Miracle-dz/UniFAR-FTUs huggingface dataset:
Zofenopril and Ramipril in Combination with Acetyl Salicylic Acid in Postmyocardial Infarction Patients with Left Ventricular Systolic Dysfunction: A Retrospective Analysis of the SMILE-4 Randomized, Double-Blind Study in Diabetic Patients.

OBJECTIVE In the SMILE-4 study, zofenopril + acetyl salicylic acid (ASA) was more effective than ramipril + ASA on 1-year prevention of major cardiovascular events (MACE) in patients with acute myocardial infarction complicated by left ventricular dysfunction. In this retrospective analysis, we evaluated drug efficacy in subgroups of patients, according to a history of diabetes mellitus. METHODS The primary study endpoint was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Diabetes was defined according to medical history (previous known diagnosis). RESULTS A total of 562 of 693 (81.0%) patients were classified as nondiabetics and 131 (18.9%) as diabetics. The adjusted rate of MACE was lower under zofenopril than under ramipril in both nondiabetics [27.9% vs. 34.9% ramipril; odds ratio, OR and 95% confidence interval: 0.55 (0.35, 0.86)] and diabetics [30.9% vs. 41.3%; 0.56 (0.18, 1.73)], although the difference was statistically significant only for the nondiabetic group (P = 0.013). Zofenopril was superior to ramipril as regards to the primary study endpoint in the subgroup of 157 patients with uncontrolled blood glucose (≥ 126 mg/dL), regardless of a previous diagnosis of diabetes [0.31 (0.10, 0.90), P = 0.030]. Zofenopril significantly reduced the risk of hospitalization for cardiovascular causes in both nondiabetics [0.64 (0.43, 0.96), P = 0.030] and diabetics [0.38 (0.15, 0.95), P = 0.038], whereas it was not better than ramipril in terms of prevention of cardiovascular deaths. CONCLUSIONS This retrospective analysis of the SMILE-4 study confirmed the good efficacy of zofenopril plus ASA in the prevention of long-term MACE also in the subgroup of patients with diabetes mellitus.
Parathyroid hormone levels and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with acetylsalicylic acid and clopidogrel or ticagrelor

Background. High on treatment platelet reactivity still represents a challenging issue, potentially vanishing the benefits of dual antiplatelet treatment in patients with coronary artery disease. However, very few is known on the determinants of suboptimal response to antiplatelet agents. Recent interests have emerged on the potential protrombotic effect of parathyroid hormone (PTH). Therefore, the aim of the present study was to assess the impact of parathyroid hormone (PTH) on platelet reactivity in patients receiving DAPT after an acute coronary syndrome or PCI. Methods. Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30-90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test > 862 AU*min (for ASA) and ADP test values >417 AU*min (for ADP-antagonists). Results. We included 362 patients on DAPT, 125 (34.5%) receiving clopidogrel and 237 (65.5%) on ticagrelor. Patients were divided according to PTH quartiles values (<45.8; 45.8-60.3; 60.4-88; ≥88.1 pg/mL). Higher PTH was associated with older age (p=0.001); renal failure (p<0.001), higher HDL cholesterol (p=0.006) and creatinine (p<0.001) and lower 25-OH cholecalciferol (p<0.001). Suboptimal response to ASA was infrequent (2.8%); and not influenced by the levels of PTH (p=0.57). ADP-mediated platelet aggregation was significantly increased in patients with higher PTH (p=0.03), with an absolute increase in the prevalence of HRPR to ADPantagonists for higher PTH (24.7% vs 40%, p=0.007 for 4 vs 1-3 quartiles, adjusted A cc ep te d A rt ic le This article is protected by copyright. All rights reserved. OR[95%CI]=2.04[1.14-3.64], p=0.02). By the use of the ROC curve, we identified PTH levels above 96.7 pg/ml as the best predictor of HRPR with ADP-antagonists, (adjusted OR[95%CI]=2.52[1.31-4.87], p=0.006). Higher rate of HRPR was confirmed for PTH >96.7 pg/ml among the subgroup of patients on clopidogrel (51.5 vs 85.7%, p=0.001; adjusted OR[95%CI]=12.5[2.6-60.9], p=0.002), but not among ticagrelor treated patients (11.3 vs 16.7%, p=0.31; adjusted OR[95%CI]=1.55[0.564.6], p=0.42). Conclusion. In patients receiving dual antiplatelet therapy for coronary artery disease, higher PTH levels are associated with an increased ADP-mediated platelet reactivity and suboptimal response to clopidogrel, especially for values above 96.7 pg/ml, while not influencing the effectiveness of ASA and ticagrelor.
The Use of Competitive Enzyme Linked Immuno-Sorbent Assay in Combination with Abattoir Survey for CBPP Surveillance in Nigeria

