New-Generation High-Definition Colonoscopes Increase Adenoma Detection when Screening a Moderate-Risk Population for Colorectal Cancer.

PubMed

Bond, Ashley; O'Toole, Paul; Fisher, Gareth; Subramanian, Sreedhar; Haslam, Neil; Probert, Chris; Cox, Trevor; Sarkar, Sanchoy

2017-03-01

Adenoma detection rate (ADR) is the most important quality indicator for screening colonoscopy, due to its association with colorectal cancer outcomes. As a result, a number of techniques and technologies have been proposed that have the potential to improve ADR. The aim of this study was to assess the potential impact of new-generation high-definition (HD) colonoscopy on ADR within the Bowel Cancer Screening Programme (BCSP). This was a retrospective single-center observational study in patients undergoing an index screening colonoscopy. The examination was performed with either standard-definition colonoscopes (Olympus Q240/Q260 series) or HD colonoscopes (Olympus HQ290 EVIS LUCERA ELITE system) with the primary outcome measures of ADR and mean adenoma per procedure (MAP) between the 2 groups. A total of 395 patients (60.5% male, mean age 66.8 years) underwent screening colonoscopy with 45% performed with HD colonoscopes. The cecal intubation rate was 97.5% on an intention-to-treat basis and ADR was 68.6%. ADR with standard-definition was 63.13%, compared with 75.71% with HD (P = .007). The MAP in the HD group was 2.1 (± 2.0), whereas in the standard-definition group it was 1.6 (± 1.8) (P = .01). There was no significant difference in withdrawal time between the 2 groups. In the multivariate regression model, only HD scopes (P = .03) and male sex (P = .04) independently influenced ADR. Olympus H290 LUCERA ELITE HD colonoscopes improved adenoma detection within the moderate-risk population. A 12% improvement in ADR might be expected to increase significantly the protection afforded by colonoscopy against subsequent colorectal cancer mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Carbon Dioxide Insufflation Increases Colonoscopic Adenoma Detection Rate Compared With Air Insufflation.

PubMed

Mills, Christopher D; McCamley, Chere; Swan, Michael P

2018-03-07

To determine the effect of carbon dioxide insufflation on the most important outcome measure of colonoscopic quality: adenoma detection rate (ADR). Bowel cancer is the second most common cause of cancer deaths in males and females in Australia. Carbon dioxide has in recent times become the insufflation methodology of choice for screening colonoscopy for bowel cancer, as this has been shown to have significant advantages when compared with traditional air insufflation. Endoscopies performed over a period of 9 months immediately before and after the implementation of carbon dioxide insufflation at endoscopy centers were eligible for inclusion. The difference in ADR between the carbon dioxide and air insufflation methods was statistically significant, with an increased ADR in the carbon dioxide group. The superiority of carbon dioxide insufflation was sustained with a logistic regression model, which showed ADR was significantly impacted by insufflation method. Carbon dioxide insufflation is known to reduce abdominal pain, postprocedural duration of abdominal pain, abdominal distension, and analgesic requirements. This study represents for the first time the beneficial effect of carbon dioxide insufflation upon the key quality colonoscopy indicator of ADR.

A Distributed, Collaborative Intelligent Agent System Approach for Proactive Postmarketing Drug Safety Surveillance

PubMed Central

Ji, Yanqing; Ying, Hao; Farber, Margo S.; Yen, John; Dews, Peter; Miller, Richard E.; Massanari, R. Michael

2014-01-01

Discovering unknown adverse drug reactions (ADRs) in postmarketing surveillance as early as possible is of great importance. The current approach to postmarketing surveillance primarily relies on spontaneous reporting. It is a passive surveillance system and limited by gross underreporting (<10% reporting rate), latency, and inconsistent reporting. We propose a novel team-based intelligent agent software system approach for proactively monitoring and detecting potential ADRs of interest using electronic patient records. We designed such a system and named it ADRMonitor. The intelligent agents, operating on computers located in different places, are capable of continuously and autonomously collaborating with each other and assisting the human users (e.g., the food and drug administration (FDA), drug safety professionals, and physicians). The agents should enhance current systems and accelerate early ADR identification. To evaluate the performance of the ADRMonitor with respect to the current spontaneous reporting approach, we conducted simulation experiments on identification of ADR signal pairs (i.e., potential links between drugs and apparent adverse reactions) under various conditions. The experiments involved over 275 000 simulated patients created on the basis of more than 1000 real patients treated by the drug cisapride that was on the market for seven years until its withdrawal by the FDA in 2000 due to serious ADRs. Healthcare professionals utilizing the spontaneous reporting approach and the ADRMonitor were separately simulated by decision-making models derived from a general cognitive decision model called fuzzy recognition-primed decision (RPD) model that we recently developed. The quantitative simulation results show that 1) the number of true ADR signal pairs detected by the ADRMonitor is 6.6 times higher than that by the spontaneous reporting strategy; 2) the ADR detection rate of the ADRMonitor agents with even moderate decision-making skills is five times higher than that of spontaneous reporting; and 3) as the number of patient cases increases, ADRs could be detected significantly earlier by the ADRMonitor. PMID:20007038

Prospective multicenter randomized controlled trial comparing adenoma detection rate in colonoscopy using water exchange, water immersion, and air insufflation.

PubMed

Hsieh, Yu-Hsi; Tseng, Chih-Wei; Hu, Chi-Tan; Koo, Malcolm; Leung, Felix W

2017-07-01

Adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma of any size, is a quality indicator. We tested the hypothesis that water exchange (WE) improves ADR but water immersion (WI) has no adverse effect on ADR compared with air insufflation (AI). A prospective study was conducted at the Dalin Tzu Chi Hospital in southern Taiwan and the Hualien Tzu Chi Hospital in eastern Taiwan on patients randomly assigned to WE, WI, or AI with stratification by the 3 study colonoscopists. The primary outcome was ADR. From July 2013 to December 2015, 651 patients were recruited and randomized into 3 groups with a 1:1:1 ratio (217 patients per group). Overall, ADR met quality standards: WE 49.8% (95% CI, 43.2%-56.4%), AI 37.8% (95% CI, 31.6%-44.4%), and WI 40.6% (95% CI, 34.2%-47.2%). Compared with AI, WE significantly increased ADR (P = .016). There was no difference between WI and WE. ADRs of WI and AI were comparable. Compared with AI, WE confirmed a longer insertion time, higher cleanliness score, but similar adenoma per positive colonoscopy (APPC) and withdrawal time with polypectomy. Subgroup analysis found WE significantly increased ADR in propofol-sedated patients. Multivariate generalized linear mixed model analysis revealed that age ≥50 years, WE (vs AI), colonoscopy indication, no previous history of colonoscopy, and withdrawal time >8 minutes were significant predictors of increased ADR. Confirmation of prior reports showing WE, but not WI, increased ADR further strengthened the validity of our observations. WE significantly increased ADR in propofol-sedated patients. The outcome differences justify assessment of the role of WE in colorectal cancer prevention. Similar APPC and withdrawal times suggest that adequate inspection was performed on colonoscope withdrawal in each of the study arms. (Clinical trial registration number: NCT01894191.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. All rights reserved.

Adenoma detection rate is not influenced by full-day blocks, time, or modified queue position.

PubMed

Lurix, Einar; Hernandez, Adrian V; Thoma, Matthew; Castro, Fernando

2012-04-01

Recent studies have shown the adenoma detection rate (ADR) to decrease from endoscopist fatigue. Our primary objective was to evaluate the afternoon ADR in half-day versus full-day blocks. Secondary objectives were to determine whether time or complexity of prior procedures (modified queue position) influence ADR. Retrospective chart review on consecutive colonoscopies. Tertiary-care teaching hospital. This study involved all patients in our database who were over age 45 and who underwent screening and surveillance colonoscopies. ADR. A total of 3085 patients were included in the study, with an overall 31% ADR. Of these procedures, 2148 (70%) were done in the morning, and 937 (30%) were done in the afternoon (512 full-day block, 425 half-day block). By multivariate analysis, there was no difference in ADR between full-day blocks compared with afternoon-only blocks (35% vs 32%; odds ratio [OR] 1.1; 95% confidence interval [CI], 0.8-1.5; P = .2). For all afternoon colonoscopies, no decrease in ADR was noted with increasing queue position (P = .9) or time (P = .3). In addition, no difference was found comparing ADR between all afternoon colonoscopies versus morning colonoscopies (33% vs 30%; OR 1.1; CI, 1.0-1.3; P = .1). No difference was found for advanced adenomas and number of adenomas between either afternoon-only blocks versus afternoon colonoscopy in full-day blocks or morning versus all afternoon cases. Retrospective study; not all withdrawal times were recorded; trainees performed some of the procedures. Our data show that colonoscopy can be performed in full-day blocks and 30-minute slots without compromising ADR. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Providing data for serrated polyp detection rate benchmarks: an analysis of the New Hampshire Colonoscopy Registry.

PubMed

Anderson, Joseph C; Butterly, Lynn F; Weiss, Julia E; Robinson, Christina M

2017-06-01

Similar to achieving adenoma detection rate (ADR) benchmarks to prevent colorectal cancer (CRC), achieving adequate serrated polyp detection rates (SDRs) may be essential to the prevention of CRC associated with the serrated pathway. Previous studies have been based on data from high-volume endoscopists at single academic centers. Based on a hypothesis that ADR is correlated with SDR, we stratified a large, diverse group of endoscopists (n = 77 practicing at 28 centers) into high performers and low performers, based on ADR, to provide data for corresponding target SDR benchmarks. By using colonoscopies in adults aged ≥50 years (4/09-12/14), we stratified endoscopists by high and low ADRs (<15%, 15%-<25%, 25%-<35%, ≥35%) to determine corresponding SDRs by using 2 SDR measures, for screening and surveillance colonoscopies separately: (1) Clinically significant SDR (CSSDR), meaning colonoscopies with any sessile serrated adenoma/polyp (SSA/P), traditional serrated adenoma (TSA), or hyperplastic polyp (HP) >1 cm anywhere in the colon or HP >5 mm in the proximal colon only divided by the total number of screening and surveillance colonoscopies, respectively. (2) Proximal SDR (PSDR) meaning colonoscopies with any serrated polyp (SSA/P, HP, TSA) of any size proximal to the sigmoid colon divided by the total number of screening and surveillance colonoscopies, respectively. A total of 45,996 (29,960 screening) colonoscopies by 77 endoscopists (28 facilities) were included. Moderately strong positive correlation coefficients were observed for screening ADR/CSSDR (P = .69) and ADR/PSDR (P = .79) and a strong positive correlation (P = .82) for CSSDR/PSDR (P < .0001 for all) was observed. For ADR ≥25%, endoscopists' median (interquartile range) screening CSSDR was 6.8% (4.3%-8.6%) and PSDR was 10.8% (8.6%-16.1%). Derived from ADR, the primary colonoscopy quality indicator, our results suggest potential SDR benchmarks (CSSDR = 7% and PSDR = 11%) that may guide adequate serrated polyp detection. Because CSSDR and PSDR are strongly correlated, endoscopists could use the simpler PSDR calculation to assess quality. Published by Elsevier Inc.

Individual polyp detection rate in routine daily endoscopy practice depends on case-mix.

PubMed

Loffeld, R J L F; Liberov, B; Dekkers, P E P

2015-07-01

The adenoma detection rate (ADR), a marker of endoscopic quality, is confounded by selection bias. It is not known what the ADR is in normal daily practice. To study the polyp detection rate (PDR) in different endoscopists in the course of years. All consecutive endoscopies of the colon done in 11 years were included. Endoscopies in the regular surveillance programme after polyp removal and after surgery because of colorectal cancer or diverticular disease were scored separately. The number of yearly procedures per endoscopist and presence of polyps, anastomoses, surveillance and cancer were noted. In the period of 11 years, 14,908 consecutive endoscopies of colon and rectum were done by four endoscopists. Two endoscopists had a significantly lower PDR than the other two (p < 0.001), these two had the longest careers in endoscopy. The two younger endoscopists did significantly less often procedures in patients with anastomoses and because of surveillance (p < 0.001, respectively). One endoscopist detected significantly less colorectal cancers than the other three endoscopists (p < 0.001). This study presents the PDR in normal routine daily endoscopy practice. It can be concluded that the PDR, implicating the ADR, in unselected patients can be lower in individual endoscopists than recommended in the literature. This highly depends on the case-mix of patients presented for endoscopy. This result debates the use of the ADR as quality indicator for individual endoscopists.

Technical interventions to increase adenoma detection rate in colonoscopy.

PubMed

Rondonotti, Emanuele; Andrealli, Alida; Amato, Arnaldo; Paggi, Silvia; Conti, Clara Benedetta; Spinzi, Giancarlo; Radaelli, Franco

2016-12-01

Adenoma detection rate (ADR) is the most robust colonoscopy quality metric and clinical studies have adopted it as the ideal method to assess the impact of technical interventions. Areas covered: We reviewed papers focusing on the impact of colonoscopy technical issues on ADR, including withdrawal time and technique, second evaluation of the right colon, patient positional changes, gastrointestinal assistant participation during colonoscopy, water-aided technique, optimization of bowel preparation and antispasmodic administration. Expert commentary: Overall, technical interventions are inexpensive, available worldwide and easy to implement. Some of them, such as the adoption of split dose regimen and slow scope withdrawal to allow a careful inspection, have been demonstrated to significantly improve ADR. Emerging data support the use of water-exchange colonoscopy. According to published studies, other technical interventions seem to provide only marginal benefit to ADR. Unfortunately, the available evidence has methodological limitations, such as small sample sizes, the inclusion of expert endoscopists only and the evaluation of single technical interventions. Additionally, larger studies are needed to clarify whether these interventions might have a higher benefit on low adenoma detectors and whether the implementation of a bundle of them, instead of a single technical maneuver, might have a greater impact on ADR.

Temporal trends and variability of colonoscopy performance in a gastroenterology practice.

PubMed

le Clercq, Chantal M C; Mooi, Rick J; Winkens, Bjorn; Salden, Bouke N H; Bakker, C Minke; van Nunen, Annick B; Keulen, Eric P T; de Ridder, Rogier J; Masclee, Ad A M; Sanduleanu, Silvia

2016-03-01

Quality measures for colonoscopy are operator dependent and vary. It is unclear whether quality measures change over time. In this study, time-dependent variation in colonoscopy performance was examined in a gastroenterology practice. Colonoscopy and histopathology records that were collected at three hospitals (one university and two non-university hospitals) over three time periods (2007, 2010, and 2013) were reviewed. Data from colonoscopists performing at least 100 procedures per year were analyzed. Inter-colonoscopist variation in performance (i. e. adjusted cecal intubation rate [aCIR], adenoma detection rate [ADR], advanced ADR, mean adenomas per procedure [MAP], proximal ADR, nonpolypoid ADR, and serrated polyp detection rate) were examined using coefficients of variation. Logistic regression analyses were also performed, adjusting for covariates. A total of 23 colonoscopists performing 6400 procedures were included. Overall, the mean aCIR, ADR, MAP, and proximal ADR improved significantly over time, from 91.9 %, 22.5 %, 0.37, and 10.2 % in 2007 to 95.3 %, 25.8 %, 0.45, and 13.4 %, respectively, in 2013 (P < 0.05). The inter-colonoscopist variation in ADR decreased from 37 % in 2007 to 15 % in 2013 (P < 0.05). In the non-university hospitals, mean values for quality measures increased significantly over time, whereas they remained stable in the university hospital. Variability in performance among colonoscopists decreased significantly within the gastroenterology clinical practice. Core quality measures improved over time, mainly through improvement of the lower performers. Measurement of inter-colonoscopist variation in performance helps to identify factors that stimulate or hinder performance, and forms the basis for interventions. http://www.trialregister.nl. © Georg Thieme Verlag KG Stuttgart · New York.

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial

PubMed Central

dos Santos, Carlos Eduardo Oliveira; Moreira, Hamilton; Pereira-Lima, Julio Carlos; Ribas, Carmen Australia Paredes Marcondes; de Quadros Onófrio, Fernanda; Czecko, Alexandre Eduardo Augusti; Ramos, Rafael Koerich; de Carvalho, Caroline Aragão

2017-01-01

OBJECTIVES: The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. METHODS: In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. RESULTS: A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). CONCLUSION: The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR. PMID:28792997

Hyoscine butylbromide for colorectal polyp detection: prospective, randomized, placebo-controlled trial.

PubMed

Dos Santos, Carlos Eduardo Oliveira; Moreira, Hamilton; Pereira-Lima, Julio Carlos; Ribas, Carmen Australia Paredes Marcondes; de Quadros Onófrio, Fernanda; Czecko, Alexandre Eduardo Augusti; Ramos, Rafael Koerich; de Carvalho, Caroline Aragão

2017-07-01

The removal of pre-malignant colorectal lesions prevents cancer. Hyoscine has been proposed as a means of improving diagnosis by reducing colonic movements. The aim of this study was to analyze whether this anti-spasmodic enhances the detection of pre-malignant colorectal lesions. In a randomized, double-blinded fashion patients received hyoscine or a saline solution in all consecutive colonoscopies in which the cecum was reached. Lesions were analysed with respect to number, size, location, histology and capillary pattern. A total of 440 colonoscopies were randomized. The overall polyp detection rate (PDR) and the adenoma detection rate (ADR) were 65.2% and 49.3%, respectively. In the hyoscine group, non-polypoid lesions were detected significantly more often (p=0.01). In the placebo group 281 lesions were diagnosed (202 adenomas) and in the hyoscine group 282 lesions were detected (189 adenomas) (p=0.23). The PDR and ADR were similar between the placebo and hyoscine groups (64% vs 66% and 50% vs 47%, respectively). No differences were observed between the two groups in the advanced-ADR or advanced neoplasia detection rate, as well the mean numbers of polyps, adenomas, advanced adenomas and advanced neoplasias detected per patient. The administration of hyoscine also did not improve the diagnostic accuracy of digital chromoendoscopy. The presence of adenomatous polyps in the right colon was detected significantly more frequently in the hyoscine group (OR 5.41 95% CI 2.7 - 11; p<0.01 vs OR 2.3 95% CI 1.1 - 4.6; p=0.02). The use of hyoscine before beginning the withdrawal of the colonoscope does not seem to enhance the PDR and the ADR.

Deep Learning Localizes and Identifies Polyps in Real Time with 96% Accuracy in Screening Colonoscopy.

PubMed

Urban, Gregor; Tripathi, Priyam; Alkayali, Talal; Mittal, Mohit; Jalali, Farid; Karnes, William; Baldi, Pierre

2018-06-18

The benefit of colonoscopy for colorectal cancer prevention depends on the adenoma detection rate (ADR). The ADR should reflect adenoma prevalence rate, estimated to be greater than 50% among the screening-age population. Yet the rate of adenoma detection by colonoscopists varies from 7% to 53%. It is estimated that every 1% increase in ADR reduces the risk of interval colorectal cancers by 3-6%. New strategies are needed to increase the ADR during colonoscopy. We tested the ability of computer-assisted image analysis, with convolutional neural networks (a deep learning model for image analysis), to improve polyp detection, a surrogate of ADR. We designed and trained deep convolutional neural networks (CNN) to detect polyps using a diverse and representative set of 8641 hand labeled images from screening colonoscopies collected from over 2000 patients. We tested the models on 20 colonoscopy videos with a total duration of 5 hours. Expert colonoscopists were asked to identify all polyps in 9 de-identified colonoscopy videos, selected from archived video studies, either with or without benefit of the CNN overlay. Their findings were compared with those of the CNN, using CNN-assisted expert review as the reference. When tested on manually labeled images, the CNN identified polyps with an area under the receiver operating characteristic curve (ROC-AUC) of 0.991 and an accuracy of 96.4%. In the analysis of colonoscopy videos in which 28 polyps were removed, 4 expert reviewers identified 8 additional polyps without CNN assistance that had not been removed and identified an additional 17 polyps with CNN assistance (45 in total). All polyps removed and identified by expert review were detected by the CNN. The CNN had a false-positive rate of 7%. In a set of 8641 colonoscopy images containing 4088 unique polyps the CNN identified polyps with a cross-validation accuracy of 96.4% and ROC-AUC value of 0.991. The CNN system can detect and localize polyps well within real-time constraints using an ordinary desktop machine with a contemporary graphics processing unit. This system could increase ADR and reduce interval colorectal cancers but requires validation in large multicenter trials. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Feasibility of full-spectrum endoscopy: Korea’s first full-spectrum endoscopy colonoscopic trial

PubMed Central

Song, Jeong-Yeop; Cho, Youn Hee; Kim, Mi A; Kim, Jeong-Ae; Lee, Chun Tek; Lee, Moon Sung

2016-01-01

AIM: To evaluate the full-spectrum endoscopy (FUSE) colonoscopy system as the first report on the utility thereof in a Korean population. METHODS: We explored the efficacy of the FUSE colonoscopy in a retrospective, single-center feasibility study performed between February 1 and July 20, 2015. A total of 262 subjects (age range: 22-80) underwent the FUSE colonoscopy for colorectal cancer screening, polyp surveillance, or diagnostic evaluation. The cecal intubation success rate, the polyp detection rate (PDR), the adenoma detection rate (ADR), and the diverticulum detection rate (DDR), were calculated. Also, the success rates of therapeutic interventions were evaluated with biopsy confirmation. RESULTS: All patients completed the study and the success rates of cecal and terminal ileal intubation were 100% with the FUSE colonoscope; we found 313 polyps in 142 patients and 173 adenomas in 95. The overall PDR, ADR and DDR were 54.2%, 36.3%, and 25.2%, respectively, and were higher in males, and increased with age. The endoscopists and nurses involved considered that the full-spectrum colonoscope improved navigation and orientation within the colon. No colonoscopy was aborted because of colonoscope malfunction. CONCLUSION: The FUSE colonoscopy yielded a higher PDR, ADR, DDR than did traditional colonoscopy, without therapeutic failure or complications, showing feasible, effective, and safe in this first Korean trial. PMID:26937150

Impact of preprocedure simethicone on adenoma detection rate during colonoscopy: a multicenter, endoscopist-blinded randomized controlled trial.

PubMed

Bai, Yu; Fang, Jun; Zhao, Sheng-Bing; Wang, Dong; Li, Yan-Qing; Shi, Rui-Hua; Sun, Zi-Qin; Sun, Ming-Jun; Ji, Feng; Si, Jian-Min; Li, Zhao-Shen

2018-02-01

 Ideal bowel preparation for colonoscopy requires complete removal of fluid and foam from the colon. Polyethylene glycol (PEG) is widely used for bowel preparation, with antifoaming agents such as simethicone commonly used in combination with PEG. Data on the effect of simethicone on the adenoma detection rate (ADR) were limited. This study therefore aimed to investigate whether preprocedure simethicone could increase the ADR.  This was a prospective, multicenter, endoscopist-blinded randomized controlled trial involving consecutive patients who underwent colonoscopy in six centers in China. Patients were randomly assigned to one of two groups: PEG plus simethicone or PEG alone. The primary outcome was ADR; secondary outcomes were quality of bowel preparation, measured by the Boston bowel preparation scale (BBPS) and bubble scores.  583 patients were included. More adenomas were detected in the PEG plus simethicone group than in the PEG alone group (ADR 21.0 % vs. 14.3 %, P  = 0.04; advanced ADR 9.0 % vs. 7.0 %, P  = 0.38). The mean number of adenomas detected was 2.20 ± 1.36 vs. 1.63 ± 0.89 ( P  = 0.02). Patients in the PEG plus simethicone group showed better bowel cleansing efficacy: BBPS ≥ 6 in 88.3 % vs. 75.2 % ( P  < 0.001) and bubble scores of 1.00 ± 1.26 vs. 3.98 ± 2.50 ( P  < 0.001). Abdominal bloating was reported less frequently in the PEG plus simethicone group (7.8 % vs . 19.7 %, P  < 0.001) than in the PEG alone group.  Combined use of PEG and simethicone is associated with a significantly increased ADR in a Chinese population. © Georg Thieme Verlag KG Stuttgart · New York.

Educational Paper: Aspects of clinical pharmacology in children--pharmacovigilance and safety.

PubMed

Choonara, Imti

2013-05-01

Adverse drug reactions (ADRs) are a significant problem in children, affecting one in ten children in hospital. Within the community, one in 500 children will experience an adverse drug reaction each year. Pharmacovigilance has been useful in detecting suspected ADRs. However, most ADRs are unreported and often not suspected. Education of health professionals in relation to drug toxicity improves the reporting rate of suspected ADRs. Clinical trials are useful to evaluate the efficacy of drugs. They are, however, not the best way of looking at ADRs where surveillance following the widespread use of a drug is more appropriate. Alongside work by the regulatory agencies, independent investigators have helped collate data. This information has been useful in developing guidelines to prevent further cases of drug toxicity. Greater awareness and understanding of drug toxicity in children should result in more rational prescribing.

Adverse drug reaction (ADR) occurrence and evaluation in elderly inpatients.

PubMed

Bowman, L; Carlstedt, B C; Hancock, E F; Black, C D

1996-01-01

Determine elderly inpatient's risk ADRs and characterize the events. This is a post-hoc analysis of a comprehensive inpatient ADR survey. Charts were reviewed every four days on all internal medicine service inpatients (1024 patients over four months). Chart review were enhanced by potential indicators such as nurses' and pharmacists' reports; targeted drug orders; 'now', 'stat', and 'hold' orders; off-service physician consults; incident reports; transfers-to-ICU; and abnormal serum drug concentrations. Potential ADRs were classified according to organ system affected, pharmacological type, severity, and Naranjo causality scale. Internal medicine wards of a 350-bed county general hospital. Of 1024 inpatients, 301 were elderly. Overall, 237 patients had an ADR (23%). Elderly patients accounted for 89 (37.5%) of the 237 patients experiencing an ADR. The ADRs experienced by the elderly tended to be more severe (p <0.05) and less idiosyncratic (p <0.05). However, no preferences for organ system (p >0.1) or differences in causality rating (p = 0.25) were detected. When statistically controlled for female gender, renal function and number of drugs, age was no longer a risk factor for ADR occurrence. The elderly experience more ADRs. However, female gender, decline in renal function and polymedicine are the independent factors that account for the elderly's risk. Furthermore, the elderly's ADRs tend to be more severe and an extension of the drug's pharmacology. Therefore, ADR prevention is both important and possible.

Adipocyte Browning and Higher Mitochondrial Function in Periadrenal But Not SC Fat in Pheochromocytoma.

PubMed

Vergnes, Laurent; Davies, Graeme R; Lin, Jason Y; Yeh, Michael W; Livhits, Masha J; Harari, Avital; Symonds, Michael E; Sacks, Harold S; Reue, Karen

2016-11-01

Patients with pheochromocytoma (pheo) show presence of multilocular adipocytes that express uncoupling protein 1 within periadrenal (pADR) and omental (OME) fat depots. It has been hypothesized that this is due to adrenergic stimulation by catecholamines produced by the pheo tumors. To characterize the prevalence and respiratory activity of brown-like adipocytes within pADR, OME, and SC fat depots in human adult pheo patients. This was an observational cohort study. The study took place in a university hospital. We studied 46 patients who underwent surgery for benign adrenal tumors (21 pheos and 25 controls with adrenocortical adenomas). We characterized adipocyte browning in pADR, SC, and OME fat depots for histological and immunohistological features, mitochondrial respiration rate, and gene expression. We also determined circulating levels of catecholamines and other browning-related hormones. Eleven of 21 pheo pADR adipose samples, but only one of 25 pADR samples from control patients exhibited multilocular adipocytes. The pADR browning phenotype was associated with higher plasma catecholamines and raised uncoupling protein 1. Mitochondria from multilocular pADR fat of pheo patients exhibited increased rates of coupled and uncoupled respiration. Global gene expression analysis in pADR fat revealed enrichment in β-oxidation genes in pheo patients with multilocular adipocytes. No SC or OME fat depots exhibited aspects of browning. Browning of the pADR depot occurred in half of pheo patients and was associated with increased catecholamines and mitochondrial activity. No browning was detected in other fat depots, suggesting that other factors are required to promote browning in these depots.

Effect of quality metric monitoring and colonoscopy performance.

PubMed

Razzak, Anthony; Smith, Dineen; Zahid, Maliha; Papachristou, Georgios; Khalid, Asif

2016-10-01

Background and aims: Adenoma detection rate (ADR) and cecal withdrawal time (CWT) have been identified as measures of colonoscopy quality. This study evaluates the impact of monitoring these measures on provider performance. Methods: Six blinded gastroenterologists practicing at a Veterans Affairs Medical Center were prospectively monitored over 9 months. Data for screening, adenoma surveillance, and fecal occult blood test positive (FOBT +) indicated colonoscopies were obtained, including exam preparation quality, cecal intubation rate, CWT, ADR, adenomas per colonoscopy (APC), and adverse events. Metrics were continuously monitored after a period of informed CWT monitoring and informed CWT + ADR monitoring. The primary outcome was impact on ADR and APC. Results: A total of 1671 colonoscopies were performed during the study period with 540 before informed monitoring, 528 during informed CWT monitoring, and 603 during informed CWT + ADR monitoring. No statistically significant impact on ADR was noted across each study phase. Multivariate regression revealed a trend towards fewer adenomas removed during the CWT monitoring phase (OR = 0.79; 95 %CI 0.62 - 1.02, P  = 0.065) and a trend towards more adenomas removed during the CWT + ADR monitoring phase when compared to baseline (OR = 1.26; 95 %CI 0.99 - 1.61, P  = 0.062). Indication for examination and provider were significant predictors for higher APC. Provider-specific data demonstrated a direct relationship between high ADR performers and increased CWT. Conclusions: Monitoring quality metrics did not significantly alter colonoscopy performance across a small heterogeneous group of providers. Non-significant trends towards higher APC were noted with CWT + ADR monitoring. Providers with a longer CWT had a higher ADR. Further studies are needed to determine the impact of monitoring on colonoscopy performance.

Longer mean colonoscopy withdrawal time is associated with increased adenoma detection: evidence from the Bowel Cancer Screening Programme in England.

PubMed

Lee, T J W; Blanks, R G; Rees, C J; Wright, K C; Nickerson, C; Moss, S M; Chilton, A; Goddard, A F; Patnick, J; McNally, R J Q; Rutter, M D

2013-01-01

Increasing colonoscopy withdrawal time (CWT) is thought to be associated with increasing adenoma detection rate (ADR). Current English guidelines recommend a minimum CWT of 6 minutes. It is known that in the Bowel Cancer Screening Programme (BCSP) in England there is wide variation in CWT. The aim of this observational study was to examine the relationship between CWT and ADR. The study examined data from 31 088 colonoscopies by 147 screening program colonoscopists. Colonoscopists were grouped in four levels of mean CWT ( < 7, 7 - 8.9, 9 - 10.9, and ≥ 11 minutes). Univariable and multivariable analysis (binary logistic and negative binomial regression) were used to explore the relationship between CWT, ADR, mean number of adenomas and number of right-sided and advanced adenomas. In colonoscopists with a mean CWT < 7 minutes, the mean ADR was 42.5 % compared with 47.1 % in the ≥ 11-minute group (P < 0.001). The mean number of adenomas detected per procedure increased from 0.77 to 0.94, respectively (P < 0.001). The increase in adenoma detection was mainly of subcentimeter or proximal adenomas; there was no increase in the detection of advanced adenomas. Regression models showed an increase in ADR from 43 % to 46.5 % for mean CWT times ranging from 6 to 10 minutes. This study demonstrates that longer mean withdrawal times are associated with increasing adenoma detection, mainly of small or right-sided adenomas. However, beyond 10 minutes the increase in ADR is minimal. Mean withdrawal times longer than 6 minutes are not associated with increased detection of advanced adenomas. Withdrawal time remains an important quality metric of colonoscopy. © Georg Thieme Verlag KG Stuttgart · New York.

Clinical coding of prospectively identified paediatric adverse drug reactions--a retrospective review of patient records.

PubMed

Bellis, Jennifer R; Kirkham, Jamie J; Nunn, Anthony J; Pirmohamed, Munir

2014-12-17

National Health Service (NHS) hospitals in the UK use a system of coding for patient episodes. The coding system used is the International Classification of Disease (ICD-10). There are ICD-10 codes which may be associated with adverse drug reactions (ADRs) and there is a possibility of using these codes for ADR surveillance. This study aimed to determine whether ADRs prospectively identified in children admitted to a paediatric hospital were coded appropriately using ICD-10. The electronic admission abstract for each patient with at least one ADR was reviewed. A record was made of whether the ADR(s) had been coded using ICD-10. Of 241 ADRs, 76 (31.5%) were coded using at least one ICD-10 ADR code. Of the oncology ADRs, 70/115 (61%) were coded using an ICD-10 ADR code compared with 6/126 (4.8%) non-oncology ADRs (difference in proportions 56%, 95% CI 46.2% to 65.8%; p < 0.001). The majority of ADRs detected in a prospective study at a paediatric centre would not have been identified if the study had relied on ICD-10 codes as a single means of detection. Data derived from administrative healthcare databases are not reliable for identifying ADRs by themselves, but may complement other methods of detection.

Under-reporting of adverse drug reactions: a challenge for pharmacovigilance in India.

PubMed

Tandon, Vishal R; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2015-01-01

The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.

Global patterns of adverse drug reactions over a decade: analyses of spontaneous reports to VigiBase™.

PubMed

Aagaard, Lise; Strandell, Johanna; Melskens, Lars; Petersen, Paw S G; Holme Hansen, Ebba

2012-12-01

Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase™, and to relate data to national income. We analysed ADR reports submitted to VigiBase™ from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. We analysed 1,359,067 ADR reports including 3,013,074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type 'skin and subcutaneous tissue disorders' and for the therapeutic groups 'antiinfectives for systemic use' and 'antineoplastic and immunomodulation agents'. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of national pharmacovigilance centres and ADR reporting practices on the large variations in ADR reporting rates within income groups.

Trends in quality of screening colonoscopy in Austria.

PubMed

Waldmann, Elisabeth; Gessl, Irina; Sallinger, Daniela; Jeschek, Philip; Britto-Arias, Martha; Heinze, Georg; Fasching, Elisabeth; Weiss, Werner; Gschwantler, Michael; Trauner, Michael; Ferlitsch, Monika

2016-12-01

Background and study aim: Screening colonoscopy only effectively prevents colorectal cancer if performed with high quality. The aim of this study was to analyze the detection rates of premalignant colorectal lesions in screening colonoscopies performed within a nationwide quality control program for screening colonoscopy in Austria. Methods: Data from electronic records of the screening program from its implementation in 2007 until December 2014 were analyzed in order to calculate detection rates for adenomas, advanced adenomas, polyps, and proximal lesions, and rates of cecal intubation, sedation, complications, and adequate bowel preparation. Results were evaluated to identify trends and changes in quality parameters over the 8-year study period. Results: During the study period, 301 endoscopists provided data from 159 246 screening colonoscopies. Mean age of screened individuals was 61.1 years, and 49.1 % were women. Significant increases over time were found for age- and sex-adjusted adenoma detection rates (ADRs), which increased from a mean of 22.2 % (SD 10.7 %) in 2007/2008 to 24.2 % (SD 11.6 %) in 2013/2014. On average, each endoscopist increased their individual ADR by + 1.5 percentage points per 2-year period (95 % confidence interval [CI] 0.9 - 2.2 percentage points; P  < 0.01). Similarly, detection rates for proximal lesions rose from 15.8 % (SD 9.8 %) to 21.7 % (SD 13.3 %  + 2.5 percentage points per 2-year period, 95 %CI 1.9 - 3.1 percentage points; P  < 0.01). ADR in men increased from 27.6 % in 2007/2008 (SD 11.1 %) to 29.2 % in 2013/2014 (SD 12.7 %; P  < 0.01); ADR in women increased from 14.2 % (SD 7.1 %) in 2007/2008 to 19.0 % (SD 10.5 %) in 2013/2014 ( P  < 0.01). Advanced adenoma detection rates decreased during the study period, from 11.4 % (SD 9.0 %) in 2007/2008 to 7.6 % (SD 5.4 %) in 2013/2014 ( P  = 0.06) in men, and from 5.5 % (SD 5.3 %) in 2007/2008 to 4.0 % (SD 4.1 %) in 2013/2014 in women ( P  = 0.21). Conclusions: This study showed an improvement in the quality of screening colonoscopies performed within a quality assurance program in Austria between 2007 and 2014. Although, overall ADR increased significantly during the study period, there was a decrease in the rate of advanced adenoma detection. © Georg Thieme Verlag KG Stuttgart · New York.

Removal of infused water predominantly during insertion (water exchange) is consistently associated with an increase in adenoma detection rate - review of data in randomized controlled trials (RCTs) of water-related methods

PubMed Central

Harker, JO; Leung, JW; Siao-Salera, RM; Mann, SK; Ramirez, FC; Friedland, S; Amato, A; Radaelli, F; Paggi, S; Terruzzi, V; Hsieh, YH

2011-01-01

Introduction Variation in outcomes in RcTs comparing water-related methods and air insufflation raises challenging questions regarding the new approach. This report reviews impact of water exchange - simultaneous infusion and removal of infused water during insertion on adenoma detection rate (ADR) defined as proportion of patients with a least one adenoma of any size. Methods Medline (2008–2011) searches, abstract of 2011 Digestive Disease Week (DDW) meeting and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of colonoscope. Results Since 2008, eleven reports of RcTs (6 published, 1 submitted and 4 abstracts, n=1728) described ADR in patients randomized to be examined by air and water-related methods. The water-related methods differed in timing of removal of the infused water -predominantly during insertion (water exchange) (n=825) or predominantly during withdrawal (water immersion) (n=903). Water immersion was associated with both increases and decreases in ADR compared to respective air method patients and the net overall change (-7%) was significant. On the other hand water exchange was associated with increases in ADR consistently and the net changes (overall, 8%; proximal overall, 11%; and proximal <10 mm, 12%) were all significant. Conclusion Comparative data generated the hypothesis that significantly larger increases in overall and proximal colon ADRs were associated with water exchange than water immersion or air insufflation during insertion. The hypothesis should be evaluated by RCTs to elucidate the mechanism of water exchange on adenoma detection. PMID:22163082

Effect of Endocuff-assisted colonoscopy on adenoma detection rate: meta-analysis of randomized controlled trials.

PubMed

Williet, Nicolas; Tournier, Quentin; Vernet, Chloé; Dumas, Olivier; Rinaldi, Leslie; Roblin, Xavier; Phelip, Jean-Marc; Pioche, Mathieu

2018-04-26

Yield of Endocuff-assisted colonoscopy (EAC) compared with standard colonoscopy is conflicting in terms of adenoma detection rate (ADR). A meta-analysis of randomized controlled trials (RCTs) appears necessary. PubMed and Google Scholar were searched in December 2017. Abstracts from Digestive Disease Week and United European Gastroenterology Week meetings were also searched to 2017. All RCTs comparing EAC with standard colonoscopy were included. Analysis was conducted by using the Mantel-Haenszel models. Heterogeneity was quantified using the I 2 test. Of the 265 articles reviewed, 12 RCTs were included, with a total of 8376 patients (EAC group 4225; standard colonoscopy group 4151). In the meta-analysis, ADR was significantly increased in the EAC group vs. the standard colonoscopy group (41.3 % vs. 34.2 %; risk ratio [RR] = 1.20, 95 % confidence interval [CI] 1.06 to 1.36; P  = 0.003; I 2  = 79 %), especially for operators with low-to-moderate ADRs (< 35 %): RR = 1.51, 95 %CI 1.35 to 1.69; P  < 0.001; I 2  = 43 %). In contrast, this benefit was not reached for operators with high ADRs (> 45 %): RR = 1.01, 95 %CI 0.93 to 1.09; P  = 0.87; I 2  = 0.0 %). The mean number of adenomas per patient tended to be higher with EAC (mean difference = 0.11 adenomas/patient, 95 %CI - 0.17 to 0.38). Similar results were shown for polyp detection rates (61.6 % vs. 51.4 %; RR = 1.20, 95 %CI 1.06 to 1.36; P  = 0.004). Use of the Endocuff did not impact the cecal intubation rate (95.1 % vs. 95.7 %; P  = 0.08), or the procedure time compared with standard colonoscopy. Adverse events related to Endocuff were rare and exclusively mild mucosal erosion (4.0 %; 95 %CI 2.0 % to 8.0 %). With moderate-quality evidence, this study showed an improvement in ADR with EAC without major adverse events, especially for operators with low-to-moderate ADRs. © Georg Thieme Verlag KG Stuttgart · New York.

