may persist for months or years. There are no antivirals that are approved for the treatment of CHIKV infection, and current treatment options consist of supportive care only. Herein, we demonstrate the efficacy of a CHIKV-specific antibody in the prophylactic and therapeutic treatment of CHIKV in mouse models of disease. The fully human anti-CHIKV monoclonal Ab SVIR023 demonstrated broad in vitro activity against representative strains from the three major CHIKV clades. Therapeutic treatment with SVIR023 administered 1- or 3-days post-infection resulted in reduced virus in various tissues in a dose- and time-dependent manner. Prophylactic treatment up to 4 weeks prior to virus challenge was also effective in preventing disease in mice. Mice treated with SVIR023 and infected with CHIKV were resistant to secondary challenge and no evidence of antibody enhancement of disease was observed. Treatment with SVIR023 was effective in mouse models of CHIKV infection and disease and further evaluation towards clinical development is warranted.

Risk Factors for Hepatic Hydrothorax in Cirrhosis Patients with Ascites - A Clinical Cohort Study.

BACKGROUND: The risk factors for hepatic hydrothorax are unknown. METHODS: We used data from three randomized trials of satavaptan treatment in patients with cirrhosis and ascites followed for up to 1 year. We excluded patients with previous hepatic hydrothorax or other causes for pleural effusion. The candidate risk factors were age, sex, heart rate, mean arterial pressure, diuretic-resistant ascites, a recurrent need for paracentesis, diabetes, hepatic encephalopathy, International Normalized Ratio, creatinine, bilirubin, albumin, sodium, platelet count, use of non-selective beta-blockers (NSBBs), spironolactone, furosemide, proton pump inhibitors, and insulin. We identified risk factors using a Fine and Gray regression model and backward selection. We reported subdistribution hazard ratios (sHR) for hepatic hydrothorax. Death without hepatic hydrothorax was a competing risk. RESULTS: Our study included 942 patients, of whom 41 developed hepatic hydrothorax and 65 died without having developed it. A recurrent need for paracentesis (sHR: 2.55, 95% CI: 1.28-5.08), bilirubin (sHR: 1.18 per 10 µmol/l increase, 95% CI: 1.09-1.28), diabetes (sHR: 2.49, 95% CI: 1.30-4.77) and non-use of non-selective beta-blockers (sHR: 2.27, 95% CI: 1.13-4.53) were risk factors for hepatic hydrothorax. Development of hepatic hydrothorax was associated with a high mortality-hazard ratio of 4.35 (95% CI: 2.76-6.97). CONCLUSIONS: In patients with cirrhosis and ascites, risk factors for hepatic hydrothorax were a recurrent need for paracentesis, a high bilirubin, diabetes and non-use of NSBBs. Among these patients with cirrhosis and ascites, development of hepatic hydrothorax increased mortality fourfold.

Treatment With Simvastatin and Rifaximin Restores the Plasma Metabolomic Profile in Patients With Decompensated Cirrhosis.

Patients with decompensated cirrhosis, particularly those with acute-on-chronic liver failure (ACLF), show profound alterations in plasma metabolomics. The aim of this study was to investigate the effect of treatment with simvastatin and rifaximin on plasma metabolites of patients with decompensated cirrhosis, specifically on compounds characteristic of the ACLF plasma metabolomic profile. Two cohorts of patients were investigated. The first was a descriptive cohort of patients with decompensated cirrhosis (n = 42), with and without ACLF. The second was an intervention cohort from the LIVERHOPE-SAFETY randomized, double-blind, placebo-controlled trial treated with simvastatin 20 mg/day plus rifaximin 1,200 mg/day (n = 12) or matching placebo (n = 13) for 3 months. Plasma samples were analyzed using ultrahigh performance liquid chromatography-tandem mass spectroscopy for plasma metabolomics characterization. ACLF was characterized by intense proteolysis and lipid alterations, specifically in pathways associated with inflammation and mitochondrial dysfunction, such as the tryptophan-kynurenine and carnitine beta-oxidation pathways. An ACLF-specific signature was identified. Treatment with simvastatin and rifaximin was associated with changes in 161 of 985 metabolites in comparison to treatment with placebo. A remarkable reduction in levels of metabolites from the tryptophan-kynurenine and carnitine pathways was found. Notably, 18 of the 32 metabolites of the ACLF signature were affected by the treatment. Conclusion: Treatment with simvastatin and rifaximin modulates some of the pathways that appear to be key in ACLF development. This study unveils some of the mechanisms involved in the effects of treatment with simvastatin and rifaximin in decompensated cirrhosis and sets the stage for the use of metabolomics to investigate new targeted therapies in cirrhosis to prevent ACLF development.

Ularitide as treatment of refractory ascites in cirrhosis- a study protocol for a randomised trial.

