Aliment Pharmacol Ther 2012; 35: 165–174
Summary
Background Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel.
Aim To examine whether PPI ...use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time‐varying drug exposure ascertainment.
Methods We conducted this population‐based cohort study in Western Denmark (population 3 million) using medical databases. We identified all 13 001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12‐month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders.
Results During follow‐up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non‐use was 0.57 95% confidence interval (CI): 0.44–0.74 among PPI users and 0.47 (95% CI: 0.42–0.53) among PPI non‐users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91–1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non‐users, independent of clopidogrel use adjusted HR = 1.24 (95% CI: 0.97–1.58) for clopidogrel users and 1.26 (95% CI: 0.97–1.63) for clopidogrel non‐users.
Conclusions The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention.
Summary
Background
In the light of the exceptionally high rates of contact allergy to the preservative methylisothiazolinone (MI), information about cross‐reactivity between MI, octylisothiazolinone ...(OIT) and benzisothiazolinone (BIT) is needed.
Objectives
To study cross‐reactivity between MI and OIT, and between MI and BIT.
Methods
Immune responses to MI, OIT and BIT were studied in vehicle and MI‐sensitized female CBA mice by a modified local lymph node assay. The inflammatory response was measured by ear thickness, cell proliferation of CD4+ and CD8+ T cells, and CD19+ B cells in the auricular draining lymph nodes.
Results
MI induced significant, strong, concentration‐dependent immune responses in the draining lymph nodes following a sensitization phase of three consecutive days. Groups of MI‐sensitized mice were challenged on day 23 with 0·4% MI, 0·7% OIT and 1·9% BIT – concentrations corresponding to their individual EC3 values. No statistically significant difference in proliferation of CD4+ and CD8+ T cells was observed between mice challenged with MI compared with mice challenged with BIT and OIT.
Conclusions
The data indicate cross‐reactivity between MI, OIT and BIT, when the potency of the chemical was taken into account in choice of challenge concentration. This means that MI‐sensitized individuals may react to OIT and BIT if exposed to sufficient concentrations.
What's already known about this topic?
Contact allergy to methylisothiazolinone (MI) in the European population is alarmingly high.
Retrospective observational studies of patients with contact allergy to MI have shown that concomitant reactions between MI, octylisothiazolinone (OIT) and benzisothiazolinone (BIT) may exist.
What does this study add?
MI induced a significant concentration‐dependent immune response after a sensitization phase of three consecutive days.
MI, OIT and BIT induced the same concentration‐dependent inflammatory response with proliferation of CD4+ and CD8+ T cells, and partly CD19+ B cells, in MI‐sensitized mice.
Cross‐reactivity was seen between MI and OIT and between MI and BIT when the potency of the chemical was taken into account in the choice of challenge concentration.
Plain language summary available online
The importance of consumer involvement in health care is widely recognised. Consumers can be involved in developing healthcare policy and research, clinical practice guidelines and patient ...information material, through consultations to elicit their views or through collaborative processes. Consultations can be single events, or repeated events, large or small scale. They can involve individuals or groups of consumers to allow debate; the groups may be convened especially for the consultation or be established consumer organisations. They can be organised in different forums and through different media. We anticipated finding few comparative evaluations that reliably evaluated the effects of consumer involvement.
To assess the effects of consumer involvement and compare different methods of involvement in developing healthcare policy and research, clinical practice guidelines, and patient information material.
We searched: the Cochrane Consumers and Communication Review Group's Specialised Register (4 May 2006); the Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1966 to January Week 2 2006); EMBASE (1980 to Week 03 2006); CINAHL (1982 to December Week 2 2005), PsycINFO (1806 to January Week 3 2006); Sociological Abstracts (1952 to 24 January 2006); and SIGLE (System for Information on Grey Literature in Europe) (1980 to 2003/1). We scanned reference lists from relevant articles and contacted authors.
Randomised and quasi-randomised trials, interrupted time series analyses, and controlled before-after studies assessing methods for involving consumers in developing healthcare policy and research, clinical practice guidelines or patient information material. The outcome measures were: participation or response rates of consumers; consumer views elicited; consumer influence on decisions, healthcare outcomes or resource utilisation; consumers' or professionals' satisfaction with the involvement process or resulting products; impact on the participating consumers; costs.
Two review authors independently selected trials for inclusion, assessed their quality and extracted data. We contacted study authors for clarification and to seek missing data. We presented results in a narrative summary and pooled data as appropriate.
Five randomised controlled trials of moderate or low methodological quality involving 1031 participants were included. There is moderate quality evidence that involving consumers in the development of patient information material results in material that is more relevant, readable and understandable to patients, without affecting their anxiety. This 'consumer-informed' material can also improve patients' knowledge. There is low quality evidence that using consumer interviewers instead of staff interviewers in satisfaction surveys can have a small influence on the survey results. There is very low quality evidence of telephone discussions and face-to-face group meetings engaging consumers better than mailed surveys in order to set priorities for community health goals, and resulting in different priorities being set for these goals.
There is little evidence from comparative studies of the effects of consumer involvement in healthcare decisions at the population level. The studies included in this review demonstrate that randomised controlled trials are feasible for providing evidence about the effects of consulting consumers to inform these decisions.
The aim of the study was to evaluate the treatment response to Interleukin-6-receptor inhibitition (IL-6Ri), primarily tocilizumab, in patients with VEXAS.
Data were obtained from review of hospital ...based clinical records and included symptoms, laboratory data, transfusion history, pathology reports, imaging, and treatment.