A total of 500 lung tissues and sera samples of cattle from CBPP endemic areas was used in this study to determine the effectiveness of combining abattoir survey with competitive Enzyme Linked Immunosorbent Assay (cELISA) as an alternative to Complement Fixation Test (CFT) in providing a better and more reliable information on CBPP surveillance in Nigeria. A total of 94 (18.8%) of the lung tissues examined had lesions (at various stages) suggestive of CBPP, while 137 (27.4%) and 160 (32%) were sero-positive for CFT and cELISA respectively. One hundred and twelve (22.4%) of the cattle were seropositive for both CFT and cELISA, while 25(5.1%) and 48(9.6%) were seropositive for only CFT and cELISA respectively. Five cattle that had lesions suggestive of CBPP were negative by both CFT and cELISA. Meanwhile, no age predisposition was particularly significant to the development of CBPP lesion in this investigation. It is concluded that the use of cELISA along with abattoir survey in the field by training veterinary officers could provide better and more reliable information on the prevalence of CBPP in Nigeria. Keyword: Contagious bovine pleuropneumonia, abattoir survey, competitive enzyme-linked immunosorbent assay, compliment fixation test, surveillance, Nigeria. Trop. Vet. Vol. 21 (2) 35-41 (2003)
Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer

Background: Oesophageal squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related death worldwide. However, the mechanism by which the OSCC develops remains largely unknown. Ion channels are important for cancer development. Whether the transient receptor potential canonical (TRPC), known as the non-selective cation channels, plays a role in OSCC development is unknown. Methods: The expression of TRPC6, a member of TRPC subfamily, was examined in samples from patients with OSCC by immunostaining and in situ hybridisation. The effects of TRPC6 channels on OSCC cell cycle progression, cell growth and in vivo tumour formation were investigated. The functional TRPC6 channels were found in OSCC cells by electrophysiology and Ca2+ imaging analysis. Results: The expression of TRPC6 at protein and mRNA levels was markedly increased in human OSCC specimens than that in normal human oesophageal tissues. Blockade of TRPC6 channels in human OSCC cells inhibited elevation of intracellular Ca2+ concentration ([Ca2+]i) and activation of Cdc2 kinase. Meanwhile, the OSCC cell cycle was arrested at G2 phase and the cell growth was suppressed. Furthermore, inhibition of TRPC6 channels suppressed in nude mice the tumour formation generated by injection of the OSCC cells. Conclusion: TRPC6 channels play a critical role in the development of OSCC. The [Ca2+]i elevation regulated by TRPC6 channels is essential for G2 phase progression and OSCC development. These channels might be a novel target for therapeutic intervention of OSCC.
Applicability of BARD score to Japanese patients with NAFLD

We read the article by Harrison et al 1 with great interest. The authors proposed an easily calculated composite score for predicting the risk of advanced fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), called the BARD score: the weighted sum of the three variables (body mass index (BMI) ⩾28 = 1 point, aspartate aminotransferase/alanine aminotransferase ratio (AAR) ⩾0.8 = 2 points, diabetes = 1 point). When a BARD score of 2–4 was used, the area under the receiver operating characteristic curve (AUROC) was found to be 0.81 with an odds ratio (OR) of 17 (95% CI 9.2 to 31.9) for detecting advanced fibrosis. The positive predictive value (PPV) and negative predictive value (NPV) were 43% and 96%, respectively. We studied the reliability of the BARD score for identifying …
Validation of single nucleotide polymorphisms in invasive aspergillosis following hematopoietic cell transplantation.

Invasive aspergillosis (IA) is a significant cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Previous studies have reported an association between IA development and single nucleotide polymorphisms (SNPs), but many SNPs have not been replicated in a separate cohort. The presence of a positive serum galactomannan assay (SGM+) has also been associated with a worse prognosis in patients with IA, and genetic determinants in this subset of patients have not been systematically studied. The study cohort included 2609 HCT recipients and their donor pairs: 483 with proven/probable IA (183 SGM+) and 2126 with no IA by standard criteria. Of 25 SNPs previously published, we analyzed 20 in 14 genes that passed quality control. Samples were genotyped via microarray, and SNPs that could not be genotyped were imputed. The primary aim was to replicate SNPs associated with proven/probable IA at 2 years; secondary goals were to explore the associations using an end point of SGM+ IA or proven/probable IA using a different genetic model or time to IA (3 months vs 2 years) compared with the original study. Two SNPs in 2 genes (PTX3, CLEC7a) were replicated. Thirteen SNPs in 9 genes had an association at P ≤ . 05 using the secondary aims (PTX3, CLEC7a, CD209, CXCL10, TLR6, S100B, IFNG, PLG, TNFR1), with hazard ratios ranging from 1.2 to 3.29. Underlying genetic differences can influence development of IA following HCT. Identification of genetic predispositions to IA could have important implications in donor screening, risk stratification of recipients, monitoring, and prophylaxis.
Psychotherapy in the UK: Results of a survey of registrants of the United Kingdom Council for Psychotherapy

