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Introduction/objectives: Among people with or without hand osteoarthritis, we aimed to identify characteristics of people (e.g., age and gender) with marginal erosions (MEs). We also examined changes in MEs during 48 months. We described radiographic severity and progression among joints with MEs, changes in MEs, or central erosions (CEs)., Design: We studied participants from the Osteoarthritis Initiative with baseline and 48-month hand radiographs. A radiologist and rheumatologist evaluated the radiographs for disease severity (Kellgren-Lawrence grades) and erosions (central or marginal), respectively. We used descriptive statistics to characterize participants and calculated frequencies at the joint level., Results: Of the 3558 participants, 89 had a ME at baseline. People with MEs were more often male, older, and ever (former and current) smokers than those without a ME. There was no difference in inflammatory biomarkers or the presence of hand pain between individuals with and without a baseline ME. Almost all hands had only one ME (80%), whereas only 50% of individuals with CEs had only one CE at baseline. Compared to CEs, MEs appeared more frequently in joints without osteoarthritis (54% vs. < 1%). Approximately 18% of joints with an ME progressed in Kellgren-Lawrence grade versus 4% without ME. Among the joints with an ME at baseline, 10% resolved by 48 months. Less than 0.1% of joints developed a new ME., Conclusion: MEs appear to be distinct from CEs. MEs are predominantly present in males, isolated to one specific joint without osteoarthritis within a hand, and possibly predictive of radiographic progression. Key Points • Marginal erosions appear to be distinct from central erosions. • Most marginal erosions occur in joints without radiographic osteoarthritis. • Radiographic progression but not hand pain is more common in joints with a marginal erosion than without one., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: To evaluate the relationship of gardening/yardwork with symptomatic and structural progression in those with pre-existing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), an observational study designed to evaluate potential and known biomarkers and risk factors of knee OA., Methods: We conducted a cohort study nested within the OAI, including participants ≥ 50 years old with radiographic OA in at least one knee at the time of OAI enrollment. A participant reported the level of gardening/yardwork activity in a self-administered survey. Logistic regression analyses were used to evaluate the association of gardening/yardwork on new frequent knee pain, Kellgren-Lawrence (KL) worsening, medial joint space narrowing (JSN) worsening, and improved frequent knee pain., Results: Of 1808 knees (1203 participants), over 60% of knees had KL grade = 2, 65% had medial JSN, and slightly more than a third had frequent knee symptoms. Gardeners/yardworkers and non-gardners/yardworkers had similar "worsening" outcomes for new knee pain (29% vs. 29%), KL worsening (19% vs. 18%), and medial JSN (23% vs. 24%). The adjusted odds ratio (OR) for the "worsening" outcomes of new knee pain, KL worsening, and medial JSN worsening were 1.0 (0.7-1.3), 1.0 (0.8-1.3), and 1.1 (0.9-1.4), respectively. The gardeners/yardworkers had an adjusted OR of 1.2 (0.9-1.7) for improved knee pain compared with non-gardners/yardworkers., Conclusion: Gardening/yardwork is not associated with knee OA progression and should not be discouraged in those with knee OA. Key Points • Gardening/yardwork is not associated with knee OA symptomatic or structural progression. • Gardening/yardwork should not be discouraged in people with knee OA., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background and Aims: Whether herbal and dietary supplements (HDS) are safer than Western conventional drugs is controversial. The aim of this study was to explore the characteristics and risk factors for HDS-induced liver injury (HILI) in Taiwan., Methods: This is a 9-year multi-center prospective study conducted in Taiwan from 2011 to 2019. Patients with HILI were compared to those with conventional drug-induced liver injury (CILI)., Results: A total of 1,297 patients were enrolled, of whom 285 (22.0%) had HILI and 1,012 (78.0%) had CILI. Compared to the CILI group, the HILI group had higher initial serum alanine aminotransferase, alkaline phosphatase (ALP), peak ALP and bilirubin levels, and higher rates of jaundice, ascites, encephalopathy, coagulopathy, sepsis and acute liver failure. In addition, the HILI group had a higher mortality rate than the CILI group (12.6 vs. 8.0%, p = 0.016). Hepatitis B carrier status, elevated baseline liver biochemical tests and the use of crude herbs (without processing) were associated with an increased risk of HILI-related mortality (adjusted hazard ratios [95% confidence intervals]: 2.90 [1.43-5.99], 2.40 [1.01-5.68] and 2.94 [1.45-5.97], respectively)., Conclusions: HDS are popular and incriminated in more than one-fifth of drug-induced liver injuries in Taiwan. The patients with HILI were more severe than those with CILI in terms of liver biochemical tests, complications and mortality. Hepatitis B carriers, those with elevated baseline liver tests and crude herb users may have a higher risk of HILI-related mortality. The prudent use of HDS is suggested in these high-risk subjects., (© 2021. Asian Pacific Association for the Study of the Liver.)