Using constrained information entropy to detect rare adverse drug reactions from medical forums.

PubMed

Yi Zheng; Chaowang Lan; Hui Peng; Jinyan Li

2016-08-01

Adverse drug reactions (ADRs) detection is critical to avoid malpractices yet challenging due to its uncertainty in pre-marketing review and the underreporting in post-marketing surveillance. To conquer this predicament, social media based ADRs detection methods have been proposed recently. However, existing researches are mostly co-occurrence based methods and face several issues, in particularly, leaving out the rare ADRs and unable to distinguish irrelevant ADRs. In this work, we introduce a constrained information entropy (CIE) method to solve these problems. CIE first recognizes the drug-related adverse reactions using a predefined keyword dictionary and then captures high- and low-frequency (rare) ADRs by information entropy. Extensive experiments on medical forums dataset demonstrate that CIE outperforms the state-of-the-art co-occurrence based methods, especially in rare ADRs detection.

[Effect of gross saponins of Tribulus terrestris on cardiocytes impaired by adriamycin].

PubMed

Zhang, Shuang; Li, Hong; Xu, Hui; Yang, Shi-Jie

2010-01-01

This study is to observe the protection of gross saponins of Tribulus terrestris (GSTT) on cardiocytes impaired by adriamycin (ADR) and approach its mechanism of action. Cardiocytes of neonate rat were cultivated for 72 hours and divided into normal control group, model (ADR 2 mg x L(-1)) group, and GSTT (100, 30, and 10 mg x L(-1)) groups. MTT colorimetric method was deployed to detect cardiocyte survival rate, activities of CK, LDH, AST, SOD, MDA and NO were detected, and apoptosis was detected with flow cytometry. Effect of GSTT on caspase-3 was detected with Western blotting. Compared with control group, contents of CK, LDH, AST, MDA and NO were increased, and activity of SOD was reduced (P < 0.05, P < 0.01, P < 0.001) by ADR. Numbers of survival cells were increased (P < 0.05, P < 0.001), contents of CK, LDH, AST, MDA and NO were decreased, and activity of SOD was increased (P < 0.05, P < 0.01, P < 0.001) by GSTT (100 and 30 mg x L(-1)). Apoptosis of cardiocytes and concentration of caspase-3 can be reduced by GSTT (100 and 30 mg x L(-1)). GSTT can protect cardiocytes impaired by ADR, which are possible involved with its effect of resisting oxygen free radical.

The frequency of adverse drug reaction related admissions according to method of detection, admission urgency and medical department specialty

PubMed Central

Brvar, Miran; Fokter, Nina; Bunc, Matjaz; Mozina, Martin

2009-01-01

Background Adverse Drug Reactions (ADRs) have been regarded as a major public health problem since they represent a sizable percentage of admissions. Unfortunately, there is a wide variation of ADR related admissions among different studies. The aim of this study was to evaluate the frequency of ADR related admissions and its dependency on reporting and method of detection, urgency of admissions and included medical departments reflecting department/hospital type within one study. Methods The study team of internal medicine specialists retrospectively reviewed 520 randomly selected medical records (3%) of patients treated in the medical departments of the primary city and tertiary referral governmental hospital for certain ADRs causing admissions regarding WHO causality criteria. All medical records were checked for whether the treating physicians recognised and documented ADRs causing admissions. The hospital information system was checked to ensure ADR related diagnoses were properly coded and the database of a national spontaneous reporting system was searched for patients with ADRs included in this study. Results The established frequency of admissions due to certain ADRs recognised by the study team and documented in medical records by the treating physicians was the same and represented 5.8% of all patients (30/520). The frequency of ADR causing admissions detected by employing a computer-assisted approach using an ICD-10 coding system was 0.2% (1/520), and no patient admitted due to ADRs was reported to the national reporting system (0/520). The recognized frequency of ADR related admissions also depends on the department's specialty (p = 0.001) and acceptance of urgently admitted patients (p = 0.001). Patients admitted due to ADRs were significantly older compared to patients without ADRs (p = 0.025). Gastrointestinal bleeding due to NSAID, acetylsalicylic acid and warfarin was the most common ADR that resulted in admission and represented 40% of all certain ADRs (12/30) according to WHO causality criteria. Conclusion ADRs cause 5.8% of admissions in medical departments in the primary city and tertiary referral hospital. The physicians recognise certain ADR related admissions according to WHO causality criteria and note them in medical records, but they rarely code and report ADRs. The established frequency of ADR related admissions depends on the detection method, department specialty and frequency of urgently admitted patients. PMID:19409112

Detection of Adverse Drug Reactions using Medical Named Entities on Twitter.

PubMed

MacKinlay, Andrew; Aamer, Hafsah; Yepes, Antonio Jimeno

2017-01-01

Adverse Drug Reactions (ADRs) are unintentional reactions caused by a drug or combination of drugs taken by a patient. The current ADR reporting systems inevitably have delays in reporting such events. The broad scope of social media conversations on sites such as Twitter means that inevitably health-related topics will be covered. This means that these sites could then be used to detect potentially novel ADRs with less latency for subsequent further investigation. In this work, we investigate ADR surveillance using a large corpus of Twitter data, containing around 50 billion tweets spanning 3 years (2012-2014), and evaluate against over 3000 drugs reported in the FAERS database. This is both a larger corpus and broader selection of drugs than previous work in the domain. We compare the ADRs identified using our method to the FDA Adverse Event Reporting System (FAERS) database of ADRs reported using more traditional techniques, and find that Twitter is a useful resource for ADR detection up to 72% micro-averaged precision. Micro-averaged recall of 6% is achievable using only 10% of Twitter, indicating that with a higher-volume or targeted feed it would be possible to detect a large percentage of ADRs.

Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence.

PubMed

Bravo-Cuellar, Alejandro; Ortiz-Lazareno, Pablo C; Lerma-Diaz, Jose M; Dominguez-Rodriguez, Jorge R; Jave-Suarez, Luis F; Aguilar-Lemarroy, Adriana; del Toro-Arreola, Susana; de Celis-Carrillo, Ruth; Sahagun-Flores, Jose E; de Alba-Garcia, Javier E Garcia; Hernandez-Flores, Georgina

2010-05-19

Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells. HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IkappaBalpha and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot. PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IkappaBalpha levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR. PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells.

Sensitization of cervix cancer cells to Adriamycin by Pentoxifylline induces an increase in apoptosis and decrease senescence

PubMed Central

2010-01-01

Background Chemotherapeutic drugs like Adriamycin (ADR) induces apoptosis or senescence in cancer cells but these cells often develop resistance and generate responses of short duration or complete failure. The methylxantine drug Pentoxifylline (PTX) used routinely in the clinics setting for circulatory diseases has been recently described to have antitumor properties. We evaluated whether pretreatment with PTX modifies apoptosis and senescence induced by ADR in cervix cancer cells. Methods HeLa (HPV 18+), SiHa (HPV 16+) cervix cancer cells and non-tumorigenic immortalized HaCaT cells (control) were treated with PTX, ADR or PTX + ADR. The cellular toxicity of PTX and survival fraction were determinated by WST-1 and clonogenic assay respectively. Apoptosis, caspase activation and ADR efflux rate were measured by flow cytometry, senescence by microscopy. IκBα and DNA fragmentation were determinated by ELISA. Proapoptotic, antiapoptotic and senescence genes, as well as HPV-E6/E7 mRNA expression, were detected by time real RT-PCR. p53 protein levels were assayed by Western blot. Results PTX is toxic (WST-1), affects survival (clonogenic assay) and induces apoptosis in cervix cancer cells. Additionally, the combination of this drug with ADR diminished the survival fraction and significantly increased apoptosis of HeLa and SiHa cervix cancer cells. Treatments were less effective in HaCaT cells. We found caspase participation in the induction of apoptosis by PTX, ADR or its combination. Surprisingly, in spite of the antitumor activity displayed by PTX, our results indicate that methylxantine, per se does not induce senescence; however it inhibits senescence induced by ADR and at the same time increases apoptosis. PTX elevates IκBα levels. Such sensitization is achieved through the up-regulation of proapoptotic factors such as caspase and bcl family gene expression. PTX and PTX + ADR also decrease E6 and E7 expression in SiHa cells, but not in HeLa cells. p53 was detected only in SiHa cells treated with ADR. Conclusion PTX is a good inducer of apoptosis but does not induce senescence. Furthermore, PTX reduced the ADR-induced senescence and increased apoptosis in cervix cancer cells. PMID:20482878

Implementation of a computer-assisted monitoring system for the detection of adverse drug reactions in gastroenterology.

PubMed

Dormann, H; Criegee-Rieck, M; Neubert, A; Egger, T; Levy, M; Hahn, E G; Brune, K

2004-02-01

To investigate the effectiveness of a computer monitoring system that detects adverse drug reactions (ADRs) by laboratory signals in gastroenterology. A prospective, 6-month, pharmaco-epidemiological survey was carried out on a gastroenterological ward at the University Hospital Erlangen-Nuremberg. Two methods were used to identify ADRs. (i) All charts were reviewed daily by physicians and clinical pharmacists. (ii) A computer monitoring system generated a daily list of automatic laboratory signals and alerts of ADRs, including patient data and dates of events. One hundred and nine ADRs were detected in 474 admissions (377 patients). The computer monitoring system generated 4454 automatic laboratory signals from 39 819 laboratory parameters tested, and issued 2328 alerts, 914 (39%) of which were associated with ADRs; 574 (25%) were associated with ADR-positive admissions. Of all the alerts generated, signals of hepatotoxicity (1255), followed by coagulation disorders (407) and haematological toxicity (207), were prevalent. Correspondingly, the prevailing ADRs were concerned with the metabolic and hepato-gastrointestinal system (61). The sensitivity was 91%: 69 of 76 ADR-positive patients were indicated by an alert. The specificity of alerts was increased from 23% to 76% after implementation of an automatic laboratory signal trend monitoring algorithm. This study shows that a computer monitoring system is a useful tool for the systematic and automated detection of ADRs in gastroenterological patients.

Information about ADRs explored by pharmacovigilance approaches: a qualitative review of studies on antibiotics, SSRIs and NSAIDs

PubMed Central

Aagaard, Lise; Hansen, Ebba Holme

2009-01-01

Background Despite surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after marketing. The aim of this article is to analyse ADRs reported by available ADR signal detection approaches and to explore which information about new and unexpected ADRs these approaches have detected. Methods We selected three therapeutic cases for the review: antibiotics for systemic use, non-steroidal anti-inflammatory medicines (NSAID) and selective serotonin re-uptake inhibitors (SSRI). These groups are widely used and represent different therapeutic classes of medicines. The ADR studies were identified through literature search in Medline and Embase. The search was conducted in July 2007. For each therapeutic case, we analysed the time of publication, the strengths of the evidence of safety in the different approaches, reported ADRs and whether the studies have produced new information about ADRs compared to the information available at the time of marketing. Results 79 studies were eligible for inclusion in the analysis: 23 antibiotics studies, 35 NSAID studies, 20 SSRI studies. Studies were mainly published from the end of the 1990s and onwards. Although the drugs were launched in different decades, both analytical and observational approaches to ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. The studies primarily dealt with analyses of ADRs of the type A and B and to a lesser extent C and D, cf. Rawlins' classification system. The therapeutic cases provided similar results with regard to detecting information about new ADRs despite different time periods and organs attacked. Approaches ranging higher in the evidence hierarchy provided information about risks of already known or expected ADRs, while information about new and previously unknown ADRs was only detected by case reports, the lowest ranking approach in the evidence hierarchy. Conclusion Although the medicines were launched in different decades, approaches to the ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. Both descriptive and analytical designs were applied. Despite the fact that analytical studies rank higher in the evidence hierarchy, only the lower ranking descriptive case reports/spontaneous reports provided information about new and previously undetected ADRs. This review underscores the importance of systems for spontaneous reporting of ADRs. Therefore, spontaneous reporting should be encouraged further and the information in ADR databases should continuously be subjected to systematic analysis. PMID:19254390

Information about ADRs explored by pharmacovigilance approaches: a qualitative review of studies on antibiotics, SSRIs and NSAIDs.

PubMed

Aagaard, Lise; Hansen, Ebba Holme

2009-03-03

Despite surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after marketing. The aim of this article is to analyse ADRs reported by available ADR signal detection approaches and to explore which information about new and unexpected ADRs these approaches have detected. We selected three therapeutic cases for the review: antibiotics for systemic use, non-steroidal anti-inflammatory medicines (NSAID) and selective serotonin re-uptake inhibitors (SSRI). These groups are widely used and represent different therapeutic classes of medicines. The ADR studies were identified through literature search in Medline and Embase. The search was conducted in July 2007. For each therapeutic case, we analysed the time of publication, the strengths of the evidence of safety in the different approaches, reported ADRs and whether the studies have produced new information about ADRs compared to the information available at the time of marketing. 79 studies were eligible for inclusion in the analysis: 23 antibiotics studies, 35 NSAID studies, 20 SSRI studies. Studies were mainly published from the end of the 1990s and onwards. Although the drugs were launched in different decades, both analytical and observational approaches to ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. The studies primarily dealt with analyses of ADRs of the type A and B and to a lesser extent C and D, cf. Rawlins' classification system. The therapeutic cases provided similar results with regard to detecting information about new ADRs despite different time periods and organs attacked. Approaches ranging higher in the evidence hierarchy provided information about risks of already known or expected ADRs, while information about new and previously unknown ADRs was only detected by case reports, the lowest ranking approach in the evidence hierarchy. Although the medicines were launched in different decades, approaches to the ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. Both descriptive and analytical designs were applied. Despite the fact that analytical studies rank higher in the evidence hierarchy, only the lower ranking descriptive case reports/spontaneous reports provided information about new and previously undetected ADRs. This review underscores the importance of systems for spontaneous reporting of ADRs. Therefore, spontaneous reporting should be encouraged further and the information in ADR databases should continuously be subjected to systematic analysis.

Adenoma Detection Rate: I Will Show You Mine if You Show Me Yours

PubMed Central

Oliveira Ferreira, Alexandre; Fidalgo, Catarina; Palmela, Carolina; Costa Santos, Maria Pia; Torres, Joana; Nunes, Joana; Loureiro, Rui; Ferreira, Rosa; Barjas, Elídio; Glória, Luísa; Santos, António Alberto; Cravo, Marília

2017-01-01

Background Colorectal cancer (CRC) is the first cause of cancer-related mortality in Portugal. CRC screening reduces disease-specific mortality. Colonoscopy is currently the preferred method for screening as it may contribute to the reduction of CRC incidence. This beneficial effect is strongly associated with the adenoma detection rate (ADR). Aim Our aim was to evaluate the quality of colonoscopy at our unit by measuring the currently accepted quality parameters and publish them as benchmarking indicators. Methods From 5,860 colonoscopies, 654 screening procedures (with and without previous fecal occult blood testing) were analyzed. Results The mean age of the patients was 66.4 ± 7.8 years, and the gender distribution was 1:1. The overall ADR was 36% (95% confidence interval [CI] 32–39), the mean number of adenomas per colonoscopy was 0.66 (95% CI 0.56–0.77), and the sessile serrate lesion detection rate was 1% (95% CI 0–2). The bowel preparation was rated as adequate in 496 (76%) patients. The adjusted cecal intubation rate (CIR) was 93.7% (95% CI 91.7–95.8). Most colonoscopies were performed under monitored anesthesia care (53%), and 35% were unsedated. The use of sedation (propofol or midazolam based) was associated with a higher CIR with an odds ratio of 3.60 (95% CI 2.02–6.40, p < 0.001). Conclusion Our data show an above-standard ADR. The frequency of poor bowel preparation and the low sessile serrated lesion detection rate were acknowledged, and actions were implemented to improve both indicators. Quality auditing in colonoscopy should be compulsory, and while many units may do so internally, this is the first national report from a high-throughput endoscopy unit. PMID:28848785

Detection rate and predictive factors of sessile serrated polyps in an organised colorectal cancer screening programme with immunochemical faecal occult blood test: the EQuIPE study (Evaluating Quality Indicators of the Performance of Endoscopy).

PubMed

Zorzi, Manuel; Senore, Carlo; Da Re, Filippo; Barca, Alessandra; Bonelli, Luigina Ada; Cannizzaro, Renato; de Pretis, Giovanni; Di Furia, Lucia; Di Giulio, Emilio; Mantellini, Paola; Naldoni, Carlo; Sassatelli, Romano; Rex, Douglas K; Zappa, Marco; Hassan, Cesare

2017-07-01

To assess detection rate and predictive factors of sessile serrated polyps (SSPs) in organised colorectal cancer (CRC) screening programmes based on the faecal immunochemical test (FIT). Data from a case series of colonoscopies of FIT-positive subjects were provided by 44 Italian CRC screening programmes. Data on screening history, endoscopic procedure and histology results, and additional information on the endoscopy centre and the endoscopists were collected, including the age-standardised and sex-standardised adenoma detection rate (ADR) of the individual endoscopists. The SSP detection rate (SSP-DR) was assessed for the study population. To identify SSP-predictive factors, multilevel analyses were performed according to patient/centre/endoscopist characteristics. We analysed 72 021 colonoscopies, of which 1295 presented with at least one SSP (SSP-DR 1.8%; 95% CI 1.7% to 1.9%). At the per-patient level, SSP-DR was associated with males (OR 1.35; 95% CI 1.17 to 1.54) and caecal intubation (OR 3.75; 95% CI 2.22 to 6.34), but not with the FIT round. The presence of at least one advanced adenoma was more frequent among subjects with SSPs than those without (OR 2.08; 95% CI 1.86 to 2.33). At the per-endoscopist level, SSP-DR was associated with ADR (third vs first ADR quartile: OR 1.55; 95% CI 1.03 to 2.35; fourth vs first quartile: OR 1.89; 95% CI 1.24 to 2.90). The low prevalence of SSPs and the lack of association with the FIT round argue against SSP as a suitable target for FIT-based organised programmes. Strict association of SSP-DR with the key colonoscopy quality indicators, namely caecal intubation rate and high ADR further marginalises the need for SSP-specific quality indicators in FIT-based programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Emergency physician recognition of adverse drug-related events in elder patients presenting to an emergency department.

PubMed

Hohl, Corinne Michèle; Robitaille, Caroline; Lord, Vicky; Dankoff, Jerrald; Colacone, Antoinette; Pham, Luc; Bérard, Anick; Pépin, Jocelyne; Afilalo, Marc

2005-03-01

The authors examined the ability of emergency physicians (EPs) to recognize adverse drug-related events (ADREs) in elder patients presenting to the emergency department (ED). This was a prospective observational study of patients at least 65 years of age who presented to the ED. ADREs were identified using a validated, standardized scoring system. EP recognition of ADREs was assessed through physician interview and subsequent chart review. A total of 161 patients were enrolled in the study. Thirty-seven ADREs were identified, which occurred in 26 patients (16.2%; 95% confidence interval [CI] = 10.5% to 22.0%). The treating EPs recognized 51.2% (95% CI = 35.2% to 67.4%) of all ADREs. There was better recognition of those ADREs related to the patient's chief complaint (91%; 95% CI = 74.1% to 100%) as compared with recognition of ADREs that were not associated with the chief complaint (32.1%; 95% CI = 14.8% to 49%). EPs recognized six of seven severe ADREs (85.7%), 13 of 23 moderate ADREs (56.5%; 95% CI = 36.8% to 77%), and none of the mild ADREs. Recognition of ADREs varied with medication class. EP performance was superior at identifying severe ADREs relating to the patients' chief complaints. However, EP performance was suboptimal with respect to identifying ADREs of lower severity, having missed a significant number of ADREs of moderate severity as well as ones unrelated to the patients' chief complaints. ADRE detection methods need to be developed for the ED to aid EPs in detecting those ADREs that are most likely to be missed.

E-pharmacovigilance: development and implementation of a computable knowledge base to identify adverse drug reactions.

PubMed

Neubert, Antje; Dormann, Harald; Prokosch, Hans-Ulrich; Bürkle, Thomas; Rascher, Wolfgang; Sojer, Reinhold; Brune, Kay; Criegee-Rieck, Manfred

2013-09-01

Computer-assisted signal generation is an important issue for the prevention of adverse drug reactions (ADRs). However, due to poor standardization of patients' medical data and a lack of computable medical drug knowledge the specificity of computerized decision support systems for early ADR detection is too low and thus those systems are not yet implemented in daily clinical practice. We report on a method to formalize knowledge about ADRs based on the Summary of Product Characteristics (SmPCs) and linking them with structured patient data to generate safety signals automatically and with high sensitivity and specificity. A computable ADR knowledge base (ADR-KB) that inherently contains standardized concepts for ADRs (WHO-ART), drugs (ATC) and laboratory test results (LOINC) was built. The system was evaluated in study populations of paediatric and internal medicine inpatients. A total of 262 different ADR concepts related to laboratory findings were linked to 212 LOINC terms. The ADR knowledge base was retrospectively applied to a study population of 970 admissions (474 internal and 496 paediatric patients), who underwent intensive ADR surveillance. The specificity increased from 7% without ADR-KB up to 73% in internal patients and from 19.6% up to 91% in paediatric inpatients, respectively. This study shows that contextual linkage of patients' medication data with laboratory test results is a useful and reasonable instrument for computer-assisted ADR detection and a valuable step towards a systematic drug safety process. The system enables automated detection of ADRs during clinical practice with a quality close to intensive chart review. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

Herbal medicine use and linked suspected adverse drug reactions in a prospective cohort of Ugandan inpatients.

PubMed

Kiguba, Ronald; Ononge, Sam; Karamagi, Charles; Bird, Sheila M

2016-05-26

Clinical history-taking can be employed as a standardized approach to elucidate the use of herbal medicines and their linked suspected adverse drug reactions (ADRs) among hospitalized patients. We sought to identify herbal medicines nominated by Ugandan inpatients; compare nomination rates by ward and gender; confirm the herbs' known pharmacological properties from published literature; and identify ADRs linked to pre-admission use of herbal medicines. Prospective cohort of consented adult inpatients designed to assess medication use and ADRs on one gynaecological and three medical wards of 1790-bed Mulago National Referral Hospital. Baseline and follow-up data were obtained on patients' characteristics, including pre-admission use of herbal medicines. Fourteen percent (26/191) of females in Gynaecology nominated at least one specific herbal medicine compared with 20 % (114/571) of inpatients on medical wards [20 % (69/343) of females; 20 % (45/228) of males]. Frequent nominations were Persea americana (30), Mumbwa/multiple-herb clay rods (23), Aloe barbadensis (22), Beta vulgaris (12), Vernonia amygdalina (11), Commelina africana (7), Bidens pilosa (7), Hoslundia opposita (6), Mangifera indica (4), and Dicliptera laxata (4). Four inpatients experienced 10 suspected ADRs linked to pre-admission herbal medicine use including Commelina africana (4), multiple-herb-mumbwa (1), or unspecified local-herbs (5): three ADR-cases were abortion-related and one kidney-related. The named herbal medicines and their nomination rates generally differed by specialized ward, probably guided by local folklore knowledge of their use. Clinical elicitation from inpatients can generate valuable safety data on herbal medicine use. However, larger routine studies might increase the utility of our method to assess herbal medicine use and detect herb-linked ADRs. Future studies should take testable samples of ADR-implicated herbal medicines for further analysis.

Fast Screening Technology for Drug Emergency Management: Predicting Suspicious SNPs for ADR with Information Theory-based Models.

PubMed

Liang, Zhaohui; Liu, Jun; Huang, Jimmy X; Zeng, Xing

2018-01-01

The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). In order to explore the latent correlations between ADRs and potentially corresponding single-nucleotide polymorphism (SNPs) in CYP450, three algorithms based on information theory are used as the main method to predict the possible relation. The study uses a retrospective case-control study to explore the potential relation of ADRs to specific genomic locations and single-nucleotide polymorphism (SNP). The genomic data collected from 53 healthy volunteers are applied for the analysis, another group of genomic data collected from 30 healthy volunteers excluded from the study are used as the control group. The SNPs respective on five loci of CYP2D6*2,*10,*14 and CYP1A2*1C, *1F are detected by the Applied Biosystem 3130xl. The raw data is processed by ChromasPro to detect the specific alleles on the above loci from each sample. The secondary data are reorganized and processed by R combined with the reports of ADRs from clinical reports. Three information theory based algorithms are implemented for the screening task: JMI, CMIM, and mRMR. If a SNP is selected by more than two algorithms, we are confident to conclude that it is related to the corresponding ADR. The selection results are compared with the control decision tree + LASSO regression model. In the study group where ADRs occur, 10 SNPs are considered relevant to the occurrence of a specific ADR by the combined information theory model. In comparison, only 5 SNPs are considered relevant to a specific ADR by the decision tree + LASSO regression model. In addition, the new method detects more relevant pairs of SNP and ADR which are affected by both SNP and dosage. This implies that the new information theory based model is effective to discover correlations of ADRs and CYP 450 SNPs and is helpful in predicting the potential vulnerable genotype for some ADRs. The newly proposed information theory based model has superiority performance in detecting the relation between SNP and ADR compared to the decision tree + LASSO regression model. The new model is more sensitive to detect ADRs compared to the old method, while the old method is more reliable. Therefore, the selection criteria for selecting algorithms should depend on the pragmatic needs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Monitoring drug safety in Astrakhan, Russia.

PubMed

Kirilochev, O O; Dorfman, I P; Umerova, A R

2015-01-01

The problem of drug safety will never disappear as new drugs are delivered in increasing numbers. They have high biological activity and adverse drug reactions (ADR) [1]. Currently, adverse drug reactions are the fourth leading cause of death for patients.There are databases of ADRs (Vigibase, Eudravigilance), but we know that ADR manifestations may vary in different countries and regions, due to the demographic, genetic characteristics of the population and the quality of manufactured drugs [2]. In this regard, the study of the ADR at the regional level is very relevant. We aimed to optimize the work on monitoring drug safety in Astrakhan region through pharmacoepidemiological research and development of computer database for analysis of information coming to the center for drug safety monitoring (CDSM). 1. To study the rates of ADR reporting and the structure in the Astrakhan region at the regional center for drug safety monitoring.2. To analyze the outcomes of registered adverse drug reactions.3. To determine the causality of adverse drug reactions.4. To identify reports on the ineffectiveness of drugs.5. To analyze the rates and structure of ADR reporting for drugs prescribed off-label. We studied spontaneous adverse event reporting. The adverse event reports received by the regional CDSM for the period of 2010 to 2014 was analyzed. The groups of drugs were categorized according by Anatomical Therapeutic Chemical classification system. The data were analyzed using Microsoft Office Excel. The likelihood of whether an ADR was actually due to the drugs was assessed with the Naranjo algorithm. The analysis of the results showed that the establishment of the CDSM in September 2010, contributed to improvement of drug safety monitoring in health facilities of the region. Noteworthy was the increasing the number of adverse event reports in 2011 and 2012, compared with the beginning of the year 2010, when the CDSM was not yet functioning.The decrease of adverse event reporting in 2013 and 2014 was due to the fact that doctors in the region had access to better ADR drug information. Along with the increasing number of adverse event reporting we also noted the increase in the number of health facilities that monitored drug safety. The number of health facilities that reported, doubled from 2010 to 2014. We observed the increase in the number of adverse event reports submitted by pharmaceutical companies. General anti-infective drugs for systemic use (class J) were the most common cause of all registered ADRs (44%). Drugs for treatment of tuberculosis (group J04A) were the cause of adverse drug reactions in 34% of reports. ADRs associated with drugs used for treating diseases of cardiovascular system accounted for 16% of case-reports; drugs belonging to the group of Alimentary tract and metabolism (class A) and to the group of Nervous System (class A) were reported to cause ADRs in 10% of cases each. Type A adverse drug reactions, which are usually a consequence of a drug's primary pharmacological effect, were detected in 45% of cases. These reactions were often registered for drugs affecting cardiovascular system (class C), nervous system (class N), dlood and blood forming organs (class B). Type B ADRs were reported in 54% of cases. These were "idiosyncratic" reactions, which could not be predicted on the basis of the drug's main pharmacological action, were not dose-related and were severe [3]. The most frequent cause of type B adverse drug reactions was the General anti-infective medicines for systemic use (Class J). The fatality rate associated with ADRs was 0.3%. Type A adverse drug reactions resulted in death in 38% of cases. Type B ADR (anaphylactic shock) accounted for 62% of the patient's deaths. The Naranjo scale determined the causality of ADRs. The "definite" ADRs were detected in 14% of reports, "probable" - in 47%, and "possible" - in 39% of cases. The rate of reporting associated with ineffectiveness of drugs amounted to 1%. Most often the lack of therapeutic effect was reported in patients receiving drugs of class C (Cardiovascular system, 31% of all cases of inefficiency of drugs). These drugs were used in accordance with their official instructions for use. The proportion of ADR reports for drugs prescribed off-label was 1.4%. The results substantiate the need to continue drug safety monitoring in the Astrakhan region. We plan to further improve the software for ADR analysis.

iADRs: towards online adverse drug reaction analysis.

PubMed

Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun

2012-12-01

Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

Water exchange for screening colonoscopy increases adenoma detection rate: a multicenter, double-blinded, randomized controlled trial.

PubMed

Cadoni, Sergio; Falt, Přemysl; Rondonotti, Emanuele; Radaelli, Franco; Fojtik, Petr; Gallittu, Paolo; Liggi, Mauro; Amato, Arnaldo; Paggi, Silvia; Smajstrla, Vit; Urban, Ondřej; Erriu, Matteo; Koo, Malcolm; Leung, Felix W

2017-05-01

Background and study aims  Single-center studies, which were retrospective and/or involved unblinded colonoscopists, have suggested that water exchange, but not water immersion, compared with air insufflation significantly increases the adenoma detection rate (ADR), particularly in the proximal and right colon. Head-to-head comparison of the three techniques with ADR as primary outcome and blinded colonoscopists has not been reported to date. In a randomized controlled trial with blinded colonoscopists, we aimed to evaluate the impact of the three insertion techniques on ADR. Patients and methods  A total of 1224 patients aged 50 - 70 years (672 males) and undergoing screening colonoscopy were randomized 1:1:1 to water exchange, water immersion, or air insufflation. Split-dose bowel preparation was adopted to optimize colon cleansing. After the cecum had been reached, a second colonoscopist who was blinded to the insertion technique performed the withdrawal. The primary outcome was overall ADR according to the three insertion techniques (water exchange, water immersion, and air insufflation). Secondary outcomes were other pertinent overall and right colon procedure-related measures. Results  Baseline characteristics of the three groups were comparable. Compared with air insufflation, water exchange achieved a significantly higher overall ADR (49.3 %, 95 % confidence interval [CI] 44.3 % - 54.2 % vs. 40.4 % 95 %CI 35.6 % - 45.3 %; P  = 0.03); water exchange showed comparable overall ADR vs. water immersion (43.4 %, 95 %CI 38.5 % - 48.3 %; P  = 0.28). In the right colon, water exchange achieved a higher ADR than air insufflation (24.0 %, 95 %CI 20.0 % - 28.5 % vs. 16.9 %, 95 %CI 13.4 % - 20.9 %; P  = 0.04) and a higher advanced ADR (6.1 %, 95 %CI 4.0 % - 9.0 % vs. 2.5 %, 95 %CI 1.2 % - 4.6 %; P  = 0.03). Compared with air insufflation, the mean number of adenomas per procedure was significantly higher with water exchange ( P  = 0.04). Water exchange achieved the highest cleanliness scores (overall and in the right colon). These variables were comparable between water immersion and air insufflation. Conclusions  The design with blinded observers strengthens the validity of the observation that water exchange, but not water immersion, can achieve significantly higher adenoma detection than air insufflation. Based on this evidence, the use of water exchange should be encouraged.Trial registered at ClinicalTrials.gov (NCT02041507). © Georg Thieme Verlag KG Stuttgart · New York.

Achieving high quality colonoscopy: using graphical representation to measure performance and reset standards.

PubMed

Rajasekhar, P T; Rutter, M D; Bramble, M G; Wilson, D W; East, J E; Greenaway, J R; Saunders, B P; Lee, T J W; Barton, R; Hungin, A P S; Rees, C J

2012-12-01

Completeness and thoroughness of colonoscopy are measured by the caecal intubation rate (CIR) and the adenoma detection rate (ADR). National standards are ≥ 90% and ≥ 10% respectively. Variability in CIR and ADR have been demonstrated but comparison between individuals and units is difficult. We aimed to assess the performance of colonoscopy in endoscopy units in the northeast of England. Data on colonoscopy performance and sedation use were collected over 3 months from 12 units. Colonoscopies performed by screening colonoscopists were included for the CIR only. Funnel plots with upper and lower 95% confidence limits for CIR and ADR were created. CIR was 92.5% (n = 5720) and ADR 15.9% (n = 4748). All units and 128 (99.2%) colonoscopists were above the lower limit for CIR. All units achieved the ADR standard with 10 above the upper limit. Ninety-nine (76.7%) colonoscopists were above 10%, 16 (12.4%) above the upper limit and 7 (5.4%) below the lower limit. Median medication doses were 2.2 mg midazolam, 29.4 mg pethidine and 83.3 μg fentanyl. In all, 15.1% of colonoscopies were unsedated. Complications were bleeding (0.10%) and perforation (0.02%). There was one death possibly related to bowel preparation. Results indicate that colonoscopies are performed safely and to a high standard. Funnel plots can highlight variability and areas for improvement. Analyses of ADR presented graphically around the global mean suggest that the national standard should be reset at 15%. © 2012 The Authors. Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.

Chemical and microbiological hazards associated with recycling of anaerobic digested residue intended for agricultural use

DOE Office of Scientific and Technical Information (OSTI.GOV)

Govasmark, Espen, E-mail: espen.govasmark@bioforsk.no; Staeb, Jessica; Holen, Borge

2011-12-15

In the present study, three full-scale biogas plants (BGP) were investigated for the concentration of heavy metals, organic pollutants, pesticides and the pathogenic bacteria Bacillus cereus and Escherichia coli in the anaerobically digested residues (ADR). The BGPs mainly utilize source-separated organic wastes and industrial food waste as energy sources and separate the ADR into an ADR-liquid and an ADR-solid fraction by centrifugation at the BGP. According to the Norwegian standard for organic fertilizers, the ADR were classified as quality 1 mainly because of high zinc (132-422 mg kg{sup -1} DM) and copper (23-93 mg kg{sup -1} DM) concentrations, but alsomore » because of high cadmium (0.21-0.60 mg kg{sup -1} DM) concentrations in the liquid-ADR. In the screening of organic pollutants, only DEHP (9.7-62.1 mg kg{sup -1}) and {Sigma} PAH 16 (0.2-1.98 mg kg{sup -1} DM) were detected in high concentrations according to international regulations. Of the 250 pesticides analyzed, 11 were detected, but only imazalil (<0.30-5.77 mg kg{sup -1} DM) and thiabendazol (<0.14-0.73 mg kg{sup -1} DM) were frequently detected in the ADR-fiber. Concentrations of imazalil and thiabendazol were highest during the winter months, due to a high consumption of citrus fruits in Norway in this period. Ten percent of the ADR-liquid samples contained cereulide-producing B. cereus, whereas no verotoxigenic E. coli was detected. The authors conclude that the risk of chemical and bacterial contamination of the food chain or the environment from agricultural use of ADR seems low.« less

Chemical and microbiological hazards associated with recycling of anaerobic digested residue intended for agricultural use.

PubMed

Govasmark, Espen; Stäb, Jessica; Holen, Børge; Hoornstra, Douwe; Nesbakk, Tommy; Salkinoja-Salonen, Mirja

2011-12-01

In the present study, three full-scale biogas plants (BGP) were investigated for the concentration of heavy metals, organic pollutants, pesticides and the pathogenic bacteria Bacillus cereus and Escherichia coli in the anaerobically digested residues (ADR). The BGPs mainly utilize source-separated organic wastes and industrial food waste as energy sources and separate the ADR into an ADR-liquid and an ADR-solid fraction by centrifugation at the BGP. According to the Norwegian standard for organic fertilizers, the ADR were classified as quality 1 mainly because of high zinc (132-422 mg kg(-1) DM) and copper (23-93 mg kg(-1) DM) concentrations, but also because of high cadmium (0.21-0.60 mg kg(-1) DM) concentrations in the liquid-ADR. In the screening of organic pollutants, only DEHP (9.7-62.1 mg kg(-1)) and ∑ PAH 16 (0.2-1.98 mg kg(-1) DM) were detected in high concentrations according to international regulations. Of the 250 pesticides analyzed, 11 were detected, but only imazalil (<0.30-5.77 mg kg(-1) DM) and thiabendazol (<0.14-0.73 mg kg(-1) DM) were frequently detected in the ADR-fiber. Concentrations of imazalil and thiabendazol were highest during the winter months, due to a high consumption of citrus fruits in Norway in this period. Ten percent of the ADR-liquid samples contained cereulide-producing B. cereus, whereas no verotoxigenic E. coli was detected. The authors conclude that the risk of chemical and bacterial contamination of the food chain or the environment from agricultural use of ADR seems low. Copyright © 2011 Elsevier Ltd. All rights reserved.

Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children

PubMed Central

Choonara, Imti; Conroy, Sharon

2017-01-01

Background Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels. Methods A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included. Results One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths). Conclusions Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR. PMID:28125632

Detection of adverse drug reactions among ordinary users of liraglutide on the occasion of drug dispensing in the community pharmacy setting.

PubMed

Christensen, Søren Troels; Bjerrum, Ole Jannik

2013-12-01

Postmarketing studies of drugs forms an essential part of safety surveillance. In particular, this concerns new drugs as safety information of these by large rests on randomized clinical studies conducted on a limited number of subjects before licensing. Pharmacists in community pharmacies are in a unique position for detection of user experienced adverse drug reactions (ADRs) in relation to drug dispensing. The study reports from a research initiative exploring prompt and proactive ADR detection of liraglutide and reporting facilitated by pharmacy students undertaking internship in a community pharmacy in Denmark. Nineteen pharmacy students undertaking regular 6 months' internship--eighth semester--in a Danish community pharmacy participated in the data collection. Before the data collection, students attended an interactive training seminar addressing ADRs in general, organ symptoms, diagnostic classification, and pharmacovigilance systems. Pharmacy students approached recurrent drug users purchasing liraglutide. Participating users were asked about experienced ADRs linked to liraglutide use. Reported ADRs were collected and analyzed. Sixty-two liraglutide users participated in the study, of whom, 38 reported 84 ADRs possibly linked to liraglutide usage. Nausea was by far the most reported ADR followed by decreased appetite, diarrhea, fatigue, and abdominal pain (upper). The reported ADRs are in accordance with previously reported ADRs. The study has demonstrated the feasibility of community pharmacy driven pharmacovigilance. The study supports the thesis that community pharmacists in the future may play a proactive and prominent role in patient-centered pharmacovigilance.

Utilizing social media data for pharmacovigilance: A review.

