scholarly journals Biomarkers of adverse drug reactions

2017 ◽  
Vol 243 (3) ◽  
pp. 291-299 ◽  
Author(s):  
Daniel F Carr ◽  
Munir Pirmohamed

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue and represent a significant burden to patients, healthcare providers, and the pharmaceutical industry. • This review details the current state of the art in biomarkers of ADRs (both genetic and circulating). There is still significant variability in patient response which cannot be explained by current knowledge of genetic risk factors for ADRs; however, we discussed how specific advances in genomics have the potential to yield better and more predictive models. • Many current clinically utilized circulating biomarkers of tissue injury are valid biomarkers for a number of ADRs. However, they often give little insight into the specific cell or tissue subtype which may be affected. Emerging circulating biomarkers with potential to provide greater information on the etiology/pathophysiology of ADRs are described.

Author(s):  
Paul S. Addison

Redundancy: it is a word heavy with connotations of lacking usefulness. I often hear that the rationale for not using the continuous wavelet transform (CWT)—even when it appears most appropriate for the problem at hand—is that it is ‘redundant’. Sometimes the conversation ends there, as if self-explanatory. However, in the context of the CWT, ‘redundant’ is not a pejorative term, it simply refers to a less compact form used to represent the information within the signal. The benefit of this new form—the CWT—is that it allows for intricate structural characteristics of the signal information to be made manifest within the transform space, where it can be more amenable to study: resolution over redundancy. Once the signal information is in CWT form, a range of powerful analysis methods can then be employed for its extraction, interpretation and/or manipulation. This theme issue is intended to provide the reader with an overview of the current state of the art of CWT analysis methods from across a wide range of numerate disciplines, including fluid dynamics, structural mechanics, geophysics, medicine, astronomy and finance. This article is part of the theme issue ‘Redundancy rules: the continuous wavelet transform comes of age’.


Author(s):  
Gajanan P. Kulkarni ◽  
Lokesh V. Patil

Objective: To assess ADRs with reference to causative drugs, organ systems involved and seriousness of reactions.Methods: A prospective study conducted over a period of 1 y. The spontaneous adverse drug reactions reported between July 2016 and July 2017 at AMC centre BRIMS, Bidar were analyzed using Naranjo’s scale. Causality assessment of suspected drugs involved, system affected, and seriousness of reactions was assessed.Results: GIT system was most commonly involved, followed by generalized features, skin and appendages, CNS i. e, extrapyramidal system and dizziness, hearing and vestibular systems.Conclusion: Majority of the ADRs reported were mild to moderate severity and 20% can be categorized as severe reactions, which needed to treat under hospitalization


Author(s):  
Kabilan K. ◽  
Sathyanarayanan V. ◽  
R. Jammuna Rani

Background: Adverse Drug Reaction(ADR) is the major limitation in providing health care to patients at a global level. It affects patient’s recovery and is an important cause of mortality and morbidity in both hospitalized and ambulatory patients. ADR can occur with any class of drugs. Early detection and evaluation of ADR is essential to reduce harm to the patients. Thus, the present study was aimed to estimate the number of ADR’s reported, analyze its spectrum and the drugs attributed to it.Methods: This was a prospective study conducted in a tertiary care teaching hospital for a period of 3 months from March 2016 to May 2016 in SRM Medical College and Hospital, Potheri. Adverse drug reactions were collected by spontaneous reporting by active and passive methods. The causality assessment of the reported ADR’s was done using Naranjo causality assessment scale.Results: A total of 38 ADR’s were reported during the study period with male predominance (58%). Most of the ADR’s (42%) were common in patients in the age group 19-39 years. More number of ADR’s were from Medicine (29%) followed by Surgery (16%) and OG (16%) departments. Most commonly affected organ systems were skin (45%) followed by GIT (24%). The drugs mostly accounted were antibiotics (55%) especially Cephalosporins (33%). Most of the reactions were type A (68%) rather than type B (32%) and thus predictable. According to Naranjo’s causality assessment, 63% of reactions were probable, 26% were possible and 11% were definite. No reactions were unlikely. Severity assessment by Modified Hartwig and Seigel scale revealed 45% ADRs to be moderate, 42% were mild and 13% were severe and life threatening.Conclusions: The study concluded that Adverse Drug Reactions are common and some of them resulted in increased healthcare cost due to need of some interventions and increased length of hospital stay. As majority of ADR is predictable (Type A), so preventable. The health system should promote the spontaneous reporting of Adverse Drug Reactions (May be done mandatory). The proper documentation and periodic reporting to regional pharmacovigilance centres to ensure drug safety.