INTRODUCTION Ascites is a frequent complication to cirrhosis. When ascites becomes refractory to standard diuretic pharmacotherapy, patients are facing a median survival of less than one year and most likely a need for frequent hospitalisations due to large-volume paracentesis or complications. An unmet need exists for new and improved treatments of refractory ascites and the present study investigates the potential of the natriuretic peptide ularitide for this indication. METHODS We aim to investigate the effects, safety and tolerability of ularitide as treatment of refractory ascites in cirrhosis patients in a randomised, double-blind, placebo-controlled trial. Participants receive ularitide or placebo as a continuous intravenous infusion during hospitalisation as an add-on to any diuretic treatment. Clinical end points include increase in diuresis and natriuresis, reduction in body weight and waist circumference, safety end points, as well as changes in plasma concentrations of renal and systemic response biomarkers and hormones. CONCLUSION This study will provide evidence concerning the potential of ularitide in treating cirrhosis patients with refractory ascites. FUNDING This investigator-initiated trial is supported by ADS AIPHIA Development Services AG. TRIAL REGISTRATION Clinicaltrials.gov (NCT04311489) and EU Drug Regulating Authorities Clinical Trials (EudraCT: 2019-002268-28). The trial will be conducted in accordance with good clinical practice, the Declaration of Helsinki and applicable demands from Danish authorities.

Arthralgia resolution rate following chikungunya virus infection.

BACKGROUND: Arthralgia, persistent pain or stiffness of the joints, is the hallmark symptom of chronic chikungunya virus (CHIKV) disease. Associated with significant disability and reduced quality of life, arthralgia can persist for many months following CHIKV infection. Understanding the expected duration of arthralgia persistence is important for managing clinical expectations at the individual-level as well as for estimating long-term burdens on population health following a CHIKV epidemic. METHODS: A review of cohort studies reporting the prevalence of arthralgia post-CHIKV infection over multiple time points was conducted. Generalized linear models were used to estimate the average rate of arthralgia resolution following CHIKV infection. RESULTS: Sixteen cohort studies matching the inclusion criteria were identified and included in the analysis. An average rate of arthralgia resolution of 10.85% (95% confidence interval (CI) 9.05-12.66%) per month was estimated across studies, corresponding to an expected median time to arthralgia resolution of 6.39 months (95% CI 5.48-7.66 months) and an expected arthralgia prevalence of 72.21% (95% CI 68.40-76.23%) at 3 months post-CHIKV infection. CONCLUSIONS: Estimates of the average rate of arthralgia resolution and the expected prevalence of arthralgia over time post-CHIKV infection were derived. These can help inform expectations regarding the long-term public health burdens associated with CHIKV epidemics.

Tender and swollen joint counts are poorly associated with disability in chikungunya arthritis compared to rheumatoid arthritis.

Chronic rheumatological manifestations similar to those of rheumatoid arthritis (RA) are described after chikungunya virus infection. We aimed to compare the relevance of joint counts and symptoms to clinical outcomes in RA and chronic chikungunya disease. Forty patients with chronic chikungunya arthralgia and 40 patients with RA were enrolled in a cross-sectional study. The association of tenderness and swelling, clinically assessed in 28 joints, and patient evaluations of pain and musculoskeletal stiffness with modified Health Assessment Questionnaire (HAQ) and quality of life (QoL) assessments were investigated. Tender and swollen joint counts, pain and stiffness scores were all associated with the HAQ disability index in RA (all r > 0.55, p ≤ 0.0002), but only stiffness was significantly associated with disability in chikungunya (r = 0.38, p = 0.02). Joint counts, pain and stiffness were also associated with most QoL domains in RA patients. In contrast, in chikungunya disease, tender joint counts were associated only with one QoL domain and swollen joints for none, while pain and stiffness were associated with several domains. Our results confirm the relevance of joint counts in RA, but suggest that in chronic chikungunya disease, joint counts have more limited value. Stiffness and pain score may be more important to quantify chikungunya arthritis impact.

Endpoints and design of clinical trials in patients with decompensated cirrhosis: Position paper of the LiverHope Consortium.

Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.

Musculoskeletal stiffness is common in healthy adults and increases with age.

INTRODUCTION/OBJECTIVE: Musculoskeletal stiffness is a common feature in rheumatologic inflammatory diseases but little is known about background joint stiffness in the healthy population. The aim of this survey was to determine the variation in musculoskeletal stiffness with age in a cohort of healthy adults using a patient reported outcome instrument designed to assess stiffness in rheumatoid arthritis. METHODS: Healthy subjects ≥18 years old were enrolled at two sites. Those with a diagnosis of rheumatological disease were excluded. Each subject completed a 21-item questionnaire designed to evaluate the severity of musculoskeletal stiffness, its physical impact and psychosocial impact, and to provide an overall stiffness score, expressed as a percentage. Scores were analyzed by age group. RESULTS: Two hundred eighty-two subjects were included with a mean age of 42 years (±17, range 18-85). More than 50% of subjects reported stiffness in each age group but with a low median overall stiffness score of 5.4% (IQR 0, 12.6). Scores were markedly higher in those aged ≥60 years, median 10.0% (IQR 2.6, 21.9), and only in this age group did the majority of subjects report a physical or psychosocial impact of stiffness. Scores in males and females were similar. CONCLUSION: The prevalence of musculoskeletal stiffness in healthy subjects of all ages is not negligible, and the high frequency of stiffness and greater severity in the upper age cohort suggest that the background joint stiffness amongst older subjects should be considered when interpreting stiffness in rheumatologic patients.