PubMed

Sarker, Abeed; Ginn, Rachel; Nikfarjam, Azadeh; O'Connor, Karen; Smith, Karen; Jayaraman, Swetha; Upadhaya, Tejaswi; Gonzalez, Graciela

2015-04-01

Automatic monitoring of Adverse Drug Reactions (ADRs), defined as adverse patient outcomes caused by medications, is a challenging research problem that is currently receiving significant attention from the medical informatics community. In recent years, user-posted data on social media, primarily due to its sheer volume, has become a useful resource for ADR monitoring. Research using social media data has progressed using various data sources and techniques, making it difficult to compare distinct systems and their performances. In this paper, we perform a methodical review to characterize the different approaches to ADR detection/extraction from social media, and their applicability to pharmacovigilance. In addition, we present a potential systematic pathway to ADR monitoring from social media. We identified studies describing approaches for ADR detection from social media from the Medline, Embase, Scopus and Web of Science databases, and the Google Scholar search engine. Studies that met our inclusion criteria were those that attempted to extract ADR information posted by users on any publicly available social media platform. We categorized the studies according to different characteristics such as primary ADR detection approach, size of corpus, data source(s), availability, and evaluation criteria. Twenty-two studies met our inclusion criteria, with fifteen (68%) published within the last two years. However, publicly available annotated data is still scarce, and we found only six studies that made the annotations used publicly available, making system performance comparisons difficult. In terms of algorithms, supervised classification techniques to detect posts containing ADR mentions, and lexicon-based approaches for extraction of ADR mentions from texts have been the most popular. Our review suggests that interest in the utilization of the vast amounts of available social media data for ADR monitoring is increasing. In terms of sources, both health-related and general social media data have been used for ADR detection-while health-related sources tend to contain higher proportions of relevant data, the volume of data from general social media websites is significantly higher. There is still very limited amount of annotated data publicly available , and, as indicated by the promising results obtained by recent supervised learning approaches, there is a strong need to make such data available to the research community. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Causality Patterns for Detecting Adverse Drug Reactions From Social Media: Text Mining Approach.

PubMed

Bollegala, Danushka; Maskell, Simon; Sloane, Richard; Hajne, Joanna; Pirmohamed, Munir

2018-05-09

Detecting adverse drug reactions (ADRs) is an important task that has direct implications for the use of that drug. If we can detect previously unknown ADRs as quickly as possible, then this information can be provided to the regulators, pharmaceutical companies, and health care organizations, thereby potentially reducing drug-related morbidity and saving lives of many patients. A promising approach for detecting ADRs is to use social media platforms such as Twitter and Facebook. A high level of correlation between a drug name and an event may be an indication of a potential adverse reaction associated with that drug. Although numerous association measures have been proposed by the signal detection community for identifying ADRs, these measures are limited in that they detect correlations but often ignore causality. This study aimed to propose a causality measure that can detect an adverse reaction that is caused by a drug rather than merely being a correlated signal. To the best of our knowledge, this was the first causality-sensitive approach for detecting ADRs from social media. Specifically, the relationship between a drug and an event was represented using a set of automatically extracted lexical patterns. We then learned the weights for the extracted lexical patterns that indicate their reliability for expressing an adverse reaction of a given drug. Our proposed method obtains an ADR detection accuracy of 74% on a large-scale manually annotated dataset of tweets, covering a standard set of drugs and adverse reactions. By using lexical patterns, we can accurately detect the causality between drugs and adverse reaction-related events. ©Danushka Bollegala, Simon Maskell, Richard Sloane, Joanna Hajne, Munir Pirmohamed. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 09.05.2018.

Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.

PubMed

Oshima, Shinji; Enjuji, Takako; Negishi, Akio; Akimoto, Hayato; Ohara, Kousuke; Okita, Mitsuyoshi; Numajiri, Sachihiko; Inoue, Naoko; Ohshima, Shigeru; Terao, Akira; Kobayashi, Daisuke

2017-09-01

In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.

[Adverse drug reaction reporting in emergency medicine].

PubMed

Milojevic, Kolia; Chassagnol, Isabelle; Brion, Nathalie; Cléro, Joël; Degrèze, Nathalie; Lambert, Yves

2004-01-01

A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at < or = 6%. A minority of physicians were responsible for the majority of ADR reporting. Sixty-four percent of emergency physicians underestimated the conditions required for ADR notification: 28% thought that certain causality was an absolute necessary condition for notification, while 37% considered that notification was required only for ADRs that were both severe and unexpected. Interventions focused on advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.

Display of adenoregulin with a novel Pichia pastoris cell surface display system.

PubMed

Ren, Ren; Jiang, Zhengbing; Liu, Meiyun; Tao, Xinyi; Ma, Yushu; Wei, Dongzhi

2007-02-01

Two Pichia pastoris cell surface display vectors were constructed. The vectors consisted of the flocculation functional domain of Flo1p with its own secretion signal sequence or the alpha-factor secretion signal sequence, a polyhistidine (6xHis) tag for detection, an enterokinase recognition site, and the insertion sites for target proteins. Adenoregulin (ADR) is a 33-amino-acid antimicrobial peptide isolated from Phyllomedusa bicolor skin. The ADR was expressed and displayed on the Pichia pastoris KM71 cell surface with the system reported. The displayed recombinant ADR fusion protein was detected by fluorescence microscopy and confocal laser scanning microscopy (CLSM). The antimicrobial activity of the recombinant adenoregulin was detected after proteolytic cleavage of the fusion protein on cell surface. The validity of the Pichia pastoris cell surface display vectors was proved by the displayed ADR.

[A study of incidence and clinical characteristics of adverse drug reactions in hospitalized patients.

PubMed

Esteban Jiménez, Óscar; Navarro Pemán, Cristina; González Rubio, Francisca; Lanuza Giménez, Francisco Javier; Montesa Lou, Cristina

2017-12-22

Adverse drug reactions (ADR) are one of the ten main causes of mortality in the world, as a cause of hospital admissions or prolongation hospitalizations days created an important health and economic impact. This study aimed to detect incidence and characterize ADRs that occurred during hospitalization and associated with admission in Internal Medicine service. Observational and prospective study of intensive RAM monitoring patients admitted in Internal Medicine services in a third level hospital over a twelve months period in 2014. The assessment consisted of a complete and protocol collecting information about the patients and related to suspected ADRs during hospitalization. Statistical analysis was performed using SPSS v.20.0. The study included 253 patients and in 54 (21,34%) ADR were detected, the risk of experiencing an ADR was associated with the age (p=0.012). ADR-related hospitalizations incidence were 7,11%, and fatal ADR incidence were 1,97%. With regard to severity 81,2% were severe. Gastrointestinal disorders represented the most common ADRs followed by metabolism and nutrition disorders and vascular disorders. The drugs most frequently associated with ADRs were cardiovascular agents, antiinfective drugs and central nervous system agents. 72.2% of the patients who suffered ADR had polypharmacy. In our study incidence of adverse drug reactions in hospitalized patients was 21,34%, this data and ADR´s related to admission to hospital or fatal ADR´s are mainly suffered by pluripathology and polymedicated elderly patients with worst renal function values. In these patients a more careful prescription should be made.

Adverse drug reactions amongst adult patients admitted in Lagos State University Teaching Hospital Lagos, Nigeria.

PubMed

Aderemi-Williams, R I; Awodele, O; Boyle, C A

2015-01-01

Adverse drug reaction (ADR) is a global drug therapy problem. It has been rated as one of the top leading causes of morbidity and mortality. In Nigeria, not much is known about ADRs especially with the existing weak post marketing surveillance for monitoring drug use, and its effect on the population. The study is aimed at determining the incidence of ADRs, presentations of ADRs, classes of drugs that frequently cause ADRs and predictors of ADRs in adult medical in-patients in LASUTH. A retrospective study of six hundred and twenty four (624) case notes of all patients admitted to the medical wards in LASUTH between January 1, 2009 and December 31, 2009 was carried out. Information obtained included age, gender, and adverse drug reaction and drug details. The results obtained were analyzed using SPSS version 16 statistical software. Level of significance was set at p ≤ 0.05. A total of 624 case notes consisting of 358 males and 266 females were assessed. The number of patients who experienced adverse drug reactions was 67 (n = 624, 10.7%). The incidence rate of ADRs in LASUTH from the study was 10.7 per 100 patients' population. Most of the ADRs observed were type A reactions (97.8%). Mostly implicated classes of drugs were antidiabetics (26.7%) and NSAIDs (29.3%). The incidence rate of ADRs was 10.7%. ADRs which are predictable and preventable occur in hospitalized patients, such may be prevented or minimized by implementing measures to target specific drugs that are commonly suspected.

Factors Associated with Adenoma Detection Rate and Diagnosis of Polyps and Colorectal Cancer during Colonoscopy in France: Results of a Prospective, Nationwide Survey

PubMed Central

Barret, Maximilien; Boustiere, Christian; Canard, Jean-Marc; Arpurt, Jean-Pierre; Bernardini, David; Bulois, Philippe; Chaussade, Stanislas; Heresbach, Denis; Joly, Isabelle; Lapuelle, Jean; Laugier, René; Lesur, Gilles; Pienkowski, Patrice; Ponchon, Thierry; Pujol, Bertrand; Richard-Molard, Bruno; Robaszkiewicz, Michel; Systchenko, Rémi; Abbas, Fatima; Schott-Pethelaz, Anne-Marie; Cellier, Christophe

2013-01-01

Introduction Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. Methods An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. Results A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). Conclusions For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy. PMID:23874822

Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France: results of a prospective, nationwide survey.

PubMed

Barret, Maximilien; Boustiere, Christian; Canard, Jean-Marc; Arpurt, Jean-Pierre; Bernardini, David; Bulois, Philippe; Chaussade, Stanislas; Heresbach, Denis; Joly, Isabelle; Lapuelle, Jean; Laugier, René; Lesur, Gilles; Pienkowski, Patrice; Ponchon, Thierry; Pujol, Bertrand; Richard-Molard, Bruno; Robaszkiewicz, Michel; Systchenko, Rémi; Abbas, Fatima; Schott-Pethelaz, Anne-Marie; Cellier, Christophe

2013-01-01

Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.

[Direct costs and clinical aspects of adverse drug reactions in patients admitted to a level 3 hospital internal medicine ward].

PubMed

Tribiño, Gabriel; Maldonado, Carlos; Segura, Omar; Díaz, Jorge

2006-03-01

Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.

New Anticoagulant Agents: Incidence of Adverse Drug Reactions and New Signals Thereof.

PubMed

Treceño-Lobato, Carlos; Jiménez-Serranía, María-Isabel; Martínez-García, Raquel; Corzo-Delibes, Francisco; Martín Arias, Luis H

2018-06-04

The aim of this study was to evaluate the adverse drug reaction (ADR) incidence rate and new signals thereof for classic compared with new anticoagulants in real-life ambulatory settings. The authors performed an observational cross-sectional study in two cohorts of surveyed patients treated with vitamin K antagonists (VKAs; acenocoumarol or warfarin) or nonvitamin K antagonist oral anticoagulants (NOACs; apixaban, edoxaban, rivaroxaban, dabigatran etexilate). Descriptive, clinical, and ADRs data were reported and analyzed through a bivariate analysis (odds ratio [OR]) to compare the ADRs incidence rate and an adaptation of Bayesian methodology (false discovery rate [FDR] < 0.05) to detect new signals. A total of 334 patients were surveyed-average international normalized ratio (INR) of 2.6-and 45.4% taking new anticoagulants. Note that 835 ADRs were reported; 2.5 per patient (2.8 in the VKA cohort, 2.1 in the NOAC cohort). The authors obtained higher risk of epistaxis (OR, 2.18; 95% confidence interval [CI], 1.01-4.74) and hematoma (OR, 2.43; 95% CI, 1.39-4.25) with VKAs and lower risk of global bleeding symptoms with NOACs (OR, 0.45; 95% CI, 0.28-0.71). After standardizing the data, a significant risk of diarrhea with VKAs was observed (OR, 3.37; 95% CI, 1.09-10.41). They also detected an intense positive signal regarding the use of VKAs and osteoporosis (FDR < 0.001), specifically acenocoumarol (FDR < 0.002). NOACs presented lower risk of bleeding, especially dabigatran (FDR < 0.031), and of dermatological pathologies with apixaban being the safest (FDR = 0.050). The lower risk of global bleeding and a potential protective effect against osteoporosis in patients treated with NOACs postulate them as safer than VKAs. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Scottish Bowel Screening Programme Colonoscopy Quality - scope for improvement?

PubMed

Quyn, A J; Fraser, C G; Stanners, G; Carey, F A; Rees, C J; Moores, B; Steele, R J

2018-06-04

The delivery of the Scottish Bowel Screening Programme (SBoSP) is rooted in the provision of a high quality, effective and participant-centred service. Safe and effective colonoscopy forms an integral part of the process. Additional accreditation as part of a multi-faceted programme for participating colonoscopists, as in England, does not exist in Scotland. This study aimed to describe the quality of colonoscopy in the SBoSP and compare this to the English national screening standards. Data were collected from the SBoSP between 2007 and 2014. End-points for analysis were caecal intubation, cancer, polyp and adenoma detection, and complications. Overall results were compared with 2012 published English national standards for screening and outcomes from 2006-2009. During the study period 53,332 participants attended for colonoscopy. Colonoscopy completion rate was 95.6% overall. The mean cancer detection rate (CDR) was 7.1%, the polyp detection rate (PDR) 45.7% and the adenoma detection rate (ADR) was 35.5%.The overall complication rate was 0.47%. Colonoscopy quality in the SBoSP has exceeded the standard set for screening colonoscopy in England, despite not adopting a multi-faceted programme for screening colonoscopy. However, the overall ADR in Scotland was 9.1% lower than that in England which has implications for colonoscopy quality and may have an impact on the cancer prevention rates, a key aim of the SBoSP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients

PubMed Central

Rosli, Rosliana; Abd Aziz, Noorizan; Manan, Mohamed Mansor

2016-01-01

Background Spontaneous reporting on adverse drug reactions (ADR) has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups. Methods Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification), category of ADR (according to system organ class) as well as the severity of the ADR. Results In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%). The most common ADRs reported were from the following system organ classes: application site disorders (32.2%), skin and appendages disorders (20.6%), body as a whole general disorders (12.8%) and central and peripheral nervous system disorders (11.2%). Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0%) were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%). Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities. Discussion ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of the ADRs manifesting in skin reactions. The majority of the ADR reports were received from nurses in the public sector, reporting ADRs associated with vaccine administration. The low fatality rate of ADR cases reported could potentially be caused by reporting bias due to the very low reporting percentage from the private healthcare institutions. This study indicates that ADR rates among Malaysian children are higher than in developed countries. Constant ADR reporting and monitoring, especially in respect to paediatric patients, should be undertaken to ensure their safety. PMID:27249414

Utilizing Social Media Data for Pharmacovigilance: A Review

PubMed Central

Sarker, Abeed; Ginn, Rachel; Nikfarjam, Azadeh; O’Connor, Karen; Smith, Karen; Jayaraman, Swetha; Upadhaya, Tejaswi; Gonzalez, Graciela

2015-01-01

Objective Automatic monitoring of Adverse Drug Reactions (ADRs), defined as adverse patient outcomes caused by medications, is a challenging research problem that is currently receiving significant attention from the medical informatics community. In recent years, user-posted data on social media, primarily due to its sheer volume, has become a useful resource for ADR monitoring. Research using social media data has progressed using various data sources and techniques, making it difficult to compare distinct systems and their performances. In this paper, we perform a methodical review to characterize the different approaches to ADR detection/extraction from social media, and their applicability to pharmacovigilance. In addition, we present a potential systematic pathway to ADR monitoring from social media. Methods We identified studies, describing approaches for ADR detection from social media from the Medline, Embase, Scopus and Web of Science databases, and the Google Scholar search engine. Studies that met our inclusion criteria were those that attempted to utilize ADR information posted by users on any publicly available social media platform. We categorized the studies into various dimensions such as primary ADR detection approach, size of data, source(s), availability, evaluation criteria, and so on. Results Twenty-two studies met our inclusion criteria, with fifteen (68.2%) published within the last two years. The survey revealed a clear trend towards the usage of annotated data with eleven of the fifteen (73.3%) studies published in the last two years relying on expert annotations. However, publicly available annotated data is still scarce, and we found only six (27.3%) studies that made the annotations used publicly available, making system performance comparisons difficult. In terms of algorithms, supervised classification techniques to detect posts containing ADR mentions, and lexicon-based approaches for extraction of ADR mentions from texts have been the most popular. Conclusion Our review suggests that interest in the utilization of the vast amounts of available social media data for ADR monitoring is increasing with time. In terms of sources, both health-related and general social media data have been used for ADR detection— while health-related sources tend to contain higher proportions of relevant data, the volume of data from general social media websites is significantly higher. There is still very limited publicly available annotated data available, and, as indicated by the promising results obtained by recent supervised learning approaches, there is a strong need to make such data available to the research community. PMID:25720841

Useful Interplay Between Spontaneous ADR Reports and Electronic Healthcare Records in Signal Detection.

PubMed

Pacurariu, Alexandra C; Straus, Sabine M; Trifirò, Gianluca; Schuemie, Martijn J; Gini, Rosa; Herings, Ron; Mazzaglia, Giampiero; Picelli, Gino; Scotti, Lorenza; Pedersen, Lars; Arlett, Peter; van der Lei, Johan; Sturkenboom, Miriam C; Coloma, Preciosa M

2015-12-01

Spontaneous reporting systems (SRSs) remain the cornerstone of post-marketing drug safety surveillance despite their well-known limitations. Judicious use of other available data sources is essential to enable better detection, strengthening and validation of signals. In this study, we investigated the potential of electronic healthcare records (EHRs) to be used alongside an SRS as an independent system, with the aim of improving signal detection. A signal detection strategy, focused on a limited set of adverse events deemed important in pharmacovigilance, was performed retrospectively in two data sources-(1) the Exploring and Understanding Adverse Drug Reactions (EU-ADR) database network and (2) the EudraVigilance database-using data between 2000 and 2010. Five events were considered for analysis: (1) acute myocardial infarction (AMI); (2) bullous eruption; (3) hip fracture; (4) acute pancreatitis; and (5) upper gastrointestinal bleeding (UGIB). Potential signals identified in each system were verified using the current published literature. The complementarity of the two systems to detect signals was expressed as the percentage of the unilaterally identified signals out of the total number of confirmed signals. As a proxy for the associated costs, the number of signals that needed to be reviewed to detect one true signal (number needed to detect [NND]) was calculated. The relationship between the background frequency of the events and the capability of each system to detect signals was also investigated. The contribution of each system to signal detection appeared to be correlated with the background incidence of the events, being directly proportional to the incidence in EU-ADR and inversely proportional in EudraVigilance. EudraVigilance was particularly valuable in identifying bullous eruption and acute pancreatitis (71 and 42 % of signals were correctly identified from the total pool of known associations, respectively), while EU-ADR was most useful in identifying hip fractures (60 %). Both systems contributed reasonably well to identification of signals related to UGIB (45 % in EudraVigilance, 40 % in EU-ADR) but only fairly for signals related to AMI (25 % in EU-ADR, 20 % in EudraVigilance). The costs associated with detection of signals were variable across events; however, it was often more costly to detect safety signals in EU-ADR than in EudraVigilance (median NNDs: 7 versus 5). An EHR-based system may have additional value for signal detection, alongside already established systems, especially in the presence of adverse events with a high background incidence. While the SRS appeared to be more cost effective overall, for some events the costs associated with signal detection in the EHR might be justifiable.

Improving adverse drug reaction reporting in hospitals: results of the French Pharmacovigilance in Midi-Pyrénées region (PharmacoMIP) network 2-year pilot study.

PubMed

Gony, Mireille; Badie, Kattalin; Sommet, Agnès; Jacquot, Julien; Baudrin, Dominique; Gauthier, Pierre; Montastruc, Jean Louis; Bagheri, Haleh

2010-05-01

Spontaneous reporting of adverse drug reactions (ADRs) is fundamental to drug safety surveillance (pharmacovigilance); however, substantial under-reporting exists and is the main limitation of the system. Several factors could favour under-reporting. The aim of this pilot study was to assess the effect of regular visits of a Clinical Research Assistant (CRA) on the improvement of ADR reporting in non-university hospitals. We set up an ADR report collecting system that involved regular visits by a CRA to non-university hospitals, which was similar to a system that already existed in university hospitals in Toulouse, France. Two areas in our region were chosen: Haute Garonne and Gers. We compared firstly the reporting rate (number of reports/number of beds) of total ADRs (i.e. spontaneously reported ADRs plus solicited ADRs collected by the CRA) and secondly, the percentage of serious ADRs reported by non-university hospitals in these two areas, in 2005 (the year prior to CRA visits) and after the start of CRA visits (2006 until the end of December 2008). We also compared the reporting rate of total ADRs in Haute Garonne and Gers non-university hospitals with those reported during the same period with a control group (the Ariège area, which has a similar number of beds to Gers and that was not visited by the CRA). The characteristics of ADRs collected by the CRA were also described. A total of 687 reports were collected by the CRA: 40% were classified as serious, including two deaths. The number of ADRs and the reporting rate increased significantly between 2005 and 2008 in non-university hospitals of Haute-Garonne and Gers, but not in Ariège. In Gers, the reporting rate was 3% in 2005 and 25% in 2008. In Haute-Garonne, the reporting rate was 11% in 2005 and 40% in 2008. The difference between the number of spontaneous and solicited reports also increased. This study shows that regular visits by a CRA increases the number of ADRs collected by a Regional Pharmacovigilance Centre. Another interesting consequence was the rise in spontaneous reporting by healthcare professionals following the set-up of this system. Further assessment of this procedure is necessary for the long-term evaluation of its effectiveness.

The mTORC2/Akt/NFκB Pathway-Mediated Activation of TRPC6 Participates in Adriamycin-Induced Podocyte Apoptosis.

PubMed

Zhang, Hai-Tao; Wang, Wei-Wei; Ren, Li-Hong; Zhao, Xia-Xia; Wang, Zhi-Hui; Zhuang, De-Li; Bai, Yun-Nuo

2016-01-01

Although increased expression and gain function of transient receptor potential cation channel 6 (TRPC6) has been associated with the pathogenesis of some proteinuric glomerular diseases, it remains elusive how TRPC6 participates in the process of podocyte damage. The potential signaling responsible for TRPC6 activation was investigated using immunoblot assays in an in vitro podocyte injury model induced by Adriamycin (ADR). Podocyte apoptosis was measured using FITC-conjugated Annexin V and Propidium Iodide staining. The channel activity of TRPC6 was assessed using the Ca2+ influx assay. Increase of TRPC6 expression was detected in ADR-treated podocytes, and TRPC6 knockdown significantly decreased ADR-induced podocytes apoptosis. Following ADR treatment, phospho-mTORSer2481 and phospho-AktSer473 was significantly increased in a time-dependent manner, whereas phospho-mTORSer2448 and phospho-p70S6KThr389 showed no change. ADR-induced apoptosis was prevented by ku0063794 (a dual mTOR complexes inhibitor), not by rapamycin (a specific mTORC1 inhibitor). Furthermore, nuclear translocation of NFκB/p65 was detected in ADR-treated podocytes, which was prevented by an Akt inhibitor triciribine. Of note, NFκB inhibitor PDTC prevented ADR-induced increase of TRPC6, and decreased ADR-induced apoptosis. We found that Akt activation and NFκB nuclear translocation was significantly inhibited by knockdown of mTORC2 protein Rictor, not by mTORC1 protein Raptor. In comparison with control, the Ca2+ influx was significantly increased in ADR-treated podocytes, which was remarkably prevented by TRPC6 knockdown. ADR-induced increase of TRPC6 channel activity was dramatically prevented by ku0063794, but not by rapamycin. Additionally, knockdown of Rictor, not Raptor, prevented ADR-induced increase of the Ca2+ influx. Moreover, the application of NFκB inhibitor PDTC also prevented the Ca2+ influx in ADR-treated podocytes. Our findings revealed that the mTORC2/Akt/NFκB pathway-mediated activation of TRPC6 participates in ADR-induced podocyte apoptosis. © 2016 The Author(s) Published by S. Karger AG, Basel.

Comparison of expression of monomeric and multimeric adenoregulin genes in Escherichia coli and Pichia pastorias.

PubMed

Zhou, Yuxun; Cao, Wei; Wang, Jinzhi; Ma, Yushu; Wei, Dongzhi

2005-05-01

Adenoregulin is a 33 amino acid antibiotic peptide who belongs to dermaseptin family which is the first vertebrate family to show lethal effects against filamentous fungi, as well as a broad spectrum of pathogenic microorganisms. Synthetic adenoregulin gene was cloned in 2, 4 and 6 tandem repeats and subcloned in pET32a and pET22b vectors. Recombinant plasmids were transformed into E. coli BL21(DE3), Fusion proteins of Trx-ADR1, Trx-ADR2 and Trx-ADR4 could be expressed after the hosts were induced by IPTG, but the expression level decreased dramatically with the number of tandem repeats increased. ADR1, ADR4 and ADR6 could not be expressed by E. coli without carrier proteins. But for Pichia pastoris GS115, ADR1 and ADR6 in the fermentation broth of the hosts could be detected by ELISA, and the bactericidal activities could also be observed.

A web-based quantitative signal detection system on adverse drug reaction in China.

PubMed

Li, Chanjuan; Xia, Jielai; Deng, Jianxiong; Chen, Wenge; Wang, Suzhen; Jiang, Jing; Chen, Guanquan

2009-07-01

To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China.

Analysis of pharmacology data and the prediction of adverse drug reactions and off-target effects from chemical structure.

PubMed

Bender, Andreas; Scheiber, Josef; Glick, Meir; Davies, John W; Azzaoui, Kamal; Hamon, Jacques; Urban, Laszlo; Whitebread, Steven; Jenkins, Jeremy L

2007-06-01

Preclinical Safety Pharmacology (PSP) attempts to anticipate adverse drug reactions (ADRs) during early phases of drug discovery by testing compounds in simple, in vitro binding assays (that is, preclinical profiling). The selection of PSP targets is based largely on circumstantial evidence of their contribution to known clinical ADRs, inferred from findings in clinical trials, animal experiments, and molecular studies going back more than forty years. In this work we explore PSP chemical space and its relevance for the prediction of adverse drug reactions. Firstly, in silico (computational) Bayesian models for 70 PSP-related targets were built, which are able to detect 93% of the ligands binding at IC(50) < or = 10 microM at an overall correct classification rate of about 94%. Secondly, employing the World Drug Index (WDI), a model for adverse drug reactions was built directly based on normalized side-effect annotations in the WDI, which does not require any underlying functional knowledge. This is, to our knowledge, the first attempt to predict adverse drug reactions across hundreds of categories from chemical structure alone. On average 90% of the adverse drug reactions observed with known, clinically used compounds were detected, an overall correct classification rate of 92%. Drugs withdrawn from the market (Rapacuronium, Suprofen) were tested in the model and their predicted ADRs align well with known ADRs. The analysis was repeated for acetylsalicylic acid and Benperidol which are still on the market. Importantly, features of the models are interpretable and back-projectable to chemical structure, raising the possibility of rationally engineering out adverse effects. By combining PSP and ADR models new hypotheses linking targets and adverse effects can be proposed and examples for the opioid mu and the muscarinic M2 receptors, as well as for cyclooxygenase-1 are presented. It is hoped that the generation of predictive models for adverse drug reactions is able to help support early SAR to accelerate drug discovery and decrease late stage attrition in drug discovery projects. In addition, models such as the ones presented here can be used for compound profiling in all development stages.

Adverse reactions of Methylphenidate in children with attention deficit-hyperactivity disorder: Report from a referral center

PubMed Central

Khajehpiri, Zahra; Mahmoudi-Gharaei, Javad; Faghihi, Toktam; Karimzadeh, Iman; Khalili, Hossein; Mohammadi, Mostafa

2014-01-01

Objective: The aim of the current study was to determine various aspects of methylphenidate adverse reactions in children with attention deficit-hyperactivity disorder (ADHD) in Iran. Methods: During the 6 months period, all children under methylphenidate treatment alone or along with other agents attending a university-affiliated psychology clinic were screened regarding all subjective and objective adverse drug reactions (ADRs) of methylphenidate. Causality and seriousness of detected ADRs were assessed by relevant World Health Organization definitions. The Schumock and Thornton questionnaire was used to determine preventability of ADRs. Findings: Seventy-one patients including 25 girls and 46 boys with ADHD under methylphenidate treatment were enrolled within the study period. All (100%) ADHD children under methylphenidate treatment developed at least one ADR. Anorexia (74.3%), irritability (57.1%), and insomnia (47.2%) were the most frequent methylphenidate-related adverse reactions. Except for one, all other detected ADRs were determined to be mild. In addition, no ADR was considered to be preventable and serious. Conclusion: Our data suggested that although methylphenidate related adverse reactions were common in children with ADHD, but they were mainly mild and nonserious. PMID:25535621

Gaze patterns hold key to unlocking successful search strategies and increasing polyp detection rate in colonoscopy.

PubMed

Lami, Mariam; Singh, Harsimrat; Dilley, James H; Ashraf, Hajra; Edmondon, Matthew; Orihuela-Espina, Felipe; Hoare, Jonathan; Darzi, Ara; Sodergren, Mikael H

2018-02-07

The adenoma detection rate (ADR) is an important quality indicator in colonoscopy. The aim of this study was to evaluate the changes in visual gaze patterns (VGPs) with increasing polyp detection rate (PDR), a surrogate marker of ADR. 18 endoscopists participated in the study. VGPs were measured using eye-tracking technology during the withdrawal phase of colonoscopy. VGPs were characterized using two analyses - screen and anatomy. Eye-tracking parameters were used to characterize performance, which was further substantiated using hidden Markov model (HMM) analysis. Subjects with higher PDRs spent more time viewing the outer ring of the 3 × 3 grid for both analyses (screen-based: r = 0.56, P  = 0.02; anatomy: r = 0.62, P  < 0.01). Fixation distribution to the "bottom U" of the screen in screen-based analysis was positively correlated with PDR (r = 0.62, P  = 0.01). HMM demarcated the VGPs into three PDR groups. This study defined distinct VGPs that are associated with expert behavior. These data may allow introduction of visual gaze training within structured training programs, and have implications for adoption in higher-level assessment. © Georg Thieme Verlag KG Stuttgart · New York.

Do Geriatric Conditions Increase Risk of Adverse Drug Reactions in Ambulatory Elders? Results From the VA GEM Drug Study

PubMed Central

Hanlon, Joseph T.; Sloane, Richard J.; Boscardin, W. John; Schmader, Kenneth E.

2011-01-01

Background. Many clinicians prescribe cautiously to older adults with common geriatric conditions for fear of causing adverse drug reactions (ADRs). However, little is known about the association between these conditions and risk of ADRs. Methods. Using data from the VA Geriatric Evaluation and Management Drug Study, we determined any, preventable, and serious ADRs in 808 elders for 12 months after hospital discharge using a validated process involving patient self-report and chart review adjudicated by two health care professionals. Eight common geriatric conditions (activities of daily living, dementia, incontinence, falls, difficulty ambulating, malnourishment, depression, and prolonged bed rest) were evaluated at study baseline through self-report and structured assessments. We used Poisson regression to model the relationship between these geriatric conditions and ADRs. Results. Participants had a mean of 2.9 ± 1.2 geriatric conditions. Over the 12-month follow-up period, 497 ADRs occurred in 269 participants, including 187 ADRs considered preventable and 127 considered severe. On multivariable analyses, participants with dependency in one or more activities of daily living were less likely to suffer ADRs than those who were fully independent (incidence rate ratio: 0.78, 95% confidence interval = 0.62–1.00). None of the other seven geriatric conditions assessed were associated with ADR risk. Results were similar for preventable and serious ADRs, although participants with a history of falls were more likely to develop serious ADRs (incidence rate ratio: 1.49, 95% confidence interval = 1.00–2.21). Conclusions. Many geriatric conditions were not associated with risk of ADRs. Although it is prudent to prescribe judiciously in patients with these conditions, excessive caution may not be warranted. PMID:21321003

Comparison of Colonoscopy Quality Measures Across Various Practice Settings and the Impact of Performance Scorecards.

PubMed

Inra, Jennifer A; Nayor, Jennifer; Rosenblatt, Margery; Mutinga, Muthoka; Reddy, Sarathchandra I; Syngal, Sapna; Kastrinos, Fay

2017-04-01

Quality performance measures for screening colonoscopy vary among endoscopists. The impact of practice setting is unknown. We aimed to (1) compare screening colonoscopy performance measures among three different US practice settings; (2) evaluate factors associated with adenoma detection; and (3) assess a scorecard intervention on performance metrics. This multi-center prospective study compared patient, endoscopist, and colonoscopy characteristics performed at a tertiary care hospital (TCH), community-based hospital (CBH), and private practice group (PPG). Withdrawal times (WT), cecal intubation, and adenoma detection rates (ADR) were compared by site at baseline and 12 weeks following scorecard distribution. Generalized linear mixed models identified factors associated with adenoma detection. Twenty-eight endoscopists performed colonoscopies on 1987 asymptomatic, average-risk individuals ≥50 years. Endoscopist and patient characteristics were similar across sites. The PPG screened more men (TCH: 42.8%, CBH: 45.0%, PPG: 54.2%; p < 0.0001). Preparation quality varied with good/excellent results in 70.6, 88.3, and 92% of TCH, CBH, and PPG cases, respectively (p < 0.0001). Male ADRs, cecal intubation, and WT exceeded recommended benchmarks despite variable results at each site; female ADRs were <15% at the PPG which screened the fewest females. Performance remained unchanged following scorecard distribution. Adenoma detection was associated with increasing patient age, male gender, WT, adequate preparation, but not practice setting. Each practice performed high-quality screening colonoscopy. Scorecards did not improve performance metrics. Preparation quality varies among practice settings and can be modified to improve adenoma detection.

[Do pediatricians identify adverse drug reactions even when they do not report them?

PubMed

Morales-Ríos, Olga; Jasso-Gutiérrez, Luis; Garduño-Espinosa, Juan; Olivar-López, Víctor; Muñoz-Hernández, Onofre

Spontaneous notification depends on the ability of pediatricians to identify adverse drug reactions (ADRs) along with their habit of reporting these incidents. During the years 2008 and 2009, the frequency of reports of ADRs to the Electronic Program of Pharmacovigilance (SISFAR) in the Hospital Infantil of Mexico Federico Gomez (HIMFG) was low (0.44% and 0.20%, respectively). Because of the above, the ability of pediatricians from the Emergency Department (ED) to identify ADRs using the clinical chart review was evaluated in 2010 in this study. A descriptive, observational, cross-sectional retrospective study was conducted in the ED from March 1 to August 31. ADRs were classified and quantified as "ADRs identified by pediatricians" when there was evidence in the clinical chart that pediatricians associated a clinical sign, symptom and laboratory value with an ADR. The numbers of notifications reported in SISFAR were quantified. Descriptive analysis was done using SPSS v.18. Considering patients who were admitted to the ED, the frequency of ADRs was 21.8%. The frequency of ADRs identified by physicians in clinical charts was 86%. The pharmacist detected 14% of ADRs. The frequency of ADRs reported by physicians was 6.1%. Although identification of ADRs in the clinical charts by pediatricians was high, it is possible that some ADRs were undetected. Because underreporting was very high, it is necessary to take actions to improve the reporting process. Copyright © 2015. Publicado por Masson Doyma México S.A.

Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis.

PubMed

Patel, Tejas K; Patel, Parvati B

2018-06-01

The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADR Ad ), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADR Ad . We identified prospective ADR Ad -related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADR Ad using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADR Ad and causative drugs. Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADR Ad was 0.20% (95% CI: 0.13-0.27%; I 2  = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADR Ad prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADR Ad in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADR Ad cases. Warfarin, aspirin, renin-angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADR Ad . ADR Ad is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADR Ad cases.

The Value of Audio Devices in the Endoscopy Room (VADER) study: a randomised controlled trial.

PubMed

Ardalan, Zaid Sm; Vasudevan, Abhinav; Hew, Simon; Schulberg, Julien; Lontos, Steve

2015-12-14

To evaluate the effect of Star Wars music (SWM) compared with endoscopist-selected popular music (PM) on quality outcomes in colonoscopy. A single-centre, prospective, randomised controlled trial conducted in an endoscopy suite within a quaternary-centre gastroenterology unit, Melbourne, Australia. The primary outcome measures were procedure time, polyp detection rate (PDR) and adenoma detection rate (ADR). The secondary outcome measure was adenomas per colonoscopy (APC). 103 colonoscopies were analysed: 58 in the SWM group and 45 in the PM group. Bowel preparation was assessed as good or excellent in 57% of the SWM group compared with 69% of the PM group (P < 0.01). The PDR was significantly higher in the SWM group than in the PM group (60% v 35%; P = 0.006). Similarly, the ADR was significantly higher in the SWM group than in the PM group (48% v 27%; P = 0.01). The APC in the SWM group was 84% compared with 35% in the PM group (P = 0.01). SWM compared with PM improves key quality outcomes in colonoscopy, despite poorer bowel preparation.

Cost-effectiveness of one-time genetic testing to minimize lifetime adverse drug reactions.

PubMed

Alagoz, O; Durham, D; Kasirajan, K

2016-04-01

We evaluated the cost-effectiveness of one-time pharmacogenomic testing for preventing adverse drug reactions (ADRs) over a patient's lifetime. We developed a Markov-based Monte Carlo microsimulation model to represent the ADR events in the lifetime of each patient. The base-case considered a 40-year-old patient. We measured health outcomes in life years (LYs) and quality-adjusted LYs (QALYs) and estimated costs using 2013 US$. In the base-case, one-time genetic testing had an incremental cost-effectiveness ratio (ICER) of $43,165 (95% confidence interval (CI) is ($42,769,$43,561)) per additional LY and $53,680 per additional QALY (95% CI is ($53,182,$54,179)), hence under the base-case one-time genetic testing is cost-effective. The ICER values were most sensitive to the average probability of death due to ADR, reduction in ADR rate due to genetic testing, mean ADR rate and cost of genetic testing.

A pilot study to evaluate a community pharmacy-based monitoring system to identify adverse drug reactions associated with paediatric medicines use.

PubMed

Tobaiqy, Mansour; Stewart, Derek; Helms, Peter J; Bond, Christine; Lee, Amanda Jane; Bateman, Nick; McCaig, Dorothy; McLay, James

2010-06-01

Current pharmacovigilance systems are limited by spontaneous reporting of adverse drug reactions (ADRs), lack of a denominator, and lower than expected reporting rates. The aim of our study was to undertake a formal pilot evaluation of a community pharmacy-led ADR monitoring system. The setting was community pharmacies in five Health Boards areas of Scotland. Subjects were parents, guardians, or children presenting prescriptions for children 16 years and under prescribed serotonin specific reuptake inhibitors (SSRI), anticonvulsants, or medicines for the treatment of attention deficit hyperactivity disorder (ADHD). All pharmacies (n = 827) were invited to participate. Over a 3-month period they were asked to identify prescriptions for targeted medicines and give out an ADR questionnaire. Questionnaire content included child demography, duration of medicine use, indication, perceived ADRs, and their description and severity. The study was approved by the North of Scotland Research Ethics Committee. Seventy-two community pharmacists (8.7%) agreed to take part. Two hundred and twenty-nine questionnaires were distributed and 55 (24%) completed and returned by parents. Forty-one questionnaires related to ADHD medications, 13 to anticonvulsants, and 1 to an SSRI. Thirty questionnaires reported 44 possible ADRs, 19 of which were related to methylphenidate. The proposed ADR monitoring system identified expected ADRs thus demonstrating face and content validity for our approach. However the process was limited by low community pharmacist participation rates and low questionnaire return rates.

Pharmacist's knowledge, practice and attitudes toward pharmacovigilance and adverse drug reactions reporting process.

