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Background: No evidence currently exists characterising global outcomes following major cancer surgery, including esophageal cancer. Therefore, this study aimed to characterise impact of high income countries (HIC) versus low and middle income countries (LMIC) on the outcomes following esophagectomy for esophageal cancer.Method: This international multi-center prospective study across 137 hospitals in 41 countries included patients who underwent an esophagectomy for esophageal cancer, with 90-day follow-up. The main explanatory variable was country income, defined according to the World Bank Data classification. The primary outcome was 90-day postoperative mortality, and secondary outcomes were composite leaks (anastomotic leak or conduit necrosis) and major complications (Clavien-Dindo Grade III - V). Multivariable generalized estimating equation models were used to produce adjusted odds ratios (ORs) and 95% confidence intervals (CI95%).Results: Between April 2018 to December 2018, 2247 patients were included. Patients from HIC were more significantly older, with higher ASA grade, and more advanced tumors. Patients from LMIC had almost three-fold increase in 90-day mortality, compared to HIC (9.4% vs 3.7%, p < 0.001). On adjusted analysis, LMIC were independently associated with higher 90-day mortality (OR: 2.31, CI95%: 1.17-4.55, p = 0.015). However, LMIC were not independently associated with higher rates of anastomotic leaks (OR: 1.06, CI95%: 0.57-1.99, p = 0.9) or major complications (OR: 0.85, CI95%: 0.54-1.32, p = 0.5), compared to HIC.Conclusion: Resections in LMIC were independently associated with higher 90-day postoperative mortality, likely reflecting a failure to rescue of these patients following esophagectomy, despite similar composite anastomotic leaks and major complication rates to HIC. These findings warrant further research, to identify potential issues and solutions to improve global outcomes following esophagectomy for cancer.

Aim: Impairment of tissue responsiveness to exogenous and endogenous nitric oxide (NO•), known as NO• resistance, occurs in many cardiovascular disease states, prominently in diabetes and especiall...

Background Conducting systematic reviews (“reviews”) requires a great deal of effort and resources. Making data extracted during reviews available publicly could offer many benefits, including reducing unnecessary duplication of effort, standardizing data, supporting analyses to address secondary research questions, and facilitating methodologic research. Funded by the US Agency for Healthcare Research and Quality (AHRQ), the Systematic Review Data Repository (SRDR) is a free, web-based, open-source, data management and archival platform for reviews. Our specific objectives in this paper are to describe (1) the current extent of usage of SRDR and (2) the characteristics of all projects with publicly available data on the SRDR website. Methods We examined all projects with data made publicly available through SRDR as of November 12, 2019. We extracted information about the characteristics of these projects. Two investigators extracted and verified the data. Results SRDR has had 2552 individual user accounts belonging to users from 80 countries. Since SRDR’s launch in 2012, data have been made available publicly for 152 of the 735 projects in SRDR (21%), at a rate of 24.5 projects per year, on average. Most projects are in clinical fields (144/152 projects; 95%); most have evaluated interventions (therapeutic or preventive) (109/152; 72%). The most frequent health areas addressed are mental and behavioral disorders (31/152; 20%) and diseases of the eye and ocular adnexa (23/152; 15%). Two-thirds of the projects (104/152; 67%) were funded by AHRQ, and one-sixth (23/152; 15%) are Cochrane reviews. The 152 projects each address a median of 3 research questions (IQR 1–5) and include a median of 70 studies (IQR 20–130). Conclusions Until we arrive at a future in which the systematic review and broader research communities are comfortable with the accuracy of automated data extraction, re-use of data extracted by humans has the potential to help reduce redundancy and costs. The 152 projects with publicly available data through SRDR, and the more than 15,000 studies therein, are freely available to researchers and the general public who might be working on similar reviews or updates of reviews or who want access to the data for decision-making, meta-research, or other purposes.

Diabetes mellitus (DM) is a metabolic disorder with growing global incidence, as 387 million people were diagnosed in 2014 with an expected projection of 642 million in 2040. Several complications are associated with DM including heart attack, stroke, kidney failure, blindness, and cancer. The latter is the second leading cause of death worldwide accounting for one in every six deaths, with liver, pancreas, and endometrium cancers are the most abundant among patients with diabetes. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a vital role in developing a wide array of pathological disorders, among them diabetes and cancer. Natural secondary metabolites that counteract the deleterious effects of reactive oxygen species (ROS) and modulate PI3K/Akt/mTOR pathway could be a promising approach in cancer therapy. Here, 717 medicinal plants with antidiabetic activities were highlighted along with 357 bioactive compounds responsible for the antidiabetic activity. Also, 43 individual plant compounds with potential antidiabetic activities against cancer via the modulation of PI3K/Akt/mTOR cascade were identified. Taken together, the available data give an insight of the potential of repurposing medicinal plants and/or the individual secondary metabolites with antidiabetic activities for cancer therapy.

In times like these, appreciating the essential nature of palliative and end-of-life care is perhaps more critical than ever. At the time of writing, more than 2.8 million confirmed cases and nearl...