Fifteen patients were treated with tocilizumab intravenously. Two patients changed treatment to subcutaneous sarilumab. Three discontinued treatment due to treatment failure.Of the 10 patients with treatment-response and prednisone use prior to IL-6Ri one was tapered off prednisone, one used it intermittently, and seven patients could be reduced to 10 mg or less daily.Three patients exhibited a marked decrease in UBA1-levels during IL-6Ri which corresponded with symptom control and normalization of haemoglobin levels. However, in most a progressive marrow failure occurred as indicated by decreasing platelet levels, increasing MCV, and for some, declining haemoglobin levels and transfusion dependence in spite of control of the inflammatory symptoms and low c-reactive protein levels.One patient became refractory to both tocilizumab and sarilumab, and had previously failed conventional DMARDs, JAK-inhibition, TNFa-inhibition, and interleukin-1R-inhibiton. Treatment with 9 cycles of azacytidine resulted in complete symptom remission, discontinuation of prednisone, normalization of biochemical parameters and undetectable UBA1 mutation levels which has now lasted for 10 months since cessation of azacytidine.
IL-6Ri induces control of inflammatory symptoms and allows decreased prednisone usage in a large subset of VEXAS patients. However, most experience progressive bone marrow failure during IL-6Ri.Azacytidine could be a promising treatment strategy and warrants further investigation.
From the characterization of the recessive resistance gene, sbm1, in pea we have identified the eukaryotic translation initiation factor, eIF4E, as a susceptibility factor required for infection with ...the Potyvirus, Pea seed-borne mosaic virus. A functional analysis of the mode of action of the product of the dominant allele revealed a novel function for eIF4E in its support for virus movement from cell-to-cell, in addition to its probable support for viral RNA translation, and hence replication. Different resistance specificities in two independent pea lines were explained by different mutations in eIF4E. On the modelled structure of eIF4E the coding changes were in both cases lying in and around the structural pocket involved in binding the 5'-m7G cap of eukaryotic mRNAs. Protein expression and cap-binding analysis showed that eIF4E encoded by a resistant plant could not bind to m7G-Sepharose, a result which may point to functional redundancy between eIF4E and the paralogous eIF(iso)4E in resistant peas. These observations, together with related findings for other potyvirus recessive resistances, provide a more complete picture of the potyvirus life cycle.
A method to measure the electrical connectivity between square superconducting plates joined by weak link interfaces is presented. It is based on observation of lines where the flow of critical ...current abruptly changes direction due to the presence of weak links, and the confinement created by the shape of the sample. The method is demonstrated using magneto-optical imaging (MOI) of systems consisting of up to 2×2 plates joined to form a larger square. The samples used in this study are Nb films with weak links created by focused ion beam machining. Common features are found in the current flow patterns, which allow to measure the electrical connectivity between the plates by observing an angle between pairs of lines indicating where the current abruptly changes flow direction, so-called discontinuity, or d-lines.
It has been suggested that neuroleptic medication may decrease cancer risk. We compared cancer risks in a population-based cohort study of 25,264 users (>or=2 prescriptions) of neuroleptic ...medications in the county of North Jutland, Denmark, during 1989-2002, with that of county residents who did not receive such prescriptions. Statistical analyses were based on age-standardisation and Poisson regression analysis, adjusting for age, calendar period, COPD, liver cirrhosis or alcoholism, use of NSAID, and, for breast cancer, additionally for use of hormone therapy, age at first birth, and number of children. Use of neuroleptic medications was associated with a decreased risk for rectal cancer in both women and men (adjusted IRRs of 0.61 (95% confidence interval, 0.41-0.91) and 0.82 (0.56-1.19), respectively) and for colon cancer in female users (0.78; 0.62-0.98). Some risk reduction was seen for prostate cancer (0.87; 0.69-1.08), but breast cancer risk was close to unity (0.93; 0.74-1.17). Overall, treatment with neuroleptic medications was not related to a reduced risk of cancer, but for cancers of the rectum, colon and prostate there were suggestive decreases in risk.
The effects of the precursor milling energy on the superconducting and microstructural homogeneity of Fe-sheathed MgB2 monocore wires and tapes have been investigated. The conductors were produced by ...the powder-in-tube method using drawing and rolling deformation methods and in situ reaction. Combined magneto-optical, structural and magnetization measurements were performed on MgB2 superconducting tapes prepared from differently milled precursors revealing hidden mechanisms controlling their critical current density. Local degradation of the superconducting properties observed in some analysed conductors has been identified and correlated with microstructural observations.
•Milling conditions of precursor significantly affect magnetic flux front profiles.•Magneto-optical images (MOI) are correlated with microstructural features.•MOI highlights superconducting inhomogeneities using particular magnetic sequences.
Scaling behaviour of dynamically driven vortex avalanches in superconducting YBa
Cu
O
films deposited on tilted crystalline substrates has been observed using quantitative magneto-optical imaging. ...Two films with different tilt angles are characterized by the probability distributions of avalanche size in terms of the number of moving vortices. It is found in both samples that these distributions follow power-laws over up to three decades, and have exponents ranging between 1.0 and 1.4. The distributions also show clear finite-size scaling, when the system size is defined by the depth of the flux penetration front - a signature of self-organized criticality. A scaling relation between the avalanche size exponent and the fractal dimension, previously derived theoretically from conservation of the number of magnetic vortices in the stationary state and shown in numerical simulations, is here shown to be satisfied also experimentally.
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