2019 ◽  
Author(s):  
Mehrdad Shoeiby ◽  
Mohammad Ali Armin ◽  
Sadegh Aliakbarian ◽  
Saeed Anwar ◽  
Lars petersson

<div>Advances in the design of multi-spectral cameras have</div><div>led to great interests in a wide range of applications, from</div><div>astronomy to autonomous driving. However, such cameras</div><div>inherently suffer from a trade-off between the spatial and</div><div>spectral resolution. In this paper, we propose to address</div><div>this limitation by introducing a novel method to carry out</div><div>super-resolution on raw mosaic images, multi-spectral or</div><div>RGB Bayer, captured by modern real-time single-shot mo-</div><div>saic sensors. To this end, we design a deep super-resolution</div><div>architecture that benefits from a sequential feature pyramid</div><div>along the depth of the network. This, in fact, is achieved</div><div>by utilizing a convolutional LSTM (ConvLSTM) to learn the</div><div>inter-dependencies between features at different receptive</div><div>fields. Additionally, by investigating the effect of different</div><div>attention mechanisms in our framework, we show that a</div><div>ConvLSTM inspired module is able to provide superior at-</div><div>tention in our context. Our extensive experiments and anal-</div><div>yses evidence that our approach yields significant super-</div><div>resolution quality, outperforming current state-of-the-art</div><div>mosaic super-resolution methods on both Bayer and multi-</div><div>spectral images. Additionally, to the best of our knowledge,</div><div>our method is the first specialized method to super-resolve</div><div>mosaic images, whether it be multi-spectral or Bayer.</div><div><br></div>


2020 ◽  
Author(s):  
Ali Fallah ◽  
Sungmin O ◽  
Rene Orth

Abstract. Precipitation is a crucial variable for hydro-meteorological applications. Unfortunately, rain gauge measurements are sparse and unevenly distributed, which substantially hampers the use of in-situ precipitation data in many regions of the world. The increasing availability of high-resolution gridded precipitation products presents a valuable alternative, especially over gauge-sparse regions. Nevertheless, uncertainties and corresponding differences across products can limit the applicability of these data. This study examines the usefulness of current state-of-the-art precipitation datasets in hydrological modelling. For this purpose, we force a conceptual hydrological model with multiple precipitation datasets in > 200 European catchments. We consider a wide range of precipitation products, which are generated via (1) interpolation of gauge measurements (E-OBS and GPCC V.2018), (2) combination of multiple sources (MSWEP V2) and (3) data assimilation into reanalysis models (ERA-Interim, ERA5, and CFSR). For each catchment, runoff and evapotranspiration simulations are obtained by forcing the model with the various precipitation products. Evaluation is done at the monthly time scale during the period of 1984–2007. We find that simulated runoff values are highly dependent on the accuracy of precipitation inputs, and thus show significant differences between the simulations. By contrast, simulated evapotranspiration is generally much less influenced. The results are further analysed with respect to different hydro-climatic regimes. We find that the impact of precipitation uncertainty on simulated runoff increases towards wetter regions, while the opposite is observed in the case of evapotranspiration. Finally, we perform an indirect performance evaluation of the precipitation datasets by comparing the runoff simulations with streamflow observations. Thereby, E-OBS yields the best agreement, while furthermore ERA5, GPCC V.2018 and MSWEP V2 show good performance. In summary, our findings highlight a climate-dependent propagation of precipitation uncertainty through the water cycle; while runoff is strongly impacted in comparatively wet regions such as Central Europe, there are increasing implications on evapotranspiration towards drier regions.