Race and ethnicity play a significant role in poststroke outcomes. This brief report describes the presence of depression among stroke survivors who received inpatient rehabilitation and whether depression differs by race. Data from eRehabData and electronic medical records were analyzed for patients who received rehabilitation after an acute ischemic or hemorrhagic stroke. Of 1501 stroke patients, 61.3% were white, 33.9% were African American, and 4.8% were of other race/ethnic backgrounds. By retrospective clinical review, depression was documented for 29.7% of stroke patients. Premorbid versus new onset of poststroke depression was documented for 13.4% and 21.6% of whites, 7.5% and 11.5% of African American, and 0% and 16.7% of patients of other race/ethnic groups. Compared with whites, African American and people of other races had a lower odds of poststroke depression (African American adjusted odds ratio = 0.52, 95% confidence interval = 0.41–0.68; other races odds ratio = 0.37, 95% confidence interval = 0.19–0.71), after adjusting for all other significant risk factors identified in the bivariate analysis (sex, hyperlipidemia, cognitive deficit, neglect). Depression was documented for one in three stroke survivors who received inpatient rehabilitation and highest among whites especially for prestroke depression. Addressing depression in rehabilitation care needs to consider individual patient characteristics and prestroke health status.

Einleitung: In bisherigen Untersuchungen von RA Patienten konnten wir zeigen, dass die zentrale Schmerzantwort auf Kompression eines schmerzhaften Gelenks hin, dargestellt durch ein funktionelles MRT des Gehirns in Abhängigkeit von Blutsauerstoffgehalt (blood-oxygen level dependent=BOLD), [zum vollständigen Text gelangen Sie über die oben angegebene URL], Deutscher Rheumatologiekongress 2020, 48. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 34. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh)

Aphasia is a language impairment caused by focal brain damage affecting multiple channels of language. Studies have shown that one third of stroke patients show some form of aphasia. One of the key characteristics of aphasia is that in most types, patients show deficits in sentence processing. This is so much so that many aphasia assessment tools utilize sentence comprehension or production tasks to determine aphasia type or severity, or perhaps to provide a more detailed profile on the symptoms. Individuals with aphasia have been known to face difficulties in processing sentences with a derived or non-canonical structure, like the passive. While numerous studies have discussed the morphosyntactic basis of this deficit, other aspects of sentence processing such as frequency of the sentence structures are often neglected. There is considerable possibility of syntactic frequency affecting sentence processing, as a large body of research has shown the impact of word-level frequency towards language processing. Could the impairment of processing non-canonical sentences be related to the low frequency of these sentences?This thesis examines sentence processing in Standard Indonesian, a language where the passive occurs at a rate that is comparable to active sentences. Individuals with aphasia and controls were tested with sentence comprehension and production tasks, and an event-related potential study of sentence processing for healthy adults were conducted. We found the passive to be unimpaired for aphasic individuals, and we also did not find any observable processing differences between the active and the passive in the neuroimaging experiment.

Background Fetal growth restriction, i.e. the restriction of genetically predetermined growth potential due to placental dysfunction, is a major cause of neonatal morbidity and mortality. The consequences of inadequate fetal growth can be life-long, but the risks can be reduced substantially if the condition is identified prenatally. Currently, screening strategies are based on ultrasound detection of a small-for-gestational age fetus and do not take into account the underlying vascular pathology in the placenta. Measurement of maternal circulating angiogenic biomarkers placental growth factor, sFlt-1 (soluble FMS-like tyrosine kinase-1) are increasingly used in studies on fetal growth restriction as they reflect the pathophysiological process in the placenta. However, interpretation of the role of angiogenic biomarkers in prediction of fetal growth restriction is hampered by the varying design, population, timing, assay technique and cut-off values used in these studies. Methods We conducted a systematic-review in PubMed (MEDLINE), EMBASE (Ovid) and Cochrane to explore the predictive performance of maternal concentrations of placental growth factor, sFlt-1 and their ratio for fetal growth restriction and small-for-gestational age, at different gestational ages, and describe the longitudinal changes in biomarker concentrations and optimal discriminatory cut-off values. Results We included 26 studies with 2514 cases with small-for-gestational age, 27 cases of fetal growth restriction, 582 cases mixed small-for-gestational age/fetal growth restriction and 29,374 reference. The largest mean differences for the two biomarkers and their ratio were found after 26 weeks of gestational age and not in the first trimester. The ROC-AUC varied between 0.60 and 0.89 with sensitivity and specificity matching the different cut-off values or a preset false-positive rate of 10%. Conclusions Most of the studies did not make a distinction between small-for-gestational age and fetal growth restriction, and therefore the small-for-gestational age group consists of fetuses with growth restriction and fetuses that are constitutionally normal. The biomarkers can be a valuable screening tool for small-for-gestational age pregnancies, but unfortunately, there is not yet a clear cut-off value to use for screening. More research is needed to see if these biomarkers are sufficiently able to differentiate growth restriction on their own and how these biomarkers in combination with other relevant clinical and ultrasound parameters can be used in clinical routine diagnostics.

Streptococcus thermophilus, Lactobacillus delbrueckii, Lactobacillus fermentum and Lactobacillus casei were successfully isolated from indigenous Indonesian fresh milk based on the general morphological and biochemical classification as described in Bergey’s manual. Verification was conducted by sequencing of 16S rRNA after selection using the classification method mentioned in the manual. All isolates exhibited antimicrobial activity against Escherichia coli and Staphylococcus aureus in the well diffusion test. The susceptibilities of the isolated S. thermophilus 24/S1 and L. delbrueckii 94/L4 against 22 different antibiotics were determined by the disc diffusion method and variable susceptibility patterns were observed. Both isolates were susceptible to amoxicillin, the most commonly prescribed antibiotic, and resistant to sulfonamide. The presence of a plasmid was not detected after extraction. S. thermophilus 24/S1 and L. delbrueckii 94/L4 starter cultures were prepared for yogurt production after 9.5 h of incubation and the yogurt was evaluated for its flavor and quality by 30 volunteers. A score of 4.93 ± 0.45 out of 7 was obtained as compared to the yogurt prepared using commercial starter cultures which yielded a score of 4.76 ± 0.30 out of 7.

