Adverse drug reactions Patton, K.; Borshoff, D. C.
Anaesthesia,
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
73, Številka:
S1
Journal Article
Recenzirano
Odprti dostop
Summary
Adverse drug reactions are a cause of significant morbidity and mortality to patients and a source of financial burden to the healthcare system. Of the wide spectrum of adverse drug ...reactions, the most concerning to the anaesthetist remain anaphylaxis and malignant hyperthermia. Although the incidence of anaphylaxis under anaesthesia is difficult to ascertain, it occurs commonly enough that most anaesthetists will manage at least one case in their career. The wide range of drugs given in the peri‐operative period and the variable presentation in the anaesthetised patient can delay diagnosis and treatment, and adversely affect outcome. Furthermore, despite improvements in testing, causative drugs can still be difficult to identify, as adverse reactions may be mediated by mechanisms other than IgE activation. With an increase in the reporting of anaphylaxis to newer anaesthetic drugs such as sugammadex, combined with change over the recent decades in the most likely causative peri‐operative agents, it is imperative anaesthetists remain up to date on recent developments. In addition, they should be vigilant to patient characteristics, including pharmacogenetic variations that may predispose to adverse drug reactions, in order to help minimise risks of a reaction. The severity of adverse drug reactions to peri‐operative drugs means morbidity and mortality remain high.
Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization. Electrophysiologists have been impacted personally and ...professionally by this global catastrophe. In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators. We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations. In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.
Left ventricular assist devices (LVADs) are an increasingly used strategy for the management of patients with advanced heart failure with reduced ejection fraction. Although these devices effectively ...improve survival, atrial and ventricular arrhythmias are common, predispose these patients to additional risk, and complicate patient management. However, there is no consensus on best practices for the medical management of these arrhythmias or on the optimal timing for procedural interventions in patients with refractory arrhythmias. Although the vast majority of these patients have preexisting cardiovascular implantable electronic devices or cardiac resynchronization therapy, given the natural history of heart failure, it is common practice to maintain cardiovascular implantable electronic device detection and therapies after LVAD implantation. Available data, however, are conflicting on the efficacy of and optimal device programming after LVAD implantation. Therefore, the primary objective of this scientific statement is to review the available evidence and to provide guidance on the management of atrial and ventricular arrhythmias in this unique patient population, as well as procedural interventions and cardiovascular implantable electronic device and cardiac resynchronization therapy programming strategies, on the basis of a comprehensive literature review by electrophysiologists, heart failure cardiologists, cardiac surgeons, and cardiovascular nurse specialists with expertise in managing these patients. The structure and design of commercially available LVADs are briefly reviewed, as well as clinical indications for device implantation. The relevant physiological effects of long-term exposure to continuous-flow circulatory support are highlighted, as well as the mechanisms and clinical significance of arrhythmias in the setting of LVAD support.
Emerging evidence suggests that an underlying atrial cardiopathy may result in thromboembolism before atrial fibrillation (AF) develops. We examined the association between various markers of atrial ...cardiopathy and the risk of ischemic stroke.
The CHS (Cardiovascular Health Study) prospectively enrolled community-dwelling adults ≥65 years of age. For this study, we excluded participants diagnosed with stroke or AF before baseline. Exposures were several markers of atrial cardiopathy: baseline P-wave terminal force in ECG lead V
, left atrial dimension on echocardiogram, and N terminal pro B type natriuretic peptide (NT-proBNP), as well as incident AF. Incident AF was ascertained from 12-lead electrocardiograms at annual study visits for the first decade after study enrollment and from inpatient and outpatient Medicare data throughout follow-up. The primary outcome was incident ischemic stroke. We used Cox proportional hazards models that included all 4 atrial cardiopathy markers along with adjustment for demographic characteristics and established vascular risk factors.
Among 3723 participants who were free of stroke and AF at baseline and who had data on all atrial cardiopathy markers, 585 participants (15.7%) experienced an incident ischemic stroke during a median 12.9 years of follow-up. When all atrial cardiopathy markers were combined in 1 Cox model, we found significant associations with stroke for P-wave terminal force in ECG lead V
(hazard ratio per 1000 μV*ms 1.04; 95% confidence interval, 1.001-1.08), log-transformed NT-proBNP (hazard ratio per doubling of NT-proBNP, 1.09; 95% confidence interval, 1.03-1.16), and incident AF (hazard ratio, 2.04; 95% confidence interval, 1.67-2.48) but not left atrial dimension (hazard ratio per cm, 0.96; 95% confidence interval, 0.84-1.10).