2021 ◽  
Vol 7 ◽  
pp. e495
Author(s):  
Saleh Albahli ◽  
Hafiz Tayyab Rauf ◽  
Abdulelah Algosaibi ◽  
Valentina Emilia Balas

Artificial intelligence (AI) has played a significant role in image analysis and feature extraction, applied to detect and diagnose a wide range of chest-related diseases. Although several researchers have used current state-of-the-art approaches and have produced impressive chest-related clinical outcomes, specific techniques may not contribute many advantages if one type of disease is detected without the rest being identified. Those who tried to identify multiple chest-related diseases were ineffective due to insufficient data and the available data not being balanced. This research provides a significant contribution to the healthcare industry and the research community by proposing a synthetic data augmentation in three deep Convolutional Neural Networks (CNNs) architectures for the detection of 14 chest-related diseases. The employed models are DenseNet121, InceptionResNetV2, and ResNet152V2; after training and validation, an average ROC-AUC score of 0.80 was obtained competitive as compared to the previous models that were trained for multi-class classification to detect anomalies in x-ray images. This research illustrates how the proposed model practices state-of-the-art deep neural networks to classify 14 chest-related diseases with better accuracy.


2020 ◽  
Vol 60 (1) ◽  
Author(s):  
Manar Amanouil Said ◽  
Liana Soido Teixeira e Silva ◽  
Aline Maria de Oliveira Rocha ◽  
Gustavo Guimarães Barreto Alves ◽  
Daniela Gerent Petry Piotto ◽  
...  

Abstract Background Adverse drug reactions (ADRs) are the sixth leading causes of death worldwide; monitoring them is fundamental, especially in patients with disorders like chronic rheumatic diseases (CRDs). The study aimed to describe the ADRs investigating their severity and associated factors and resulting interventions in pediatric patients with CRDs. Methods A retrospective, descriptive and analytical study was conducted on a cohort of children and adolescents with juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM). The study evaluated medical records of the patients to determine the causality and the management of ADRs. In order to investigate the risk factors that would increase the risk of ADRs, a logistic regression model was carried out on a group of patients treated with the main used drug. Results We observed 949 ADRs in 547 patients studied. Methotrexate (MTX) was the most frequently used medication and also the cause of the most ADRs, which occurred in 63.3% of patients, followed by glucocorticoids (GCs). Comparing synthetic disease-modifying anti-rheumatic drugs (sDMARDs) vs biologic disease-modifying anti-rheumatic drugs (bDMARDs), the ADRs attributed to the former were by far higher than the latter. In general, the severity of ADRs was moderate and manageable. Drug withdrawal occurred in almost a quarter of the cases. In terms of risk factors, most patients who experienced ADRs due to MTX, were 16 years old or younger and received MTX in doses equal or higher than 0.6 mg/kg/week. Patients with JIA and JDM had a lower risk of ADRs than patients with JSLE. In the multiple regression model, the use of GCs for over 6 months led to an increase of 0.5% in the number of ADRs. Conclusions Although the ADRs highly likely affect a wide range of children and adolescents with CRDs they were considered moderate and manageable cases mostly. However, triggers of ADRs need further investigations.


2019 ◽  
Vol 99 (4) ◽  
pp. 2015-2113 ◽  
Author(s):  
S. F. Pedersen ◽  
L. Counillon

Na+/H+exchangers play pivotal roles in the control of cell and tissue pH by mediating the electroneutral exchange of Na+and H+across cellular membranes. They belong to an ancient family of highly evolutionarily conserved proteins, and they play essential physiological roles in all phyla. In this review, we focus on the mammalian Na+/H+exchangers (NHEs), the solute carrier (SLC) 9 family. This family of electroneutral transporters constitutes three branches: SLC9A, -B, and -C. Within these, each isoform exhibits distinct tissue expression profiles, regulation, and physiological roles. Some of these transporters are highly studied, with hundreds of original articles, and some are still only rudimentarily understood. In this review, we present and discuss the pioneering original work as well as the current state-of-the-art research on mammalian NHEs. We aim to provide the reader with a comprehensive view of core knowledge and recent insights into each family member, from gene organization over protein structure and regulation to physiological and pathophysiological roles. Particular attention is given to the integrated physiology of NHEs in the main organ systems. We provide several novel analyses and useful overviews, and we pinpoint main remaining enigmas, which we hope will inspire novel research on these highly versatile proteins.