Although our understanding of reading acquisition has grown, the study of dyslexia in Standard Indonesian (SI) is still in its infancy. A recently developed assessment battery for young readers of SI was used to test the feasibility of Pennington et al.’s (2012) multiple-case approach to dyslexia in the highly transparent orthography of SI. Reading, spelling, phonological skills, and nonverbal IQ were assessed in 285 first, second, and third graders. Deficits in reading-related cognitive skills were classified and regression analyses were conducted to test the fit of single and multiple deficit models. Naming speed (NS) was the main predictor of reading and decoding fluency, followed by phonological awareness (PA), and verbal working memory (VWM). Accounting for 33% of the cases that satisfied both methods of individual prediction (i.e., classification of deficits and regression analysis), the hybrid model proved the best fit. None of the deficits in PA, NS, or VWM alone was sufficient to predict a risk of dyslexia in the present sample, nor was a deficit in PA necessary. Hence, there are multiple pathways to being at risk of dyslexia in SI, some involving single deficits, some multiple deficits, and some without deficits in PA, NS, or VWM.

Introduction: Myelofibrosis (MF) is the most severe myeloproliferative neoplasia (MPN), with a very variable survival, which can be beyond 20 years to less than two years. The only curative treatment is allogeneic bone marrow transplantation (ABMT), but this is restricted to patients of less advanced age and is associated with significant mortality and disease relapse. Adequate prognostic characterization is essential for therapeutic decision-making, and modern prognostic indexes using molecular and cytogenetic data have been replacing the traditional indexes. Materials and methods: Clinical and laboratory data were evaluated, bone marrow and peripheral blood karyotype were studied, and BCR-ABL1, JAK2, CALR, MPL, ASXL1, SRSF2, EZH2, IDH1, IDH2, U2AF1 mutations were investigated. The classic IPSS, DIPSS, DIPSS plus, and the most recent MIPSS70, MIPSS70 plus, MIPSS 70 plus 2.0, GIPSS, and MYSEC-PM indexes were applied to a population of 230 patients from 8 Brazilian institutions with primary myelofibrosis (MFP) and secondary myelofibrosis polycythemia vera (PV-MF) and essential thrombocythemia (TE-MF) and compared among themselves. Results and conclusions: The median-age was 65 years-old, the overall survival was 8.1 years (CI 95%, 7,2 – 10,7), with a 5 years estimated survival of 61% (53 – 70). Comparing the prognostic indexes with each other identified a greater accuracy of the prognostic indexes that use mutational and cytogenetic data on the classic prognostic indexes. In the univariate analysis, advanced age, male gender, spleen size, hemoglobin, white blood cell count, peripheral blood blast percentage, SRSF2 mutation, triple-negative patients, IPSS, DIPSS and DIPSS plus stratification, MIPSS70 high risk and MIPSS70 plus high and very high risk showed impact in survival. In the multivariate analysis, triple-negative for JAK2 V617F, CARL, and MPL (p = 0,002) and stratification by IPSS (p < 0,0001) maintained significance as risk factors for overall survival. The present study is the most extensive Brazilian cohort study of patients with MF evaluating these variables.

Purpose To determine the number of cases required to achieve competency in phacoemulsification in terms of the posterior capsule rupture rate. Setting Singapore National Eye Centre, Singapore. Design Retrospective cohort study. Methods The posterior capsule rupture rate of the first 300 phacoemulsification cases performed by each trainee in the Singapore National Eye Centre (2004 to 2012) was charted using cumulative sum graphs. Competency was primarily defined as a posterior capsule rupture rate of 2% or lower and secondarily as 5% or lower. Results Twenty trainees fulfilled the inclusion criteria. Four trainees (20%) and 19 trainees (95%) achieved a posterior capsule rupture rate of 2% and 5%, respectively. At least 41 cases were required to achieve a 5% posterior capsule rupture rate (mean 106, median 83). Conclusions There was considerable variation in the trainees’ abilities. Only 20% of the trainees achieved a posterior capsule rupture rate of 2% or lower and required at least 212 cases.

With its transparent orthography, Standard Indonesian is spoken by over 160 million inhabitants and is the primary language of instruction in education and the government in Indonesia. An assessment battery of reading and reading-related skills was developed as a starting point for the diagnosis of dyslexia in beginner learners. Founded on the International Dyslexia Association's definition of dyslexia, the test battery comprises nine empirically motivated reading and reading-related tasks assessing word reading, pseudoword reading, arithmetic, rapid automatized naming, phoneme deletion, forward and backward digit span, verbal fluency, orthographic choice (spelling), and writing. The test was validated by computing the relationships between the outcomes on the reading-skills and reading-related measures by means of correlation and factor analyses. External variables, i.e., school grades and teacher ratings of the reading and learning abilities of individual students, were also utilized to provide evidence of its construct validity. Four variables were found to be significantly related with reading-skill measures: phonological awareness, rapid naming, spelling, and digit span. The current study on reading development in Standard Indonesian confirms findings from other languages with transparent orthographies and suggests a test battery including preliminary norm scores for screening and assessment of elementary school children learning to read Standard Indonesian.