PubMed

Suyagh, Maysa; Farah, Doaa; Abu Farha, Rana

2015-04-01

Adverse drug reactions (ADRs) are a major cause of drug related morbidity and mortality. Pharmacovigilance is the science that plays an essential role in the reduction of ADRs, thus the evolution and growth of this science are critical for effective and safe clinical practice. This study is considered the first study in the region to evaluate pharmacist's knowledge, practice and attitudes toward ADRs reporting after establishing the national ADRs reporting center in Jordan. A cross sectional study was used to evaluate pharmacist knowledge and attitude toward ADRs reporting. A structured validated questionnaire was developed for this purpose and a total of 208 pharmacists were recruited to participate in this study. The majority of pharmacists have insufficient awareness and lack of knowledge about pharmacovigilance and ADRs reporting. Also the rate of reporting of ADRs was extremely poor. Several factors were found to discourage pharmacists from reporting ADRs, which include inadequate information available from the patient, unavailability of pharmacist ADRs form when needed, unawareness of the existence of the national ADRs reporting system. Also pharmacists think that ADRs are unimportant or they did not know how to report them. The results of this study suggest that pharmacists have insufficient knowledge about the concept of pharmacovigilance and spontaneous ADRs reporting. On the other hand, pharmacists had positive attitudes toward pharmacovigilance, despite their little experience with ADRs reporting. Educational programs are needed to increase pharmacist's role in the reporting process, and thus to have a positive impact on the overall patient caring process.

Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs.

PubMed

Liu, Mei; Wu, Yonghui; Chen, Yukun; Sun, Jingchun; Zhao, Zhongming; Chen, Xue-wen; Matheny, Michael Edwin; Xu, Hua

2012-06-01

Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases.

Characterization in vitro and in vivo of progressively adriamycin-resistant B16-BL6 mouse melanoma cells.

PubMed

Ganapathi, R; Grabowski, D; Schmidt, H; Bell, D; Melia, M

1987-07-01

Adriamycin (ADR)-resistant sublines of B16-BL6 mouse melanoma selected by exposure to increasing concentrations of ADR were characterized in vitro for growth properties and in vivo for tumorigenicity and pulmonary metastases. The progressively resistant sublines adapted to grow in the presence of 0.025, 0.05, 0.1, and 0.25 microgram/ml ADR in monolayer culture were found to be 5-, 10-, 20-, and 40-fold ADR-resistant, respectively, compared to the parental sensitive cells, using a soft-agar colony assay and continuous ADR treatment for 7 days. The doubling time in monolayer culture of the parent sensitive and progressively ADR-resistant sublines of B16-BL6 melanoma cells was approximately 16-18 h. Although the colony-forming efficiency in soft agar of parental sensitive cells was only 0.5-4%, the 5-, 10-, 20-, and 40-fold ADR-resistant sublines had colony-forming efficiencies of 15, 20, 30, and 77%, respectively. Tumorigenicity in C57BL/6 mice of progressively ADR-resistant sublines was similar to parental sensitive cells following s.c. and i.p. implantation of 10(5)-10(6) tumor cells. Experimental pulmonary metastases were significantly lower in ADR-resistant sublines with progressive resistance. Additionally, unlike the parental sensitive and 5-fold ADR-resistant B16-BL6 cells, the 10-, 20-, and 40-fold ADR-resistant sublines were spontaneously nonmetastatic. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunochemical detection of P-glycoprotein revealed the presence of a Mr 170,000 plasma membrane glycoprotein in the 40-fold ADR-resistant subline and its counterpart maintained for 1 year in ADR-free medium. Results from this study suggest that progressively ADR-resistant B16-BL6 mouse melanoma cells selected in vitro demonstrate a marked increase in colony formation in soft agar and a decrease in the ability to produce pulmonary metastases, without alterations in tumorigenicity.

Statistical Signal Process in R Language in the Pharmacovigilance Programme of India.

PubMed

Kumar, Aman; Ahuja, Jitin; Shrivastava, Tarani Prakash; Kumar, Vipin; Kalaiselvan, Vivekanandan

2018-05-01

The Ministry of Health & Family Welfare, Government of India, initiated the Pharmacovigilance Programme of India (PvPI) in July 2010. The purpose of the PvPI is to collect data on adverse reactions due to medications, analyze it, and use the reference to recommend informed regulatory intervention, besides communicating the risk to health care professionals and the public. The goal of the present study was to apply statistical tools to find the relationship between drugs and ADRs for signal detection by R programming. Four statistical parameters were proposed for quantitative signal detection. These 4 parameters are IC 025 , PRR and PRR lb , chi-square, and N 11 ; we calculated these 4 values using R programming. We analyzed 78,983 drug-ADR combinations, and the total count of drug-ADR combination was 4,20,060. During the calculation of the statistical parameter, we use 3 variables: (1) N 11 (number of counts), (2) N 1. (Drug margin), and (3) N .1 (ADR margin). The structure and calculation of these 4 statistical parameters in R language are easily understandable. On the basis of the IC value (IC value >0), out of the 78,983 drug-ADR combination (drug-ADR combination), we found the 8,667 combinations to be significantly associated. The calculation of statistical parameters in R language is time saving and allows to easily identify new signals in the Indian ICSR (Individual Case Safety Reports) database.

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir (I): a drug use investigation.

PubMed

Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2014-11-01

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. We conducted a drug use investigation of peramivir from October 2010 to February 2012 and evaluated its safety and effectiveness under routine clinical settings. We collected data of 1309 patients from 189 facilities across Japan and examined safety in 1174 patients and effectiveness in 1158 patients. In total, 143 adverse events were observed with an incidence rate of 7.33% (86/1174). Of these, 78 events were adverse drug reactions (ADRs) with an incidence rate of 4.34% (51/1174). The most frequently reported ADRs were diarrhea, vomiting, and nausea, with incidence rates of 1.87% (22/1174), 0.85% (10/1174), and 0.68% (8/1174), respectively. Moreover, no ADR was reported as serious. ADR onset was within 3 days after the start of peramivir administration in 91.0% (71 events) of the 78 ADRs, and ADRs were resolved or improved within 7 days after onset in 96.2% (75 events) of the 78 ADRs. Neither patient characteristics nor treatment factors appeared to significantly affect drug safety. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. The present study demonstrates the safety and effectiveness of peramivir under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Mesenchymal stem cells protective effect in adriamycin model of nephropathy.

PubMed

Magnasco, Alberto; Corselli, Mirko; Bertelli, Roberta; Ibatici, Adalberto; Peresi, Monica; Gaggero, Gabriele; Cappiello, Valentina; Chiavarina, Barbara; Mattioli, Girolamo; Gusmano, Rosanna; Ravetti, Jean Louis; Frassoni, Francesco; Ghiggeri, Gian Marco

2008-01-01

Mesenchymal stem cells (MSCs) may be of value in regeneration of renal tissue after damage; however, lack of biological knowledge and variability of results in animal models limit their utilization. We studied the effects of MSCs on podocytes in vitro and in vivo utilizing adriamycin (ADR) as a model of renal toxicity. The in vivo experimental approach was carried out in male Sprague-Dawley rats (overall 60 animals) treated with different ADR schemes to induce acute and chronic nephrosis. MSCs were given a) concomitantly to ADR in tail vein or b) in aorta and c) in tail vein 60 days after ADR. Homing was assessed with PKH26-MSCs. MSCs rescued podocytes from apoptosis induced by ADR in vitro. The maximal effect (80% rescue) was obtained with MSCs/podocytes coculture ratio of 1:1 for 72 h. All rats treated with ADR developed nephrosis. MSCs did not modify the clinical parameters (i.e., proteinuria, serum creatinine, lipids) but protected the kidney from severe glomerulosclerosis when given concomitantly to ADR. Rats given MSCs 60 days after ADR developed the same severe renal damage. Only a few MSCs were found in renal tubule-interstitial areas 1-24 h after injection and no MSCs were detected in glomeruli. MSCs reduced apoptosis of podocytes treated with ADR in vitro. Early and repeated MSCs infusion blunted glomerular damage in chronic ADR-induced nephropathy. MSCs did not modify proteinuria and progression to renal failure, which implies lack of regenerative potential in this model.

Ocular toxoplasmosis: adverse reactions to treatment in a Brazilian cohort.

PubMed

Guaraldo, Lusiele; Villar, Bianca Balzano de la Fuente; Durão, Nicolle Marins Gomes; Louro, Virgínia Clare; Quintana, Marcel de Souza Borges; Curi, André Luiz Land; Neves, Elizabeth Souza

2018-05-19

The purpose of this study was to estimate the frequency and describe the adverse drug reactions (ADRs) associated with the classic treatment of ocular toxoplasmosis (OT), namely sulfadiazine, pyrimethamine, corticosteroids and folinic acid. We performed a descriptive study of a prospective cohort of patients with OT treated with the classic therapy. Data were collected during medical consultations and treatment. Of the 147 patients studied, 85% developed one or more ADR. Women presented more ADRs than men (95% vs 77%). Of the total reactions (n=394), 82% were mild, but we found one life-threatening event (Stevens-Johnson syndrome). The most frequent types (71%) of ADRs were gastrointestinal, skin and neurological or psychiatric. The majority of ADRs (90.3%) occurred before the second week of treatment. A third of the patients were treated for the ADR and 10% dropped out of OT treatment. Most (70%) of the ADRs were characterized as being probably caused by the drugs and may be associated with prednisone, sulfadiazine and sulfadiazine/prednisone. Six percent of ADRs were not previously described, such as taste alteration, constipation/bloating, dyspnoea, sweating and somnolence. Our results suggest a high rate of ADRs to OT classic treatment, which requires careful follow-up in order to identify and treat ADRs early.

The Patient's Voice in Pharmacovigilance: Pragmatic Approaches to Building a Patient-Centric Drug Safety Organization.

PubMed

Smith, Meredith Y; Benattia, Isma

2016-09-01

Patient-centeredness has become an acknowledged hallmark of not only high-quality health care but also high-quality drug development. Biopharmaceutical companies are actively seeking to be more patient-centric in drug research and development by involving patients in identifying target disease conditions, participating in the design of, and recruitment for, clinical trials, and disseminating study results. Drug safety departments within the biopharmaceutical industry are at a similar inflection point. Rising rates of per capita prescription drug use underscore the importance of having robust pharmacovigilance systems in place to detect and assess adverse drug reactions (ADRs). At the same time, the practice of pharmacovigilance is being transformed by a host of recent regulatory guidances and related initiatives which emphasize the importance of the patient's perspective in drug safety. Collectively, these initiatives impact the full range of activities that fall within the remit of pharmacovigilance, including ADR reporting, signal detection and evaluation, risk management, medication error assessment, benefit-risk assessment and risk communication. Examples include the fact that manufacturing authorization holders are now expected to monitor all digital sources under their control for potential reports of ADRs, and the emergence of new methods for collecting, analysing and reporting patient-generated ADR reports for signal detection and evaluation purposes. A drug safety department's ability to transition successfully into a more patient-centric organization will depend on three defining attributes: (1) a patient-centered culture; (2) deployment of a framework to guide patient engagement activities; and (3) demonstrated proficiency in patient-centered competencies, including patient engagement, risk communication and patient preference assessment. Whether, and to what extent, drug safety departments embrace the new patient-centric imperative, and the methods and processes they implement to achieve this end effectively and efficiently, promise to become distinguishing factors in the highly competitive biopharmaceutical industry landscape.

Deep learning for pharmacovigilance: recurrent neural network architectures for labeling adverse drug reactions in Twitter posts.

PubMed

Cocos, Anne; Fiks, Alexander G; Masino, Aaron J

2017-07-01

Social media is an important pharmacovigilance data source for adverse drug reaction (ADR) identification. Human review of social media data is infeasible due to data quantity, thus natural language processing techniques are necessary. Social media includes informal vocabulary and irregular grammar, which challenge natural language processing methods. Our objective is to develop a scalable, deep-learning approach that exceeds state-of-the-art ADR detection performance in social media. We developed a recurrent neural network (RNN) model that labels words in an input sequence with ADR membership tags. The only input features are word-embedding vectors, which can be formed through task-independent pretraining or during ADR detection training. Our best-performing RNN model used pretrained word embeddings created from a large, non-domain-specific Twitter dataset. It achieved an approximate match F-measure of 0.755 for ADR identification on the dataset, compared to 0.631 for a baseline lexicon system and 0.65 for the state-of-the-art conditional random field model. Feature analysis indicated that semantic information in pretrained word embeddings boosted sensitivity and, combined with contextual awareness captured in the RNN, precision. Our model required no task-specific feature engineering, suggesting generalizability to additional sequence-labeling tasks. Learning curve analysis showed that our model reached optimal performance with fewer training examples than the other models. ADR detection performance in social media is significantly improved by using a contextually aware model and word embeddings formed from large, unlabeled datasets. The approach reduces manual data-labeling requirements and is scalable to large social media datasets. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Does patient reporting lead to earlier detection of drug safety signals? A retrospective comparison of time to reporting between patients and healthcare professionals in a global database.

PubMed

Rolfes, Leàn; van Hunsel, Florence; Caster, Ola; Taavola, Henric; Taxis, Katja; van Puijenbroek, Eugène

2018-03-09

To explore if there is a difference between patients and healthcare professionals (HCPs) in time to reporting drug-adverse drug reaction (ADR) associations that led to drug safety signals. This was a retrospective comparison of time to reporting selected drug-ADR associations which led to drug safety signals between patients and HCPs. ADR reports were selected from the World Health Organization Global database of individual case safety reports, VigiBase. Reports were selected based on drug-ADR associations of actual drug safety signals. Primary outcome was the difference in time to reporting between patients and HCPs. The date of the first report for each individual signal was used as time zero. The difference in time between the date of the reports and time zero was calculated. Statistical differences in timing were analysed on the corresponding survival curves using a Mann-Whitney U test. In total, 2822 reports were included, of which 52.7% were patient reports, with a median of 25% for all included signals. For all signals, median time to signal detection was 10.4 years. Overall, HCPs reported earlier than patients: median 7.0 vs. 8.3 years (P < 0.001). Patients contributed a large proportion of reports on drug-ADR pairs that eventually became signals. HCPs reported 1.3 year earlier than patients. These findings strengthen the evidence on the value of patient reporting in signal detection and highlight an opportunity to encourage patients to report suspected ADRs even earlier in the future. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics.

PubMed

Elzagallaai, A A; Greff, Mje; Rieder, M J

2017-06-01

Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population. © 2017 American Society for Clinical Pharmacology and Therapeutics.

An evaluation of knowledge, attitude and practice of Indian pharmacists towards adverse drug reaction reporting: A pilot study

PubMed Central

Ahmad, Akram; Patel, Isha; Balkrishnan, Rajesh; Mohanta, G. P.; Manna, P. K.

2013-01-01

Background: Pharmacovigilance is a useful to assure the safety of medicines and protect consumers from their harmful effects. Healthcare professionals should consider Adverse Drug Reaction (ADR) reporting as part of their professional obligation and participate in the existent pharmacovigilance programs in their countries. In India, the National PV Program was re-launched in July 2010. Objectives: This survey was conducted in order to assess the knowledge, attitude and practice of Indian pharmacists with the aim of exploring the pharmacists’ participation in ADR reporting system, identifying the reasons of under reporting and determining the steps that could be adopted to increase reporting rates. Materials and Methods: A cross-sectional survey was carried out among the pharmacists in India using a pretested questionnaire with 33 questions (10 questions on knowledge, 6 on attitude, 7 on practice, 7 on future of ADR reporting in India and 3 on benefits of reporting ADRs.). The study was conducted, over a period of 3 months from May 2012 to July 2012. Results: Out of the 600 participants to whom the survey was administered, a total of 400 were filled. The response rate of the survey was 67%. 95% responders were knowledgeable about ADRs. 90% participants had a positive attitude towards making ADRs reporting mandatory for practicing pharmacists. 87.5% participants were interested in participating in the National Pharmacovigilance program, in India. 47.5% respondents had observed ADRs in their practice, and 37% had reported it to the national pharmacovigilance center. 92% pharmacists believed reporting ADRs immensely helped in providing quality care to patients. Conclusion: The Indian pharmacists have poor knowledge, attitude, and practice (KAP) towards ADR reporting and pharmacovigilance. Pharmacists with higher qualifications such as the pharmacists with a PharmD have better KAP. With additional training on Pharmacovigilance, the Indian Pharmacists working in different sectors can become part of ADR reporting system. PMID:24312887

Natural Language Processing As an Alternative to Manual Reporting of Colonoscopy Quality Metrics

PubMed Central

RAJU, GOTTUMUKKALA S.; LUM, PHILLIP J.; SLACK, REBECCA; THIRUMURTHI, SELVI; LYNCH, PATRICK M.; MILLER, ETHAN; WESTON, BRIAN R.; DAVILA, MARTA L.; BHUTANI, MANOOP S.; SHAFI, MEHNAZ A.; BRESALIER, ROBERT S.; DEKOVICH, ALEXANDER A.; LEE, JEFFREY H.; GUHA, SUSHOVAN; PANDE, MALA; BLECHACZ, BORIS; RASHID, ASIF; ROUTBORT, MARK; SHUTTLESWORTH, GLADIS; MISHRA, LOPA; STROEHLEIN, JOHN R.; ROSS, WILLIAM A.

2015-01-01

BACKGROUND & AIMS The adenoma detection rate (ADR) is a quality metric tied to interval colon cancer occurrence. However, manual extraction of data to calculate and track the ADR in clinical practice is labor-intensive. To overcome this difficulty, we developed a natural language processing (NLP) method to identify patients, who underwent their first screening colonoscopy, identify adenomas and sessile serrated adenomas (SSA). We compared the NLP generated results with that of manual data extraction to test the accuracy of NLP, and report on colonoscopy quality metrics using NLP. METHODS Identification of screening colonoscopies using NLP was compared with that using the manual method for 12,748 patients who underwent colonoscopies from July 2010 to February 2013. Also, identification of adenomas and SSAs using NLP was compared with that using the manual method with 2259 matched patient records. Colonoscopy ADRs using these methods were generated for each physician. RESULTS NLP correctly identified 91.3% of the screening examinations, whereas the manual method identified 87.8% of them. Both the manual method and NLP correctly identified examinations of patients with adenomas and SSAs in the matched records almost perfectly. Both NLP and manual method produce comparable values for ADR for each endoscopist as well as the group as a whole. CONCLUSIONS NLP can correctly identify screening colonoscopies, accurately identify adenomas and SSAs in a pathology database, and provide real-time quality metrics for colonoscopy. PMID:25910665

Unplanned medication discontinuation as a potential pharmacovigilance signal: a nested young person cohort study

PubMed Central

2014-01-01

Background Because of relatively small treatment numbers together with low adverse drug reaction (ADR) reporting rates the timely identification of ADRs affecting children and young people is problematic. The primary objective of this study was to assess the utility of unplanned medication discontinuation as a signal for possible ADRs in children and young people. Methods Using orlistat as an exemplar, all orlistat prescriptions issued to patients up to 18 years of age together with patient characteristics, prescription duration, co-prescribed medicines and recorded clinical (Read) codes were identified from the Primary Care Informatics Unit database between 1st Jan 2006-30th Nov 2009. Binary logistic regression was used to assess association between characteristics and discontinuation. Results During the study period, 79 patients were prescribed orlistat (81% female, median age 17 years). Unplanned medication discontinuation rates for orlistat were 52% and 77% at 1 and 3-months. Almost 20% of patients were co-prescribed an anti-depressant. One month unplanned medication discontinuation was significantly lower in the least deprived group (SIMD 1–2 compared to SIMD 9–10 OR 0.09 (95% CI0.01 – 0.83)) and those co-prescribed at least one other medication. At 3 months, discontinuation was higher in young people (≥17 yr versus, OR 3.07 (95% CI1.03 – 9.14)). Read codes were recorded for digestive, respiratory and urinary symptoms around the time of discontinuation for 24% of patients. Urinary retention was reported for 7.6% of patients. Conclusions Identification of unplanned medication discontinuation using large primary care datasets may be a useful tool for pharmacovigilance signal generation and detection of potential ADRs in children and young people. PMID:24594374

Safety Concerns Reported by Patients Identified in a Collaborative Signal Detection Workshop using VigiBase: Results and Reflections from Lareb and Uppsala Monitoring Centre.

PubMed

Watson, Sarah; Chandler, Rebecca E; Taavola, Henric; Härmark, Linda; Grundmark, Birgitta; Zekarias, Alem; Star, Kristina; van Hunsel, Florence

2018-02-01

Patient reporting in pharmacovigilance is important and contributes to signal detection. However, descriptions of methodologies for using patient reports in signal detection are scarce, and published experiences of how patient reports are used in pharmacovigilance are limited to a few individual countries. Our objective was to explore the contribution of patient reports to global signal detection in VigiBase. Data were retrieved from VigiBase in September 2016. Drug-event-combination series were restricted to those with >50% patient reports, defined as reporter type "Consumer/non-health professional" per E2B reporting standard. vigiRank was applied to patient reports to prioritize combinations for assessment. Product information for healthcare professionals (HCPs) as well as patient information leaflets (PILs) were used as reference for information on adverse drug reactions (ADRs). Staff from the Uppsala Monitoring Centre and the Netherlands Pharmacovigilance Centre Lareb categorized the combinations. Potential signals proceeded to a more in-depth clinical review to determine whether the safety concern should be communicated as a "signal." Of the 212 combinations assessed, 20 (9%) resulted in eight signals communicated within the World Health Organization (WHO) programme for international drug monitoring. Review of PILs revealed insufficient ADR descriptions for patients and examples of poor consistency with product information for HCPs. Patient narratives provided details regarding the experience and impact of ADRs and evidence that patients make causality and personal risk assessments. Safety concerns described in patient reports can be identified in a global database including previously unknown ADRs as well as new aspects of known ADRs. Patient reports provide unique information valuable in signal assessment and should be included in signal detection. Novel approaches to highlighting patient reports in statistical signal detection can further improve the contribution of patient reports to pharmacovigilance.

Using text-mining techniques in electronic patient records to identify ADRs from medicine use.

PubMed

Warrer, Pernille; Hansen, Ebba Holme; Juhl-Jensen, Lars; Aagaard, Lise

2012-05-01

This literature review included studies that use text-mining techniques in narrative documents stored in electronic patient records (EPRs) to investigate ADRs. We searched PubMed, Embase, Web of Science and International Pharmaceutical Abstracts without restrictions from origin until July 2011. We included empirically based studies on text mining of electronic patient records (EPRs) that focused on detecting ADRs, excluding those that investigated adverse events not related to medicine use. We extracted information on study populations, EPR data sources, frequencies and types of the identified ADRs, medicines associated with ADRs, text-mining algorithms used and their performance. Seven studies, all from the United States, were eligible for inclusion in the review. Studies were published from 2001, the majority between 2009 and 2010. Text-mining techniques varied over time from simple free text searching of outpatient visit notes and inpatient discharge summaries to more advanced techniques involving natural language processing (NLP) of inpatient discharge summaries. Performance appeared to increase with the use of NLP, although many ADRs were still missed. Due to differences in study design and populations, various types of ADRs were identified and thus we could not make comparisons across studies. The review underscores the feasibility and potential of text mining to investigate narrative documents in EPRs for ADRs. However, more empirical studies are needed to evaluate whether text mining of EPRs can be used systematically to collect new information about ADRs. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Using text-mining techniques in electronic patient records to identify ADRs from medicine use

PubMed Central

Warrer, Pernille; Hansen, Ebba Holme; Juhl-Jensen, Lars; Aagaard, Lise

2012-01-01

This literature review included studies that use text-mining techniques in narrative documents stored in electronic patient records (EPRs) to investigate ADRs. We searched PubMed, Embase, Web of Science and International Pharmaceutical Abstracts without restrictions from origin until July 2011. We included empirically based studies on text mining of electronic patient records (EPRs) that focused on detecting ADRs, excluding those that investigated adverse events not related to medicine use. We extracted information on study populations, EPR data sources, frequencies and types of the identified ADRs, medicines associated with ADRs, text-mining algorithms used and their performance. Seven studies, all from the United States, were eligible for inclusion in the review. Studies were published from 2001, the majority between 2009 and 2010. Text-mining techniques varied over time from simple free text searching of outpatient visit notes and inpatient discharge summaries to more advanced techniques involving natural language processing (NLP) of inpatient discharge summaries. Performance appeared to increase with the use of NLP, although many ADRs were still missed. Due to differences in study design and populations, various types of ADRs were identified and thus we could not make comparisons across studies. The review underscores the feasibility and potential of text mining to investigate narrative documents in EPRs for ADRs. However, more empirical studies are needed to evaluate whether text mining of EPRs can be used systematically to collect new information about ADRs. PMID:22122057

[Drug resistance reversal of HL-60/ADR cells by simultaneous suppression of XIAP and MRP].

PubMed

Wang, Xiao-Fang; Wang, Chun; Qin, You-Wen; Yan, Shi-Ke; Gao, Yan-Rong

2006-12-01

This study was purposed to explore the mechanisms of drug resistance of HL-60/ADR cells and to compare the reversal drug-resistance effects of antisense oligonucleotides (AS ODN) of XIAP (X-linked inhibitor of apoptosis protein) and AS ODNs of MRP (multidrug resistance-associated protein) by use alone or in combination. Reverse transcription-PCR and Western blot were applied to detect the expression of XIAP, BCL-2, MRP and MDR1 in mRNA and protein levels of HL-60 cells and HL-60/ADR cells, respectively. Fully phosphorothioated AS ODN of XIAP and MRP was delivered into HL-60/ADR cells with Lipofectamine 2000 in the form of liposome-ODN complexes alone or in combination. CCK-8 cell viability assay was used to determine the effect of AS ODN of XIAP and MRP used alone or in combination on the chemotherapy sensitivity of HL-60/ADR cells to daunorubicin (DNR). Reverse transcription-PCR and Western blot were applied to examine the changes of XIAP, MRP in mRNA and protein levels respectively. The results showed that MRP and XIAP were both significantly higher in HL-60/ADR cells than those in HL-60 cells. AS ODN of XIAP and MRP down-regulated the expression of XIAP and MRP in HL-60/ADR cells and increased the sensitivity of HL-60/ADR cells to DNR, respectively. AS ODN of XIAP + MRP did not enhance the inhibition expression of XIAP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly as compared with AS ODN of XIAP (P < 0.05). AS ODN of XIAP + MRP did not increase the concentration of DNR nor enhanced the inhibition expression of MRP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly (P < 0.05), as compared with AS ODN of MRP. It is concluded that both XIAP and MRP may be involved in the drug resistance mechanisms of HL-60/ADR cells. Drug-resistance of HL-60/ADR cells can be reversed significantly when antisense oligonucleotides of XIAP and MRP were used in combination.

Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

PubMed

Mangoni, Arduino A

2012-05-01

Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings.

Adverse reactions due to directly observed treatment strategy therapy in Chinese tuberculosis patients: a prospective study.

PubMed

Lv, Xiaozhen; Tang, Shaowen; Xia, Yinyin; Wang, Xiaomeng; Yuan, Yanli; Hu, Daiyu; Liu, Feiying; Wu, Shanshan; Zhang, Yuan; Yang, Zhirong; Tu, Dehua; Chen, Yixin; Deng, Peiyuan; Ma, Yu; Chen, Ru; Zhan, Siyan

2013-01-01

More than 1 million tuberculosis (TB) patients are receiving directly observed treatment strategy (DOTS) therapy in China every year. As to the profile of adverse drug reactions (ADRs) due to DOTS therapy, no consensus has been reached. There is no report regarding ADRs due to DOTS therapy with a large Chinese TB population. This study aimed to determine the incidence and prognosis of ADRs due to DOTS therapy, and to evaluate their impact on anti-TB treatment in China. A prospective population-based cohort study was performed during 2007-2008. Sputum smear positive pulmonary TB patients who received DOTS therapy were included and followed up for six to nine months in 52 counties of four regions in China. The suspected ADRs were recorded and reviewed by Chinese State Food and Drug Administration. A total of 4304 TB patients were included in this study. 649 patients (15.08%) showed at least one ADR and 766 cases in total were detected. The incidence (count) of ADR based on affected organ was: liver dysfunction 6.34% (273), gastrointestinal disorders 3.74% (161), arthralgia 2.51% (108), allergic reactions 2.35% (101), neurological system disorders 2.04% (88), renal impairment 0.07% (3) and others 0.05% (2). Most cases of ADRs (95%) had a good clinical outcome, while two with hepatotoxicity and one with renal impairment died. Compared with patients without ADRs, patients with ADRs were more likely to have positive smear test results at the end of the intensive phase (adjusted OR, 2.00; 95%CI, 1.44-2.78) and unsuccessful anti-TB outcomes (adjusted OR, 2.58; 95%CI, 1.43-4.68). The incidence of ADRs due to DOTS therapy was 15.08%. Those ADRs had a substantial impact on TB control in China. This highlighted the importance of developing strategies to ameliorate ADRs both to improve the quality of patient care and to control TB safely.

An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions.

PubMed

Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne; Darsø, Perle; Christophersen, Anette Kvindebjerg; Borck, Bille; Christensen, Catrine; Hansen, Melissa Voigt; Halladin, Natalie Monica Løvland; Christensen, Mikkel Bring; Harboe, Kirstine Moll; Lund, Marie; Jimenez-Solem, Espen

2017-01-01

Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region of Denmark. The ADEM assists healthcare professionals in reporting suspected ADRs to the Danish Health Authority. The aim of this retrospective observational study was to quantify and describe ADRs reported via the ADEM in 2014. All ADR reports handled by the ADEM in 2014 were recorded anonymously and analysed descriptively. A total of 484 ADRs were reported through the ADEM in 2014 (the median number of reports per month was 37; range: 17-78). The majority of the reports came from departments of internal medicine (61%), psychiatry (14%) and dermatology, ophthalmology or otorhinolaryngology (11%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR reporting and helps raise awareness about ADRs, including how and why they should be reported. Hopefully, this will assist national and European spontaneous reporting systems in their work to increase patient safety nationally and abroad. none. not relevant. .

Mining Adverse Drug Reactions in Social Media with Named Entity Recognition and Semantic Methods.

PubMed

Chen, Xiaoyi; Deldossi, Myrtille; Aboukhamis, Rim; Faviez, Carole; Dahamna, Badisse; Karapetiantz, Pierre; Guenegou-Arnoux, Armelle; Girardeau, Yannick; Guillemin-Lanne, Sylvie; Lillo-Le-Louët, Agnès; Texier, Nathalie; Burgun, Anita; Katsahian, Sandrine

2017-01-01

Suspected adverse drug reactions (ADR) reported by patients through social media can be a complementary source to current pharmacovigilance systems. However, the performance of text mining tools applied to social media text data to discover ADRs needs to be evaluated. In this paper, we introduce the approach developed to mine ADR from French social media. A protocol of evaluation is highlighted, which includes a detailed sample size determination and evaluation corpus constitution. Our text mining approach provided very encouraging preliminary results with F-measures of 0.94 and 0.81 for recognition of drugs and symptoms respectively, and with F-measure of 0.70 for ADR detection. Therefore, this approach is promising for downstream pharmacovigilance analysis.

Clinical observation of the adverse drug reactions caused by non-ionic iodinated contrast media: results from 109,255 cases who underwent enhanced CT examination in Chongqing, China.

PubMed

Li, X; Chen, J; Zhang, L; Liu, H; Wang, S; Chen, X; Fang, J; Wang, S; Zhang, W

2015-03-01

To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40-49 years (204 cases, 0.43%; p < 0.01) or who underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had significantly higher incidence rates of ADRs. The symptoms and signs of most of the ADRs were resolved spontaneously within 24 h after appropriate treatment without sequelae. The occurrence of ADRs is caused by the combined effects of multiple factors. The ADRs induced by non-ionic iodinated contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably.

Clinical observation of the adverse drug reactions caused by non-ionic iodinated contrast media: results from 109,255 cases who underwent enhanced CT examination in Chongqing, China

PubMed Central

Li, X; Chen, J; Zhang, L; Liu, H; Wang, S; Chen, X; Fang, J; Wang, S

2015-01-01

Objective: To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Methods: Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. Results: A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40–49 years (204 cases, 0.43%; p < 0.01) or who underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had significantly higher incidence rates of ADRs. The symptoms and signs of most of the ADRs were resolved spontaneously within 24 h after appropriate treatment without sequelae. Conclusion: The occurrence of ADRs is caused by the combined effects of multiple factors. The ADRs induced by non-ionic iodinated contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. Advances in knowledge: The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably. PMID:25582519

Evaluation of a Novel System to Enhance Clinicians' Recognition of Preadmission Adverse Drug Reactions.

PubMed

Smith, Joshua C; Chen, Qingxia; Denny, Joshua C; Roden, Dan M; Johnson, Kevin B; Miller, Randolph A

2018-04-01

 Often unrecognized by providers, adverse drug reactions (ADRs) diminish patients' quality of life, cause preventable admissions and emergency department visits, and increase health care costs.  This article evaluates whether an automated system, the Adverse Drug Effect Recognizer (ADER), could assist clinicians in detecting and addressing inpatients' ongoing preadmission ADRs.  ADER uses natural language processing to extract patients' medications, findings, and past diagnoses from admission notes. It compares excerpted information to a database of known medication adverse effects and promptly warns clinicians about potential ongoing ADRs and potential confounders via alerts placed in patients' electronic health records (EHRs). A 3-month intervention trial evaluated ADER's impact on antihypertensive medication ordering behaviors. At the time of patient admission, ADER warned providers on the Internal Medicine wards of Vanderbilt University Hospital about potential ongoing preadmission antihypertensive medication ADRs. A retrospective control group, comprised similar physicians from a period prior to the intervention, received no alerts. The evaluation compared ordering behaviors for each group to determine if preadmission medications changed during hospitalization or at discharge. The study also analyzed intervention group participants' survey responses and user comments.  ADER identified potential preadmission ADRs for 30% of both groups. Compared with controls, intervention providers more often withheld or discontinued suspected ADR-causing medications during the inpatient stay ( p  < 0.001). Intervention providers who responded to alert-related surveys held or discontinued suspected ADR-causing medications more often at discharge ( p  < 0.001).  Results indicate that ADER helped physicians recognize ADRs and reduced ordering of suspected ADR-causing medications. In hospitals using EHRs, ADER-like systems could improve clinicians' recognition and elimination of ongoing ADRs. Schattauer GmbH Stuttgart.

The development and test of an intervention to improve ADR screening in nursing homes.

PubMed

Dilles, Tinne; Vander Stichele, Robert H; Van Bortel, Lucas M; Elseviers, Monique M

2013-05-01

The aim of this study was to develop and test the effect of an instrument, Pharmanurse, to facilitate nurse-driven adverse drug reaction (ADR) screening as an input for interdisciplinary medication review in nursing homes. Intervention study with a pre-posttest design All residents of a convenience sample of 8 nursing homes of more than 80 beds were eligible if they resided at least 1 month in the nursing home and took 4 or more different medications. Residents receiving palliative care were excluded. The intervention consisted of interdisciplinary medication review, prepared by nurse observations of potential ADRs using personalized screening lists generated by the Pharmanurse software. Pharmanurse is specifically adapted to use by nurses and to use in nursing homes. Outcome parameters were the number of ADRs detected by nurses, ADRs confirmed by general practitioners, and medication changes. After the intervention, health care professionals involved completed a questionnaire to evaluate the value and the feasibility of the intervention. Nurses observed 1527 potential ADRs in 81% of the 418 residents (mean per resident 3.7). Physicians confirmed 821 ADRs in 60% of the residents (mean per resident 2.0). As a result, 214 medication changes were planned in 21% of the residents (mean per resident 0.5) because of ADRs. Health care professionals gave the Pharmanurse intervention a score of 7 of 10 for the potential to improve pharmacotherapy and 83% of the physicians were satisfied about nurses' screening for ADRs. The Pharmanurse intervention supports nurses in ADR screening and may have the potential to improve pharmacotherapy. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

Cross-sectional study exploring barriers to adverse drug reactions reporting in community pharmacy settings in Dhaka, Bangladesh

PubMed Central

Amin, Mohammad Nurul; Khan, Tahir Mehmood; Dewan, Syed Masudur Rahman; Islam, Mohammad Safiqul; Moghal, Mizanur Rahman

2016-01-01

Objectives To assess community pharmacists'/pharmacy technicians' knowledge and perceptions about adverse drug reactions (ADRs) and barriers towards the reporting of such reactions in Dhaka, Bangladesh. Method A cross-sectional study was planned to approach potential respondents for the study. A self-administered questionnaire was delivered to community pharmacists/pharmacy technicians (N=292) practising in Dhaka, Bangladesh. Results The overall response to the survey was 69.5% (n=203). The majority of the sample was comprised of pharmacy technicians (152, 74.9%) who possessed a diploma in pharmacy, followed by pharmacists (37, 18.2%) and others (12, 5.9%). Overall, 72 (35.5%) of the respondents disclosed that they had experienced an ADR at their pharmacy, yet more than half (105, 51.7%) were not familiar with the existence of an ADR reporting body in Bangladesh. Exploring the barriers to the reporting of ADRs, it was revealed that the top four barriers to ADR reporting were ‘I do not know how to report (Relative Importance Index (RII)=0.998)’, ‘reporting forms are not available (0.996)’, ‘I am not motivated to report (0.997)’ and ‘Unavailability of professional environment to discuss about ADR (RII=0.939)’. In addition to these, a majority (141, 69.46%) were not confident about the classification of ADRs (RII=0.889) and were afraid of legal liabilities associated with reporting ADRs (RII=0.806). Moreover, a lack of knowledge about pharmacotherapy and the detection of ADRs was another major factor hindering their reporting (RII=0.731). Conclusions The Directorate of Drug Administration in Bangladesh needs to consider the results of this study to help it improve and simplify ADR reporting in Bangladeshi community pharmacy settings. PMID:27489151

Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study.

PubMed

Paggi, Silvia; Mogavero, Giuseppe; Amato, Arnaldo; Rondonotti, Emanuele; Andrealli, Alida; Imperiali, Gianni; Lenoci, Nicoletta; Mandelli, Giovanna; Terreni, Natalia; Conforti, Francesco Simone; Conte, Dario; Spinzi, Giancarlo; Radaelli, Franco

2018-04-01

 Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).  Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI-WLI group) and vice versa (WLI-LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.  Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI-WLI and 24.7 % in WLI-LCI). At per-polyp analysis, double inspection of the right colon in the LCI-WLI and WLI-LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively ( P  < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI - WLI group and in 13 of 300 patients (4.3 %) in the WLI - LCI group ( P  = 0.01).  LCI could reduce the miss rate of neoplastic lesions in the right colon. © Georg Thieme Verlag KG Stuttgart · New York.

Dose-specific adverse drug reaction identification in electronic patient records: temporal data mining in an inpatient psychiatric population.

PubMed

Eriksson, Robert; Werge, Thomas; Jensen, Lars Juhl; Brunak, Søren

2014-04-01

Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. We used a psychiatric hospital's EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five antipsychotics [corrected] exhibited a significant difference (p<0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). The developed method can be used to extract dose-dependent ADR information from already collected EPR data. Large-scale AE extraction from EPRs may complement or even replace current drug safety monitoring methods in the future, reducing or eliminating manual reporting and enabling much faster ADR detection.

Medical malpractice reform: the role of alternative dispute resolution.

PubMed

Sohn, David H; Bal, B Sonny

2012-05-01

Alternative dispute resolution (ADR) refers to techniques used to resolve conflicts without going to the courtroom. As healthcare and malpractice costs continue to rise, there is growing interest in tactics such as early apology, mediation, and arbitration in the medical arena. (1) Why is ADR needed? (2) Is ADR useful in health care? (3) What are the current legal and political developments favoring ADR? (4) What obstacles remain? We performed MEDLINE, PubMed, and Google Scholar searches with key words "medical malpractice", "ADR", and "alternative dispute resolution" to obtain public policy studies, law review articles, case analyses, ADR surveys, and healthcare review articles. Early apology and disclosure programs report 50% to 67% success in avoiding litigation as well as substantial reductions in the amount paid per claim. Mediation boasts 75% to 90% success in avoiding litigation, cost savings of $50,000 per claim, and 90% satisfaction rates among both plaintiffs and defendants. Arbitration is viewed as less satisfying and less efficient than mediation but still more time- and cost-effective than litigation. The current legal environment is favorable to ADR with recent court decisions upholding pretreatment arbitration clauses. The main obstacle to ADR is the mandatory reporting requirement of the National Practitioner Data Bank (NPDB). ADR has the potential to help reform the current tort system, reducing cost and increasing both parties' satisfaction. Easing the reporting requirements for the NPDB would lead to more widespread acceptance of ADR among physicians.