MELD remains the best predictor of mortality in outpatients with cirrhosis and severe ascites.

BACKGROUND: The Model for Endstage Liver Disease (MELD) score may put patients with severe ascites at a disadvantage because they often have a poor quality of life and high mortality despite a favourable MELD score. AIM: To develop a model that is better than the MELD score at predicting 1-year mortality among patients with cirrhosis, severe ascites and MELD ≤18. METHODS: We used data from a randomised trial (SPARe-1) of patients with cirrhosis and severe ascites to develop a model to predict 1-year mortality. We used stepwise backward elimination and Cox regression to identify the strongest predictors. Performance was assessed with the C index and the Brier score. We examined performance in an external cohort of trial participants with cirrhosis and severe ascites (SPARe-2 participants). RESULTS: We included 308 patients with a 1-year mortality of 20.4%. The final prediction model (Severe Ascites Mortality score, "SAM score") included four variables: serum bilirubin, serum sodium, history of SBP (yes or no) and diabetes (yes or no). No indicators of quality of life were included. After correction for optimism bias, the SAM and MELD scores had nearly identical predictive ability. The external validation cohort included 149 patients whose 1-year mortality was 22.4%. The MELD score performed marginally better in this cohort, partly because the effects of SBP and diabetes on mortality were much smaller in this cohort. CONCLUSION: We did not succeed in developing a prediction model that was superior to the MELD score among patients with cirrhosis and severe ascites.

Persistent chikungunya arthritis in Roraima, Brazil.

BACKGROUND: The Amazon region of Brazil experienced a large epidemic of East Central South African (ECSA) chikungunya virus (CHIKV) in 2017 and continuous transmission of CHIKV persists. The impact of chronic arthritis caused by ECSA CHIKV is unknown. OBJECTIVE: The study aim was to describe the duration, severity, and characteristics of CHIKV arthritis in Roraima, Brazil, in comparison with local controls to further understand the long-term rheumatologic impact of ECSA CHIKV infection. METHODS: We performed a cross-sectional analysis comparing clinical arthritis outcomes among 40 cases with chronic (> 3 months) arthritis attributed to their CHIKV disease (n = 40) with control participants who were exposed to CHIKV but did not develop chronic arthritis (n = 40), rheumatoid arthritis controls (n = 40), and healthy controls lacking CHIKV exposure and arthritis (n = 40). FINDINGS: Our primary finding is that over 2 years post-infection, patients report moderate arthritis disease severity comparable with rheumatoid arthritis with the most significant impact on decreased quality of life from pain. MAIN CONCLUSIONS: These findings suggest that chronic arthritis caused by ECSA CHIKV infection has had a moderate impact in the Americas. Key Points • Chikungunya infection is responsible for moderate arthritis disease severity. • The East Central South African (ECSA) strain of CHIKV is a cause of persistent arthritis in Roraima, Brazil.

Stiffness, pain, and joint counts in chronic chikungunya disease: relevance to disability and quality of life.

INTRODUCTION/OBJECTIVES: To characterize the importance of musculoskeletal stiffness in a cohort of chikungunya patients with chronic joint symptoms. METHOD: Eighty-two patients were followed up 3 years after chikungunya infection. Tender and swollen joint counts, a pain intensity scale, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the EuroQol EQ-5D quality of life instrument were completed. A musculoskeletal stiffness questionnaire provided scores for overall stiffness and its components: stiffness severity, physical impact, and psychosocial impact. RESULTS: Patients had a mean age 51 ± 14 years. Sixty-seven patients were still experiencing chronic arthralgia. Musculoskeletal stiffness was reported by 43/67 patients with arthralgia and 3/15 patients without arthralgia. A physical impact of stiffness was reported by 87% patients and psychosocial impact by 71% patients. Mean tender joint count in patients reporting arthralgia was 6 ± 7, mean pain intensity 65 ± 20 out of 100, mean HAQ-DI was 0.54 ± 0.52, and mean EQ-VAS global health perception was 68 ± 62 out of 100. Stiffness severity was correlated with tender joint counts (ρ = 0.46) and pain intensity (ρ = 0.40). All three measures were equally well correlated with the EuroQol-VAS global health perception. Pain and tender joints were better correlated with the HAQ-DI (ρ = 0.68 and ρ = 0.63), but stiffness was more strongly correlated with several quality of life domains, including mobility. Swollen joints were a poor predictor of outcomes. CONCLUSIONS: Musculoskeletal stiffness following chikungunya infection is distinct from arthralgia. It does not always occur in the same patients or with a corresponding intensity. Joint pain and stiffness may be independently associated with disability and quality of life assessments.