Background and Aim: The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy., Methods: A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44 years., Results: Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65 year-old, BMI ≥ 27 kg/m 2 , FIB-4 ≥ 3.25, eGFR < 60 ml/min/1.73 m 2 , and non-HCV SVR, but not HBV co-infection., Conclusion: Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups., (© 2021. Asian Pacific Association for the Study of the Liver.)

Background: Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can be markedly heterogeneous with varying prognosis. This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy., Methods: We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n = 622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n = 774, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n = 460)., Results: In the training cohort, significant factors associated with OS were largest tumor size ≥ 10 cm, extrahepatic spread, macrovascular invasion, and Child-Pugh class, which provided the basis, together with aged ≥ 75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI] 32.2-53.7), 20.6 months (CI 14.1-25.9), 11.5 months (CI 8.02-14.1), 5.7 months (CI 4.02-5.98), and 3.2 months (CI 2.41-3.59), respectively, (p < 0.05). OS remained distinct among the proposed substages in the Taiwan validation cohort as well as the international validation cohort. The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0-C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or palliative therapy., Conclusion: Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients., (© 2021. Asian Pacific Association for the Study of the Liver.)

Introduction/objective: We aimed to establish sex-specific reference values of objective physical function tests among individuals with or at risk for knee osteoarthritis (KOA) across subsets of age, radiographic KOA severity, and body mass index (BMI)., Method: We included Osteoarthritis Initiative participants with data for objective physical function tests, sex, age, BMI, and radiographic KOA severity (Kellgren-Lawrence [KL] grade) at baseline. Objective physical function was quantified with 20-m walk speed, chair-stand speed, 400-m walk time, and knee extension and flexion strength. We created participant characteristic subsets for sex, age, KL grade, and BMI. Reference values were created as percentiles from minimum to maximum in 10% increments for each combination of participant characteristic subsets. Previously established clinically important differences for 20-m walk speed and knee extension strength were used to highlight clinically relevant differences., Results: Objective physical function reference values tables and an interactive reference value table were created across all combinations of sex, age, KL grade, and BMI among 3860 individuals with or at risk for KOA. Clinically relevant differences exist for 20-m walk speed and knee extension strength between males and females across age groups, KL grades, and BMI categories., Conclusions: Establishing an individual's relative level of objective physical function by comparing their performance to individuals with similar sex, age, KL grade, or BMI may help improve interpretation of physical function performance. The interactive reference value table will provide clinicians and researchers a clinically accessible avenue to use these reference values.Key Points• Since greater age, radiographic knee osteoarthritis severity, and body mass index are all associated with worse objective physical function, reference values should consider the complex inter-play among these patient characteristics.• This study provides objective physical function reference values among subsets of individuals across the spectrum of sex, age groups, radiographic knee osteoarthritis severity, and body mass index categories.• These reference values offer a more patient-centered approach for interpreting an individual's relative level of objective physical function by comparing them to a more homogeneous group of individuals with similar participant characteristics.• We have provided a clinically accessible interactive table that will enable clinicians and researchers to input their patient's data to quickly and efficiently determine a patient's relative objective physical function compared to individual's with similar characteristics.

Background and Aims: One-third of the global hepatitis C virus (HCV) burden is found in Asia. Real-world data from diverse East Asian cohorts remain limited. This study addressed the real-world status of direct-acting antiviral (DAA) therapy among patients from East Asia., Methods: Chronic hepatitis C (CHC) patients from clinical sites in Japan, Taiwan, South Korea, and Hong Kong were recruited in the REAL-C registry, an observational chart review registry. The primary outcome was sustained virologic response (SVR12, HCV RNA PCR < 25 IU/mL 12 week post-therapy)., Results: A total of 6287 CHC patients were enrolled. Compared to other East Asian patients, patients from Japan were older (66.3 vs. 61.5 years, p < 0.0001), had lower body mass indices (22.9 kg/m 2 vs. 24.6 kg/m 2 , p < 0.001), and were more likely to have non-liver malignancy history (12.2% vs. 5.0%, p < 0.001).The overall SVR12 rate was 96.4%, similar to patients both inside and outside Japan (96.6% vs. 96%, p = 0.21). The SVR12 rate ranged from 91.1 to 99.4% except treatment-experienced cirrhotic HCV genotype-1 patients who received daclatasvir/asunaprevir (85.9%) and the treatment-experienced cirrhotic HCV genotype-2 patients treated with sofosbuvir/ribavirin (87%). The overall rate of drug discontinuation was 1.9%, also similar across regions. On multivariate regression analyses, there was no significant association between geographic region and SVR outcomes., Conclusions: In this large multinational CHC cohort from the East Asia, oral DAAs were highly effective and well tolerated across the region. Policies should encourage treatment for all CHC patients with DAAs in Asia with its heavy burden of HCV.