Antegrade Dissection and Reentry as Part of the Hybrid Chronic Total Occlusion Revascularization Strategy: A Subanalysis of the RECHARGE Registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom).

PubMed

Maeremans, Joren; Dens, Jo; Spratt, James C; Bagnall, Alan J; Stuijfzand, Wynand; Nap, Alexander; Agostoni, Pierfrancesco; Wilson, William; Hanratty, Colm G; Wilson, Simon; Faurie, Benjamin; Avran, Alexandre; Bressollette, Erwan; Egred, Mohaned; Knaapen, Paul; Walsh, Simon

2017-06-01

Development of the CrossBoss and Stingray devices for antegrade dissection and reentry (ADR) of chronic total occlusions has improved historically suboptimal outcomes. However, the outcomes, safety, and failure modes of the technique have to be studied in a larger patient cohort. This preplanned substudy of the RECHARGE registry (Registry of CrossBoss and Hybrid Procedures in France, the Netherlands, Belgium and United Kingdom) aims to evaluate the value and use of ADR and determine its future position in contemporary chronic total occlusion intervention. Patients were selected if an ADR strategy was applied. Outcomes, safety, and failure modes of the technique were assessed. The ADR technique was used in 23% (n=292/1253) of the RECHARGE registry and was mainly applied for complex lesions (Japanese chronic total occlusion score=2.7±1.1). ADR was the primary strategy in 30% (n=88/292), of which 67% were successful. Bail-out ADR strategies were successful in 63% (n=133/210). The Controlled ADR (ie, combined CrossBoss-Stingray) subtype was applied most frequently (32%; n=93/292) and successfully (81%; n=75/93). Overall per-lesion success rate was 78% (n=229/292), after use of additional bail-out strategies. The inability to reach the distal target zone (n=48/100) or to reenter (n=43/100) most commonly led to failure. ADR-associated major events occurred in 3.4% (n=10/292). Although mostly applied as a bail-out strategy for complex lesions, the frequency, outcomes, and low complication rate of the ADR technique and its subtypes confirm the benefit and value of the technique in hybrid chronic total occlusion percutaneous coronary intervention, especially when antegrade wiring or retrograde approaches are not feasible. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02075372. © 2017 American Heart Association, Inc.

Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006)

PubMed Central

2010-01-01

Background Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health cost. Methods Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalization that were code as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalizations per year, annual incidence of hospital admissions, average length of stay in the hospital, and case-fatality rate, were calculated. Results During the 2001-2006 periods, the total number of hospitalized patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-2006 (p < 0.05). More than five percent of patients (n = 19,734) died during an ADR-related hospitalization. The drugs most commonly associated with ADR-related hospitalization were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006. Conclusions Approximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalization to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths. PMID:20942906

International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes

PubMed Central

Manickam, Ponnaiah; Mehendale, Sanjay M.; Nagaraju, Bathyala; Katoch, Kiran; Jamesh, Abdul; Kutaiyan, Ramalingam; Jianping, Shen; Mugudalabetta, Shivakumar; Jadhav, Vitthal; Rajkumar, Prabu; Padma, Jayasree; Kaliaperumal, Kanagasabai; Pannikar, Vijayakumar; Krishnamurthy, Padabettu; Gupte, Mohan D.

2016-01-01

Background & objectives: Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Methods: Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. Results: A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. Interpretation & conclusions: We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696] PMID:28256460

International open trial of uniform multidrug therapy regimen for leprosy patients: Findings & implications for national leprosy programmes.

PubMed

Manickam, Ponnaiah; Mehendale, Sanjay M; Nagaraju, Bathyala; Katoch, Kiran; Jamesh, Abdul; Kutaiyan, Ramalingam; Jianping, Shen; Mugudalabetta, Shivakumar; Jadhav, Vitthal; Rajkumar, Prabu; Padma, Jayasree; Kaliaperumal, Kanagasabai; Pannikar, Vijayakumar; Krishnamurthy, Padabettu; Gupte, Mohan D

2016-10-01

Uniform therapy for all leprosy patients will simplify leprosy treatment. In this context, we evaluated six-month multidrug therapy (MDT) currently recommended for multibacillary (MB) patients as uniform MDT (U-MDT) in a single-arm open trial under programme conditions. Primary objective was to determine efficacy to prevent five-year cumulative five per cent relapse. Secondary objectives were to assess acceptability, safety and compliance. Newly detected, treatment-naive leprosy patients were enrolled in India (six sites) and P. R. China (two sites). Primary outcome was clinically confirmed relapse of occurrence of one or more new skin patches consistent with leprosy, without evidence of reactions post-treatment. Event rates per 100 person years as well as five-year cumulative risk of relapse, were calculated. A total of 2091 paucibacillary (PB) and 1298 MB leprosy patients were recruited from the 3437 patients screened. Among PB, two relapsed (rate=0.023; risk=0.11%), eight had suspected adverse drug reactions (ADRs) (rate=0.79) and rate of new lesions due toreactions was 0.24 (n=23). Rates of neuritis, type 1 and type 2 reactions were 0.39 (n=37), 0.54 (n=51) and 0.03 (n=3), respectively. Among MB, four relapsed (rate=0.07; risk=0.37%) and 16 had suspected ADR (rate=2.64). Rate of new lesions due to reactions among MB was 1.34 (n=76) and rates of neuritis, type 1 and type 2 reactions were 1.37 (n=78), 2.01 (n=114) and 0.49 (n=28), respectively. Compliance to U-MDT was 99 per cent. Skin pigmentation due to clofazimine was of short duration and acceptable. We observed low relapse, minimal ADR and other adverse clinical events. Clofazimine-related pigmentation was acceptable. Evidence supports introduction of U-MDT in national leprosy programmes. [CTRI No: 2012/ 05/ 002696].

[Pharmacovigilance of vaccines].

PubMed

Autret-Leca, E; Bensouda-Grimaldi, L; Jonville-Béra, A P; Beau-Salinas, F

2006-02-01

Safety of vaccines must be excellent to make vaccine's strategy acceptable, since it usually has a deferred individual benefit but immediate adverse drug reactions (ADRs). Pharmacovigilance of vaccines after their marketing is crucial because, prior to its availability on the market, the size of clinical trials is insufficient to identify rare or deferred adverse effects. The Pharmacovigilance is based on "spontaneous reporting" of ADRs to the Pharmacovigilance Regional Centre (PVRC) which establishes a relationship between each drug taken by the patient and the ADRs occurrence (imputability). This method is crucial to generate alerts, but under-estimates the real frequency of ADRs (1 to 10% of severe ADRs are reported). Thus pharmacoepidemiology studies are necessary to confirm the alerts identified by spontaneous reporting. ADRs can be specific, related to the antigen of an attenuated alive virus vaccine (lymphocyte meningitis after anti-mumps vaccine) or non-specific, related to a component different from the antigen (aluminium hydroxide involved in the "macrophagic myofasciitis", allergic reactions to neomycin, latex, egg or gelatine). Importance of Pharmacovigilance of vaccines is illustrated. Data, especially case-control studies, about the relationship between multiple sclerosis and hepatitis B vaccine are summarised. Data about the relationship between Crohn's disease or autism and MMR vaccine are analysed. As vaccines are used in healthy people, their safety must be excellent to be accepted. To monitor them after their marketing is the unique way to detect rare ADRs. This surveillance is made through reporting of ADRs to the PVRC. However, an active and intensive surveillance of ADRs as the one set up from the marketing of Prevenar should be systematic.

Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation.

PubMed

Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei

2016-11-01

Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions. Copyright © 2016 Elsevier Inc. All rights reserved.

Use of antegrade dissection re-entry in coronary chronic total occlusion percutaneous coronary intervention in a contemporary multicenter registry.

PubMed

Danek, Barbara Anna; Karatasakis, Aris; Karmpaliotis, Dimitri; Alaswad, Khaldoon; Yeh, Robert W; Jaffer, Farouc A; Patel, Mitul; Bahadorani, John; Lombardi, William L; Wyman, Michael R; Grantham, J Aaron; Doing, Anthony; Moses, Jeffrey W; Kirtane, Ajay; Parikh, Manish; Ali, Ziad A; Kalra, Sanjog; Kandzari, David E; Lembo, Nicholas; Garcia, Santiago; Rangan, Bavana V; Thompson, Craig A; Banerjee, Subhash; Brilakis, Emmanouil S

2016-07-01

We assessed efficacy and safety of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using antegrade dissection re-entry (ADR). We examined outcomes of ADR among 1313 CTO PCIs performed at 11 US centers between 2012-2015. 84.1% of patients were men. Prevalence of prior coronary artery bypass graft surgery was 34.3%. Overall technical and procedural success were 90.1% and 88.7%, respectively. In-hospital major adverse cardiovascular events (MACE) occurred in 31 patients (2.4%). ADR was used in 458 cases (34.9%), and was the first strategy in 169 cases (12.9%). ADR cases were angiographically more complex than non-ADR cases (mean J-CTO score: 2.8±1.2 vs. 2.4±1.2, p<0.001). ADR was performed using the CrossBoss catheter in 246 of 458 (53.7%) and the Stingray system in 251 ADR cases (54.8%). Compared with non-ADR cases, ADR cases had lower technical (86.9% vs. 91.8%, p=0.005) and procedural success (85.0% vs. 90.7%, p=0.002), but similar risk for MACE (2.9% vs. 2.2%, p=0.42). ADR was associated with longer procedure and fluoroscopy time, and higher patient air kerma dose and contrast volume (all p<0.001). After excluding retrograde cases, ADR and antegrade wire escalation (AWE) had similar technical success (92.7% vs. 94.2%, p=0.43), procedural success (91.8% vs. 94.1%, p=0.23), and MACE (2.1% vs. 0.6%, p=0.12). ADR is used relatively frequently in contemporary CTO PCI, especially for challenging lesions and after failure of other strategies. ADR is associated with similar success rates and risk for complications as compared with AWE, and is important for achieving high procedural success. Published by Elsevier Ireland Ltd.

Use of Antegrade Dissection Re-entry in Coronary Chronic Total Occlusion Percutaneous Coronary Intervention in a Contemporary Multicenter Registry

PubMed Central

Danek, Barbara Anna; Karatasakis, Aris; Karmpaliotis, Dimitri; Alaswad, Khaldoon; Yeh, Robert W.; Jaffer, Farouc A.; Patel, Mitul; Bahadorani, John; Lombardi, William L.; Wyman, Michael R.; Grantham, J. Aaron; Doing, Anthony; Moses, Jeffrey W.; Kirtane, Ajay; Parikh, Manish; Ali, Ziad; Kalra, Sanjog; Kandzari, David E.; Lembo, Nicholas; Garcia, Santiago; Rangan, Bavana V.; Thompson, Craig A.; Banerjee, Subhash; Brilakis, Emmanouil S.

2016-01-01

Background We assessed efficacy and safety of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) using antegrade dissection re-entry (ADR). Methods We examined outcomes of ADR among 1,313 CTO PCIs performed at 11 US centers between 2012-2015. Results 84.1% of patients were men. Prevalence of prior coronary artery bypass graft surgery was 34.3%. Overall technical and procedural success were 90.1% and 88.7%, respectively. In-hospital major adverse cardiovascular events (MACE) occurred in 31 patients (2.4%). ADR was used in 458 cases (34.9%), and was the first strategy in 169 cases (12.9 %). ADR cases were angiographically more complex than non-ADR cases (mean J-CTO score: 2.8±1.2 vs. 2.4±1.2, p<0.001). ADR was performed using the CrossBoss catheter in 246 of 458 (53.7%) and the Stingray system in 251 ADR cases (54.8%). Compared with non-ADR cases, ADR cases had lower technical (86.9% vs. 91.8%, p=0.005) and procedural success (85.0% vs. 90.7%, p=0.002), but similar risk for MACE (2.9% vs. 2.2%, p=0.42). ADR was associated with longer procedure and fluoroscopy time, and higher patient air kerma dose and contrast volume (all p<0.001). After excluding retrograde cases, ADR and antegrade wire escalation (AWE) had similar technical success (92.7% vs. 94.2%, p=0.43) procedural success (91.8% vs. 94.1%, p=0.23), and MACE (2.1% vs. 0.6%, p=0.12). Conclusions ADR is used relatively frequently in contemporary CTO PCI, especially for challenging lesions and after failure of other strategies. ADR is associated with similar success rates and risk for complications as compared with AWE, and is important for achieving high procedural success. PMID:27088405

Adverse Drug Reactions (ADR) and Emergencies.

PubMed

Schurig, A Marlen; Böhme, Miriam; Just, Katja S; Scholl, Catharina; Dormann, Harald; Plank-Kiegele, Bettina; Seufferlein, Thomas; Gräff, Ingo; Schwab, Matthias; Stingl, Julia C

2018-04-13

Adverse drug reactions (ADR) are a common reason for emergency room visits and for hospitalization. An ADR is said to have occurred when the patient's symptoms and signs are considered to be possibly, probably, or definitely related to the intake of a drug. In four large hospital emergency departments, one in each of four German cities ( Ulm, Fürth, Bonn, and Stuttgart), the percentage of suspected ADR cases among all patients presenting to the emergency room was determined during a 30-day period of observation. ADRs were ascertained by screening the digital records of all patients seen in the emergency room; causality was assessed as specified by the WHO-UMC (Uppsala Monitoring Center). ADR were sought in a total of 10 174 emergency department visits. 665 cases of suspected ADR were found, yielding a prevalence of 6.5%. The prevalence of ADR among patients with documented drug intake was 11.6%. Among the patients with documented suspected ADRs, 89% were hospitalized (in contrast to the 43.7% hospitalization rate in the entire group of 10 174 emergency department visits). A possible causal relationship between the patient's symptoms and signs and the intake of a drug was found in 74-84% of cases. Patients with ADR were found to be taking a median of 7 different drugs simultaneously. Adverse drug reactions are a relevant cause of emergency department visits, accounting for 6.5% of the total visits in this study, and often lead to hospital admission. The ADRED (Adverse Drug Reactions in Emergency Departments) study, which is now being conducted, is intended to shed further light on their causes, patient risk factors, and potential avoidability.

[Use of Nadis(®) software to improve adverse drug reaction reporting of antiretroviral drugs: experience in south west of France (midi-pyrénées)].

PubMed

Pochard, Liselotte; Hauviller, Laurent; Cuzin, Lise; Eyvrard, Fréderic; Sommet, Agnès; Montastruc, Jean-Louis; Bagheri, Haleh

2014-01-01

To study the value of the module of pharmacovigilance in Nadis® to improve the antiretroviral (ARV) drugs-induced adverse drug reactions (ADRs) reporting. We collected the ADRs reported for 17 months from November 2010 until April 2012. Following data were recorded: characteristics of patients, ADRs, ARV drugs. The number of ADRs was compared to those collected in the same period (17 months) before use of Nadis®. The 119 ADRs reported (an increase of 183%) for 109 patients ADRs were mainly gastrointestinal (21.8%) followed by renal (20.2%), neuro-psychiatric (16.8%), hepatic (13.5%), cutaneous (8.4%), metabolic (6.7%) and others (12.6%). The repartition of ARV drugs was: nucleoside (31.8%), nucleotide (13.6%) reverse transcriptase inhibitors respectively, non-nucleoside reverse transcriptase inhibitors (13.1%), protease inhibitors (36.4%), and integrase inhibitors (5.1%). Our results show the improvement of ARV-induced ADRs reporting by Nadis® which could be used to reduce the rate of under-reporting in patients exposed to these drugs. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.

PubMed Central

Ohe, M.; Munakata, M.; Hizawa, N.; Itoh, A.; Doi, I.; Yamaguchi, E.; Homma, Y.; Kawakami, Y.

1995-01-01

BACKGROUND--Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS--The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS--A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS--These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma. Images PMID:7785006

Stress and depression scales in aphasia: relation between the aphasia depression rating scale, stroke aphasia depression questionnaire-10, and the perceived stress scale.

PubMed

Laures-Gore, Jacqueline S; Farina, Matthew; Moore, Elliot; Russell, Scott

2017-03-01

Assessment and diagnosis of post-stroke depression (PSD) among patients with aphasia presents unique challenges. A gold standard assessment of PSD among this population has yet to be identified. The first aim was to investigate the association between two depression scales developed for assessing depressive symptoms among patients with aphasia. The second aim was to evaluate the relation between these scales and a measure of perceived stress. Twenty-five (16 male; 9 female) individuals with history of left hemisphere cerebrovascular accident (CVA) were assessed for depression and perceived stress using the Stroke Aphasic Depression Questionnaire-10 (SADQ-10), the Aphasia Depression Rating Scale (ADRS), and the Perceived Stress Scale (PSS). SADQ-10 and ADRS ratings were strongly correlated with each other (r = 0.708, p < 0.001). SADQ-10 ratings were strongly correlated with PSS ratings (r = 0.620, p = 0.003), while ADRS ratings were moderately correlated (r = 0.492, p = 0.027). Item analysis of each scale identified items which increased both inter-scale correlation and intra-scale consistency when excluded. The SADQ-10 and ADRS appear to be acceptable measures of depressive symptoms in aphasia patients. Measurements of perceived stress may also be an important factor in assessment of depressive symptoms.

Quality in Colonoscopy: Beyond the Adenoma Detection Rate Fever

PubMed Central

Taveira, Filipe; Areia, Miguel; Elvas, Luís; Alves, Susana; Brito, Daniel; Saraiva, Sandra; Cadime, Ana Teresa

2017-01-01

Background Colonoscopy quality is a hot topic in gastroenterological communities, with several actual guidelines focusing on this aspect. Although the adenoma detection rate (ADR) is the single most important indicator, several other metrics are described and need reporting. Electronic medical reports are essential for the audit of quality indicators; nevertheless, they have proved not to be faultless. Aim The aim of this study was to analyse and audit quality indicators (apart from ADR) using only our internal electronic endoscopy records as a starting point for improvement. Methods An analysis of electronically recorded information of 8,851 total colonoscopies from a single tertiary centre from 2010 to 2015 was performed. Results The mean patient age was 63.4 ± 8.5 years; 45.5% of them were female, and in 14.6% sedation was used. Photographic documentation was done in 98.4% with 10.7 photographs on average, and 37.4% reports had <8 pictures per exam. Bowel preparation was rated as adequate in 67%, fair in 27% and inadequate in 4.9% of cases. The adjusted caecal intubation rate (CIR) was 92%, while negative predictors were inadequate preparation (OR 119, 95% CI 84–170), no sedation (OR 2.39, 95% CI 1.81–3.15), female gender (OR 1.61, 95% CI 1.38–1.88) and age ≥65 years (OR 1.56, 95% CI 1.34–1.82). In 28% of patients, a snare polypectomy was performed, correlating with adequate preparation (OR 5.75, 95% CI 3.90–8.48), male gender (OR 1.82, 95% CI 1.64–2.01) and age ≥65 years (OR 1.25, 95% CI 1.13–1.37; p < 0.01) as positive predictors. An annual evolution was observed with improvements in photographic documentation (10.7 vs. 12.9; p < 0.001), CIR (91 vs. 94%; p = 0.002) and “adequate” bowel preparation (p = 0.004). Conclusions: There is much more to report than the ADR to ensure quality in colonoscopy practice. Better registry systematization and integrated software should be goals to achieve in the short term. PMID:29255755

Promoting spontaneous adverse drug reaction reporting in hospitals using a hyperlink to the online reporting form: an ecological study in Portugal.

PubMed

Ribeiro-Vaz, Inês; Santos, Cristina; da Costa-Pereira, Altamiro; Cruz-Correia, Ricardo

2012-05-01

Spontaneous adverse drug reaction (ADR) reporting has been described as an efficient method to detect drug safety signals. However, under-reporting is a major issue undermining the effectiveness of spontaneous reports. Among hospitalized patients, ADRs are a particularly serious problem because these patients are often treated with more than one drug, and these drugs are often new and aggressive. To promote spontaneous ADR reporting by healthcare professionals working in hospitals in the northern regions of Portugal, we propose the inclusion of a hyperlink to an online ADR reporting form on hospitals' electronic patient records (EPRs). The main aim of this study was to evaluate the impact of these hyperlinks on the number of spontaneous ADR reports to the Northern Pharmacovigilance Centre (UFN - Unidade de Farmacovigilância do Norte). We also assess the number of daily UFN website visits before and after the inclusion of the hyperlinks. An ecological study was performed in northern Portuguese hospitals from 2006 to 2010. The hyperlinks were included in either EPRs or on computer desktops. The median of spontaneous ADR reports (total and online) per month and the respective ranges were presented before and after the intervention in all hospitals in this study. The comparisons were performed using the Mann-Whitney U-test. Sixteen hospital centres were involved in the study (27 hospitals). Eleven centres (18 hospitals) included the hyperlinks. Considering the hospitals with hyperlink access to the EPRs, the median ADR reports per month significantly increased, from two (range 0-12) to five reports (range 1-17). The median of ADR reports per month using the online form also increased significantly, from one (range 0-5) before the intervention to four (range 1-17) after it. Moreover, serious ADRs increased 3-fold, and non-previously described ADRs increased 4.5-fold. None of these significant increases were observed in the hospitals where the hyperlink was not installed. We also found a significant increase in daily UFN website visits, from ten before the intervention to 27 after it (p < 0.001). The increase in ADR reporting shows that the inclusion of hyperlinks to online ADR reporting forms is an easy and cost-effective way to change health professional behaviours with regard to spontaneous ADR reports.

The prevalence and impact of antimicrobial allergies and adverse drug reactions at an Australian tertiary centre.

PubMed

Trubiano, Jason A; Cairns, Kelly A; Evans, Jacqui A; Ding, Amally; Nguyen, Tuan; Dooley, Michael J; Cheng, Allen C

2015-12-16

The prevalence and impact of antimicrobial "allergy" labels and Adverse Drug Reactions (ADRs) on antibiotic usage and antimicrobial stewardship initiatives is ill defined. We sought to examine the rate of antimicrobial "allergy labels" at our tertiary referral centre and impacts on antimicrobial usage and appropriateness. Two inpatient antimicrobial prevalence surveys were conducted over a 1-week period in November 2013 and 2014 as part of the prospective National Antimicrobial Prescribing Survey (NAPS). Post survey, patients recorded in the NAPS database were assigned to two groups based upon recorded antimicrobial "allergy label" and ADR: (i) Antimicrobial Allergy/ADR (AA) or (ii) No Antimicrobial Allergy/ADR (NAA). Antimicrobial usage and antimicrobial appropriateness were compared between AA and NAA groups. From 509 identified patients the prevalence of an antimicrobial allergy or ADR was 25 %. The prevalence of "allergy labels"/ADR was 10 % (51/509) for penicillin V/G, 5 % (24/509) cephalosporins, 4 % (22/509) trimethroprim-sulfamethoxazole and 3 % (17/509) aminopenicillins. One thousand and seventy antimicrobials were prescribed during the study periods, the median antimicrobial duration was longer in the AA versus NAA group (6 days vs. 4 days; p = 0.018), and proportion of inappropriate antimicrobial prescribing higher in the AA group compared with NAA (29 %; 35/120 vs. 23 %; 86/367, p = 0.22). Oral antimicrobial administration was higher in the NAA than AA group (60 %; 177/297 vs. 46 %; 356/793, p = 0.0001). The proportion of patients that received a β-lactam was lower in the AA versus NAA group (60 % vs. 79 %, p = 0.0001). In an Australian tertiary referral centre an antimicrobial "allergy" or ADR label was found to significantly impacted on rate of oral antimicrobial administration, beta-lactam usage, antimicrobial duration and antimicrobial appropriateness.

Public awareness and perception toward Adverse Drug Reactions reporting in Riyadh, Saudi Arabia.

PubMed

Sales, Ibrahim; Aljadhey, Hisham; Albogami, Yasser; Mahmoud, Mansour A

2017-09-01

Purpose: To assess the general public awareness and perception about Adverse Drug Reactions (ADRs) reporting and pharmacovigilance. Method: A cross-sectional study conducted on June 2012 during awareness campaign held in two malls in Riyadh city for two days. A self-administered questionnaire consisting of three parts was distributed to the attendees who accepted to participate in the study. Results: A total of 204 questionnaires were collected with a response rate of 68%. Twenty-three percent could correctly define ADRs. Only 13(15.7%) of responders were familiar with the term "Pharmacovigilance" and only 78.6% were aware about the Saudi Pharmacovigilance Center. Sixty-seventy percent indicated that their physicians or pharmacists don't actively encourage them to report ADRs that may occur when they take their medications. The majority of responders (73.2%) believed that the medical team, rather than consumers, should report ADRs. When asked why patients do not report ADRs, 19.1(48.5%) believed that patients do not know whether the ADR is from the medication or not, 18.1(46.1%) stated that the reason was because patients don't know about the Pharmacovigilance Center, 16(40.7%) think that patients don't know about the importance of ADRs reporting, and 14(36.3%) responded that patients probably don't know how to report ADRs. Conclusion: The general public in Saudi Arabia are not aware about ADRs reporting and the pharmacovigilance system. The Saudi Food and Drug Authorities (FDA) need to put more efforts to increasing public awareness about the importance of ADRs reporting process and the importance of pharmacovigilance system in promoting patient safety.

Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

PubMed

Andrade, Paulo Henrique Santos; Lobo, Iza Maria Fraga; da Silva, Wellington Barros

2017-01-01

The present study aims to identify the risk factors for adverse drug reactions (ADR) in pediatric inpatients. A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used. A total of 173 children (208 admissions) and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%). In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR) 2.44; 95% confidence interval (CI) 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54), antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98) and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56) were identified risk factors for ADR. We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital.

PubMed

Desai, Chetna K; Iyer, Geetha; Panchal, Jigar; Shah, Samidh; Dikshit, R K

2011-10-01

Spontaneous reporting is an important tool in pharmacovigilance. However, its success depends on cooperative and motivated prescribers. Under-reporting of adverse drug reactions (ADRs) by prescribers is a common problem. The present study was undertaken to evaluate the knowledge, attitude, and practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital, Ahmedabad, to get an insight into the causes of under-reporting of ADRs. A pretested KAP questionnaire comprising of 15 questions (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers. The questionnaires were assessed for their completeness (maximum score 20) and the type of responses regarding ADR reporting. Microsoft Excel worksheet (Microsoft Office 2007) and Chi-Square test were used for statistical analysis. A total of 260 (61%) prescribers completed the questionnaire (mean score of completion 18.04). The response rate of resident doctors (70.7%) was better than consultants (34.5%) (P < 0.001). ADR reporting was considered important by 97.3% of the respondents; primarily for improving patient safety (28.8%) and identifying new ADRs (24.6%). A majority of the respondents opined that they would like to report serious ADRs (56%). However, only 15% of the prescribers had reported ADRs previously. The reasons cited for this were lack of information on where (70%) and how (68%) to report and the lack of access to reporting forms (49.2%). Preferred methods for reporting were e-mail (56%) and personal communication (42%). The prescribers are aware of the ADRs and the importance of their reporting. However, under reporting and lack of knowledge about the reporting system are clearly evident. Creating awareness about ADR reporting and devising means to make it easy and convenient may aid in improving spontaneous reporting.

A prospective study of adverse drug reactions in hospitalized children

PubMed Central

Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

1999-01-01

Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

Immunosuppressive Drug Discontinuation in Noninfectious Uveitis From Real-Life Clinical Practice: A Survival Analysis.

PubMed

Abásolo, Lydia; Rosales, Zulema; Díaz-Valle, David; Gómez-Gómez, Alejandro; Peña-Blanco, Rayma C; Prieto-García, Ángela; Benítez-Del-Castillo, José Manuel; Pato, Esperanza; García-Feijoo, Julián; Fernández-Gutiérrez, Benjamín; Rodriguez-Rodriguez, Luis

2016-09-01

To assess in uveitis patients the rate of immunosuppressive drug (ISD) discontinuation in real-life clinical practice, comparing this rate among ISDs. Longitudinal retrospective cohort study. We included uveitis patients attending a tertiary eye referral center from Madrid (Spain) between 1989 and 2015, prescribed any ISDs (cyclosporine, methotrexate, azathioprine, anti-TNF drugs, or others). Our main outcome was discontinuation of all ISDs owing to clinical efficacy, inefficacy, adverse drug reaction (ADR), and other medical causes. Discontinuation rates (DRs) per 100 patient-years were estimated. Variables associated with specific-cause discontinuations were analyzed using Cox bivariate and multivariate models. We analyzed 110 patients with 263 treatment courses and 665.2 patient-years of observation. Cyclosporine (66.4%), methotrexate (47.3%), azathioprine (30.9%), and anti-TNFs (30.9%) were the most frequently used ISDs. Treatment was suspended in 136 cases (mostly owing to clinical efficacy [38.2%], inefficacy [26.5%], and ADRs [22.8%]). All-cause DR with 95% confidence interval was 20.4 [17.3-24.2]. Retention rates at 1 and 10 years were 74% and 16%, respectively. In the multivariate analysis, combined treatment exhibited higher DRs owing to clinical efficacy than other ISDs in monotherapy. Conversely, nonbiologic combination therapy with azathioprine exhibited the highest DR owing to ADRs. Clinical efficacy was the most frequent cause for ISD discontinuation, followed by inefficacy and ADRs. DR owing to efficacy was higher for combination therapy. Furthermore, nonbiologic combination therapy with azathioprine was associated with a higher DR owing to ADRs. Copyright © 2016 Elsevier Inc. All rights reserved.

Patient-Reported Safety Information: A Renaissance of Pharmacovigilance?

PubMed

Härmark, Linda; Raine, June; Leufkens, Hubert; Edwards, I Ralph; Moretti, Ugo; Sarinic, Viola Macolic; Kant, Agnes

2016-10-01

The role of patients as key contributors in pharmacovigilance was acknowledged in the new EU pharmacovigilance legislation. This contains several efforts to increase the involvement of the general public, including making patient adverse drug reaction (ADR) reporting systems mandatory. Three years have passed since the legislation was introduced and the key question is: does pharmacovigilance yet make optimal use of patient-reported safety information? Independent research has shown beyond doubt that patients make an important contribution to pharmacovigilance signal detection. Patient reports provide first-hand information about the suspected ADR and the circumstances under which it occurred, including medication errors, quality failures, and 'near misses'. Patient-reported safety information leads to a better understanding of the patient's experiences of the ADR. Patients are better at explaining the nature, personal significance and consequences of ADRs than healthcare professionals' reports on similar associations and they give more detailed information regarding quality of life including psychological effects and effects on everyday tasks. Current methods used in pharmacovigilance need to optimise use of the information reported from patients. To make the most of information from patients, the systems we use for collecting, coding and recording patient-reported information and the methodologies applied for signal detection and assessment need to be further developed, such as a patient-specific form, development of a severity grading and evolution of the database structure and the signal detection methods applied. It is time for a renaissance of pharmacovigilance.

Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

PubMed Central

2012-01-01

Background Data on adverse drug reactions (ADRs) related to antiretroviral (ARV) use in public health practice are few indicating the need for ART safety surveillance in clinical care. Objectives To evaluate the incidence, type and risk factors associated with adverse drug reactions (ADRs) among patients on antiretroviral drugs (ARV). Methods Patients initiated on ARVs between May 2006 and May 2009 were evaluated in a retrospective cohort analysis in three health facilities in Nigeria. Regimens prescribed include nucleoside backbone of zidovudine (AZT)/lamivudine (3TC), stavudine (d4T)/3TC, or tenofovir (TDF)/3TC in combination with either nevirapine (NVP) or efavirenz (EFV). Generalized Estimating Equation (GEE) model was used to identify risk factors associated with occurrence of ADR. Results 2650 patients were followed-up for 2456 person-years and reported 114 ADRs (incidence rate = 4.6/100 person-years).There were more females 1706(64%) and 73(64%) of the ADRs were reported by women. Overall, 61(54%) of ADRs were reported by patients on AZT with 54(47%) of these occurring in patients on AZT/NVP. The commonest ADRs reported were pain 25(30%) and skinrash 10(18%). Most ADRs were grade 1(39%) with only 1% being life threatening (grade 4). Adjusted GEE analysis showed that ADR was less likely to occur in patients on longer duration of ART compared to the first six months on treatment; 6-12 months AOR 0.38(95% CI:0.16-0.91) and 12-24 months AOR 0.34(95% CI:0.16-0.73) respectively. Compared to patients on TDF, ADR was less likely to occur in patients on d4T and AZT AOR 0.18(95% CI 0.05-0.64) and AOR 0.24(95% CI:0.7-0.9) respectively. Age, gender and CD4 count were not significantly associated with ADRs. Conclusion ADRs are more likely to occur within the first six months on treatment. Close monitoring within this period is required to prevent occurrence of severe ADR and improve ART adherence. Further research on the tolerability of tenofovir in this environment is recommended. PMID:22369677

Controlling the Growth of Future LEO Debris Populations with Active Debris Removal

NASA Technical Reports Server (NTRS)

Liou, J.-C.; Johnson, N. L.; Hill, N. M.

2008-01-01

Active debris removal (ADR) was suggested as a potential means to remediate the low Earth orbit (LEO) debris environment as early as the 1980s. The reasons ADR has not become practical are due to its technical difficulties and the high cost associated with the approach. However, as the LEO debris populations continue to increase, ADR may be the only option to preserve the near-Earth environment for future generations. An initial study was completed in 2007 to demonstrate that a simple ADR target selection criterion could be developed to reduce the future debris population growth. The present paper summarizes a comprehensive study based on more realistic simulation scenarios, including fragments generated from the 2007 Fengyun-1C event, mitigation measures, and other target selection options. The simulations were based on the NASA long-term orbital debris projection model, LEGEND. A scenario, where at the end of mission lifetimes, spacecraft and upper stages were moved to 25-year decay orbits, was adopted as the baseline environment for comparison. Different annual removal rates and different ADR target selection criteria were tested, and the resulting 200-year future environment projections were compared with the baseline scenario. Results of this parametric study indicate that (1) an effective removal strategy can be developed based on the mass and collision probability of each object as the selection criterion, and (2) the LEO environment can be stabilized in the next 200 years with an ADR removal rate of five objects per year.

Parental reporting of adverse drug reactions associated with attention-deficit hyperactivity disorder (ADHD) medications in children attending specialist paediatric clinics in the UK.

PubMed

Tobaiqy, Mansour; Stewart, Derek; Helms, Peter J; Williams, Justin; Crum, Jackie; Steer, Christopher; McLay, James

2011-03-01

The development of systems to ensure appropriate and informed use of medicines in children is a global priority. Current pharmacovigilance systems, such as the UK Yellow Card Scheme, are limited by opportunistic reporting of adverse drug reactions (ADRs), lack of a denominator and lower than expected reporting rates. To develop a pharmacovigilance system able to target specific patient populations such as children, and specific medicines of interest, using specialist medical clinics. Between January and March 2010, parents of 578 children (3-16 years of age) receiving pharmacological therapy for attention-deficit hyperactivity disorder and attending a child and adolescent clinic in the UK were sent an ADR questionnaire to elicit information on possible ADRs associated with their child's medication use. Two approaches, free text and a symptom tick list, were used to elicit possible ADRs. Two hundred and seven questionnaires were returned, of which 200 were evaluable, giving a response rate of 35.9%. 123 questionnaires reported a total of 213 free-text ADRs perceived by the parents to be due to the medications under study. Two-thirds of reported ADRs were considered to be ongoing at the time of reporting. Duration of reported ADRs ranged from 1 week to 3 years. 81 returned questionnaires reported 134 different ADRs for methylphenidate monotherapy. For methylphenidate, the most frequently reported ADRs were loss of appetite (34.3%), headache (17.9%), mood and emotional problems (14.9%), stomach upset (14.9%), sleep disturbance (10.4%), and rash and other skin problems (5.2%). 467 possible drug-related symptoms were reported using the tick-list approach. Using the tick list, the most frequently reported symptoms were mood and emotional problems (28.1% [131/467]), stomach and abdominal problems (13.3% [62/467]), insomnia (12.8% [60/467]) and lack of appetite (12.6% [59/467]). The symptom tick list identified a broader range of possible adverse effects not reported as free-text ADRs, such as schooling difficulties, hearing problems, cough and blurred vision. The results of our study demonstrate the feasibility of using specialist clinics to target both at-risk patient populations and/or medicines of interest. We have also clearly demonstrated the practicality and feasibility of parental reporting. Parents reported common and less common ADRs, such as suicidal ideation, using both the free text and symptom tick-list approach.

A Survey on Pharmacovigilance Activities in ASEAN and Selected Non-ASEAN Countries, and the Use of Quantitative Signal Detection Algorithms.

PubMed

Chan, Cheng Leng; Ang, Pei San; Li, Shu Chuen

2017-06-01

Most Countries have pharmacovigilance (PV) systems in place to monitor the safe use of health products. The process involves the detection and assessment of safety issues from various sources of information, communicating the risk to stakeholders and taking other relevant risk minimization measures. This study aimed to assess the PV status in Association of Southeast Asian Nation (ASEAN) countries, sources for postmarket safety monitoring, methods used for signal detection and the need for a quantitative signal detection algorithm (QSDA). Comparisons were conducted with centres outside ASEAN. A questionnaire was sent to all PV centres in ASEAN countries, as well as seven other countries, from November 2015 to June 2016. The questionnaire was designed to collect information on the status of PV, with a focus on the use of a QSDA. Data were collected from nine ASEAN countries and seven other countries. PV activities were conducted in all these countries, which were at different stages of development. In terms of adverse drug reaction (ADR) reports, the average number received per year ranged from 3 to 50,000 reports for ASEAN countries and from 7000 to 1,103,200 for non-ASEAN countries. Thirty-three percent of ASEAN countries utilized statistical methods to help detect signals from ADR reports compared with 100% in the other non-ASEAN countries. Eighty percent agreed that the development of a QSDA would help in drug signal detection. The main limitation identified was the lack of knowledge and/or lack of resources. Spontaneous ADR reports from healthcare professionals remains the most frequently used source for safety monitoring. The traditional method of case-by-case review of ADR reports prevailed for signal detection in ASEAN countries. As the reports continue to grow, the development of a QSDA would be useful in helping detect safety signals.

Surface protein Adr2 of Rickettsia rickettsii induced protective immunity against Rocky Mountain spotted fever in C3H/HeN mice.

PubMed

Gong, Wenping; Xiong, Xiaolu; Qi, Yong; Jiao, Jun; Duan, Changsong; Wen, Bohai

2014-04-11

Rickettsia rickettsii is the pathogen of Rocky Mountain spotted fever (RMSF), a life-threatening tick-transmitted infection. Adr2 was a surface-exposed adhesion protein of R. rickettsii and its immunoprotection against RMSF was investigated in mice. Recombinant Adr2 (rAdr2) was used to immunize C3H/HeN mice, and the rickettsial loads in organs of the mice were detected after challenge with R. rickettsii. The levels of specific antibodies of sera from the immunized mice were determined and the sera from immunized mice were applied to neutralize R. rickettsii. Proliferation and cytokine secretion of CD4(+) and CD8(+) T cells isolated from R. rickettsii-infected mice were also assayed after rAdr2 stimulation. After R. rickettsii challenge, the rickettsial loads in spleens, livers, and lungs were significantly lower and the impairment degrees of these organs in rAdr2-immunized mice were markedly slighter, compared with those in negative control mice. The ratio of specific IgG2a/IgG1 of rAdr2-immunized mice kept increasing during the immunization. After treatment with rAdr2-immunized sera, the total number of R. rickettsii organisms adhering and invading host cells was significantly lower than that treated with PBS-immunized sera. Interferon-γ secretion by CD4(+) or CD8(+) T cells and tumor necrosis factor-α secretion by CD4(+) T cells from R. rickettsii-infected mice were respectively significantly greater than those from uninfected mice after rAdr2 stimulation. Adr2 is a protective antigen of R. rickettsii. Protection offered by Adr2 is mainly dependent on antigen-specific cell-mediated immune responses, including efficient activity of CD4(+) and CD8(+) T cells to produce great amount of TNF-α and/or IFN-γ as well as rapid increase of specific IgG2a, which synergistically activate and opsonize host cells to killing intracellular rickettsiae. Copyright © 2014 Elsevier Ltd. All rights reserved.