In addition to clinically apparent AF, other evidence of abnormal atrial substrate is associated with subsequent ischemic stroke. This finding is consistent with the hypothesis that thromboembolism from the left atrium may occur in the setting of several different manifestations of atrial disease.
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, ...numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs.
A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments.
Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones).
Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
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•We conducted an electronic systematic review of mechanistic studies of glyphosate/GBF.•Studies were assessed for evidence of the ten key characteristics of carcinogens.•We uncovered strong evidence for KCs 2, 4, 5, 6, and 8.•We found limited evidence for KCs 1 and 3, and inadequate evidence for KCs 7, 9, and 10.
The number and quality of oocytes within the ovarian reserve largely determines fertility and reproductive lifespan in mammals. An oocyte-specific transcription factor cascade controls oocyte ...development, and some of these transcription factors, such as newborn ovary homeobox gene (
), are candidate genes for primary ovarian insufficiency in women. Transcription factors are frequently modified by the post-translational modification SUMOylation, but it is not known whether SUMOylation is required for function of the oocyte-specific transcription factors or if SUMOylation is required in oocytes during their development within the ovarian follicle. To test this, the sole E2 SUMO-conjugating enzyme,
, was ablated in mouse oocytes beginning in primordial follicles. Loss of oocyte
resulted in female infertility with major defects in stability of the primordial follicle pool, ovarian folliculogenesis, ovulation and meiosis. Transcriptomic profiling of ovaries suggests that loss of oocyte
caused defects in both oocyte- and granulosa cell-expressed genes, including NOBOX and some of its known target genes. Together, these studies show that SUMOylation is required in the mammalian oocyte during folliculogenesis for both oocyte development and communication with ovarian somatic cells.
In this paper, we present results from the weak-lensing shape measurement GRavitational lEnsing Accuracy Testing 2010 (GREAT10) Galaxy Challenge. This marks an order of magnitude step change in the ...level of scrutiny employed in weak-lensing shape measurement analysis. We provide descriptions of each method tested and include 10 evaluation metrics over 24 simulation branches.
GREAT10 was the first shape measurement challenge to include variable fields; both the shear field and the point spread function (PSF) vary across the images in a realistic manner. The variable fields enable a variety of metrics that are inaccessible to constant shear simulations, including a direct measure of the impact of shape measurement inaccuracies, and the impact of PSF size and ellipticity, on the shear power spectrum. To assess the impact of shape measurement bias for cosmic shear, we present a general pseudo-C
ℓ formalism that propagates spatially varying systematics in cosmic shear through to power spectrum estimates. We also show how one-point estimators of bias can be extracted from variable shear simulations.
The GREAT10 Galaxy Challenge received 95 submissions and saw a factor of 3 improvement in the accuracy achieved by other shape measurement methods. The best methods achieve sub-per cent average biases. We find a strong dependence on accuracy as a function of signal-to-noise ratio, and indications of a weak dependence on galaxy type and size. Some requirements for the most ambitious cosmic shear experiments are met above a signal-to-noise ratio of 20. These results have the caveat that the simulated PSF was a ground-based PSF. Our results are a snapshot of the accuracy of current shape measurement methods and are a benchmark upon which improvement can be brought. This provides a foundation for a better understanding of the strengths and limitations of shape measurement methods.
Background
The subcutaneous implantable cardioverter defibrillator (S‐ICD) is a novel implanted defibrillator for the prevention of sudden cardiac death that avoids intravascular access. Use of this ...device is limited by its inability to provide backup pacing. Combined use of the S‐ICD with a permanent pacemaker may be the optimal choice in certain situations though experience with the use of both devices together remains limited.
Methods
We reviewed our single‐center experience with the S‐ICD from March 2011 to November 2015. Four patients with concomitant use of the S‐ICD and a permanent pacemaker were identified. Clinical indication for device therapy, operative details, and subsequent follow‐up was reviewed. During implantation, S‐ICD sensing of paced morphologies was evaluated at maximal voltage output. After S‐ICD implant, if feasible, the upper rate was adjusted to ≤50% of the S‐ICD tachycardia zone to minimize risk of inappropriate shocks.
Results
After a mean follow‐up of over 1 year, no adverse events occurred, including no inappropriate shock, lead malfunction, or device infection. One patient had a total of eight appropriate shocks, while another individual had no inappropriate shocks despite having a unipolar pacing lead.
Conclusions
In unique situations, combined use of the S‐ICD and a permanent pacemaker may be preferable to alternative options. In our experience, this approach was successful in varying conditions including complex congenital heart disease, recurrent device infection, and limited vascular access.
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