Purpose To assess the role of femtosecond laser technology in the management of severely subluxated cataracts. Design Retrospective, interventional case series. Methods All eyes with subluxated cataract seen between July 2012 and June 2015 were assessed for suitability for femtosecond laser–assisted cataract surgery, with the use of capsular tension devices. Participants with subluxated cataracts of at least 6 clock hours of zonular weakness were included in the study. Data collected included patient demographics, preoperative and postoperative best-corrected visual acuity (BCVA), nuclear density, extent of zonular weakness, completeness of capsulotomy, and complications. Poor visual outcome was defined as BCVA of worse than 20/40. Main outcome measure was the retention of the capsular bag. Results Of the 72 eyes with subluxated cataracts undergoing surgery during the study period, 47 eyes of 47 patients were eligible for analysis. Mean age of the patients was 60.7 years (standard deviation [SD] 13.2 years). The majority were male (32, 68.1%) and Chinese (38, 80.8%). The mean duration of follow-up was 8 months (SD 5.6 months). The main identifiable cause of lens subluxation was trauma (11 eyes). Almost two thirds (30 eyes) had more than 9 clock hours of zonular weakness. Seventy percent of cataracts (33) were nuclear sclerosis grade 3 and above. The capsular bag was preserved in 43 eyes (91.5%). The intraocular lens was stable and centered at the last follow-up in all these 43 eyes. An anterior capsule tear occurred in 6 eyes, all of which had cataracts of nuclear sclerosis grade 3 and above, with posterior extension occurring in 3 eyes. Primary posterior capsule rupture occurred in 1 eye. At 1 month 37 eyes (80.4%) had a BCVA of 20/40 or better. There was significant improvement in BCVA at 1 month (mean of 0.92 logMAR units [SD 0.88] to 0.22 [SD 0.38] [ P t test]), which was maintained at 1 year. Conclusions Selected cases of severely subluxated cataracts may be managed using femtosecond laser technology to perform the capsulotomy and nuclear fragmentation, with successful preservation of the capsular bag in 90% of eligible cases, especially in eyes with soft cataracts.

Introduction: Glucocorticoids represent a cornerstone in the treatment of rheumatoid arthritis. Their effect as a disease-modifying treatment in rheumatoid arthritis is well established. Despite this, the risk of adverse events of glucocorticoids, especially in high doses and over a long time, is constantly highlighted. Data on the prevalence and impact of glucocorticoid-related adverse effects in rheumatoid arthritis is needed, therefore, to be regularly revisited. Areas covered: In this review, our primary aim was to provide an update of evidence from randomized controlled trials and observational cohort studies on the safety of glucocorticoid treatment in rheumatoid arthritis. Our secondary aim was to provide a critical overview of the concerns raised with both study designs–randomized clinical trials versus nonrandomized observational studies–regarding the assessment of the safety of glucocorticoids in rheumatoid arthritis. Expert opinion: In the meantime, adherence to recommendations and consensus on standardized methodologies for monitoring and reporting adverse events is essential to improve our knowledge and competence in the best management of glucocorticoids.

Sherwood, Matthew/0000-0002-4305-5883; Taskinen, Marja-Riitta/0000-0002-6229-3588; Leonardi, Sergio/0000-0002-4800-6132; Raffel, Owen C/0000-0001-5470-7050; Muenzel, Thomas/0000-0001-5503-4150; Ersanli, Murat/0000-0003-1847-3087; Gislason, Gunnar H/0000-0002-0548-402X; bastos, jose/0000-0002-9526-3123; Abbate, Antonio/0000-0002-1930-785X; Chumakova, Galina A/0000-0002-2810-6531; Nikolaev, Konstantin/0000-0003-4601-6203; Tse, Hung Fat/0000-0002-9578-7808; Keskin, Kudret/0000-0002-9049-1530; Reshetko, Olga/0000-0003-3107-7636; Podoleanu, Cristian/0000-0001-9987-2519; Aylward, Philip/0000-0002-5358-8552; LETIERCE, Alexia/0000-0001-6679-5772, WOS: 000483334800002, PubMed: 31466614, BACKGROUND Patients with acute coronary syndrome (ACS) and history of coronary artery bypass grafting (CABG) are at high risk for recurrent cardiovascular events and death. OBJECTIVES This study sought to determine the clinical benefit of adding alirocumab to statins in ACS patients with prior CABG in a pre-specified analysis of ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). METHODS Patients (n = 18,924) 1 to 12 months post-ACS with elevated atherogenic lipoprotein levels despite high-intensity statin therapy were randomized to alirocumab or placebo subcutaneously every 2 weeks. Median follow-up was 2.8 years. the primary composite endpoint of major adverse cardiovascular events (MACE) comprised coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Patients were categorized by CABG status: no CABG (n = 16,896); index CABG after qualifying ACS, but before randomization (n = 1,025); or CABG before the qualifying ACS (n = 1,003). RESULTS in each CABG category, hazard ratios (95% confidence intervals) for MACE (no CABG 0.86 [0.78 to 0.95], index CABG 0.85 [0.54 to 1.35], prior CABG 0.77 [0.61 to 0.98]) and death (0.88 [ 0.75 to 1.03], 0.85 [0.46 to 1.59], 0.67 [0.44 to 1.01], respectively) were consistent with the overall trial results (0.85 [ 0.78 to 0.93] and 0.85 [0.73 to 0.98], respectively). Absolute risk reductions (95% confidence intervals) differed across CABG categories for MACE (no CABG 1.3% [0.5% to 2.2%], index CABG 0.9% [-2.3% to 4.0%], prior CABG 6.4% [0.9% to 12.0%]) and for death (0.4% [-0.1% to 1.0%], 0.5% [-1.9% to 2.9%], and 3.6% [0.0% to 7.2%]). CONCLUSIONS Among patients with recent ACS and elevated atherogenic lipoproteins despite intensive statin therapy, alirocumab was associated with large absolute reductions in MACE and death in those with CABG preceding the ACS event. (ODYSSEY OUTCOMES: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402) (C) 2019 by the American College of Cardiology Foundation., Fondation Assistance Publique-Hopitaux de Paris, Paris, France, The authors thank the patients, study coordinators, and investigators who participated in this trial. Sophie Rushton-Smith, PhD (MedLink Healthcare Communications, London) provided editorial assistance in the preparation of the manuscript (limited to editing for style, referencing, and figure and table editing) and was funded by Fondation Assistance Publique-Hopitaux de Paris, Paris, France.