Objective: Validation of a symptom measure for early knee OA may help identify new treatments and modifiable risk factors. Symptom measures that consider pain in the context of activity level may provide better discrimination than pain alone. Therefore, we aimed to compare sensitivity to change for radiographic progression between Ambulation Adjusted Score for Knee pain (AASK), which accounts for self-reported ambulation, and Western Ontario McMaster Osteoarthritis (WOMAC) knee pain score., Design: Participants were assessed annually up to 48 months using WOMAC, Physical Activity Scale for the Elderly (PASE) ambulation, and knee radiographs. AASK was defined as ((WOMAC pain) + 1)/((average daily hours of walking) + 1). Radiographs were scored for Kellgren-Lawrence (KL) grade. Linear regression, stratified by OA status, evaluated relationships between changes in AASK and WOMAC pain and KL grade over time., Results: For 4191 people (8030 knees), the mean age was 61.2 (+ 9.2) years old and BMI was 28.6 (+ 4.8) kg/m 2 ; 58% female. Over 40% of knees had WOMAC pain scores of 0; by design, no knees had AASK scores of 0. Annual changes in AASK were more sensitive to changes in KL than changes in WOMAC in those without baseline OA (0.20 and 0.16 change per unit KL change, p = 0.005 and 0.070 respectively), but performed similarly in knees with OA., Conclusion: AASK is simple to assess using existing validated questionnaires. AASK performs well in individuals with and without OA and should be considered in clinical trials and observational studies of early knee OA.

Higher levels of moderate to vigorous physical activity improve all-cause mortality and cardiovascular events. However, the effect of running, a moderate to vigorous activity, in those with knee osteoarthritis (OA), a common arthritis that occurs with aging, a high-risk group for mortality and cardiovascular events, is unclear. Therefore, we aimed to evaluate the association of self-selected running on OA symptom and structure progression in people with knee OA. This nested cohort study within the Osteoarthritis Initiative (OAI) (2004-2014) included those at least 50 years old with OA in at least one knee. Runners were defined using a self-administered questionnaire at the 96-month visit. At baseline and 48-months, symptoms were assessed and radiographs were scored for Kellgren-Lawrence (KL) grade (2-4) and medial Joint Space Narrowing (JSN) score (0-3). We evaluated the association of self-selected running with outcomes: KL worsening, medial JSN worsening, new knee pain, and improved knee pain over 48 months, adjusting for baseline age, sex, body mass index (BMI), KL score, contralateral KL score, contralateral knee pain, and injury. If data were not available at the 48-month visit, then they were imputed from the 36-month visit. One thousand two hundred three participants had a mean age of 63.2 (7.9) years, BMI of 29.5 (4.6) kg/m 2 , 45.3% male, and 11.5% runners. Data from 8% of participants required imputation. Adjusted odds ratios for KL grade worsening and new frequent knee pain were 0.9 (0.6-1.3) and 0.9 (0.6-1.6) respectively. Adjusted odds ratio for frequent knee pain resolution was 1.7 (1.0-2.8). Among individuals 50 years old and older with knee OA, self-selected running is associated with improved knee pain and not with worsening knee pain or radiographically defined structural progression. Therefore, self-selected running, which is likely influenced by knee symptoms and may result in lower intensity and shorter duration sessions of exercise, need not be discouraged in people with knee OA.