Author(s):  
GAYATRI SUJIVE ◽  
BENSAM T MATHEW ◽  
MAMATHA K ◽  
ANURADHA HV

Objective: The process of aging involves an individual’s structural and functional depravity of their organ systems often results in compromised pharmacological principles of the prescribed drugs. Multimorbidity and polypharmacy along with change in pharmacokinetic and pharmacodynamic responses of drugs predispose the elderly to adverse drug reactions (ADRs). The present study was aimed to identify and report the characteristics and incidence of ADRs among geriatrics in an outpatient clinic. Methods: This was a 6-month prospective hospital-based observational study among patients of either sex aged 60 years and above visiting an outpatient clinic at the study site. The suspected ADRs were categorized according to the Will’s and Brown classification system. Causality of these ADRs was verified by applying the WHO-UMC criteria and the Naranjo’s scale. Severity and preventability of the ADRs were classified using the modified Hartwig and Siegel scale and modified Schumock and Thornton scale, respectively. Multivariate logistic regression was used to determine the risk factors for developing ADRs. Results: Among the 365 patients monitored, 57 (15%) patients experienced 60 ADRs. Therapeutic classes of drugs frequently associated with ADRs were the drugs used in hypertension (27 [45%]). Patients presenting with amlodipine (9 [15%]) induced pedal edema were observed with the highest frequency of ADRs. Polypharmacy (OR: 1.619, 95% confidence interval: 0.957−2.741, p=0.021) was observed as the influential risk factor for ADRs. Conclusion: Pharmacist’s services and involvement in geriatric patient’s centered care can be associated with their improved health, quality of life and economic outcomes, a reduction in medicine-related adverse events, and limiting the morbidity and mortality in this age band.


Author(s):  
Samer Imad Mohammed ◽  
Amna Fouad Abdul Al-razaq

Objectives:Adverse drug reactions (ADR‎s) can lead to many complications associated with the use of medications .In Iraq where a wide range of medications misused widely due to different reasons, the Iraqi pharmacovigilance program started out few years ago to collect information about adverse drugs reactions and since the success of this program depends on the effective participation of all medical staffs including pharmacists in this program. This study aimed to assess the knowledge, attitude, and degree of awareness of Iraqi pharmacists in Baghdad community toward adverse drugs reactions monitoring and pharmacovigilance program.Methods: This study was a cross-sectional descriptive survey based on individual questionnairethat administered in the English language to a convenience sample of 150 pharmacists working in 3 colleges of pharmacy, 20 community pharmacies and 3 hospitals situated in different areas of Baghdad which are the capital of Iraq. The questionnaire consists of three parts that collect demographic data on the ‎participants and their knowledge, attitudes toward Pharmacovigilance‎. Results: Although about (62%) of pharmacists have observed ADRs in their practice‎ only half of the respondents have heard about the term pharmacovigilance, 48% were aware of the national PV program ‎‎.Moreover , (‎47.33%‎) of the respondents mentioned that ADRs associated with herbal ‎products should not be reported. Although ‎79% of the respondents thought that reporting ADRs is a pharmacist’s duty nevertheless 82% of them  ‎thought that ADRs reporting in Iraq is not widely promoted by the relevant authority .The study showed a high tendency for participation in an adverse drug reaction  monitoring program. Interestingly,‎ 60% of respondents report that their workplace ‎doesn’t encourage them for reporting ADRs, while 48% of respondents indicated that they don’t ‎have enough time for reporting ADRs and 38% of them declared their fearing of facing ‎legal problem from that .  ‎Conclusion: Iraqi pharmacists although have a high tendency in participation in ADR monitoring  program but have  a poor knowledge about pharmacovigilance practices; they lack ‎understanding of the details about the national PV system and ADRs ‎reporting process and may need more information on how ADRs ‎reporting are performed. Keywords: Knowledge, Attitudes, Adverse drug reactions, Pharmacovigilance.


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