ObjectiveTo assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], pConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Increased vascular stiffness and reduced endothelial nitric oxide (NO) bioavailability are characteristic of diabetes. Whether these are evident at a more moderate levels of hyperglycaemia has not been investigated. The objectives of this study were to examine the association between the level of glycaemia and resistance vasculature phenotype, incorporating both arterial stiffness and endothelial function. Diabetes was induced in male Sprague Dawley rats with streptozotocin (STZ; 55mg/kg i.v.) and followed for 8 weeks. One week post STZ, diabetic rats were allocated to either moderate (∼20mM blood glucose, 6-7U/insulins.c. daily) or severe hyperglycaemia (∼30mM blood glucose, 1-2U/insulins.c. daily as required). At study end, rats were anesthetized, and the mesenteric arcade was collected. Passive mechanical wall properties were assessed by pressure myography. Responses to the endothelium-dependent vasodilator acetylcholine (ACh) were assessed using wire myography. Our results demonstrated for the first time that mesenteric arteries from both moderate and severely hyperglycaemic diabetic rats exhibited outward hypertrophic remodelling and increased axial stiffness compared to arteries from non-diabetic rats. Secondly, mesenteric arteries from severely (∼30mM blood glucose), but not moderately hyperglycaemic (∼20mM blood glucose) rats exhibit a significant reduction to ACh sensitivity compared to their non-diabetic counterparts. This endothelial dysfunction was associated with significant reduction in endothelium-derived hyperpolarisation and endothelium-dependent NO-mediated relaxation. Interestingly, endothelium-derived nitroxyl (HNO)-mediated relaxation was intact. Therefore, moderate hyperglycaemia is sufficient to induce adverse structural changes in the mesenteric vasculature, but more severe hyperglycaemia is essential to cause endothelial dysfunction.

Aims To determine the role of enhanced depth imaging optical coherence tomography (EDI-OCT) in chronic Vogt-Koyanagi-Harada (VKH) disease. Methods Records of all consecutive patients with VKH seen at the Singapore National Eye Centre were retrospectively reviewed for concurrent EDI-OCT and indocyanine green angiograms (ICGAs) obtained six or more months after disease onset, demographics and duration of disease. The ICGAs were scored based on the following signs: early choroidal stromal vessel hyperfluorescence and leakage, hypofluorescent dark dots, fuzzy vascular pattern of large stromal vessels and disc hyperfluorescence, and correlated with the subfoveal choroidal thickness (SFCT) measured using EDI-OCT. Only images of one eye were analysed. Results 105 pairs of EDI-OCT and ICGA of 52 patients were included. Mean age was 51.7 years. Half of the patients (26) were male and the majority were Chinese (39 patients, 75.0%). Mean duration of disease was 106.3 months. There were 79 ICGA active episodes. Mean SFCT was thinner when ICGA was quiet (mean=187.31 μ), than when the ICGA was active (mean=272.38 μ, p=0.002). There was a positive correlation of the SFCT with the ICGA score but a negative correlation with age and duration of disease. Multivariate analysis showed that age, duration of disease and ICGA were the main factors affecting SFCT. Conclusions The positive correlation of SFCT measurements with ICGA score suggests that it may be used to monitor disease activity in chronic VKH in addition to ICGA, possibly reducing the number of ICGAs required.

Background: Comprehension of reversible sentences that have derived word order has often been reported as impaired in agrammatic aphasia. Most accounts of this phenomenon refer to the syntactic differences between derived and base word order of the arguments. However, it has been demonstrated that in agrammatic spontaneous speech in standard Indonesian (SI) passives are produced at a rate that is proportional to that of healthy speakers. The main difference between passives in SI and in other languages is the frequency with which passives are used: passives in SI are highly frequent. The high frequency can be explained by the fact that passives are used for politeness reasons, saliency of the passive morphology, earlier acquisition, and formal simplicity of the passive structure.Aims: The purpose of the current study is to investigate comprehension of the passive as a derived structure in SI and the influence of frequency.Methods & Procedures: A sentence-to-picture matching task was developed to test four reversible sentence types (active, passive, subject cleft and object cleft). There are three variables that are of interest, that is, word order, embedding and relative frequency of structures. Eleven agrammatic speakers classified as suffering from Broca's aphasia were tested.Outcomes & Results: The passive sentences were comprehended equally well as the active sentences. Embedding had limited effects: subject clefts were understood as well as actives and passives. Object clefts, however, were understood poorly and significantly worse than the three other sentence types.Conclusions: The sentence comprehension deficit pattern shown in SI individuals with Broca's aphasia introduces frequency of a syntactic structure as an additional factor to consider. Whether frequency or pragmatic constraints protects against erosion of the passive in Broca's aphasia in SI remains an open question.