ABCB1 c.2677G>T variation is associated with adverse reactions of OROS-methylphenidate in children and adolescents with ADHD.

PubMed

Kim, So Won; Lee, Ji Hyun; Lee, Sung Hee; Hong, Hyun Ju; Lee, Min Goo; Yook, Ki-Hwan

2013-08-01

Osmotic-release oral system (OROS)-methylphenidate (MPH) is a safe and well-tolerated drug. Some patients cannot continue this regimen with adverse drug reactions (ADRs). As drug efflux transporters of the central nervous system, ABCB1 plays an important role in the clearance of psychotropic drugs and their metabolites from brain tissues. We hypothesized that genetic variations in the ABCB1 gene may affect ADRs to OROS-MPH. We analyzed ADRs of OROS-MPH in 134 children and adolescents with attention-deficit hyperactivity disorder who completed a 4-week trial of OROS-MPH. The ADRs of OROS-MPH were evaluated by administering the Barkley Stimulant Side Effects Rating Scale. Our study proved that MPH is a substrate for ABCB1 by using membrane vesicle assay. We analyzed the influence of ABCB1 polymorphisms on ADRs to OROS-MPH. From the association study between ABCB1 polymorphisms and ADRs of OROS-MPH, c.2677G>T (p.Ala893Ser, rs2032582) showed a strong association with OROS-MPH-related ADRs (P = 0.008; odds ratio, 5.72). Furthermore, logistic regression analysis indicated that the TT genotype at the ABCB1 2677 locus is an independent determinant of ADRs attributed to OROS-MPH. In a functional study, the 893Ser variant markedly reduced MPH transport across the cell membrane. This is the first study to demonstrate that the TT genotype at position 2677 in the ABCB1 gene is associated with ADRs to OROS-MPH.

Adverse drug reaction reporting among health care workers at Mulago National Referral and Teaching hospital in Uganda.

PubMed

Katusiime, Barbra; Semakula, Daniel; Lubinga, Solomon J

2015-12-01

Adverse Drug Reactions (ADRs) are an important contributor to patient morbidity and hospitalisation in Uganda. Under-reporting of ADRs may increase medicine-induced morbidity and mortality among patients. This study determined the extent of ADR reporting, and associated factors, among healthcare workers in Uganda. A quantitative, cross-sectional, study was conducted. Pretested, semi-structured questionnaires were administered to 289 randomly sampled healthcare workers over a three-month period in Mulago National Referral Hospital, Uganda. The primary outcome was the proportion of healthcare workers who had ever reported an ADR. Data was double-entered in Epidata version 3.0, cleaned and exported to STATA version 10.1 for analysis. The overall response rate was 77.2% (n=223). The majority of the respondents were females (139, 62.3%). The median age of all respondents was 32.6 years (min-23; max-65). Only about 16.6% (n=37) of healthcare workers had ever reported an ADR. Very few (n= 84, 37.7%) healthcare workers knew the tools used in ADR reporting. Less than a quarter (n=41, 18.4%) of the healthcare workers knew where to report ADRs. Lack of training was reported as the major (56.5%, 126) deterrent to reporting ADRs by healthcare workers. Adverse drug reactions are under-reported in Uganda, and healthcare workers have insufficient knowledge of existing pharmacovigilance systems, including ADR reporting systems. To address these challenges, there is need to sensitize and train healthcare workers in patient-centred aspects of medicine surveillance, so as to provide appropriate care while optimising patient safety.

Mechanism-based Pharmacovigilance over the Life Sciences Linked Open Data Cloud.

PubMed

Kamdar, Maulik R; Musen, Mark A

2017-01-01

Adverse drug reactions (ADR) result in significant morbidity and mortality in patients, and a substantial proportion of these ADRs are caused by drug-drug interactions (DDIs). Pharmacovigilance methods are used to detect unanticipated DDIs and ADRs by mining Spontaneous Reporting Systems, such as the US FDA Adverse Event Reporting System (FAERS). However, these methods do not provide mechanistic explanations for the discovered drug-ADR associations in a systematic manner. In this paper, we present a systems pharmacology-based approach to perform mechanism-based pharmacovigilance. We integrate data and knowledge from four different sources using Semantic Web Technologies and Linked Data principles to generate a systems network. We present a network-based Apriori algorithm for association mining in FAERS reports. We evaluate our method against existing pharmacovigilance methods for three different validation sets. Our method has AUROC statistics of 0.7-0.8, similar to current methods, and event-specific thresholds generate AUROC statistics greater than 0.75 for certain ADRs. Finally, we discuss the benefits of using Semantic Web technologies to attain the objectives for mechanism-based pharmacovigilance.

Effect of azimuthal diversion rail on an ATON-type Hall thruster

NASA Astrophysics Data System (ADS)

Xu, Zhang; Liqiu, Wei; Liang, Han; Yongjie, Ding; Daren, Yu

2017-03-01

A newly designed azimuthal diversion rail (ADR) is studied and used to enhance the ionization process in an ATON-type Hall thruster. The diversion rail efficiently reduces the neutral flow axial velocity, and hence, increases the resistance time of atoms in the discharge channel of the Hall thruster. Thrust performances, in terms of thrust, anode efficiency and ion beam divergence, are found to be improved because of the application of the diversion rail, especially at low mass flow rate conditions. Experiment results reveal that the ADR increases the mass utilization under insufficient mass flow rate operating conditions. The design of the ADR broadens the efficient operating range of Hall thrusters and has significant contribution to multi-mode Hall thruster development.

Liposomal curcumin alters chemosensitivity of breast cancer cells to Adriamycin via regulating microRNA expression.

PubMed

Zhou, Siying; Li, Jian; Xu, Hanzi; Zhang, Sijie; Chen, Xiu; Chen, Wei; Yang, Sujin; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

2017-07-30

Emerging evidence suggests that curcumin can overcome drug resistance to classical chemotherapies, but poor bioavailability and low absorption have limited its clinical use and the mechanisms remain unclear. Also, Adriamycin (Adr) is one of the most active cytotoxic agents in breast cancer; however, the high resistant rate of Adr leads to a poor prognosis. We utilized encapsulation in liposomes as a strategy to improve the bioavailability of curcumin and demonstrated that liposomal curcumin altered chemosensitivity of Adr-resistant MCF-7 human breast cancer (MCF-7/Adr) by MTT assay. The miRNA and mRNA expression profiles of MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr cells were analyzed by microarray and further confirmed by real-time PCR. We focused on differentially expressed miR-29b-1-5p to explore the involvement of miR-29b-1-5p in the resistance of Adr. Candidate genes of dysregulated miRNAs were identified by prediction algorithms based on gene expression profiles. Networks of KEGG pathways were organized by the selected dysregulated miRNAs. Moreover, protein-protein interaction (PPI) was utilized to map protein interaction networks of curcumin regulated proteins. We first demonstrated liposomal curcumin could rescue part of Adriamycin resistance in breast cancer and further identified 67 differentially expressed microRNAs among MCF-7/S, MCF-7/Adr and curcumin-treated MCF-7/Adr. The results showed that lower expressed miR-29b-1-5p decreased the IC50 of MCF-7/Adr cells and higher expressed miR-29b-1-5p, weaken the effects of liposomal curcumin to Adr-resistance. Besides, we found that 20 target genes (mRNAs) of each dysregulated miRNA were not only predicted by prediction algorithms, but also differentially expressed in the microarray. The results showed that MAPK, mTOR, PI3K-Akt, AMPK, TNF, Ras signaling pathways and several target genes such as PPARG, RRM2, SRSF1and EPAS1, may associate with drug resistance of breast cancer cells to Adr. We determined that an altered miRNA expression pattern is involved in acquiring resistance to Adr, and that liposomal curcumin could change the resistance to Adr through miRNA signaling pathways in breast cancer MCF-7 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions

PubMed Central

2013-01-01

Background Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. Methods We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. Results A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). Conclusions ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries. PMID:24228998

Performance of the XRS/ASTRO-E engineering model ADR.

NASA Astrophysics Data System (ADS)

Serlemitsos, A. T.; Sansebastian, M.; Kunes, E. S.; Behr, J.

1999-04-01

NASA's Goddard Space Flight Center (GSFC) has developed an X-ray Spectrometer (XRS) to be flown aboard ASTRO-E, in cooperation with the Japanese Institute of Space and Astronomical Science (ISAS). XRS uses an array of 32 microcalorimeters capable of detecting X-rays in the energy range of 0.3 - 10 keV with a resolution of 12 eV. In order to accomplish this, the detectors must be operated at a temperature of 0.065K. In space, an Adiabatic Demagnetization Refrigerator (ADR) must be used to cool the detectors to that temperature. A spaceworthy ADR has been developed at GSFC to be used in the XRS. Originally, the ADR was developed to be flown aboard the Advanced X-ray Astrophysics Facility (AXAF). The allowable average thermal load of the ADR to the LHe dewar was changed from 2.6 mW to 270 μW. Time constraints did not allow a complete redesign of the ADR. The original shape and size were left unchanged and the new specifications were met by streamlining the heat switch and lengthening the salt pill magnetization cycle time. For a LHe bath temperature of 1.3K the gas gap heat switch presently used has an on/off ratio of 22000 and a parasitic heat leak of 2.9 μW/K.

Preventable statin adverse reactions and therapy discontinuation. What can we learn from the spontaneous reporting system?

PubMed

Sessa, Maurizio; Rafaniello, Concetta; Scavone, Cristina; Mascolo, Annamaria; di Mauro, Gabriella; Fucile, Annamaria; Rossi, Francesco; Sportiello, Liberata; Capuano, Annalisa

2018-05-01

Statin treatment is often associated with poor adherence, which may be due to the onset of adverse drug reactions (ADRs). We investigated on potential risk factors related to preventable cases of statin-induced ADRs and to the discontinuation of statin therapy. We performed a study using the database of Italian spontaneous reporting. The target population for the preventability assessment was all patients with suspected statin-induced ADRs deriving from Campania Region (a territory of Southern Italy) between 2012 and 2017. Additionally, a local sentinel surveillance site involving General Practitioners was selected to countercheck in routine clinical practice the role of ADRs for statin discontinuation. In total, 34 of 655 (5.19%) regional cases were preventable and among detected risk factors 90.0% was related to healthcare professionals' practices and 10.0% to patient behaviour. In 81.4% (533/655) of cases, statin therapy was discontinued due to ADRs, mainly classified as not serious and associated with a positive prognosis. These results were also confirmed in the active sentinel site. Our findings suggest an inappropriate use of statins among the identified preventable cases and a potential inappropriate statin discontinuation due to ADRs. These factors may be useful for targeting interventions to improve statin adherence.

A 100 micro Kelvin bolometer system for SIRTF

NASA Technical Reports Server (NTRS)

Bernstein, G. M.; Timbie, P. T.; Richards, P. L.

1989-01-01

Progress toward a prototype of 100 mK bolometric detection system for the Space Infrared Telescope Facility (SIRTF) is described. Two adiabatic demagnetization refrigerators (ADR's) were constructed and used to investigate the capabilities necessary for orbital operation. The first, a laboratory ADR, demonstrated a hold time at 0.1 K of over 12 hours, with temperature stability approx. 3 micro-K RMS achieved by controlling the magnetic field. A durable salt pill and an efficient support system have been demonstrated. A second ADR, the SIRTF flight prototype, has been built and will be flown on a balloon. Techniques for magnetic shielding, low heat leak current leads, and a mechanical heat switch are being developed in this ADR. Plans for construction of 100 mK bolometers are discussed. Three important cosmological investigations which will be carried out by these longest wavelength SIRTF detectors are described.

Combing signals from spontaneous reports and electronic health records for detection of adverse drug reactions

PubMed Central

Harpaz, Rave; Vilar, Santiago; DuMouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol

2013-01-01

Objective Data-mining algorithms that can produce accurate signals of potentially novel adverse drug reactions (ADRs) are a central component of pharmacovigilance. We propose a signal-detection strategy that combines the adverse event reporting system (AERS) of the Food and Drug Administration and electronic health records (EHRs) by requiring signaling in both sources. We claim that this approach leads to improved accuracy of signal detection when the goal is to produce a highly selective ranked set of candidate ADRs. Materials and methods Our investigation was based on over 4 million AERS reports and information extracted from 1.2 million EHR narratives. Well-established methodologies were used to generate signals from each source. The study focused on ADRs related to three high-profile serious adverse reactions. A reference standard of over 600 established and plausible ADRs was created and used to evaluate the proposed approach against a comparator. Results The combined signaling system achieved a statistically significant large improvement over AERS (baseline) in the precision of top ranked signals. The average improvement ranged from 31% to almost threefold for different evaluation categories. Using this system, we identified a new association between the agent, rasburicase, and the adverse event, acute pancreatitis, which was supported by clinical review. Conclusions The results provide promising initial evidence that combining AERS with EHRs via the framework of replicated signaling can improve the accuracy of signal detection for certain operating scenarios. The use of additional EHR data is required to further evaluate the capacity and limits of this system and to extend the generalizability of these results. PMID:23118093

Training mid-career internists to perform high-quality colonoscopy: a pilot training programme to meet increasing demands for colonoscopy.

PubMed

Shah-Ghassemzadeh, Nicole K; Jackson, Christian S; Juma, David; Strong, Richard M

2017-08-01

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the USA. Despite a recent rise in CRC screening there remains an increasing demand for colonoscopy, yet a limited supply of gastroenterologists who can meet this need. To determine if a mid-career general internist (GIN) could be trained to perform high-quality colonoscopes via an intensive training programme. A GIN trained 2-3 days/week, 4-5 hours/day, for 7 months with an experienced gastroenterologist. Their independent performance was then compared with that of a gastroenterology attending (GA), with and without a gastroenterology fellow (GF). The primary outcome was to compare caecal intubation rates, adenoma detection rates (ADRs), interval CRC rates and complications between the three groups. 989 patients were initially included in the study, and 818 were included in the final analysis. Caecal intubation rates were 95%, 94% and 93% for the GIN, GA+GF and GA, respectively (p=0.31). The overall polyp detection rates were 68%, 39% and 44% among the GIN, GA+GF and GA, respectively (p<0.0001). The ADRs were 56%, 33% and 34% for the GIN, GA+GF and GA, respectively (p<0.0001). Three complications occurred, all within the GA group. No interval cancers were diagnosed within a 5-year surveillance period, across all three groups. The GIN attained high success rates in all quality measures. Training mid-career GINs to perform high-quality screening colonoscopes, through a standardised curriculum, may be a reasonable approach to address the growing demand for colonoscopists. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Online reporting of adverse drug reactions: a study from a French regional pharmacovigilance center.

PubMed

Abadie, Delphine; Chebane, Leyla; Bert, Max; Durrieu, Geneviève; Montastruc, Jean-Louis

2014-01-01

In France, online reporting via a website is a new method for notifying adverse drug reactions (ADRs). The French Midi-Pyrénées Regional Pharmacovigilance Center (RPVC) set up in July, 2010 a Web-based ADR reporting tool in order to improve ADR reporting rate. To assess feasibility, use and performances of this new ADR reporting system. To evaluate the main characteristics of these online reports. In a retrospective study, we evaluated characteristics (numbers, ADR reporting and file processing times, type of reporters, suspected drugs, "seriousness" and nature of ADRs) of online notifications reported to the RPVC between July 7(th), 2010 (first online notification) and December 31(th), 2011. We performed comparisons to a random sample of "conventional" notifications, i.e. spontaneously reported to the RPVC via traditional tools (post, fax, e-mail or telephone) during the same period. The total number of online reports was 312 over the 18-month period. There was a 45% increase in numbers of reports from ambulatory healthcare professionals after the implementation of the new reporting tool. Online reports were transmitted to the French Medicine Agency on average almost one month (26 days) earlier than "conventional" ones. This difference was mainly due to a faster ADR notification process via the online form (on average, the reporting period was decreased by 19 days with the new tool). In comparison to "conventional" notifications, online reports came more often from ambulatory healthcare professionals, and involved more frequently neuropsychiatric drugs and neuropsychiatric ADRs. None difference was observed for "seriousness" of ADRs. It is feasible to deploy an online ADR reporting system used by health professionals in current practice. We underline the efficiency of this new online reporting tool for increasing ADRs reporting. Moreover, this is the first published study demonstrating that an online reporting tool can help to save time on the ADR reporting period and file processing, which is essential to generate early safety signals. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Increased cardiac output, not pulmonary artery systolic pressure, increases intrapulmonary shunt in healthy humans breathing room air and 40% O2

PubMed Central

Elliott, Jonathan E; Duke, Joseph W; Hawn, Jerold A; Halliwill, John R; Lovering, Andrew T

2014-01-01

Blood flow through intrapulmonary arteriovenous anastomoses (IPAVAs) has been demonstrated to increase in healthy humans during a variety of conditions; however, whether or not this blood flow represents a source of venous admixture (/) that impairs pulmonary gas exchange efficiency (i.e. increases the alveolar-to-arterial difference (A–aDO2)) remains controversial and unknown. We hypothesized that blood flow through IPAVAs does provide a source of /. To test this, blood flow through IPAVAs was increased in healthy humans at rest breathing room air and 40% O2: (1) during intravenous adrenaline (epinephrine) infusion at 320 ng kg−1 min−1 (320 ADR), and (2) with vagal blockade (2 mg atropine), before and during intravenous adrenaline infusion at 80 ng kg−1 min−1 (ATR + 80 ADR). When breathing room air the A–aDO2 increased by 6 ± 2 mmHg during 320 ADR and by 5 ± 2 mmHg during ATR + 80 ADR, and the change in calculated / was +2% in both conditions. When breathing 40% O2, which minimizes contributions from diffusion limitation and alveolar ventilation-to-perfusion inequality, the A–aDO2 increased by 12 ± 7 mmHg during 320 ADR, and by 9 ± 6 mmHg during ATR + 80 ADR, and the change in calculated / was +2% in both conditions. During 320 ADR cardiac output () and pulmonary artery systolic pressure (PASP) were significantly increased; however, during ATR + 80 ADR only was significantly increased, yet blood flow through IPAVAs as detected with saline contrast echocardiography was not different between conditions. Accordingly, we suggest that blood flow through IPAVAs provides a source of intrapulmonary shunt, and is mediated primarily by increases in rather than PASP. PMID:25085889

Optimization Strategies for Single-Stage, Multi-Stage and Continuous ADRs

NASA Technical Reports Server (NTRS)

Shirron, Peter J.

2014-01-01

Adiabatic Demagnetization Refrigerators (ADR) have many advantages that are prompting a resurgence in their use in spaceflight and laboratory applications. They are solid-state coolers capable of very high efficiency and very wide operating range. However, their low energy storage density translates to larger mass for a given cooling capacity than is possible with other refrigeration techniques. The interplay between refrigerant mass and other parameters such as magnetic field and heat transfer points in multi-stage ADRs gives rise to a wide parameter space for optimization. This paper first presents optimization strategies for single ADR stages, focusing primarily on obtaining the largest cooling capacity per stage mass, then discusses the optimization of multi-stage and continuous ADRs in the context of the coordinated heat transfer that must occur between stages. The goal for the latter is usually to obtain the largest cooling power per mass or volume, but there can also be many secondary objectives, such as limiting instantaneous heat rejection rates and producing intermediate temperatures for cooling of other instrument components.

Thermodynamic Analysis of the 3-Stage ADR for the Astro-H Soft X-Ray Spectrometer Instrument

NASA Technical Reports Server (NTRS)

Shirron, Peter; Kimball, Mark; DiPirro, Michael; Bialas, Tom; Sneiderman, Gary; Porter, Scott; Kelley, Richard

2015-01-01

The Soft X-ray Spectrometer (SXS) instrument on Astro-H will use a 3-stage ADR to cool the microcalorimeter array to 50 mK. In the primary operating mode, two stages of the ADR cool the detectors using superfluid helium at 1.20 K as the heat sink. In the secondary mode, which is activated when the liquid helium is depleted, two of the stages continuously cool the (empty) helium tank using a 4.5 K Joule-Thomson cooler as the heat sink, and the third stage cools the detectors. In the design phase, a high-fidelity model of the ADR was developed in order to predict both the cooling capacity and heat rejection rates in both operating modes. The primary sources of heat flow are from the salt pills, hysteresis heat from the magnets and magnetic shields, and power dissipated by the heat switches. The flight instrument dewar, ADR, detectors and electronics were integrated in mid-2014 and have since undergone extensive performance testing, in part to validate the performance model. This paper will present the thermodynamic performance of the ADR, including cooling capacity, heat rejection to the heat sinks, and various measures of efficiency.

Pharmacovigilance in oncology: evaluation of current practice and future perspectives.

PubMed

Baldo, Paolo; De Paoli, Paolo

2014-10-01

Pharmacovigilance (PV), or drug safety monitoring, aims to improve patient safety through the detection and management of drug-related adverse reactions. It is implemented both by spontaneous reporting of adverse drug reactions (ADRs) and by careful detection of signals suggestive of drug toxicity. PV is an important clinical topic in clinical practice and pharmacotherapy, assuring the maintenance of a safe risk/benefit ratio throughout the commercial life cycle of a drug. We conducted a structured literature search on PubMed, Scopus, Cinahl and the Cochrane Library. We also performed manual searches in international databases of ADR individual reports to outline a structured profile on the topic. Our goal was to review key elements that affect safety monitoring of cancer drugs and their appropriate use, highlighting the strengths and weaknesses of PV in oncology. This paper provides an understanding of the methodologies used by PV in current clinical practice and particularly in cancer drug therapy; a focus upon reporting of ADRs by health professionals and patients; and a focus upon methods used by PV to detect new signals of risk/harm related to medicines utilization. To our knowledge, few articles focus upon the importance of PV and post-marketing surveillance of cancer drug therapies. Structured management of spontaneous reports of ADRs and data collection is essential to monitoring the safe use of drugs in this field in which pharmacotherapy is affected by high incidence of drug-related complications and by a narrow benefit/risk ratio. © 2014 John Wiley & Sons, Ltd.

Estimation of the prevalence of adverse drug reactions from social media.

PubMed

Nguyen, Thin; Larsen, Mark E; O'Dea, Bridianne; Phung, Dinh; Venkatesh, Svetha; Christensen, Helen

2017-06-01

This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora. Agreement between these measures for a sample of ten popular psychiatric drugs was evaluated using the Pearson correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel neural learning framework, was utilized to improve the coverage of variants of ADR terms in the unstructured text by identifying syntactically or semantically similar terms. Improved correlation coefficients, between 0.29 and 0.59, demonstrates the capability of advanced techniques in machine learning to aid in the discovery of meaningful patterns from medical data, and social media data, at scale. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigating patient narratives posted on Internet and their informativeness level for pharmacovigilance purpose: The example of comments about statins.

PubMed

Kheloufi, Farid; Default, Anne; Blin, Olivier; Micallef, Joelle

2017-09-01

Health-related networks like patient health forums may be considered as potential sources of information to early detect pharmacovigilance issues or complete data on drug safety. However, the clinical and pharmacological relevancy of such a source has not been clearly explored. We aimed to describe the characteristics and the informativeness level of Internet narratives posted by patients and mentioning adverse drug reactions (ADRs) related to statins. A retrospective cross-sectional study was conducted on an Internet website dedicated to share experience on medicines. One day of December 2012, postings about simvastatin, rosuvastatin and atorvastatin publicly available on the website were collected. Their informativeness according to 16 key elements of information (including drug start and stop date, duration of treatment, time to onset and duration of the ADR, outcome, medical history, concomitant medication) was assessed. General information about reported ADRs was also investigated. Among the 96 postings related to statins, 72 (40 women, 32 men; mean age: 59 [40-78]) mentioned at least one ADR accounting for a total of 176 ADRs. Musculoskeletal and connective tissue disorders (42.6%) and nervous system disorders (15.3%) were the main represented ADRs. Only 2 patients mentioned ADRs that could be considered as serious but 24 patients mentioned they stopped or switched their treatment toward another lipid modifying agent because of the ADR. Mean number of available key elements of information per narrative was 6/16. Time to onset and duration of the ADR were respectively available in only 31% and 3% of the narratives. Medical history and concomitant medication were respectively lacking in 87% and 86% of the narratives. Outcome was found only in 39% of the narratives. Patient narratives posted on Internet include mainly non-serious expected ADR. However, their informativeness level is very incomplete and makes difficult their assessment and use for pharmacovigilance purpose. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

(/sup 3/H)adrenaline release from hypothalamic synaptosomes and its modulation by clonidine: effects of chronic antidepressant drug regimens

DOE Office of Scientific and Technical Information (OSTI.GOV)

McWilliam, J.R.; Campbell, I.C.

1987-07-13

(/sup 3/H)Adrenaline ((/sup 3/H)ADR, 40nM) was accumulated by rat hypothalamic synaptosomes (P/sub 2/) more rapidly and in significantly greater amounts than by similar preparations from cerebral cortex. There was no significant difference between these two tissues in the rate or amount of (/sup 3/H)noradrenaline ((/sup 3/H)NA, 40nM) accumulation. Talusupram (10..mu..M), maximally inhibited the uptake of (/sup 3/H)ADR into hypothalamic synaptosomes by 60%. Nomifensine further inhibited uptake by 14%. From these observations it was concluded that some (/sup 3/H)ADR was accumulated into non adrenergic neuronal terminals. The effects of desipramine (DMI, 10mg/kg/day and clorgyline (1mg/kg/day) administration for 28 days on K/supmore » +/-evoked release of (/sup 3/H)ADR was investigated using superfused hypothalamic synaptosomes. After both chronic antidepressant drug regimens, total (/sup 3/H)ADR release (spontaneous + evoked) was significantly reduced. Evoked release of (numberH)ADR (by KCl, 16mM) was significantly reduced after the DMI but not the clorgyline regimens. Presynaptic ..cap alpha../sub 2/-adrenoceptor function in the hypothalamus was assessed during superfusion by measuring the reduction in /sup +/-evoked release of (/sup 3/H)ADR caused by clonidine (1/sup +/M). 30 references, 3 figures, 1 table.« less

Gadobutrol for contrast-enhanced magnetic resonance imaging in elderly patients: review of the safety profile from clinical trial, post-marketing surveillance, and pharmacovigilance data.

PubMed

Endrikat, J; Schwenke, C; Prince, M R

2015-07-01

To assess the safety of gadobutrol administration in elderly patients (≥65 years) by comparing the incidence of adverse drug reactions (ADRs) following gadobutrol-enhanced magnetic resonance imaging (MRI) procedures in elderly patients with that in adults aged 18-64 years. Safety data on gadobutrol administration from clinical trials, post-marketing surveillance (PMS) studies, and pharmacovigilance reports were collected in three databases. In each dataset, absolute and relative frequencies of ADRs between age groups were analysed, along with odds ratios and 95% confidence intervals. Logistic regression was used to identify significant influencing factors on ADRs in the PMS and pharmacovigilance data. Rates of reported ADRs were lower in elderly patients versus adults aged <65 years due to a reduced incidence of non-serious ADRs; this was statistically significant for the clinical trials and pharmacovigilance populations, with a trend in the PMS database. Serious ADRs occurred infrequently in the clinical trials and PMS populations (too low for statistical comparison), and pharmacovigilance data demonstrated a low incidence (<0.005%) in both age groups. This evaluation involving three large databases demonstrated no greater incidence of ADRs following gadobutrol-enhanced MRI in elderly patients (≥65 years) compared with younger adults, with gadobutrol having a favourable safety profile in both age groups. Copyright © 2015 The Royal College of Radiologists. All rights reserved.

Impact of the Quality of Bowel Cleansing on the Efficacy of Colonic Cancer Screening: A Prospective, Randomized, Blinded Study

PubMed Central

2015-01-01

Objectives Efficacy of two low volume bowel cleansing preparations, polyethylene glycol plus ascorbate (PEG+Asc) and sodium picosulfate/magnesium citrate (NaPic/MgCit), were compared for polyp and adenoma detection rate (PDR and ADR) and overall cleansing ability. Primary endpoint was PDR (the number of patients with ≥1 polypoid or flat lesion recorded by the colonoscopist). Methods Diagnostic, surveillance or screening colonoscopy patients were enrolled into this investigator-blinded, multi-center Phase IV study and randomized 1:1 to receive PEG+Asc (administered the evening before and the morning of colonoscopy, per label) or NaPic/MgCit (administered in the morning and afternoon the day before colonoscopy, per label). The blinded colonoscopist documented any lesion and assessed cleansing quality (Harefield Cleansing Scale). Results Of 394 patients who completed the study, 393 (PEG+Asc, N=200; NaPic/MgCit, N=193) had a colonoscopy. Overall PDR for PEG+Asc versus NaPic/MgCit was 51.5% versus 44.0%, p=0.139. PDR and ADR on the right side of the bowel were significantly higher with PEG+Asc versus NaPic/MgCit (PDR: 56[28.0%] versus 32[16.6%], p=0.007; ADR: 42[21.0%] versus 23[11.9%], p=0.015), as was detection of flat lesions (43[21.5%] versus 25[13.0%], p=0.025). Cleansing quality was better with PEG+Asc than NaPic/MgCit (98.5% versus 57.5% considered successful cleansing). Overall, there were 132 treatment-emergent adverse events (93 versus 39 for PEG+Asc and NaPic/MgCit, respectively). These were mainly mild abdominal symptoms, all of which were reported for higher proportions of patients in the PEG+Asc than NaPic/MgCit group. Twice as many patients in the NaPic/MgCit versus the PEG+Asc group reported tolerance of cleansing solution as ‘very good’. Conclusions Compared with NaPic/MgCit, PEG+Asc may be more efficacious for overall cleansing ability, and subsequent detection of right-sided and flat lesions. This is likely attributable to the different administration schedules of the two bowel cleansing preparations, which may positively impact the detection and prevention of colorectal cancer, thereby improving mortality rates. Trial Registration ClinicalTrials.gov NCT01689792. PMID:25950434

A New Zealand platform to enable genetic investigation of adverse drug reactions.

PubMed

Maggo, Simran Ds; Chua, Eng Wee; Chin, Paul; Cree, Simone; Pearson, John; Doogue, Matthew; Kennedy, Martin A

2017-12-01

A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is to provide a genetic explanation of drug-induced ADRs using methods ranging from Sanger sequencing to whole exome and whole genome sequencing. Participants for the UDRUGS study are recruited from various sources, mainly via referral through clinicians working in Canterbury District Health Board, but also from district health boards across New Zealand. Participants have also self-referred to us from word-of-mouth communication between participants. We have recruited various ADRs across most drug classes. Where possible, we have conducted genetic analyses in single or a cohort of cases to identify known and novel genetic association(s) to offer an explanation to why the ADR occurred. Any genetic results relevant to the ADR are communicated back to the referring clinician and/or participant. In conclusion, we have developed a programme for studying the genetic basis of severe, rare or unusual ADR cases resulting from pharmacological treatment. Genomic analyses could eventually identify most genetic variants that predispose to ADRs, enabling a priori detection of such variants with high throughput DNA tests.

The knowledge and attitude of the Turkish community pharmacists toward pharmacovigilance in the Kadikoy district of Istanbul.

PubMed

Toklu, Hale Zerrin; Uysal, Meral Keyer

2008-10-01

We investigated the knowledge and attitudes of community pharmacists towards pharmacovigilance and adverse drug reactions (ADRs) in Kadiköy district of Istanbul (Turkey). The community pharmacies in Kadikoy. Kadikoy is one of the biggest districts of Istanbul and has the largest number of pharmacies. Kadikoy district was divided into two regions, the central and the peripheral. Between December 2005 and June 2006 we conducted a survey about the knowledge and attitude of community pharmacists (n = 219) using a face-to-face questionnaire. The questionnaire consisted of questions about the sociodemographic characteristics of the pharmacists, their knowledge of pharmacovigilance and their attitudes towards ADR reporting. The knowledge of pharmacovigilance practice, ADR reporting compliance rates, reasons for not reporting ADR and perceptions of the Turkish community pharmacists on pharmacovigilance practice were evaluated. Although all 411 pharmacies in the Kadikoy district were visited, only 53% of the community pharmacists (n = 219) consented to participate in the study. Of those that did respond, only 17.2% of the pharmacists had any knowledge about 'pharmacovigilance'. Sixty-five percent of the pharmacists stated that patients reported an ADR to them during the previous 12 months, and 21% of pharmacists reported to the concerned organizations. Our survey showed that only 7% actually reported an ADR to the national pharmacovigilance center. On the other hand, 89% of the pharmacists believed that the role of the pharmacist in ADR reporting was essential. The results show that Turkish community pharmacists have poor knowledge about pharmacovigilance. There is an urgent need for educational programs to train them about pharmacovigilance and ADR reporting.

Postmarketing Safety Surveillance and Reevaluation of Danhong Injection: Clinical Study of 30888 Cases

PubMed Central

Li, Xue-Lin; Tang, Jin-Fa; Li, Wei-Xia; Li, Chun-Xiao; Zhao, Tao; Zhao, Bu-Chang; Wang, Yong; Zhang, Hui; Chen, Xiao-Fei; Xu, Tao; Zhu, Ming-Jun

2015-01-01

Traditional Chinese medicine injections (TCMIs) have played an irreplaceable role for treating some clinical emergency, severe illness, and infectious diseases in China. In recent years, the incidence rates of adverse drug reactions (ADRs) of TCMIs have increased year by year. Danhong injection (DHI) is one representative TCMI comprised of Danshen and Honghua for treating cardiovascular and cerebrovascular diseases in clinic. In present study, the postmarketing safety surveillance and reevaluation of DHI were reported. Total 30888 patients in 37 hospitals from 6 provinces participated in the study. The results showed that the ADR incidence rate of DHI was 3.50‰. Seventeen kinds of new adverse reactions of DHI were found. The main type of ADRs of DHI was type A (including sweating, dizziness, headache, flushing, vasodilation, eye hemorrhage, faintness, chest pain, palpitations, breathlessness, anxious, nausea, flatulence, vomiting, hypotension, hypertension, local numbness, dyspnea, joint disease, and tinnitus) accounting for 57.75%. The severities of most ADRs of DHI were mild and moderate reactions accounting for 25.93% and 66.67%, respectively. The main disposition of ADRs of DHI was drug withdrawal and without any treatments. The results can provide basis for amendment and improvement of the instructions of DHI, as well as demonstration and reference for the postmarketing safety surveillance and reevaluation of other TCMIs. And the rationality, scientificity, and safety of clinical applications of TCMIs could be improved. PMID:26508981

Human biology-based drug safety evaluation: scientific rationale, current status and future challenges.

PubMed

Kenna, J Gerry

2017-05-01

Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness. Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients. The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern. Especially promising assays, which have been described recently in peer-reviewed scientific literature, are highlighted. Expert opinion: Effective interpretation of in vitro toxicity data requires integration of endpoints from multiple assays, which each address different mechanisms, and must also take account of human systemic and tissue drug exposure in vivo. Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.

Procedural and longer-term outcomes of wire- versus device-based antegrade dissection and re-entry techniques for the percutaneous revascularization of coronary chronic total occlusions.

PubMed

Azzalini, Lorenzo; Dautov, Rustem; Brilakis, Emmanouil S; Ojeda, Soledad; Benincasa, Susanna; Bellini, Barbara; Karatasakis, Aris; Chavarría, Jorge; Rangan, Bavana V; Pan, Manuel; Carlino, Mauro; Colombo, Antonio; Rinfret, Stéphane

2017-03-15

There are few data regarding the procedural and follow-up outcomes of different antegrade dissection/re-entry (ADR) techniques for chronic total occlusion (CTO) percutaneous coronary intervention (PCI). We compiled a multicenter registry of consecutive patients undergoing ADR-based CTO PCI at four high-volume specialized institutions. Patients were divided according to the specific ADR technique used: subintimal tracking and re-entry (STAR), limited antegrade subintimal tracking (LAST), or device-based with the CrossBoss/Stingray system (Boston Scientific, Marlborough, MA). Major adverse cardiac events (MACE: cardiac death, target-vessel myocardial infarction and target-vessel revascularization) on follow-up were the main outcome of this study. Independent predictors of MACE were sought with Cox regression analysis. A total of 223 patients were included (STAR n=39, LAST n=68, CrossBoss/Stingray n=116). Baseline characteristics were similar across groups. Technical and procedural success was lower with STAR (59% and 59%), as compared with LAST (96% and 96%) and CrossBoss/Stingray (89% and 87%; p<0.001 for both). At 24-month follow-up, MACE rates were higher in STAR (15.4%) and LAST (17.5%), as compared with device-based ADR with CrossBoss/Stingray (4.3%, p=0.02), driven by TVR (7.7% vs. 15.5% vs. 3.1%, respectively; p=0.02). Multivariable Cox regression analysis identified wire-based ADR (STAR and LAST) and total stent length as independent predictors of MACE. In this multicenter cohort of patients undergoing CTO PCI with ADR techniques, STAR had lower success rates, as compared with the CrossBoss/Stingray system and LAST. The CrossBoss/Stingray system was independently associated with lower risk of MACE on follow-up, as compared with wire-based ADR techniques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exploring Spanish health social media for detecting drug effects.

PubMed

Segura-Bedmar, Isabel; Martínez, Paloma; Revert, Ricardo; Moreno-Schneider, Julián

2015-01-01

Adverse Drug reactions (ADR) cause a high number of deaths among hospitalized patients in developed countries. Major drug agencies have devoted a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Reporting systems are available in order for both healthcare professionals and patients to alert about possible ADRs. However, several studies have shown that these adverse events are underestimated. Our hypothesis is that health social networks could be a significant information source for the early detection of ADRs as well as of new drug indications. In this work we present a system for detecting drug effects (which include both adverse drug reactions as well as drug indications) from user posts extracted from a Spanish health forum. Texts were processed using MeaningCloud, a multilingual text analysis engine, to identify drugs and effects. In addition, we developed the first Spanish database storing drugs as well as their effects automatically built from drug package inserts gathered from online websites. We then applied a distant-supervision method using the database on a collection of 84,000 messages in order to extract the relations between drugs and their effects. To classify the relation instances, we used a kernel method based only on shallow linguistic information of the sentences. Regarding Relation Extraction of drugs and their effects, the distant supervision approach achieved a recall of 0.59 and a precision of 0.48. The task of extracting relations between drugs and their effects from social media is a complex challenge due to the characteristics of social media texts. These texts, typically posts or tweets, usually contain many grammatical errors and spelling mistakes. Moreover, patients use lay terminology to refer to diseases, symptoms and indications that is not usually included in lexical resources in languages other than English.

Knowledge of Adverse Drug Reaction Reporting Among Healthcare Professionals in Bhutan: A Cross-Sectional Survey.