The United Kingdom Council for Psychotherapy (UKCP) was formed to provide a professional body for all psychotherapists in the UK. It maintains a register of trained practitioners who abide by the ethical standards ratified by UKCP, which includes psychotherapists working in all the modalities recognized by UKCP irrespective of their primary professional training. In the absence of statutory registration, there is no fully representative list of UK psychotherapists, but the UKCP register is probably the nearest thing to it. The UKCP board recognized that a survey of registrants would provide a snapshot of the state of UK psychotherapy, which would be valuable in understanding the contribution of psychotherapists to health services in the UK. A questionnaire was designed, and sent out to all 4005 practitioners registered by UKCP in December 1997. One thousand three hundred and thirty-one questionnaires were returned, a response rate of 34 per cent. The respondents were representative of all registered psychotherapists in 1998 in those characteristics that are published in the paper register, or that can be inferred from it. The respondents were aged 51 years on average, predominantly white (97 per cent described themselves this way) women (69 per cent) practising in London and the South East of England (55 per cent). All the respondents described themselves as being influenced by psychotherapeutic approaches rooted in psycho-analysis. Ninety-five per cent of respondents had another profession previous to psychotherapy. This was most commonly teaching (27 per cent), social work (22 per cent) or counselling (21 per cent). Only 11 per cent of respondents were psychologists. The contribution of UKCP registrants to the National Health Service has never previously been estimated. A breakdown of the diaries provided by respondents in this survey suggests that UKCP registrants may contribute as many as 44,760 hours of psychotherapy per week to the British National Health Service and other health sectors. Assuming that a whole-time-equivalent psychotherapist works 37 hours per week, this means that UKCP registrants may provide the equivalent work to health service organizations, both public and private, of more than 1,311 full-time psychotherapists.
Professionals' perceptions of the Mental Health Recovery Star

Purpose – The Mental Health Recovery Star (MHRS) has received focus at a national policy level in consideration of outcome measurement within mental health services. The purpose of this paper is to seek the views of mental health professionals about its use within clinical practice. Design/methodology/approach – The paper employed a qualitative, exploratory design to interview 12 participants. Thematic analysis was used. Findings – Four main themes were identified: “the utility of the Recovery Star”; “not for everybody”; “service user involvement”; and “the status of the Recovery Star within the Trust”. A range of factors was found to influence participants’ use of the tool with service users. Research limitations/implications – The paper involved a small number of participants due to a low response rate. Future research could include larger studies and more detailed exploration of factors identified as limiting the use of the MHRS. Practical implications – The MHRS is a potentially useful tool but its li.
Acute appendicitis is characterised by local invasion with Fusobacterium nucleatum/necrophorum

Background Acute appendicitis is a local intestinal inflammation with unclear origin. The aim was to test whether bacteria in appendicitis differ in composition to bacteria found in caecal biopsies from healthy and disease controls. Methods and patients We investigated sections of 70 appendices using rRNA-based fluorescence in situ hybridisation. Four hundred caecal biopsies and 400 faecal samples from patients with inflammatory bowel disease and other conditions were used as controls. A set of 73 group-specific bacterial probes was applied for the study. Results The mucosal surface in catarrhal appendicitis showed characteristic lesions of single epithelial cells filled with a mixed bacterial population (‘pinned cells’) without ulceration of the surroundings. Bacteria deeply infiltrated the tissue in suppurative appendicitis. Fusobacteria (mainly Fusobacterium nucleatum and necrophorum) were a specific component of these epithelial and submucosal infiltrates in 62% of patients with proven appendicitis. The presence of Fusobacteria in mucosal lesions correlated positively with the severity of the appendicitis and was completely absent in caecal biopsies from healthy and disease controls. Main faecal microbiota represented by Bacteroides, Eubacterium rectale (Clostridium group XIVa), Faecalibacterium prausnitzii groups and Akkermansia muciniphila were inversely related to the severity of the disease. The occurrence of other bacterial groups within mucosal lesions of acute appendicitis was not related to the severity of the appendicitis. No Fusobacteria were found in rectal swabs of patients with acute appendicitis. Conclusions Local infection with Fusobacterium nucleatum/necrophorum is responsible for the majority of cases of acute appendicitis.
Contrasting US and European approaches to colorectal cancer screening: which is best?