The brown seaweed, Sargassum polycystum C. Agardh, was evaluated as a potential agent against acne vulgaris. The antioxidant and in vitro antibacterial properties of four methanol fractions (F1–F4) obtained through column chromatography were studied. F1 showed the highest activity against Propionibacterium acnes with minimal inhibitory and bactericidal concentrations of 0.25 and 0.50 mg mL−1, respectively. Additionally, treatment of P. acnes lipase with F1 resulted in the highest lipase inhibition at 71.90 %. The highest scavenging activity against DPPH· (16.567 ± 1.824 mg AAE g−1 extract) and ABTS·+ (4.075 ± 0.091 mg TE g−1 extract) was exhibited by F2. The mass spectrometry profile of F1 and F2 revealed chlorophyll a and fucoxanthin as the major anti-acne constituents. These findings suggest that extracts of S. polycystum serve as a promising source that could be developed for topical application against acne vulgaris.

The current study investigates predictors of reading abilities of adolescents in Standard Indonesian (SI). Reading predictors typically signify, with some degree of error, essential cognitive skills needed for individuals to read effectively. This is crucial since it forms a key part of the initial steps to assess or identify reading-related language impairments such as dyslexia. In addition to measures of reading itself and nonverbal intelligence, the present research examines six empirically motivated potential predictors of reading and decoding: phonological awareness; phonological short-term memory; verbal and semantic fluency; rapid automated naming (RAN); motor control; familial risk; and, self-reported factors. The results show that RAN is a dominant predictor among the other factors that were considered in adolescent SI speakers. The results also show strong support for the notion that the importance of RAN increases as children age. Moreover, it is consistent with previous studies that have argued that RAN is a vital predictor of reading development in transparent orthographies.

Background A BASDAI ≥4 has been often required to start TNFi therapy in patients with axSpA. However, this cut-off of high disease activity (HDA) is largely arbitrary. Unlike BASDAI, ASDAS incorporates objective measures (e.g. CRP) and has a validated definition of HDA (≥2.1). It has thus been suggested that ASDAS could also be used to guide treatment decisions, but evidence to support this is still scarce. Objectives To compare the impact of applying the ASDAS and BASDAI definitions of HDA in selecting patients for TNFi-treatment in daily clinical practice Methods Patients from Reuma.pt (Rheumatic Diseases Portuguese Register), with diagnosis of axSpA according to their rheumatologists (both treated and not treated with their first TNFi), with complete baseline BASDAI and ASDAS data, and complete 6 month of follow-up (i.e. baseline, 3 and 6 months visits available) were included. Four subgroups [cross-tabulation between ASDAS (≥2.1) and BASDAI (≥4) definitions of HDA], were compared according to baseline demographic and clinical characteristics in the ‘eligible population’ (i.e. irrespective of TNFi-treatment). In addition, for patients starting TNFi and with complete follow-up BASDAI/ASDAS data (‘efficacy population’), the subgroups were also compared according to different response criteria (see table 1), at 3 and 6 months. Results In total, 466 patients were included (59% males and 66% HLA-B27 positive). The large majority (n=382; 82%) fulfilled the definition of HDA according to both BASDAI and ASDAS at baseline (i.e. BASDAI≥4 and ASDAS≥2.1). The frequency of ASDAS≥2.1, if BASDAI Conclusions Our results show that the ASDAS-HDA definition (ASDAS≥2.1) is more inclusive than the BASDAI-HDA definition (≥4) in selecting axSpA patients for TNFi treatment. Importantly, the additionally ‘captured’ patients respond better and have higher likelihood of predictors thereof. These results support the use of ASDAS≥2.1 as a selection criterion for treatment decisions. Acknowledgements Supported in part by a research Grant from Investigator-Initiated Studies program of MSD Disclosure of Interest J. Marona Grant/research support from: MSD, A. Sepriano Grant/research support from: MSD, S. Rodrigues-Manica Grant/research support from: MSD, F. Pimentel-Santos Grant/research support from: MSD, A. Mourao Grant/research support from: MSD, N. Gouveia Grant/research support from: MSD, J. Branco Grant/research support from: MSD, F. Vinagre Grant/research support from: MSD, R. Roque Grant/research support from: MSD, J. Rovisco Grant/research support from: MSD, M. Marques Grant/research support from: MSD, J. Tavares-Costa Grant/research support from: MSD, J. Silva Grant/research support from: MSD, H. Santos Grant/research support from: MSD, N. Madeira Grant/research support from: MSD, E. Vieira-Sousa Grant/research support from: MSD, R. Machado Grant/research support from: MSD, M. Bernardes Grant/research support from: MSD, R. Ferreira Grant/research support from: MSD, S. Ramiro Grant/research support from: MSD

Background: SLEDAI is a widely used instrument to measure disease activity of systemic lupus erythematosus (SLE). However, it lacks sensitivity to discriminate improvement/worsening as it only scores items categorically and does not include several relevant lupus features, such as hemolytic anemia. Objectives: To derive and validate a SLE Disease Activity Score (SLE-DAS) with improved sensitivity to change, while maintaining the high specificity and simplicity of use of the SLEDAI. Methods: 324 patients fulfilling ACR’97 and/or SLICC’12 classification criteria for SLE and regularly followed at a tertiary care lupus clinic from January 2014 to December 2017 were included. At each outpatient visit, clinical and laboratory data were collected and disease activity (last 30 days) was scored with Physician Global Assessment (PGA) (0–3 scale) and SLEDAI-2K. To derive the SLE-DAS we analyzed data from the study visit with higher disease activity from each patient, applying multivariate linear regression analysis, with PGA as dependent variable/gold-standard. Independent variables tested in the models included items from SLEDAI-2K and continuous variables for swollen joint count, proteinuria, platelet and white blood cells counts. Some features absent from SLEDAI, such as hemolytic anemia, gastrointestinal and cardiopulmonary involvement were added to the model. To assess correlation validity we performed a Spearman’s correlation between the SLE-DAS, PGA and SLEDAI-2K at last follow-up visit. We tested performance of SLEDAI-2K (change ≥4) and SLE-DAS to discriminate a clinically meaningful worsening and improvement in SLE disease activity (change in PGA ≥0.3) using Receiver Operating Characteristic (ROC) curve analysis. We determined the best cut-offs values of SLE-DAS to detect changes in PGA ≥0.3 and calculated the sensitivity, specificity, positive and negative predictive values (PPV, NPV). Statistical significance was set at 0.05. Results: The final SLE-DAS model included 17 items. The SLE-DAS score at last follow-up visit presented high correlation with PGA (rho=0.975, p Conclusions: The SLE-DAS presents good construct validity and much higher discriminative power to detect changes in SLE disease activity as compared to SLEDAI-2K. External validation in another SLE cohort is underway. Disclosure of Interest: None declared