PubMed

Dorji, Choki; Tragulpiankit, Pramote; Riewpaiboon, Arthorn; Tobgay, Tashi

2016-12-01

The Bhutan National Pharmacovigilance Centre (NPC) became an official member of the WHO Programme for International Drug Monitoring in December 2014; however, the number of adverse drug reactions (ADRs) reported is very low (50 reports per 773,722 inhabitants over 10 years). Surveys of healthcare professionals (HCPs) in similar countries have indicated that adequate knowledge of both ADRs and ADR reporting is likely to increase the number of ADR reports submitted. The aim of this study was to investigate the level of knowledge of both ADRs and ADR reporting among HCPs, including traditional medicine practitioners. A cross-sectional survey was conducted, using a validated self-administered questionnaire. The questionnaires were distributed to 670 HCPs, including clinical doctors, nurses, pharmacists and traditional medicine practitioners from four referral hospitals. The survey consisted of 12 questions pertaining to ADRs and 10 questions pertaining to knowledge of ADR reporting. The collected response was then analysed descriptively and results presented as mean ± standard deviation (SD) using SPSS version 20. The overall response rate was 434 (65 %) questionnaires, with HCPs consisting of clinical doctors (94, 22 %), nurses (257, 59 %), pharmacists (52, 12 %) and traditional medicine practitioners (31, 7 %). The overall mean ± SD score with regard to the level of knowledge of ADRs was 6.52 ± 2.81 out of a maximum score of 12, among which clinical doctors scored 7.48 ± 2.95, nurses 6.15 ± 2.47, pharmacists 8.15 ± 2.49 and traditional medicine practitioners 4.13 ± 3.18. The mean ± SD score with regard to the level of knowledge of ADR reporting among HCPs was 3.94 ± 1.89 out of a maximum score of 10, among which clinical doctors scored 3.93 ± 1.81, nurses 3.75 ± 1.74, pharmacists 5.00 ± 1.81 and traditional medicine practitioners 4.00 ± 1.77. Clinical doctors and pharmacists have better knowledge of ADRs than nurses and traditional medicine practitioners, while knowledge of ADR reporting was low for all HCPs surveyed.

How to promote adverse drug reaction reports using information systems - a systematic review and meta-analysis.

PubMed

Ribeiro-Vaz, Inês; Silva, Ana-Marta; Costa Santos, Cristina; Cruz-Correia, Ricardo

2016-03-01

Adverse drug reactions (ADRs) are a well-recognized public health problem and a major cause of death and hospitalization in developed countries. The safety of a new drug cannot be established until it has been on the market for several years. Keeping drug reactions under surveillance through pharmacovigilance systems is indispensable. However, underreporting is a major issue that undermines the effectiveness of spontaneous reports. Our work presents a systematic review on the use of information systems for the promotion of ADR reporting. The aim of this work is to describe the state of the art information systems used to promote adverse drug reaction reporting. A systematic review was performed with quantitative analysis of studies describing or evaluating the use of information systems to promote adverse drug reaction reporting. Studies with data related to the number of ADRs reported before and after each intervention and the follow-up period were included in the quantitative analysis. From a total of 3865 articles, 33 articles were included in the analysis; these articles described 29 different projects. Most of the projects were on a regional scale (62 %) and were performed in a hospital context (52 %). A total of 76 % performed passive promotion of ADR reporting and used web-based software (55 %). A total of 72 % targeted healthcare professionals and 24 % were oriented to patient ADR reporting. We performed a meta-analysis of 7 of the 29 projects to calculate the aggregated measure of the ADR reporting increase, which had an overall measure of 2.1 (indicating that the interventions doubled the number of ADRs reported). We found that most of the projects performed passive promotion of ADR reporting (i.e., facilitating the process). They were developed in hospitals and were tailored to healthcare professionals. These interventions doubled the number of ADR reports. We believe that it would be useful to develop systems to assist healthcare professionals with completing ADR reporting within electronic health records because this approach seems to be an efficient method to increase the ADR reporting rate. When this approach is not possible, it is essential to have a tool that is easily accessible on the web to report ADRs. This tool can be promoted by sending emails or through the inclusion of direct hyperlinks on healthcare professionals' desktops.

The AXAF/XRS ADR - Engineering model

NASA Technical Reports Server (NTRS)

Serlemitsos, Aristides T.; Sansebastian, Marcelino; Kunes, Evan S.

1991-01-01

A spaceworthy Adiabatic Demagnetization Refrigerator is under development at Goddard Space Flight Center as part of the X-Ray Spectrometer (XRS), an instrument on the Advanced X-ray Astrophysics Facility (AXAF). XRS will employ an array of 32 microcalorimeters capable of detecting X-rays in the energy range of 0.3 - 10 keV. In order to achieve a desired resolution of 12 eV, these detectors must be operated at a temperature of 0.065 - 0.100 K. An ADR must be used to cool these detectors in space. A breadboard model was designed and built less than two years ago, and provided excellent results. We are presently at the development stage of the engineering model. Several changes have been made to the original design in order to improve the efficiency of the ADR, to reduce its weight, and to strengthen the salt pill suspension system so that the ADR can survive launch loads and have low sensitivity to microphonic inputs. We shall report on the results of these changes; what worked and what did not.

Therapeutic effect of ozone and rutin on adriamycin-induced testicular toxicity in an experimental rat model.

PubMed

Salem, E A; Salem, N A; Hellstrom, W J

2017-02-01

To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)-induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C-reactive protein, monocyte chemoattractant proteins-1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels. © 2016 Blackwell Verlag GmbH.

Therapeutic monoclonal antibodies and the need for targeted pharmacovigilance in India

PubMed Central

Kalaivani, M; Singh, Abhishank; Kalaiselvan, V

2015-01-01

A growing number of innovative mAb therapeutics are on the global market, and biosimilar versions have now also been approved, including in India. Although efficacy and safety is demonstrated prior to approval, targeted pharmacovigilance is essential for the identification and assessment of risk for any mAb products. We analyzed the ADR data related to mAbs reported to the NCC-PvPI through the spontaneous reporting system Vigiflow during April 2011 to February 2014 to identify mAbs with the highest number of ADR including fatal/serious ADR. Only 0.72% reports were related to mAbs. Although 15 mAbs are approved in the country, only 6 mAbs were reported through Vigiflow. Rituximab was highly reported, and no fatal/serious ADR related to any mAbs were reported during the study period. Our study shows that PvPI is effective and robust system in the detection and assessment of risks associated with the use of mAbs. PMID:25523367

Safety Profile of Oral Iron Chelator Deferiprone in Chinese Children with Transfusion-Dependent Thalassaemia.

PubMed

Botzenhardt, Sebastian; Sing, Chor W; Wong, Ian C K; Chan, Godfrey Chi-Fung; Wong, Lisa Y L; Felisi, Mariagrazia; Rascher, Wolfgang; Ceci, Adriana; Neubert, Antje

2016-01-01

There is a lack of knowledge regarding the incidence of serious adverse drug reactions (ADR) to the oral iron chelator deferiprone in Chinese children with transfusion-dependent thalassaemia. In this retrospective population-based cohort study, paediatric thalassaemia patients in Hong Kong were screened for serious and medically important adverse events related to deferiprone therapy using diagnosis codes, laboratory data and hospital admissions. Potential ADRs were assessed by reviewing concomitant medications, diagnoses and laboratory data and evaluated using standardised causality assessment. Eighty-seven patients contributing 169.8 person-years were included. Thirty ADRs were identified in 21 patients. Most ADRs (56.0%) occurred in the first three months of therapy. Neutropenia occurred in 11 patients (12.6%; incidence rate 6.5 per 100 patient-years) and severe neutropenia (agranulocytosis) was observed in 5 patients (5.7%, incidence rate 2.9 per 100 patient-years). Other identified ADRs involve severe arthropathy, elevated liver enzymes and mild thrombocytopenia. In conclusion, the safety profile of DFP therapy in Chinese children suffering from transfusion-dependent thalassaemia is in line with previous studies of non-Chinese children. However, unlike previous studies, we observed a relatively high incidence of agranulocytosis and neutropenia in patients with simultaneous combined therapy. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy. Further prospective clinical and pharmacogenetic studies are required to better evaluate this important safety signal. • Half of the identified ADRs related to deferiprone therapy occurred during the first three months of treatment. • A relatively high incidence of agranulocytosis and neutropenia. Hence close monitoring for white blood cell counts is advised in Chinese children under combined iron chelation therapy.

Adiabatic diesel engine component development: Reference engine for on-highway applications

NASA Technical Reports Server (NTRS)

Hakim, Nabil S.

1986-01-01

The main objectives were to select an advanced low heat rejection diesel reference engine (ADRE) and to carry out systems analysis and design. The ADRE concept selection consisted of: (1) rated point performance optimization; (2) study of various exhaust energy recovery scenarios; (3) components, systems and engine configuration studies; and (4) life cycle cost estimates of the ADRE economic worth. The resulting ADRE design proposed a reciprocator with many advanced features for the 1995 technology demonstration time frame. These included ceramic air gap insulated hot section structural components, high temperature tribology treatments, nonmechanical (camless) valve actuation systems, and elimination of the cylinder head gasket. ADRE system analysis and design resulted in more definition of the engine systems. These systems include: (1) electro-hydraulic valve actuation, (2) electronic common rail injection system; (3) engine electronic control; (4) power transfer for accessory drives and exhaust energy recovery systems; and (5) truck installation. Tribology and performance assessments were also carried out. Finite element and probability of survival analyses were undertaken for the ceramic low heat rejection component.

Pharmacovigilance and adverse drug reaction reporting: a perspective of community pharmacists and pharmacy technicians in Sana'a, Yemen.

PubMed

Al-Worafi, Yaser Mohammed; Kassab, Yaman Walid; Alseragi, Wafa Mohammed; Almutairi, Masaad Saeed; Ahmed, Ali; Ming, Long Chiau; Alkhoshaiban, Ali Saleh; Hadi, Muhammad Abdul

2017-01-01

The aim of this study was to compare the knowledge, attitude and barriers of pharmacy technicians and pharmacists toward pharmacovigilance, adverse drug reactions (ADRs) and ADR reporting in community pharmacies in Yemen. This cross-sectional survey was conducted among community pharmacists and pharmacy technicians in the capital of Yemen, Sana'a. A total of 289 community pharmacies were randomly selected. The validated and pilot-tested questionnaire consisted of six sections: demographic data, knowledge about pharmacovigilance, experience with ADR reporting, attitudes toward ADR reporting, and the facilitators to improve ADR reporting. A total of 428 pharmacy technicians and pharmacists were contacted and 179 went on to complete a questionnaire (response rate: 41.8%). Of the 179 respondents, 21 (11.7%) were pharmacists and 158 (88.3%) were pharmacy technicians, of which, 176 (98.3%) were male and 3 (1.7%) were female. The mean age of the respondents was 25.87±2.63 years. There was a significant difference between the pharmacists and pharmacy technicians in terms of knowledge scores ( P <0.05). The mean knowledge scores for pharmacists was 3.33±2.852 compared to 0.15±0.666 for pharmacy technicians. With regard to attitudes toward ADR reporting, all pharmacists (100%) showed a positive attitude, while only 43% of pharmacy technicians showed a positive attitude. Pharmacists have a significantly better knowledge than pharmacy technicians with regard to pharmacovigilance. More than half of pharmacy technicians showed a negative attitude toward ADR reporting. Therefore, educational interventions and training is very important for community pharmacists and pharmacy technicians in Yemen to increase their awareness and participation in ADR reporting.

Pharmacovigilance and adverse drug reaction reporting: a perspective of community pharmacists and pharmacy technicians in Sana’a, Yemen

PubMed Central

Al-Worafi, Yaser Mohammed; Kassab, Yaman Walid; Alseragi, Wafa Mohammed; Almutairi, Masaad Saeed; Ahmed, Ali; Ming, Long Chiau; Alkhoshaiban, Ali Saleh; Hadi, Muhammad Abdul

2017-01-01

Objective The aim of this study was to compare the knowledge, attitude and barriers of pharmacy technicians and pharmacists toward pharmacovigilance, adverse drug reactions (ADRs) and ADR reporting in community pharmacies in Yemen. Methods This cross-sectional survey was conducted among community pharmacists and pharmacy technicians in the capital of Yemen, Sana’a. A total of 289 community pharmacies were randomly selected. The validated and pilot-tested questionnaire consisted of six sections: demographic data, knowledge about pharmacovigilance, experience with ADR reporting, attitudes toward ADR reporting, and the facilitators to improve ADR reporting. Results A total of 428 pharmacy technicians and pharmacists were contacted and 179 went on to complete a questionnaire (response rate: 41.8%). Of the 179 respondents, 21 (11.7%) were pharmacists and 158 (88.3%) were pharmacy technicians, of which, 176 (98.3%) were male and 3 (1.7%) were female. The mean age of the respondents was 25.87±2.63 years. There was a significant difference between the pharmacists and pharmacy technicians in terms of knowledge scores (P<0.05). The mean knowledge scores for pharmacists was 3.33±2.852 compared to 0.15±0.666 for pharmacy technicians. With regard to attitudes toward ADR reporting, all pharmacists (100%) showed a positive attitude, while only 43% of pharmacy technicians showed a positive attitude. Conclusion Pharmacists have a significantly better knowledge than pharmacy technicians with regard to pharmacovigilance. More than half of pharmacy technicians showed a negative attitude toward ADR reporting. Therefore, educational interventions and training is very important for community pharmacists and pharmacy technicians in Yemen to increase their awareness and participation in ADR reporting. PMID:28924350

Review of the rational use and adverse reactions to human serum albumin in the People’s Republic of China

PubMed Central

Zhou, Ting; Lu, Saihua; Liu, Xiufeng; Zhang, Ye; Xu, Feng

2013-01-01

Human serum albumin (HSA) is an ideal natural colloid that has been widely used in clinical practice for supplemental albumin or as a plasma substitute during therapeutic plasma exchanges to redress hypoproteinemia. However, a paucity of well-designed clinical trials, a lack of a clear cut survival benefit, and frequent case reports of adverse drug reaction (ADR) make the use of HSA controversial. This study aims to review and to comment on the reported ADRs of HSA in the People’s Republic of China, so as to provide the basis for rational HSA use in clinical settings. Data on the ADR case reports from HSA administration between January 1990 and December 2012 available from the China National Knowledge Infrastructure (CNKI) database, Wanfang data (WF), and Chinese Biomedical Literature (CBM) were reviewed. The reasons for using HSA, the types of ADRs, the causality of ADRs and the rationality for HSA administration were extracted and analyzed. In total, 61 cases of ADR reports were identified of which the primary disease of patients using HSA was malignant tumor (34.42%). The primary ADR was anaphylaxis (59.02%). Of the 61 cases, 30 were caused by irrational use of HSA. The most common irrational use was off-label use (56.67%), followed by inappropriate infusion rate. Therefore, we conclude that to avoid the occurrence of ADRs, guidelines for using HSA are needed to guarantee its rational use and HSA should be used strictly according to these guidelines. In addition, medical staff, including clinical pharmacists and nurses, should pay more attention to the patients who inject HSA to ensure its safe use in the clinic. PMID:24348023

Post-marketing safety and effectiveness evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir. II: a pediatric drug use investigation.

PubMed

Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Ariyasu, Yasuyuki; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

2015-03-01

Peramivir is the only intravenous formulation among anti-influenza neuraminidase inhibitors currently available. Peramivir was approved for manufacturing and marketing in Japan in January 2010. In October 2010, an additional indication for pediatric use was approved. We conducted a pediatric drug use investigation of peramivir from October 2010 to February 2012 and evaluated its real-world safety and effectiveness in pediatric patients. We collected the data of 1254 peramivir-treated pediatric patients from 161 facilities across Japan and examined the safety in 1199 patients and effectiveness in 1188 patients. In total, 245 adverse events were observed with an incidence rate of 14.01% (168/1199). Of these, 115 events were adverse drug reactions (ADRs) with an incidence rate of 7.67% (92/1199). Common ADRs were diarrhea and abnormal behavior, with incidence rates of 2.50% (30/1199) and 2.25% (27/1199), respectively. Fourteen serious ADRs were observed in 12 patients (1.00%), including 5 cases each of abnormal behavior and neutrophil count decreased. While 87.0% (100 events) of ADRs occurred within 3 days after the initiation of peramivir administration, 87.8% (101 events) resolved or improved within 7 days after onset. Multivariate analyses indicated that the presence or absence of underlying diseases/complications was significantly related to ADR incidence. With regard to effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration. Thus, this study confirms the pediatric safety of peramivir without any concerns about effectiveness under routine clinical settings. Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Prevalence of flat lesions in a large screening population and their role in colonoscopy quality improvement.

PubMed

Reinhart, K; Bannert, C; Dunkler, D; Salzl, P; Trauner, M; Renner, F; Knoflach, P; Ferlitsch, A; Weiss, W; Ferlitsch, M

2013-01-01

Flat lesions pose new challenges for endoscopists, but the importance of detecting them is still controversial. Most screening studies do not survey macroscopic polyp morphology. The aims were to evaluate the percentage of flat polyp findings in a large asymptomatic adult screening population (n = 52 521), to assess the impact of shape and size on malignant transformation, and to assess the role of flat lesions regarding quality assurance in colorectal cancer prevention. Retrospective analysis of screening colonoscopies performed between 2007 and 2011 according to the Austrian "Quality management for colon cancer prevention" program. 17 771 patients with polyps were included in the study. Patients with flat polyps represented 24.2 % (n = 4293), 62.4 % (n = 11 097) were classified as having sessile and 13.4 % (n = 2381) as pedunculated polyps. Among those with flat polyps 51.4 % had adenomas (n = 2207). High grade dysplasia (HGD) was found in 2.1 % (n = 47) of flat adenomas, in 1.5 % (n = 89) of sessile adenomas and 4.7 % (n = 92) of pedunculated adenomas (P < 0.0001. The risk for containing HGD was 1.0 % for flat lesions ≤ 10 mm in size compared with 10.3 % for lesions > 10 mm, and 1.0 % for polypoid lesions ≤ 10 mm compared with 9.3 % for lesions > 10 mm (P < 0.0001). Multivariable logistic regression showed that polyp size (P < 0.0001) but not polyp shape (P = 0.438) is an independent predictor for HGD. Adenoma detection rate (ADR) correlated weakly with the flat polyp detection rate (Pearson r = 0.24). Malignant potential of polyps is mostly affected by size but not by shape. Since flat polyp detection rate only correlates poorly with ADR we do not recommend its incorporation in quality assured screening colonoscopy. © Georg Thieme Verlag KG Stuttgart · New York.

Risk factors of early adverse drug reactions with phenytoin: A prospective inpatient cohort.

PubMed

Uribe-San-Martín, Reinaldo; Ciampi, Ethel; Uslar, Wilhelm; Villagra, Silvana; Plaza, Jose; Godoy, Jaime; Mellado, Patricio

2017-11-01

Phenytoin (PHT) is an effective and inexpensive antiepileptic drug (AED). However, its use has been limited for fear of adverse drug reactions (ADRs) and is being replaced by newer AED, increasing the costs and causing major budget problems, particularly for developing countries. The objective of this study was to determine ADR frequency, explore, and establish related risk factors. Prospective data were collected from a cohort of inpatients using PHT for the first time. Pharmacovigilance was performed during hospitalization and after one month from the discharge. Clinical variables, plasma levels, and concomitant medications were collected and their association with the occurrence of different ADRs was explored. One hundred patients were included: 59 were women, and mean age was 59±21years. Thirty-three patients presented ADR, all moderate and idiosyncratic. The most frequent were rash (17%), fever (10%), and elevated transaminases (10%). Female gender (85% vs 52%, p=0.029), younger age (mean age: 49 vs 62years, p=0.032), and higher PHT plasmatic levels after IV-PO load (mean plasmatic levels: 18.6 vs 13.9μg/mL, p=0.040) were found to be associated with rash. A higher number of concomitant medications were also found to be associated with the risk for developing any ADR. The multivariate analysis revealed an association between rash and younger age (cut-off: 35years old; relative risk (RR)=11.7; p=0.026), and higher PHT plasmatic levels (cut-off: 16μg/mL; RR=12.5; p=0.021); and increased risk of elevated transaminases with use of PHT inductors (RR=18; p=0.006). A longer hospital stay was found in patients who developed fever (mean: 43days, p<0.0001) and elevated transaminases (mean: 26days, p=0.041) compared with patients without ADR (mean: 17days). Phenytoin is a widely used AED associated with easily detectable ADR through structured pharmacovigilance. The development of ADR is associated with longer hospital stays. Recognition of local risk factors may lead to ADR prevention in a near future. Larger studies are needed to better define PHT-related ADR risk profile and to individualize treatment regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

Toward multimodal signal detection of adverse drug reactions.

PubMed

Harpaz, Rave; DuMouchel, William; Schuemie, Martijn; Bodenreider, Olivier; Friedman, Carol; Horvitz, Eric; Ripple, Anna; Sorbello, Alfred; White, Ryen W; Winnenburg, Rainer; Shah, Nigam H

2017-12-01

Improving mechanisms to detect adverse drug reactions (ADRs) is key to strengthening post-marketing drug safety surveillance. Signal detection is presently unimodal, relying on a single information source. Multimodal signal detection is based on jointly analyzing multiple information sources. Building on, and expanding the work done in prior studies, the aim of the article is to further research on multimodal signal detection, explore its potential benefits, and propose methods for its construction and evaluation. Four data sources are investigated; FDA's adverse event reporting system, insurance claims, the MEDLINE citation database, and the logs of major Web search engines. Published methods are used to generate and combine signals from each data source. Two distinct reference benchmarks corresponding to well-established and recently labeled ADRs respectively are used to evaluate the performance of multimodal signal detection in terms of area under the ROC curve (AUC) and lead-time-to-detection, with the latter relative to labeling revision dates. Limited to our reference benchmarks, multimodal signal detection provides AUC improvements ranging from 0.04 to 0.09 based on a widely used evaluation benchmark, and a comparative added lead-time of 7-22 months relative to labeling revision dates from a time-indexed benchmark. The results support the notion that utilizing and jointly analyzing multiple data sources may lead to improved signal detection. Given certain data and benchmark limitations, the early stage of development, and the complexity of ADRs, it is currently not possible to make definitive statements about the ultimate utility of the concept. Continued development of multimodal signal detection requires a deeper understanding the data sources used, additional benchmarks, and further research on methods to generate and synthesize signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of a Cryogen-Free Continuous ADR for the Constellation-X Mission

NASA Technical Reports Server (NTRS)

Shirron, Peter; Canavan, Ed; DiPirro, Michael; Francis, John; Jackson, Michael; Tuttle, James; King, Todd; Grabowski, Matt

2003-01-01

Constellation-X is a multi-satellite x-ray astronomy mission presently being planned for launch in the 2010 time frame. Each of 4 identical satellites will contain a telescope and instruments for imaging and spectroscopic analysis of both hard and soft x-rays. The X- ray Microcalorimeter Spectrometer (XMS) instrument will use arrays of microcalorimeters to detect X-rays with energies from 0.2 to 6 keV. The technologies under development for this instrument include Transition-Edge Sensors (TES) with multiplexed SQUID readouts and NTD-Ge detectors with JFET readouts. Both will be operated at temperatures in the 50-60 mK range and both have a projected cooling power requirement of approximately 5 microwatts. In addition, in order to meet the lifetime requirement of 6 years (with a goal of 10 years), a mechanical cryocooler will be used to provide a heat sink for the low temperature cooler. The required performance is 20 mW at 6 K, with a goal of 4 K operation. In this paper we present the development status of an adiabatic demagnetization refigerator (ADR) that meets the cooling requirements of the X M S instrument. At present we have demonstrated a 4-stage ADR that operates continuously at 50 mK using a 4.2 K helium bath as a heat sink. The cooling power is 21 microwatts at 100 mK and 6 microwatts at 50 mK. Its efficiency when operating at 50 mK is 1 1 % of Carnot (accounting for all dissipation at 4.2 K and below, but not including power dissipation in the room temperature electronics), but this is expected to rise to 25% in the next generation system in which active gas-gap heat switches are replaced with passive devices. This will reduce the peak heat rejection rate of the ADR to less than 7 mW at 6 K. Details of the ADR s design and operation, as well as the development program leading up to a flight-qualified instrument, will be discussed.

Is water exchange superior to water immersion for colonoscopy? A systematic review and meta-analysis.

PubMed

Chen, Zhihao; Li, Zhengqi; Yu, Xinying; Wang, Guiqi

2018-06-05

Recently, water exchange (WE) instead of water immersion (WI) for colonoscopy has been proposed to decrease pain and improve adenoma detection rate (ADR). This systematic review and meta-analysis is conducted to assess whether WE is superior to WI based on the published randomized controlled trials (RCTs). We searched studies from PubMed, Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE. Only RCTs were eligible for our study. The pooled risk ratios (RRs), pooled mean difference (MD), and pooled 95% confidence intervals (CIs) were calculated by using the fixed-effects model or random-effects model based on heterogeneity. Five RCTs consisting of 2229 colonoscopies were included in this study. WE was associated with a significantly higher ADR than WI (RR = 1.18; CI = 1.05-1.32; P = 0.004), especially in right colon (RR = 1.31; CI = 1.07-1.61; P = 0.01). Compared with WI, WE was confirmed with lower pain score, higher Boston Bowel Preparation Scale score, but more infused water during insertion. There was no statistical difference between WE and WI in cecal intubation rate and the number of patients who had willingness to repeat the examination. Furthermore, both total procedure time and cecal intubation time in WE were significantly longer than that in WI (MD = 2.66; CI = 1.42-3.90; P < 0.0001; vs MD = 4.58; CI = 4.01-5.15; P < 0.0001). This meta-analysis supports the hypothesis that WE is superior to WI in improving ADR, attenuating insertion pain and providing better bowel cleansing, but inferior in time and consumption of infused water consumption during insertion.

Drug induced hepatotoxicity: data from the Serbian pharmacovigilance database.

PubMed

Petronijevic, Marija; Ilic, Katarina; Suzuki, Ayako

2011-04-01

The main aim of this study was to determine the most frequently reported drugs to the Serbian Pharmacovigilance Database (SPD) with suspected induced hepatotoxicity. Additionally, reasons for the low reporting rate of adverse drug reactions (ADRs) in Serbia were identified. Retrospective observational study of spontaneously reported ADRs recorded in the SPD from January 1995 to December 2008 was performed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify cases of hepatobiliary disorders (HD). Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification. Medline and WHO-UMC databases were used to address specific queries suggested by our results. The questionnaire was used to investigate the health care professionals' knowledge and practice related to spontaneous reporting. Among the 1804 reports of ADRs recorded in the SPD between 1995 and 2008, 70 (3.9%) cases of HD were identified. Drugs most frequently associated with hepatotoxicity were anti-infectives for systemic use, drugs affecting the nervous system, herbal products, hypolipemics, and anticoagulant drugs (26.83, 24.39, 12.20, 9.76, and 8.54% cases, respectively). Four cases (5.71%) of liver injury resulted in death, which accounted for 10.26% of all ADR fatalities reported to the SPD. The main reasons for not reporting ADRs were lack of reporting knowledge (30.26%), well-known ADRs (29.89%), and insecurity about causality relationship (15.50%). Anti-infectives, nervous system drugs, and herbal products were the most common drug classes reported for hepatotoxicity in Serbia. There is a need for additional education about ADRs, and enhanced reporting by health care professionals. Copyright © 2011 John Wiley & Sons, Ltd.

The cellular uptake mechanism, intracellular transportation, and exocytosis of polyamidoamine dendrimers in multidrug-resistant breast cancer cells.

PubMed

Zhang, Jie; Liu, Dan; Zhang, Mengjun; Sun, Yuqi; Zhang, Xiaojun; Guan, Guannan; Zhao, Xiuli; Qiao, Mingxi; Chen, Dawei; Hu, Haiyang

2016-01-01

Polyamidoamine dendrimers, which can deliver drugs and genetic materials to resistant cells, are attracting increased research attention, but their transportation behavior in resistant cells remains unclear. In this paper, we performed a systematic analysis of the cellular uptake, intracellular transportation, and efflux of PAMAM-NH2 dendrimers in multidrug-resistant breast cancer cells (MCF-7/ADR cells) using sensitive breast cancer cells (MCF-7 cells) as the control. We found that the uptake rate of PAMAM-NH2 was much lower and exocytosis of PAMAM-NH2 was much greater in MCF-7/ADR cells than in MCF-7 cells due to the elimination of PAMAM-NH2 from P-glycoprotein and the multidrug resistance-associated protein in MCF-7/ADR cells. Macropinocytosis played a more important role in its uptake in MCF-7/ADR cells than in MCF-7 cells. PAMAM-NH2 aggregated and became more degraded in the lysosomal vesicles of the MCF-7/ADR cells than in those of the MCF-7 cells. The endoplasmic reticulum and Golgi complex were found to participate in the exocytosis rather than endocytosis process of PAMAM-NH2 in both types of cells. Our findings clearly showed the intracellular transportation process of PAMAM-NH2 in MCF-7/ADR cells and provided a guide of using PAMAM-NH2 as a drug and gene vector in resistant cells.

Determining the Optimal Design for a New ADR Mechanical Support

NASA Astrophysics Data System (ADS)

Waldvogel, Kelly; Stacey, Gordon; Nikola, Thomas; Parshley, Stephen

2018-01-01

ZEUS-2 is a grating spectrometer that is used to observe emission lines in submillimeter wavelengths. It is capable of detecting redshifted fine structure lines of galaxies over a wide redshift range. ZEUS-2 can observe carbon, nitrogen, and oxygen lines, which will in turn allow for modeling of optically thick molecular clouds, provide information about star temperatures, and help gain insight about the interstellar medium and gases from which stars form. The detections collected by ZEUS-2 can provide a glimpse into star formation in the early universe and improve the current understanding of the star formation process.ZEUS-2 utilizes an Adiabatic Demagnetization Refrigerator (ADR) to cool its detectors to around 100 mK. Copper rods connect the salt pills within the ADR and the mechanical supports. These supports are comprised of three main pieces: a base member, an inner member, and a guard member. On two separate mechanical supports, the Kevlar strands have broken. This led to thermal contact between the three members, preventing the detector from reaching its final operating temperature. It is clear that a replacement mechanical support system is necessary for operation.

Exploring Spanish health social media for detecting drug effects

PubMed Central

2015-01-01

Background Adverse Drug reactions (ADR) cause a high number of deaths among hospitalized patients in developed countries. Major drug agencies have devoted a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Reporting systems are available in order for both healthcare professionals and patients to alert about possible ADRs. However, several studies have shown that these adverse events are underestimated. Our hypothesis is that health social networks could be a significant information source for the early detection of ADRs as well as of new drug indications. Methods In this work we present a system for detecting drug effects (which include both adverse drug reactions as well as drug indications) from user posts extracted from a Spanish health forum. Texts were processed using MeaningCloud, a multilingual text analysis engine, to identify drugs and effects. In addition, we developed the first Spanish database storing drugs as well as their effects automatically built from drug package inserts gathered from online websites. We then applied a distant-supervision method using the database on a collection of 84,000 messages in order to extract the relations between drugs and their effects. To classify the relation instances, we used a kernel method based only on shallow linguistic information of the sentences. Results Regarding Relation Extraction of drugs and their effects, the distant supervision approach achieved a recall of 0.59 and a precision of 0.48. Conclusions The task of extracting relations between drugs and their effects from social media is a complex challenge due to the characteristics of social media texts. These texts, typically posts or tweets, usually contain many grammatical errors and spelling mistakes. Moreover, patients use lay terminology to refer to diseases, symptoms and indications that is not usually included in lexical resources in languages other than English. PMID:26100267

Tolerability and safety of the intravenous immunoglobulin octagam® 10% in patients with immune thrombocytopenia: a post-authorisation safety analysis of two non-interventional phase IV trials.

PubMed

Wietek, Stefan; Svorc, Daniel; Debes, Anette; Svae, Tor-Einar

2018-05-01

To provide detailed data on the tolerability and safety of octagam ® 10%, a ready-to-use intravenous immunoglobulin, in a subgroup of patients with immune thrombocytopenia (ITP) involved in an integrated analysis of post-authorisation safety surveillance (PASS) studies. A subgroup analysis was conducted using data collected from two non-interventional studies that included patients with ITP treated with octagam ® 10%. Patients were observed and monitored for possible adverse drug reactions (ADRs) during or after administration of octagam ® 10%, with a particular focus on thromboembolic events (TEEs). ADRs were analysed at the case and event level. In this analysis of 112 patients receiving octagam ® 10% (mean dose 0.4 g/kg/infusion), there were five cases with at least one adverse drug reaction (ADR) associated with 626 infusions of octagam ® 10% (case incidence of 0.8% per infusion). ADRs were of mild or moderate severity. There were a total of 10 events, most commonly back pain (n = 3) and headache (n = 2). Nausea, dizziness and a sensation of heaviness were also reported. The remaining two events involved drug exposure during pregnancy. There were no TEEs or other serious ADRs. In this subgroup analysis of patients who received octagam ® 10% (manufactured using an amended process) in two PASS studies, the overall ADR rate was low, with ADRs occurring in only 0.8% of all infusions. No TEEs or other serious ADRs were reported. Routine clinical use of octagam ® 10% was safe and well tolerated, with no unexpected safety issues, in patients with ITP. The two studies from which data were taken are registered with the International Standard Randomised Controlled Trial Number Registry, numbers ISRCTN58800347 and ISRCTN02245668.

Application of Atomic Dielectric Resonance Spectroscopy for the screening of blood samples from patients with clinical variant and sporadic CJD

PubMed Central

Fagge, Timothy J; Barclay, G Robin; Stove, G Colin; Stove, Gordon; Robinson, Michael J; Head, Mark W; Ironside, James W; Turner, Marc L

2007-01-01

Background Sub-clinical variant Creutzfeldt-Jakob disease (vCJD) infection and reports of vCJD transmission through blood transfusion emphasise the need for blood screening assays to ensure the safety of blood and transplanted tissues. Most assays aim to detect abnormal prion protein (PrPSc), although achieving required sensitivity is a challenge. Methods We have used innovative Atomic Dielectric Resonance Spectroscopy (ADRS), which determines dielectric properties of materials which are established by reflectivity and penetration of radio/micro waves, to analyse blood samples from patients and controls to identify characteristic ADR signatures unique to blood from vCJD and to sCJD patients. Initial sets of blood samples from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) were screened as training samples to determine group-specific ADR characteristics, and provided a basis for classification of blinded sets of samples. Results Blood sample groups from vCJD, sCJD, non-CJD neurological diseases and normal healthy adults (blood donors) screened by ADRS were classified with 100% specificity and sensitivity, discriminating these by a co-variance expert analysis system. Conclusion ADRS appears capable of recognising and discriminating serum samples from vCJD, sCJD, non-CJD neurological diseases, and normal healthy adults, and might be developed to provide a system for primary screening or confirmatory assay complementary to other screening systems. PMID:17760958

[Optimization of cultural condition of genetic engineering strain for antibiotic peptide adenoregulin and research on its fed-batch cultivation].

PubMed

Zhou, Yu-Xun; Cao, Wei; Wei, Dong-Zhi; Luo, Qing-Ping; Wang, Jin-Zhi

2005-07-01

33 amino acid antibiotic peptide adenoregulin (ADR), which were firstly isolated from the skin of South America arboreal frog Phyllomedusa bicolor, forms alpha-helix amphipathic structure in apolar medium and has a wide spectrum of antimicrobial activity and high potency of lytic ability. Adr gene was cloned in pET32a and transformed into Escherichia coli BL21(DE3) . The cultural and inductive conditions of E. coli BL21(DE3)/pET32a-adr have been optimized. The effect of three factors which were time point of induction, concentration of IPTG in the culture and time of induction on the expression level of Trx-ADR was investigated. The results indicated that the expression level was affected by the time point of induction most predominantly. 9 veriaties of media in which BL21 (DE3)/pET32a-adr was cultured and induced were tested to achieve high expression level of target protein. It was found that glucose in the medium played an important role in keeping stable and high expression level of Trx-ADR. The optimal inductive condition is as follows: the culture medium is 2 x YT + 0.5% glucose, the time point of induction is OD600 = 0.9, the final concentration of IPTG in the culture is 0.1 mmol/L and the induction time is 4 h. BL21 (DE3)/pET32a-adr was cultivated according to the strategy of constant pH at early stage and exponential feeding at later stage to obtain high cell density. During the entire fed-batch phase, by controlling the feeding of glucose, the specific growth rate of the culture was controlled at about 0.15 h(-1), the accumulation of acetic acid was controlled at low level (<2 g/L), but the plasmid stability could not be maintained well. At the end of the cultivation, 40% of the bacteria in the culture lost their plasmids. As a result, the expression level of the target protein declined dramatically, but 90% of Trx-ADR was in soluble form. The expressed fusion protein showed no antibacterial activity, while the native form of ADR lysed from Trx-ADR showed distinct antibacterial activity.

Filtering big data from social media--Building an early warning system for adverse drug reactions.

PubMed

Yang, Ming; Kiang, Melody; Shang, Wei

2015-04-01

Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides satisfactory performance in identifying ADR related posts for post-marketing drug surveillance. The overall design of our system also points out a potentially fruitful direction for building other early warning systems that need to filter big data from social media networks. Copyright © 2015 Elsevier Inc. All rights reserved.

Adverse Drug Reactions for Medicines Newly Approved in Japan from 1999 to 2013: Hypertension and Hypotension.

PubMed

Nagayama, Takashi; Nishida, Minoru; Hizue, Masanori; Ogino, Yamato; Fujiyoshi, Masato

2016-04-01

In this survey, the correlation between adverse drug reactions (ADRs) in human and animal toxicities was investigated for 393 medicines which were approved in Japan from September 1999 to March 2013. ADRs were collected from each Japanese package insert. Comparable animal toxicities with ADRs were collected by thorough investigation of common technical documents. The results of this survey show that hypertension and/or hypotension were mainly observed in medicines affecting the central nervous system. Hypertension was also observed in antipyretics, analgesics, anti-inflammatory agents, vasoconstrictors and agents using antibody. Concordance between human ADRs and animal toxicities was analysed. True-positive rate for hypertension and hypotension is 0.29 and 0.52, respectively. Positive likelihood ratio and inverse negative likelihood ratio are 1.98 and 1.21, respectively, in hypertension and 1.67 and 1.44, respectively, in hypotension. Concordance between human ADRs and animal toxicities is not so high in hypertension and hypotension. Identified mechanisms as on-target for hypertension and hypotension are 29.8% and 30.5%, respectively. More than half of the causative factors of hypertension and hypotension were unable to be elucidated. Our results show that the intake of medicines is often linked to blood pressure variations that are not predicted in animal toxicity studies. Improvement of drug development processes may be necessary to provide safer medicines because current animal toxicity studies are insufficient to predict all ADRs in human beings. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes.

PubMed

Aydin, Suleyman; Kuloglu, Tuncay; Aydin, Suna; Eren, Mehmet Nesimi; Yilmaz, Musa; Kalayci, Mehmet; Sahin, Ibrahim; Kocaman, Nevin; Citil, Cihan; Kendir, Yalcin

2013-08-01

We have investigated how diabetes affects the expression of adropin (ADR) in rat brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The rats in the diabetic group were administered an intraperitoneal (i.p.) injection of a single dose of 60 mg/kg streptozotocin (STZ) dissolved in a 0.1 M phosphate-citrate buffer (pH 4.5). The rats were maintained in standard laboratory conditions in a temperature between 21 and 23 °C and a relative humidity of 70 %, under a 12-h light/dark cycle. The animals were fed a standard commercial pellet diet. After 10 weeks, the animals were sacrified. ADR concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to follow the expression of the hormones in the brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The quantities were then compared. Increased ADR immunoreaction was seen in the brain, cerebellum, kidneys, heart, liver, and pancreas in the diabetes-induced rats compared to control subjects. ADR was detected in the brain (vascular area, pia mater, neuroglial cell, and neurons), cerebellum (neuroglial cells, Purkinje cells, vascular areas, and granular layer), kidneys (glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells), heart (endocardium, myocardium, and epicardium), liver (sinusoidal cells), and pancreas (serous acini). Its concentrations (based on mg/wet weight tissues) in these tissues were measured by using ELISA showed that the levels of ADR were higher in the diabetic rats compared to the control rats. Tissue ADR levels based on mg/wet weight tissues were as follows: Pancreas > liver > kidney > heart > brain > cerebellar tissues. Evidence is presented that shows ADR is expressed in various tissues in the rats and its levels increased in STZ-induced diabetes; however, this effect on the pathophysiology of the disorder remains to be understood.