We aimed to determine if knees with incident accelerated knee osteoarthritis (AKOA) were more likely to receive a knee replacement (KR) than those with common knee osteoarthritis (KOA) or no KOA. We conducted a nested cohort study using data from baseline and the first 9 years of the Osteoarthritis Initiative (OAI). Eligible knees had no radiographic KOA at baseline (Kellgren-Lawrence [KL] < 2). We classified 3 groups using KL grades from the first 8 years of the OAI: 1) AKOA: knee progressed to advance-stage KOA (KL 3/4) in ≤ 4 years, 2) common KOA: knee increased in KL grade (excluding AKOA), and 3) No KOA: no change in KL grade by 8 years. The outcome was a KR (partial or total) at or before the 9-year OAI visit. We conducted a logistic regression with generalized linear mixed model and adjusted for age, body mass index, and sex. Overall, 14% of knees with AKOA received a KR by the 9th year compared with 1% and < 1% of those with common or no KOA, respectively. Knees that developed AKOA were > 80x and ~ 25x more likely to receive a KR than knees with no KOA or incident common KOA (adjusted odds ratio = 25.08; 95% confidence interval = 9.63-65.34). In conclusion, approximately 1 in 7 knees that develop AKOA received a KR; however, KRs were rare in the OAI among other knees with no radiographic KOA at baseline. Urgent steps are needed to identify adults at high-risk for AKOA and develop prevention strategies regarding the modifiable risk factors.

Acute esophageal variceal hemorrhage is a dreaded complication of portal hypertension. Its management has evolved rapidly in recent years. Endoscopic therapy is often employed to arrest bleeding varices as well as to prevent early rebleeding. The combination of vasoconstrictor and endoscopic therapy is superior to vasoconstrictor or endoscopic therapy alone for control of acute esophageal variceal hemorrhage. After control of acute variceal bleeding, combination of banding ligation and beta-blockers is generally recommended to prevent variceal rebleeding. To prevent the catastrophic event of acute variceal bleeding, endoscopic banding ligation is an important tool in the prophylaxis of first bleeding. Endoscopic obturation with cyanoacrylate is usually utilized to arrest acute gastric variceal hemorrhage as well as to prevent rebleeding. It can be concluded that endoscopic therapies play a pivotal role in management of portal hypertensive bleeding.

We evaluated the relationship of systolic blood pressure, diastolic blood pressure, pulse pressure, and treatment with antihypertensives with knee osteoarthritis incidence in a US cohort. We performed a longitudinal study (2004-2010) nested within the Osteoarthritis Initiative Study including only individuals without knee osteoarthritis at baseline. Systolic blood pressure, diastolic blood pressure, and pulse pressure were assessed at baseline, 12-, 24-, and 36-month visits. Knee radiographs at baseline, 12-, 24-, 36- and 48-month visits defined radiographic osteoarthritis, Kellgren and Lawrence grade ≥2. We performed logistic regression, adjusting for age, sex, body mass index, NSAID use, number of antihypertensive medications, diabetic medications, and cholesterol medications. One thousand nine hundred and thirty people (6040 observations) were included. Annual incidence rates of radiographic osteoarthritis by systolic blood pressure quartiles (lowest to highest) were 2.1, 3.4, 3.7, and 3.7%. Fully adjusted odds ratios of incident radiographic osteoarthritis (OA) for the 2nd-4th quartiles were 1.6, 1.7, and 1.6 relative to the lowest quartile (p for trend = 0.03). Pulse pressure results were similar. There was no association with diastolic blood pressure. Compared to those not taking any antihypertensive medications, those taking ≥3 had decreased odds (0.4, 0.1-1.0) of developing incident OA. In a US cohort, higher systolic blood pressure and pulse pressure are associated with increased incidence of radiographic knee osteoarthritis while treatment with ≥3 antihypertensive medications was associated with reduced incidence. These findings suggest a new and promising avenue for research on disease modification in knee osteoarthritis.

The purpose of this study was to examine if adults who develop accelerated knee osteoarthritis (KOA) have greater knee symptoms with certain activities than those with or without incident common KOA. We conducted a case-control study using data from baseline and the first four annual visits of the Osteoarthritis Initiative. Participants had no radiographic KOA at baseline (Kellgren-Lawrence (KL) <2). We classified 3 groups as follows: (1) accelerated KOA: > = 1 knee developed advance-stage KOA (KL = 3 or 4) within 48 months, (2) common KOA: > = 1 knee increased in radiographic severity (excluding those with accelerated KOA), and (3) no KOA: no change in radiographic severity by 48 months. We focused on individual items from the WOMAC pain/function subscales and KOOS pain/symptoms subscales. The index visit was a year before a person met the definition for accelerated, common, or no KOA. To examine group difference in knee symptoms, we used ordinal logistic regression models for each symptom. Results are reported as odds ratios (OR) and 95% confidence intervals (CI). Individuals who developed accelerated KOA were more likely to report greater difficulty with lying down (OR = 2.10, 95% CI = 1.04 to 4.25), pain with straightening the knee fully (OR = 2.04, 95% CI = 1.08, 3.85), and pain walking (OR = 2.49, 95% CI = 1.38, 4.84) than adults who developed common KOA. Individuals who develop accelerated KOA report greater symptoms with certain activities than those with common KOA. Our results may help identify individuals at risk for accelerated KOA or with early-stage accelerated KOA.