ᅟ This is a response to a Letter. Data abstraction is a time-consuming and error-prone systematic review task. Shokraneh and Adams categorize available techniques for tracking data during data abstraction into three methods: simple annotation, descriptive addressing, and Cartesian coordinate system. While we agree with the categorization of the techniques, we disagree with the authors’ statement that descriptive addressing is a PDF-independent method, i.e., any sort of descriptive addressing must reference a specific version of PDF file and not just any PDF of said report. Different versions of PDFs of the same report might place text and tables on different locations of the same page and/or on different pages. Consequently, it is our opinion that any kind of source location information should be accompanied by the source or linked by an intermediary service such as the Data Abstraction Assistant (DAA).

Introduction Retesting Chlamydia trachomatis (CT) treated people after 3–12 months is recommended as it can yield substantial numbers of reinfections. A test-of-cure (TOC) shortly after treatment (within 3 months) is not advisable due to the likelihood of false positive findings leading to overtreatment. Spatial analyses are useful to detect geographical areas of low guideline adherence to inform local testing policies and targeted interventions. The aim was to assess geographical variation in test practices of general practitioners (GPs) in The Netherlands. Methods Retrospective laboratory data containing CT tests of 48 GPs in 4 municipalities were obtained (2011–2015) from the public laboratory in the south western part of the Netherlands (183 thousand residents). First recorded urogenital positive CT tests of men (n=249; 39.2%) and women (n=386;60.8%)≥16 years between January 2011 and July 2015 were included in the analyses and TOC and retests were outcomes. Logistic regression was used for analyses. Results Overall, 8,275 CT tests were performed (positivity 8.4%;n=691);only 0.4% (n=43) from extra genital sites. On a GP level, the number of CT tests varied geographically from 1 to 2421 (p Conclusion Testing at extra genital sites and the overall proportion of retests was low at GP practices. Almost one out of five CT cases returned within three months, and many (re-)infections were probably missed. Moreover, it seems that there are geographical variations in test practices of GPs. Thus, targeted interventions at the local level are needed to increase CT testing and retesting practices of GPs.

Aphasia is a language disorder caused by focal brain injury. The Token Test is a tool to detect aphasic symptoms and measure aphasic severity in individuals who suffer brain damage causing language impairment. While Indonesia has a diagnostic test battery for aphasia (TADIR), it has yet to be able to quantify aphasic severity. In this study, we tested 49 individuals: 26 healthy adults, 7 non-aphasic post-stroke individuals, and 16 aphasic individuals. A series of tests were administered: the TADIR, Token Test, and the Verb and Sentence Test. The Token Test was sensitive enough to distinguish between the three groups and was also correlated with all other language tests including the TADIR.

Background: Patient Global Assessment (PGA) plays an important role in disease activity assessment and treatment decisions in rheumatoid arthritis (RA). However, the meaning of PGA is open to patient interpretation and this may affect the validity and reliability of clinical assessments. Objectives: We aimed to explore: (i) patients' perspective on PGA and its different formulations (ii) how patients' perspective may be improved by a brief explanation from a health care professional (HCP). Please download the structured abstract to read more.

Background The Rheumatoid Arthritis Impact of Disease (RAID) score1 assesses 7 impact domains of interest for people with rheumatoid arthritis (RA). Its use in research and clinical practice has been growing, and it is already translated into over 70 languages2 but the cross-cultural validity of the Portuguese RAID has not been well established. Objectives To validate the Portuguese RAID for use in Portugal. Methods This was a single centre, cross-sectional validation study involving 2 phases: (i) cognitive debriefing with 38 patients to determine comprehension of the existing2 Portuguese RAID (ii) cross-cultural validation using data from adult patients who were willing and able to complete the Portuguese RAID unaided. Analyses included fit to the Rasch model (implying construct validity, reliability and statistical sufficiency), tests for unidimensionality and invariance across different patient subgroups i.e. age, gender, education background, disease duration, function and culture. To test invariance to culture, the Portugal dataset was compared with datasets from France (n=195) and the UK (n=205).3 RUMM2030 software was used in all analyses. Results Phase I led to minor changes in phrasing 3 items to enhance understanding and conceptual equivalence between the original RAID and the Portuguese version. In Phase II, 288 patients were included: mean (SD) age=60 (12) years, 82% females, 76% with disease duration ≥5 years, 30% on biologics. The Portuguese RAID was shown to have adequate fit to the Rasch model and high internal consistency (Table 1). Unidimensionality and invariance to age, gender, disease duration and function were confirmed (data not shown). The scale was well targeted for patients with different levels of disease impact (Figure 1). Pooling the datasets from Portugal, France and the UK revealed no cultural response bias (Table 1). RAID was then calibrated into logit-based scores to enable parametric analyses and bias-free cross-cultural comparisons if desired (data not shown). Conclusions This study confirms the Portuguese RAID as a robust unidimensional tool for use in Portugal. The raw scores of the 7-item RAID can be used with confidence in clinical practice. Conversion charts are available to enable accurate cross-cultural comparisons across Portugal, France and the UK. References Gossec L, et al. Ann Rheum Dis, 2011;70:935–42. EULAR RAID and PsAID Questionnaires. Available from http://www.eular.org/tools_products_.cfm Accessed 25th Jan. 2017. Hewlett S, et al. Ann Rheum Dis, 2015;74:Suppl 2:559. Disclosure of Interest None declared