In the recent 1–2 decades, we have seen a considerable development in colorectal cancer (CRC) screening modalities and programme implementation, but major challenges remain. While CRC is still the second leading cause of cancer death in both the USA and Europe, there are limited data on the efficacy and effectiveness of all screening modalities except for the faecal occult blood test (FOBT). Newer screening tests, such as faecal immunochemical tests, molecular markers and CT colonography are being introduced and variably adopted, though overall rates of screening are suboptimal. Professional societies and governmental bodies have endorsed screening, though recommended approaches are quite variable, which may help to explain the great variation in screening practices. Unfortunately, quality assurance programmes are underutilised. Comparing the USA and Europe there may be more variation in CRC screening recommendation and practice within each continent than between them, but there seems to be a stronger emphasis on programmatic screening in Europe, facilitating quality assurance. The much debated need for randomised trials as new screening modalities emerge could be more easily handled if running screening programmes are regarded as natural platforms for testing out and evaluating presumed improvements in the service—including new emerging screening modalities.
A Review and Update of Red Yeast Rice

Dyslipidemia is a growing concern causing significant morbidity and mortality. High cholesterol levels increase the risk of individuals developing heart disease, stroke, and other disease states. Dietary modification is the initial approach for treatment, but many patients require statins (3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors) to reduce cardiovascular risk. Unfortunately, a number of patients cannot tolerate statins, leading to practitioners searching for alternative regimens. One alternative that has been extensively studied is red yeast rice (Monascus purpureus), a dietary supplement. In patients with dyslipidemia, red yeast rice was efficacious and safe for short-term use (<16 weeks). Red yeast rice has also been studied head to head with statins and was shown to be noninferior in reducing cholesterol levels and cardiovascular risk. Because of the positive clinical effects seen in dyslipidemia, researchers have begun to study its use in other disease states.
Optimisation of processing and properties of medical grade Nitinol wire

The purpose of this paper is to review the current processing and resultant properties of standard Nitinol wire for guide-wire applications. Optimised Ti-50.8at%Ni wire was manufactured according to industry standards by precise control of the composition, cold work and continuous strain-age annealing. Mechanical properties of this wire are reported from -100°C to 200°C to demonstrate the effects of test temperature. Within the ‘superelastic window’ the plateau stresses are linearly related to test temperature. Additional ageing treatments can be used as a tool to fine-tune transformation temperatures and mechanical properties. A review of the fatigue properties of thermomechanically-treated Nitinol wire shows that they are affected by test temperature, stress and strain.
Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis

Objective The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) has anticolorectal cancer activity in vitro and in preclinical models. The present study tested whether a novel, enteric-coated formulation of EPA, as the free fatty acid (EPA-FFA), has chemopreventative efficacy in patients with familial adenomatous polyposis (FAP), in a randomised, double-blind, placebo-controlled trial. Methods Patients undergoing endoscopic surveillance of their retained rectum postcolectomy were randomised to EPA-FFA (SLA Pharma) 2 g daily or placebo for 6 months. The number and size of polyps in an area of mucosa defined by a tattoo were determined before and after intervention. Global rectal polyp burden was scored (−1, 0, +1) by examination of video endoscopy records. Mucosal fatty acid content was measured by gas chromatography–mass spectrometry. Results 55 patients with FAP were evaluated by an intention-to-treat analysis (EPA-FFA 28, placebo 27). Treatment with EPA-FFA for 6 months was associated with a mean 22.4% (95% CI 5.1% to 39.6%) reduction in polyp number (p=0.012) and a 29.8% (3.6% to 56.1%) decrease in the sum of polyp diameters (p=0.027). Global polyp burden worsened over 6 months in the placebo group (−0.34) unlike the EPA-FFA group (+0.09, difference 0.42 (0.10–0.75), p=0.011). EPA-FFA treatment led to a mean 2.6-fold increase in mucosal EPA levels (p=0.018 compared with placebo). EPA-FFA was well tolerated with an incidence of adverse events similar to placebo. Conclusions EPA-FFA has chemopreventative efficacy in FAP, to a degree similar to that previously observed with selective cyclo-oxygenase-2 inhibitors. EPA holds promise as a colorectal cancer chemoprevention agent with a favourable safety profile. Clinical trial number NCT00510692.
Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL.

Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or TP53 status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing <8 days (10.9 months vs not reached). These results support sustained adherence to once-daily ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at www.clinicaltrials. gov as #NCT01578707.