We described a definition of end-stage knee osteoarthritis (esKOA) and evaluated its association with health outcomes and osteoarthritis risk factors. We included Osteoarthritis Initiative participants with or at risk for knee osteoarthritis who had complete baseline data. We defined esKOA by adapting a validated appropriateness algorithm for total knee replacement based on data from baseline and the first four follow-up visits. We performed person-based analyses, including both knees from all participants. Participants met the definition of esKOA at the visit at which ≥1 knee reached the esKOA criteria. We assessed differences in individual characteristics between groups at baseline and over time and tested if incident esKOA (outcome) was associated with osteoarthritis risk factors (e.g., age, maximum adult weight, and quadriceps strength). The cohort consisted of 3916 participants with mean age of 61 (SD = 9) years and mean body mass index of 28.4 (4.7) kg/m(2); 59 % were female and 9.7 % developed incident esKOA. Those with incident esKOA had poorer health outcomes at baseline and greater declines in health outcomes, with the exception of SF-12 mental health score. Five out of nine tested risk factors were associated with incident esKOA in unadjusted analyses, with older age (≥65 years; odds ratio = 1.44, 95 % confidence interval = 1.19 to 1.83) and quadriceps weakness (odds ratio = 0.78, 95 % confidence interval = 0.71 to 0.86) remaining significant in adjusted models. Older age and quadriceps weakness predicted esKOA. esKOA is also characterized by poor health-related outcomes. This definition of esKOA could be a new clinically relevant outcome measure for osteoarthritis research., Competing Interests: The authors declare they have no conflicts of interest with regard to this work.

We evaluated whether accelerated knee osteoarthritis (AKOA) was associated with greater pain and other outcomes and if outcomes varied over time differently among those with incident AKOA or common knee osteoarthritis (KOA), which we defined as a gradual onset of disease. We conducted longitudinal analyses among participants in the Osteoarthritis Initiative who had no radiographic KOA at baseline (Kellgren-Lawrence [KL] <2). Participants were considered AKOA if ≥1 knees progressed to KL grade ≥3 and common KOA if ≥1 knees increased in radiographic scoring within 48 months. We defined the index visit as the study visit when they met the AKOA or common KOA criteria. Our observation period included up to 3 years before and after the index visit. Our primary outcome was WOMAC pain converted to an ordinal scale: none (pain score = 0/1 out of 20), mild (pain score = 2/3), and moderate-severe pain (pain score >3). We explored 11 other secondary outcome measures. We performed an ordinal logistic regression or linear models with generalized estimating equations. The predictors were group (AKOA or common KOA), time (seven visits), and a group-by-time interaction. Overall, individuals with AKOA (n = 54) had greater pain, functional disability, and global rating scale as well as slower chair-stand and walking pace compared with those with common KOA (n = 187). There was no significant interaction between group and time for knee pain; however, there was for chair-stand pace and global rating scale. In conclusion, AKOA may be a painful and disabling phenotype that warrants more attention by clinicians and researchers.

We explored whether age and body mass index (BMI) can help identify a subset of individuals who are at high risk for accelerated knee osteoarthritis (AKOA) compared with common knee osteoarthritis (KOA). In the Osteoarthritis Initiative, a multicenter observational cohort study of KOA (n = 4796), we studied participants without KOA at baseline (Kellgren-Lawrence (KL) <2). Participants could have one of three outcomes: (1) AKOA, ≥1 knee progressed to end-stage KOA within 48 months; (2) common KOA, ≥1 knee increased in radiographic scoring within 48 months (excluding those with AKOA); and (3) no KOA, no change in KL grade in either knee. After verifying an interaction between age, BMI, and recent knee injury, we determined if we could identify a specific subset of individuals at high risk for AKOA instead of KOA. First, we reviewed three-dimensional graphs with age, BMI, and probability of AKOA versus KOA on the axes. We then conducted a logistic regression with AKOA as the outcome and age-BMI groups as the predictor. In our main analyses, we found that older individuals with a BMI <35 kg/m(2) were more likely to develop AKOA than common KOA (n = 64; mean [SD] BMI = 27.3 [3.1] kg/m(2); odds ratio = 3.47, 95 % confidence interval = 1.70 to 7.10), especially if they had a recent knee injury. While older age and greater BMI are independently associated with AKOA, we found that older individuals who had a higher BMI, particularly if they have an injury, were more likely to develop AKOA than common KOA.