Background Patient global assessment (PGA) of disease activity is included in a large number of composite indices of disease activity and definitions of remission in Rheumatoid Arthritis (RA). However, the actual question is formulated in a variety of different ways according to the instrument considered. Objectives To evaluate how 6 different formulations of PGA affect patient estimates and impact upon disease activity and remission rates as assessed by 4 Disease Activity Indices. Methods Consecutive RA patients followed in a Rheumatology outpatient department were included in this cross-sectional study. Data collection comprised: 28 joint counts (tender and swollen), C-reactive protein (CRP) and 6 different PGA formulations. The chosen formulations were the ones stated in the: v1) Portuguese National Registry Reuma.pt, the locally used formulation; v2) ACR/EULAR provisional definition of remission (considered in this study as the “standard”); v3) CDAI and SDAI; v4) Disease Activity Score (DAS28) assessment of general health; v5) DAS28 assessment of disease activity (the currently used); v6) one, exploratory, developed by the investigators, including idiomatic cultural expressions. ACR/EULAR Boolean criteria, CDAI, SDAI, and DAS28-CRP (4v) were used to test how these 6 PGA formulations change the rates of remission. PGA differences were assessed by descriptive analyses (including patients with PGA ≤10 and ≤20mm) and Bland-Altman test. Results In total, 193 patients were included (82% female, mean (SD) age of 59 (13) years, mean disease duration of 12 (9) years and 31% under biologics). The average PGA ranged from 42.3 (25.3) to 48.1 (26.7)mm as measured in different formulations. The ACR/EULAR (v2) formulation yielded the largest proportion of patients scoring ≤10mm (16.1%), corresponding to a difference of up to 4.7% versus other PGAs. Similar results were found for the ≤20 cut-off (Table 1). By using different PGA9s formulations the rates of remission calculated with different indices can vary between 4.7% and 6.7% (Table 2). Bland-Altman chart confirmed the low agreement between ACR/EULAR formulation and the other PGA formulations (p Conclusions The use of different PGA formulations has clinical implications in disease activity, which, in turn, can influence therapeutic decisions. The establishment of a single standardised formulation seems warranted. Disclosure of Interest None declared

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

Dengue is a significant cause of morbidity in tropical countries with a rapidly increasing incidence. The incidence of ocular involvement ranges from 7 % to 60 % depending on the severity of the systemic disease. The two mechanisms involved in pathogenesis of ocular lesions are thrombocytopenia which manifests as haemorrhagic events such as the relatively common but benign subconjunctival haemorrhage or retinal haemorrhages and an immune-mediated reaction giving rise to rare but potentially sight-threatening uveitis, maculopathy or optic neuropathy.

Background The incidence and risk factors of amiodarone-induced thyroid dysfunction are variable in the literature. Objective The aim of this study was to investigate the clinical and biochemical features and risk factors of amiodarone-induced thyroid dysfunction in Taiwan. Setting This study was conducted at a tertiary referral center for arrhythmia. Method Retrospective analysis of patients treated with amiodarone during the years 2008–2009 was performed. Main outcome measure Incidence and risk factors of amiodarone-induced thyrotoxicosis (AIT) and amiodarone-induced hypothyroidism (AIH) were assessed. Results Of the 527 patients, 437 (82.9 %) remained euthyroid, 21 (4.0 %) developed AIT, and 69 (13.1 %) were affected with AIH. In univariate analysis, AIT was associated with younger age, and the risk factors for AIH included older age, higher baseline thyroid stimulating hormone (TSH) titer, lower baseline free T4 level, lower cumulative amiodarone dosage, and shorter amiodarone treatment duration. Cox regression analysis was performed to determine the different risk categories in the elderly population of age 65–74 (young-old), 75–84 (old-old), and ≥85 years old (oldest-old). Additionally increased risk of AIH was found in the groups of old-old (HR 2.09, 95 % CI 1.11–3.96) and oldest-old (HR 2.57, 95 % CI 1.21–4.75). In the multivariate analysis of risk factors for AIH, baseline TSH level (HR 1.38, 95 % CI 1.12–1.70) and cumulative amiodarone dosage (HR 0.95, 95 % CI 0.93–0.97) remained statistically significant. Conclusion AIH was much more common than AIT in Taiwan, an area with sufficient iodine intake. Higher baseline TSH level was the predominant independent risk factor for the development of AIH.

Objective Patients with type 2 diabetes mellitus (T2DM) and peripheral arterial disease are classified as having very high cardiovascular risks. We therefore sought to determine whether assessments of the ankle brachial index (ABI) and brachial ankle pulse wave velocity (baPWV) together exhibited a superior association with the outcomes of T2DM. Methods A retrospective analysis of patients receiving ABI and baPWV during the period 2005-2007 was performed. Patients A total of 452 subjects were enrolled and followed-up for a mean 5.8 years after being grouped according to the ABI (