Ontology-based literature mining and class effect analysis of adverse drug reactions associated with neuropathy-inducing drugs.

PubMed

Hur, Junguk; Özgür, Arzucan; He, Yongqun

2018-06-07

Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of drugs and their associated ADRs. Furthermore, our analysis of drug class effects identified 3 benzimidazole drugs sharing 43 ADRs, leading to new hypothesis generation and possible mechanism understanding of drug-induced peripheral neuropathy.

Are we pharmacovigilant enough in ophthalmic practice?

PubMed Central

Dubey, Ashok; Handu, Shailendra S

2013-01-01

No drug is absolutely safe. Pharmacovigilance is the science related to detection, assessment, understanding and prevention of adverse effects or any other possible drug-related problems. The ocular medications and devices can cause localized and systemic adverse effects. Not all adverse effects are known when a drug or device is launched in market because of limitations of clinical trials. Many adverse effects are recognized due to the spontaneous reporting of the vigilant doctors who observe and report such events encountered in their practice. Despite a large ophthalmic patient population base, India does not have robust adverse drug reaction (ADR) database because of lack of reporting culture. Government of India recently launched the Pharmacovigilance Programme of India (PvPI) to monitor ADRs and create awareness among the healthcare professionals about the importance of ADRs. Suspecting and reporting a possible drug reaction is very important in developing a safe and rational ophthalmic practice. PMID:23571233

[Adverse reactions and other drug-related problems in an emergency service department].

PubMed

Güemes Artiles, M; Sanz Alvarez, E; Garcia Sánchez-Colomer, M

1999-01-01

Adverse Drug Reactions (ADR) and Drug-Related Problems (DRP's) are a frequency cause of hospital emergency room visits and require better assessment. An analysis was made of 1097 consecutive admission to the emergency room at the Nuestra Senora de los Volcanes, Hospital (currently the General Hospital of Lanzarote) in Arrecife de Lanzarote (Canary Islands) over a three-month period in order to detect any possible DAR or any other drug-related problems. Nineteen (19) of the 1097 admissions were due to Adverse Drug Reactions (ADR) (1.73%; 95% IC:0.96%-2.5%). Some of the most outstanding of the other "Drug-Related Problems" (DRP's) were medication overdose, which was diagnosed in 5 (0.45%) of the patients; the worsening of the symptoms due to ceasing to take the medication was involved in 8 (0.72%), and incorrect treatments which involved medical care at the emergency room totaled 11 (1.0%). The number of drug-related problems (DRP's) in the sample totaled 43 (3.9%). The drug-related problems (DRP's) led to hospitalization in 1.9% of the cases seen in the emergency room and led to hospitalization in 9.6% of all of hospital admission through the emergency room for the period of time under study. The ADR led to 4.1% of the hospital admissions. Drug-related problems are a frequent, major problem which has not been well-analyzed in the emergency rooms. Additionally, emergency rooms can function as the first point of detection of a ADR among an outpatient population.

Volume to dissolve applied dose (VDAD) and apparent dissolution rate (ADR): tools to predict in vivo bioavailability from orally applied drug suspensions.

PubMed

Muenster, Uwe; Pelzetter, Christian; Backensfeld, Thomas; Ohm, Andreas; Kuhlmann, Thomas; Mueller, Hartwig; Lustig, Klemens; Keldenich, Jörg; Greschat, Susanne; Göller, Andreas H; Gnoth, Mark Jean

2011-08-01

Low solubility of drug candidates generated in research contributes to their elimination during subsequent development due to insufficient oral bioavailability (BA) of crystalline compound. Therefore, the purpose of the study was to identify critical in vitro solubility and dissolution parameter that would predict critical in vivo dissolution by means of in vitro-in vivo correlation. Thermodynamic solubility and apparent dissolution rate (ADR) were determined using the shake-flask method and mini-flow-through-cell, respectively. Oral BA studies in rats and humans were conducted from drug solution and suspension/tablets. Relative BA was calculated using F(rel) [%]=AUC(suspension)/AUC(solution)*100, representing a measure of in vivo dissolution. Roughly, F(rel) rat >50% translates into F(rel) human of >90%. Both, ADR and log volume to dissolve applied dose (VDAD), when plotted against F(rel) rat, revealed certain threshold levels, (ADR, ∼150-200 μg of compound dissolved under respective assay conditions; VDAD, ∼100-500 ml/kg) which translate into F(rel) in rats of >50%. Thus, assuming that F(rel)>50% in rats is indicative of sufficient in vivo dissolution in humans after oral application, drugs should exhibit a VDAD of ∼100-500 ml/kg or less in aqueous media to avoid insufficient or varying drug absorption. Copyright © 2011 Elsevier B.V. All rights reserved.

An adaptive strategy for active debris removal

NASA Astrophysics Data System (ADS)

White, Adam E.; Lewis, Hugh G.

2014-04-01

Many parameters influence the evolution of the near-Earth debris population, including launch, solar, explosion and mitigation activities, as well as other future uncertainties such as advances in space technology or changes in social and economic drivers that effect the utilisation of space activities. These factors lead to uncertainty in the long-term debris population. This uncertainty makes it difficult to identify potential remediation strategies, involving active debris removal (ADR), that will perform effectively in all possible future cases. Strategies that cannot perform effectively, because of this uncertainty, risk either not achieving their intended purpose, or becoming a hindrance to the efforts of spacecraft manufactures and operators to address the challenges posed by space debris. One method to tackle this uncertainty is to create a strategy that can adapt and respond to the space debris population. This work explores the concept of an adaptive strategy, in terms of the number of objects required to be removed by ADR, to prevent the low Earth orbit (LEO) debris population from growing in size. This was demonstrated by utilising the University of Southampton’s Debris Analysis and Monitoring Architecture to the Geosynchronous Environment (DAMAGE) tool to investigate ADR rates (number of removals per year) that change over time in response to the current space environment, with the requirement of achieving zero growth of the LEO population. DAMAGE was used to generate multiple Monte Carlo projections of the future LEO debris environment. Within each future projection, the debris removal rate was derived at five-year intervals, by a new statistical debris evolutionary model called the Computational Adaptive Strategy to Control Accurately the Debris Environment (CASCADE) model. CASCADE predicted the long-term evolution of the current DAMAGE population with a variety of different ADR rates in order to identify a removal rate that produced a zero net growth for that particular projection after 200 years. The results show that using an adaptive ADR rate generated by CASCADE, alongside good compliance with existing mitigation measures, increases the probability of achieving a constant LEO population of objects greater than 10 cm. This was shown to be 12% greater compared with removing five objects per year, with the additional advantage of requiring only 3.1 removals per year, on average.

The Top 10 Questions for Active Debris Removal

NASA Technical Reports Server (NTRS)

Liou, J. -C.

2010-01-01

This slide presentation reviews the requirement and issues around removal of debris from the earth orbital environment. The 10 questions discussed are: 1. Which region (LEO/MEO/GEO) has the fastest projected growth rate and the highest collision activities? 2. Can the commonly-adopted mitigation measures stabilize the future environment? 3. What are the objectives of active debris removal (ADR)? 4. How can effective ADR target selection criteria to stabilize the future LEO environment be defined? 5. What are the keys to remediate the future LEO environment? 6. What is the timeframe for ADR implementation? 7. What is the effect of practical/operational constraints? 8. What are the collision probabilities and masses of the current objects? 9. What are the benefits of collision avoidance maneuvers? 10. What is the next step?

Mapping of the WHO-ART terminology on Snomed CT to improve grouping of related adverse drug reactions.

PubMed

Alecu, Iulian; Bousquet, Cedric; Mougin, Fleur; Jaulent, Marie-Christine

2006-01-01

The WHO-ART and MedDRA terminologies used for coding adverse drug reactions (ADR) do not provide formal definitions of terms. In order to improve groupings, we propose to map ADR terms to equivalent Snomed CT concepts through UMLS Metathesaurus. We performed such mappings on WHO-ART terms and can automatically classify them using a description logic definition expressing their synonymies. Our gold standard was a set of 13 MedDRA special search categories restricted to ADR terms available in WHO-ART. The overlapping of the groupings within the new structure of WHO-ART on the manually built MedDRA search categories showed a 71% success rate. We plan to improve our method in order to retrieve associative relations between WHO-ART terms.

AmeriFlux US-ADR Amargosa Desert Research Site (ADRS)

DOE Data Explorer

Moreo, Michael [U.S. Geological Survey

2018-01-01

This is the AmeriFlux version of the carbon flux data for the site US-ADR Amargosa Desert Research Site (ADRS). Site Description - This tower is located at the Amargosa Desert Research Site (ADRS). The U.S. Geological Survey (USGS) began studies of unsaturated zone hydrology at ADRS in 1976. Over the years, USGS investigations at ADRS have provided long-term "benchmark" information about the hydraulic characteristics and soil-water movement for both natural-site conditions and simulated waste-site conditions in an arid environment. The ADRS is located in a creosote-bush community adjacent to disposal trenches for low-level radioactive waste.

Treatment efficacy and safety of low-dose azathioprine in chronic active ulcerative colitis patients: A meta-analysis and systemic review.

PubMed

Luan, Zi Jian; Li, Yue; Zhao, Xin Yu; Wang, Li; Sun, Ying Hao; Wang, Shi Yao; Qian, Jia Ming

2016-10-01

To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC). A literature search of Medline, Embase, the Cochrane Library, Web of Science, Wanfang Database, CNKI, SinoMed, VIP Chinese Science and the Technology Journals Database was conducted to identify eligible studies that evaluated the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active UC published up to 15 July 2015. Data were extracted from the studies, including clinical efficacy (response rate, adverse drug reaction [ADR] rate, steroid withdrawal rate and relapse rate) and endoscopic improvement (endoscopic remission rate and mucosal healing rate). Six studies with 211 patients were eligible for the analysis. The overall response rates after 6 and 12 months of treatment were 78.0% (95% confidence interval [CI] 71.0-85.0%) and 88.0% (95% CI 80.0-96.0%), respectively. The overall ADR rate was 25.0% (95% CI 18.0-31.0%). Endoscopic response rate was around 85.0%, while the endoscopic remission rates and mucosal healing rates after 6 and 12 months of treatment were above 60.0% and 70.0%, respectively. The steroid withdrawal rate and relapse rate were in moderate to high heterogeneity. Egger's test indicated that there was no publication bias for studies regarding the 6-month response rate and ADR rate. Low-dose AZA is effective and safe in the treatment of chronic active UC patients. However, randomized controlled trials with large sample sizes are needed to draw definitive conclusions. © 2016 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

A cross sectional pilot study on assessing the knowledge, attitude and behavior of community pharmacists to adverse drug reaction related aspects in the Sultanate of Oman.

PubMed

Jose, Jimmy; Jimmy, Beena; Al-Ghailani, Aliya Said Hamed; Al Majali, Maryam Abdullah

2014-04-01

Adverse drug reaction (ADR) monitoring and reporting requires a multidisciplinary approach and pharmacists have a major role to play in it. The present pilot study was conducted to assess the knowledge, attitude and behavior of community pharmacists to ADR related aspects in the Sultanate of Oman. A self-administered questionnaire comprising of 21 questions were distributed to a random sample of pharmacists in two Governorates in the Sultanate of Oman. It assessed the knowledge of pharmacists on some of the selected basic aspects of drug safety. Further, the knowledge and attitude of community pharmacists toward ADR reporting and their behavior on ADR related aspects were assessed. A scoring scheme was used to estimate the median total score of participants for various parameters. Obtained scores were correlated with the demographics of the respondents. A total of 107 community pharmacists participated in the survey giving a response rate of 72.3%. The responses of the pharmacists to the questions on the drug safety of individual drugs were incorrect for some important and practical questions. Consequently, total median score corresponding to these questions was 5 (Inter Quartile Range, IQR 2) out of a possible maximum score of 9, which was below the acceptable score. Total median score based on knowledge, attitude and behavior was 38 (IQR 8) out of a possible maximum of 50 which shows a moderate score. Lack of awareness on how to report an ADR and concern that the report may be wrong were the most common factors discouraging pharmacists from reporting ADRs. Qualification as well as years of experience were the only demographic parameters which had an influence on the score obtained by the pharmacists. Even though the pharmacists had an acceptable knowledge, attitude and behavior on ADR reporting and related aspects, a good number of them had below than acceptable knowledge on drug safety related aspects of specific drugs. Educational programs have to be continued to generate awareness on how to report ADR and stimulate pharmacists' more active participation in the pharmacovigilance program. There is a genuine need to have training programs to improve the knowledge of pharmacists on ADR related aspects which are of benefit on a daily basis which could greatly have an impact on patient safety.

A cross sectional pilot study on assessing the knowledge, attitude and behavior of community pharmacists to adverse drug reaction related aspects in the Sultanate of Oman

PubMed Central

Jose, Jimmy; Jimmy, Beena; Al-Ghailani, Aliya Said Hamed; Al Majali, Maryam Abdullah

2013-01-01

Background and objectives Adverse drug reaction (ADR) monitoring and reporting requires a multidisciplinary approach and pharmacists have a major role to play in it. The present pilot study was conducted to assess the knowledge, attitude and behavior of community pharmacists to ADR related aspects in the Sultanate of Oman. Methods A self-administered questionnaire comprising of 21 questions were distributed to a random sample of pharmacists in two Governorates in the Sultanate of Oman. It assessed the knowledge of pharmacists on some of the selected basic aspects of drug safety. Further, the knowledge and attitude of community pharmacists toward ADR reporting and their behavior on ADR related aspects were assessed. A scoring scheme was used to estimate the median total score of participants for various parameters. Obtained scores were correlated with the demographics of the respondents. Results A total of 107 community pharmacists participated in the survey giving a response rate of 72.3%. The responses of the pharmacists to the questions on the drug safety of individual drugs were incorrect for some important and practical questions. Consequently, total median score corresponding to these questions was 5 (Inter Quartile Range, IQR 2) out of a possible maximum score of 9, which was below the acceptable score. Total median score based on knowledge, attitude and behavior was 38 (IQR 8) out of a possible maximum of 50 which shows a moderate score. Lack of awareness on how to report an ADR and concern that the report may be wrong were the most common factors discouraging pharmacists from reporting ADRs. Qualification as well as years of experience were the only demographic parameters which had an influence on the score obtained by the pharmacists. Conclusions Even though the pharmacists had an acceptable knowledge, attitude and behavior on ADR reporting and related aspects, a good number of them had below than acceptable knowledge on drug safety related aspects of specific drugs. Educational programs have to be continued to generate awareness on how to report ADR and stimulate pharmacists’ more active participation in the pharmacovigilance program. There is a genuine need to have training programs to improve the knowledge of pharmacists on ADR related aspects which are of benefit on a daily basis which could greatly have an impact on patient safety. PMID:24648829

Attitudes and knowledge of hospital pharmacists to adverse drug reaction reporting

PubMed Central

Green, Christopher F; Mottram, David R; Rowe, Philip H; Pirmohamed, Munir

2001-01-01

Aims To investigate the attitudes of UK hospital pharmacists towards, and their understanding, of adverse drug reaction (ADR) reporting. Methods A postal questionnaire survey of 600 randomly selected hospital pharmacists was conducted. Results The response rate was 53.7% (n = 322). A total of 217 Yellow Cards had been submitted to the CSM/MCA by 78 (25.6%) of those responding. Half of those responding felt that ADR reporting should be compulsory and over three-quarters felt it was a professional obligation. However, almost half were unclear as to what should be reported, while the time available in clinical practice and time taken to complete forms were deemed to be major deterrents to reporting. Pharmacists were not dissuaded from reporting by the need to consult a medical colleague or by the absence of a fee. Education and training had a significant influence on pharmacists' participation in the Yellow Card Scheme. Conclusions Pharmacists have a reasonable knowledge and are supportive of the Yellow Card spontaneous ADR reporting scheme. However, education and training will be important in maintaining and increasing ADR reports from pharmacists. PMID:11167664

Portable automatic text classification for adverse drug reaction detection via multi-corpus training.

PubMed

Sarker, Abeed; Gonzalez, Graciela

2015-02-01

Automatic detection of adverse drug reaction (ADR) mentions from text has recently received significant interest in pharmacovigilance research. Current research focuses on various sources of text-based information, including social media-where enormous amounts of user posted data is available, which have the potential for use in pharmacovigilance if collected and filtered accurately. The aims of this study are: (i) to explore natural language processing (NLP) approaches for generating useful features from text, and utilizing them in optimized machine learning algorithms for automatic classification of ADR assertive text segments; (ii) to present two data sets that we prepared for the task of ADR detection from user posted internet data; and (iii) to investigate if combining training data from distinct corpora can improve automatic classification accuracies. One of our three data sets contains annotated sentences from clinical reports, and the two other data sets, built in-house, consist of annotated posts from social media. Our text classification approach relies on generating a large set of features, representing semantic properties (e.g., sentiment, polarity, and topic), from short text nuggets. Importantly, using our expanded feature sets, we combine training data from different corpora in attempts to boost classification accuracies. Our feature-rich classification approach performs significantly better than previously published approaches with ADR class F-scores of 0.812 (previously reported best: 0.770), 0.538 and 0.678 for the three data sets. Combining training data from multiple compatible corpora further improves the ADR F-scores for the in-house data sets to 0.597 (improvement of 5.9 units) and 0.704 (improvement of 2.6 units) respectively. Our research results indicate that using advanced NLP techniques for generating information rich features from text can significantly improve classification accuracies over existing benchmarks. Our experiments illustrate the benefits of incorporating various semantic features such as topics, concepts, sentiments, and polarities. Finally, we show that integration of information from compatible corpora can significantly improve classification performance. This form of multi-corpus training may be particularly useful in cases where data sets are heavily imbalanced (e.g., social media data), and may reduce the time and costs associated with the annotation of data in the future. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Portable Automatic Text Classification for Adverse Drug Reaction Detection via Multi-corpus Training

PubMed Central

Gonzalez, Graciela

2014-01-01

Objective Automatic detection of Adverse Drug Reaction (ADR) mentions from text has recently received significant interest in pharmacovigilance research. Current research focuses on various sources of text-based information, including social media — where enormous amounts of user posted data is available, which have the potential for use in pharmacovigilance if collected and filtered accurately. The aims of this study are: (i) to explore natural language processing approaches for generating useful features from text, and utilizing them in optimized machine learning algorithms for automatic classification of ADR assertive text segments; (ii) to present two data sets that we prepared for the task of ADR detection from user posted internet data; and (iii) to investigate if combining training data from distinct corpora can improve automatic classification accuracies. Methods One of our three data sets contains annotated sentences from clinical reports, and the two other data sets, built in-house, consist of annotated posts from social media. Our text classification approach relies on generating a large set of features, representing semantic properties (e.g., sentiment, polarity, and topic), from short text nuggets. Importantly, using our expanded feature sets, we combine training data from different corpora in attempts to boost classification accuracies. Results Our feature-rich classification approach performs significantly better than previously published approaches with ADR class F-scores of 0.812 (previously reported best: 0.770), 0.538 and 0.678 for the three data sets. Combining training data from multiple compatible corpora further improves the ADR F-scores for the in-house data sets to 0.597 (improvement of 5.9 units) and 0.704 (improvement of 2.6 units) respectively. Conclusions Our research results indicate that using advanced NLP techniques for generating information rich features from text can significantly improve classification accuracies over existing benchmarks. Our experiments illustrate the benefits of incorporating various semantic features such as topics, concepts, sentiments, and polarities. Finally, we show that integration of information from compatible corpora can significantly improve classification performance. This form of multi-corpus training may be particularly useful in cases where data sets are heavily imbalanced (e.g., social media data), and may reduce the time and costs associated with the annotation of data in the future. PMID:25451103

Are consumers ready to take part in the Pharmacovigilance System?--a Portuguese preliminary study concerning ADR reporting.

PubMed

Matos, Cristiano; van Hunsel, Florence; Joaquim, João

2015-07-01

New pharmacovigilance legislation allows consumers to report adverse drug reactions (ADRs) directly to competent authorities in all European Union countries. Consumer reporting is available in Portugal since July 2012. In 2013, the National Pharmacovigilance System (SNF) had received 3461 spontaneous ADR reports, of which only 1.4% (n = 50) were from consumers. Consumer reporting could be one opportunity to reduce underreporting. The aim of this study was to describe the attitudes and knowledge of the general public regarding spontaneous reporting and the reasons and opinions that can influence consumers' ADR underreporting. A descriptive-correlational study was performed looking for consumers' attitudes and knowledge regarding spontaneous reporting. A 6-month survey was conducted from June to November 2013 in general adult consumers from a community pharmacy in Coimbra, Portugal, who used prescribed medicines or over-the-counter (OTC) drugs. Attitudes and opinions were surveyed by personal interview in a closed-answer questionnaire using a Likert scale. Questionnaires from healthcare professionals or incomplete ones were not considered. Data were analyzed using descriptive statistics, chi-square (χ(2)) tests, and Spearman's correlation coefficients. One thousand eighty-four questionnaires were collected (response rate of 81.1%) and 948 completed were selected for analysis. Of the respondents, 44.1% never heard about SNF. Younger people and those with a higher education were significantly more likely to be aware of SNF. Only one consumer had previously reported directly an ADR. Reporting ADRs indirectly through a healthcare professional (HCP) was preferred by 62.4%. The main reasons for consumers reporting spontaneous ADR would be the severity of reactions (81.1% agreed or strongly agreed) and worries about their situation (73.4% agreed or strongly agreed). Only weak and moderate correlations were found between studied statements.. Consumers are more likely to do spontaneous report about severe reactions or if they are worried about the symptoms. Tailored and proactive information on ADR reporting and educational interventions on consumers could increase the number of reports from consumers in Portugal.

Impact of ethyl pyruvate on Adriamycin-induced cardiomyopathy in rats

PubMed Central

Liu, Menglin; Wang, Menglong; Liu, Jianfang; Luo, Zhen; Shi, Lei; Feng, Ying; Li, Li; Xu, Lin; Wan, Jun

2016-01-01

Ethyl pyruvate (EP), a derivative of pyruvic acid, is known to have protective effects against ischemic cardiomyopathy and other disorders. However, little is known about its role in Adriamycin (ADR)-induced cardiomyopathy. The present study was designed to investigate the impact of EP on ADR-induced cardiomyopathy in an animal model. Sixty male Sprague-Dawley (SD) rats were divided into four groups: Normal control, EP, ADR and ADR + EP groups (n=15/group). Rats in the ADR and ADR + EP groups were treated with ADR (2.5 mg/kg/week intraperitoneally) for 6 weeks. From the eighth week, rats in the EP and ADR + EP groups received EP via gastric lavage at a dose of 50 mg/kg/day for 30 days. After completing the EP treatment, cardiac function was assessed by echocardiography and then rats were sacrificed. Hearts were harvested for subsequent analysis. Compared with rats in the normal control and EP groups (without ADR treatment), rats in the ADR and ADR + EP groups showed significant impairments in terms of cardiac function, apoptosis, severe oxidative stress and fibrosis in the heart. However, these impairments were alleviated by EP treatment in the ADR + EP group. Upon EP treatment, cardiac function was significantly improved. The levels of oxidative stress, fibrosis and apoptosis in the myocardial tissues were also significantly reduced. These findings indicated that EP treatment attenuated, at least partially, ADR-induced cardiomyopathy in rats. PMID:27882138

Chaetominine reduces MRP1-mediated drug resistance via inhibiting PI3K/Akt/Nrf2 signaling pathway in K562/Adr human leukemia cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Jingyun; Wei, Xing; Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 130 Meilong Road, Shanghai

Drug resistance limits leukemia treatment and chaetominine, a cytotoxic alkaloid that promotes apoptosis in a K562 human leukemia cell line via the mitochondrial pathway was studied with respect to chemoresistance in a K562/Adr human resistant leukemia cell line. Cytotoxicity assays indicated that K562/Adr resistance to adriamycin (ADR) did not occur in the presence of chaetominine and that chaetominine increased chemosensitivity of K562/Adr to ADR. Data show that chaetominine enhanced ADR-induced apoptosis and intracellular ADR accumulation in K562/Adr cells. Accordingly, chaetominine induced apoptosis by upregulating ROS, pro-apoptotic Bax and downregulating anti-apoptotic Bcl-2. RT-PCR and western-blot confirmed that chaetominine suppressed highly expressedmore » MRP1 at mRNA and protein levels. But little obvious alternation of another drug transporter MDR1 mRNA was observed. Furthermore, inhibition of MRP1 by chaetominine relied on inhibiting Akt phosphorylation and nuclear Nrf2. In summary, chaetominine strongly reverses drug resistance by interfering with the PI3K/Akt/Nrf2 signaling, resulting in reduction of MRP1-mediated drug efflux and induction of Bax/Bcl-2-dependent apoptosis in an ADR-resistant K562/Adr leukemia cell line. - Highlights: • Chaetominine enhanced chemosensitivity of ADR against K562/Adr cells. • Chaetominine increased intracellular ADR levels via inhibiting MRP1. • Chaetominine induced apoptosis of K562/Adr cells through upregulation of ROS and modulation of Bax/Bcl-2. • Inhibition of MRP1 and Nrf2 by chaetominine treatment was correlative with blockade of PI3K/Akt signaling.« less

48 CFR 833.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... resolution (ADR). 833.214 Section 833.214 Federal Acquisition Regulations System DEPARTMENT OF VETERANS... Alternative dispute resolution (ADR). Contracting officers and contractors are encouraged to use alternative dispute resolution (ADR) procedures. CBCA guidance on ADR may be obtained at http://www.cbca.gsa.gov. ...

48 CFR 33.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... resolution (ADR). 33.214 Section 33.214 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... dispute resolution (ADR). (a) The objective of using ADR procedures is to increase the opportunity for relatively inexpensive and expeditious resolution of issues in controversy. Essential elements of ADR include...

48 CFR 33.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... resolution (ADR). 33.214 Section 33.214 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... dispute resolution (ADR). (a) The objective of using ADR procedures is to increase the opportunity for relatively inexpensive and expeditious resolution of issues in controversy. Essential elements of ADR include...

48 CFR 833.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... resolution (ADR). 833.214 Section 833.214 Federal Acquisition Regulations System DEPARTMENT OF VETERANS... Alternative dispute resolution (ADR). Contracting officers and contractors are encouraged to use alternative dispute resolution (ADR) procedures. CBCA guidance on ADR may be obtained at http://www.cbca.gsa.gov. ...

Sex Differences in Reported Adverse Drug Reactions of Selective Serotonin Reuptake Inhibitors.

PubMed

Ekhart, Corine; van Hunsel, Florence; Scholl, Joep; de Vries, Sieta; van Puijenbroek, Eugene

2018-02-26

Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men. The aim of this explorative study was to investigate whether differences exist in reported ADRs of selective serotonin reuptake inhibitors (SSRIs) for men and women in the database of the Netherlands Pharmacovigilance Centre Lareb. A ratio of reports concerning women and men, corrected for the number of users, was calculated for all the ADRs reported on SSRIs. We found that 16 ADRs were statistically significantly more reported in women than men, and four ADRS were reported more in men than women. ADRs more reported in women than men when using SSRIs were usually dose-related ADRs or commonly occurring ADRs. Differences in the pharmacokinetics of SSRIs between men and women may explain why these reports of dose-related ADRs when using SSRIs concern women more than men.

The knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria.

PubMed

Oreagba, I A; Ogunleye, O J; Olayemi, S O

2011-01-01

Community Pharmacists both have an important responsibility in monitoring the ongoing safety of medicines and are widely accessible to do it. This study aims to investigate the knowledge, perceptions and practice of Pharmacovigilance amongst community pharmacists in Lagos State, South West Nigeria A cross-sectional observational survey was used in this study. A multistage random sampling technique was employed in the selection of 420 community pharmacies in Lagos. About 55% of respondents have ever heard of the word 'Pharmacovigilance' out of which less than half (representing only 18% of all respondents) could define the term 'Pharmacovigilance'. Forty percent of the respondents stated that patients reported ADRs to them at least once a month, and 20% reported to the relevant authorities. However only 3% of respondents actually reported an ADR to the National Pharmacovigilance Centre. The most important reason for poor reporting was lack of knowledge about how to report ADRs (44.6%).Meanwhile, 90% of respondents believed that the role of the pharmacists in ADR reporting was important. Most community pharmacists were willing to practice pharmacovigilance if they were trained. Community pharmacists in Lagos had poor knowledge about pharmacovigilance. Reporting rate was also poor. There is an urgent need for educational programs to train pharmacists about pharmacovigilance and ADR reporting. Copyright © 2010 John Wiley & Sons, Ltd.

Old dog begging for new tricks – Current practices and future directions in the diagnosis of delayed antimicrobial hypersensitivity

PubMed Central

Konvinse, KC; Phillips, E; White, KD; Trubiano, JA

2016-01-01

Purpose of review Antimicrobials are a leading cause of severe T-cell-mediated adverse drug reactions (ADRs). The purpose of this review is to address the current understanding of antimicrobial cross-reactivity and the ready availability of and evidence for in vitro, in vivo and ex vivo diagnostics for T-cell-mediated ADRs. Recent findings Recent literature has evaluated the efficacy of traditional antibiotic allergy management including patch testing, skin prick testing, intradermal testing and oral challenge. While patch and intradermal testing are specific for the diagnosis of immune-mediated (IM) ADRs, they suffer from drug-specific limitations in sensitivity. The use of ex vivo diagnostics, especially ELISpot has been highlighted as a promising new approach to assigning causality. Knowledge of true rates of antimicrobial cross-reactivity aids empirical antibiotic choice in the setting of previous IM-ADRs. Summary In an era of increasing antimicrobial resistance and use of broad-spectrum antimicrobial therapy, ensuring patients are assigned the correct “allergy label” is essential. Re-exposure to implicated antimicrobials, especially in the setting of severe adverse cutaneous reaction is associated with significant morbidity and mortality. The process through which an antibiotic label gets assigned, acted on and maintained is still imprecise. Predicting T-cell-mediated ADRs via personalised approaches, including HLA-typing may pave future pathways to safer antimicrobial prescribing guidelines. PMID:27753687

Community pharmacists' attitudes, perceptions, and barriers toward adverse drug reaction reporting in Malaysia: a quantitative insight.

PubMed

Elkalmi, Ramadan Mohamed; Hassali, Mohamed Azmi; Ibrahim, Mohamed Izham M; Jamshed, Shazia Qasim; Al-Lela, Omer Qutaiba B

2014-06-01

This study was designed to explore awareness and attitudes of community pharmacists toward the national ADR reporting system activities in the northern states of Malaysia. A cross-sectional survey using a validated self-administered questionnaire was used in this study. The questionnaire was delivered to all community pharmacists (N = 470) practicing in the four northern states of Malaysia (Perlis, Kedah, Pulau Pinang and Perak) during the study period. A total of 470 survey forms were sent with one wave of reminders. Only 116 pharmacists responded to the survey (response rate of 25.2%). The total number of usable responses was 104 (24.7%). The survey findings revealed that nearly three-quarters of pharmacists (n = 75; 72.1%) were not aware of the pharmacovigilance activities run by the drug regulatory authority in Malaysia. Although more than half (n = 65, 61.5%) of the surveyed pharmacists emphasized the importance of ADR reporting, only 13 pharmacists (12.9%) claimed that they submitted ADR reports to the Malaysia Adverse Drug Reaction Advisory Committee (MADRAC) before this survey. Barriers which prevent community pharmacists from ADR reporting were identified. These included lack of knowledge on how to report (n = 36; 34.7%), the unavailability of reporting forms (n = 44; 42.6%), and ignorance of where the report should be sent to (n = 46; 44.6%). Despite the unfamiliarity and the common misconceptions, the study results show that community pharmacists in the northern states of Malaysia have a very positive attitude toward the ADR reporting system in the country. However, the study findings highlight the urgent need for special education programs to establish continuous efforts to promote ADR reporting among community pharmacists. Further studies at the national level aimed at identifying and removing barriers that prevent community pharmacists from performing ADR reporting are required.

Adverse drug reactions in Colombian patients, 2007-2013: Analysis of population databases.

PubMed

Machado-Alba, Jorge Enrique; Londoño-Builes, Manuel José; Echeverri-Cataño, Luis Felipe; Ochoa-Orozco, Sergio Andrés

2016-03-03

Recognizing adverse drug reactions (ADRs) is becoming more important in clinical practice.  To determine the frequency of adverse drug reactions and ADR suspicions among the population affiliated to the Colombian health system and to describe the drugs, reactions and associated variables.  We revised ADRs and ADRs suspicion databases from drugs dispensed by Audifarma, S.A., both for inpatient and outpatient care from 2007 to 2013. Variables included ADR report date, city, drug, drug's Anatomical Therapeutic Classification (ATC), ADR severity, ADR type, ADR classification and ADR probability according to the World Health Organization's definitions.  We obtained 5,342 reports for 468 different drugs. The ATC groups with the most reports were anti-infectives for systemic use (25.5%), nervous system agents (17.1%) and cardiovascular system drugs (15.0%). The drugs with the highest number of reports were metamizole (4.2%), enalapril (3.8%), clarithromycin (2.8%), warfarin (2.5%) and ciprofloxacin (2.4%). The most common ADR, classified following the World Health Organization adverse reaction terminology, were: skin and appendages disorders (35.3%), general disorders (14.2%) and gastrointestinal system disorders (11.8%). Overall, 49.4% of the ADRs were classified as "moderate" and 45.1% as "mild".  An increasing number of ADR reports were found coinciding with a worldwide tendency. Differences between inpatient and outpatient ADR reports were found when compared to scientific publications. The information on ADR reports, mainly gathered by the Instituto Nacional de Vigilancia de Medicamentos y Alimentos - Invima, should be made public for academic and institutional use.

Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

PubMed

Sunara, Petra; Krnic, Darko; Puljak, Livia

2017-11-01

Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Evaluation of Internet Social Networks using Net scoring Tool: A Case Study in Adverse Drug Reaction Mining.

PubMed

Katsahian, Sandrine; Simond Moreau, Erica; Leprovost, Damien; Lardon, Jeremy; Bousquet, Cedric; Kerdelhué, Gaétan; Abdellaoui, Redhouane; Texier, Nathalie; Burgun, Anita; Boussadi, Abdelali; Faviez, Carole

2015-01-01

Suspected adverse drug reactions (ADR) reported by patients through social media can be a complementary tool to already existing ADRs signal detection processes. However, several studies have shown that the quality of medical information published online varies drastically whatever the health topic addressed. The aim of this study is to use an existing rating tool on a set of social network web sites in order to assess the capabilities of these tools to guide experts for selecting the most adapted social network web site to mine ADRs. First, we reviewed and rated 132 Internet forums and social networks according to three major criteria: the number of visits, the notoriety of the forum and the number of messages posted in relation with health and drug therapy. Second, the pharmacist reviewed the topic-oriented message boards with a small number of drug names to ensure that they were not off topic. Six experts have been chosen to assess the selected internet forums using a French scoring tool: Net scoring. Three different scores and the agreement between experts according to each set of scores using weighted kappa pooled using mean have been computed. Three internet forums were chosen at the end of the selection step. Some criteria get high score (scores 3-4) no matter the website evaluated like accessibility (45-46) or design (34-36), at the opposite some criteria always have bad scores like quantitative (40-42) and ethical aspect (43-44), hyperlinks actualization (30-33). Kappa were positives but very small which corresponds to a weak agreement between experts. The personal opinion of the expert seems to have a major impact, undermining the relevance of the criterion. Our future work is to collect results given by this evaluation grid and proposes a new scoring tool for Internet social networks assessment.

OntoADR a semantic resource describing adverse drug reactions to support searching, coding, and information retrieval.

PubMed

Souvignet, Julien; Declerck, Gunnar; Asfari, Hadyl; Jaulent, Marie-Christine; Bousquet, Cédric

2016-10-01

Efficient searching and coding in databases that use terminological resources requires that they support efficient data retrieval. The Medical Dictionary for Regulatory Activities (MedDRA) is a reference terminology for several countries and organizations to code adverse drug reactions (ADRs) for pharmacovigilance. Ontologies that are available in the medical domain provide several advantages such as reasoning to improve data retrieval. The field of pharmacovigilance does not yet benefit from a fully operational ontology to formally represent the MedDRA terms. Our objective was to build a semantic resource based on formal description logic to improve MedDRA term retrieval and aid the generation of on-demand custom groupings by appropriately and efficiently selecting terms: OntoADR. The method consists of the following steps: (1) mapping between MedDRA terms and SNOMED-CT, (2) generation of semantic definitions using semi-automatic methods, (3) storage of the resource and (4) manual curation by pharmacovigilance experts. We built a semantic resource for ADRs enabling a new type of semantics-based term search. OntoADR adds new search capabilities relative to previous approaches, overcoming the usual limitations of computation using lightweight description logic, such as the intractability of unions or negation queries, bringing it closer to user needs. Our automated approach for defining MedDRA terms enabled the association of at least one defining relationship with 67% of preferred terms. The curation work performed on our sample showed an error level of 14% for this automated approach. We tested OntoADR in practice, which allowed us to build custom groupings for several medical topics of interest. The methods we describe in this article could be adapted and extended to other terminologies which do not benefit from a formal semantic representation, thus enabling better data retrieval performance. Our custom groupings of MedDRA terms were used while performing signal detection, which suggests that the graphical user interface we are currently implementing to process OntoADR could be usefully integrated into specialized pharmacovigilance software that rely on MedDRA. Copyright © 2016 Elsevier Inc. All rights reserved.

The relation between the effect of a subhypnotic dose of thiopental on claw pain threshold in rats and adrenalin, noradrenalin and dopamine levels.

PubMed

Aksoy, Mehmet; Ahiskalioglu, Ali; Ince, Ilker; Celik, Mine; Dostbil, Aysenur; Kuyrukluyildiz, Ufuk; Altuner, Durdu; Kurt, Nezahat; Suleyman, Halis

2015-01-01

Thiopental sodium (TPS) needs to be applied together with adrenalin in order to establish its analgesic effect in general anesthesia. We aimed to investigate the effect of TPS on the claw pain threshold in rats and evaluated its relationship with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels. Intact and adrenalectomized rats were used in the experiment. Intact animals were divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and 0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP levels were measured. The TS group's claw pain threshold was found low. However, the claw pain thresholds of the ATS and ADR groups increased significantly. In the A-TS group, the pain threshold decreased compared with normal, and in the A-ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR levels in intact rats; however, no significant changes were observed in the NDR and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in rats. The present study shows that to achieve analgesic activity, TPS needs to be applied together with ADR.

The relation between the effect of a subhypnotic dose of thiopental on claw pain threshold in rats and adrenalin, noradrenalin and dopamine levels

PubMed Central

Aksoy, Mehmet; Ahiskalioglu, Ali; Ince, Ilker; Celik, Mine; Dostbil, Aysenur; Kuyrukluyildiz, Ufuk; Altuner, Durdu; Kurt, Nezahat; Suleyman, Halis

2015-01-01

Thiopental sodium (TPS) needs to be applied together with adrenalin in order to establish its analgesic effect in general anesthesia. We aimed to investigate the effect of TPS on the claw pain threshold in rats and evaluated its relationship with endogenous adrenalin (ADR), noradrenalin (NDR), and dopamine (DOP) levels. Intact and adrenalectomized rats were used in the experiment. Intact animals were divided into the following groups: 15 mg/kg TPS (TS), 0.3 mg/kg ADR+15 mg/kg TPS (ATS) and 0.3 mg/kg ADR alone (ADR). Adrenalectomized animals were divided into the following groups: 15 mg/kg TPS (A-TS), 0.3 mg/kg ADR+15 mg/kg TPS (A-ATS) and 0.3 mg/kg ADR alone (A-ADR). Claw pain threshold and blood ADR, NDR, and DOP levels were measured. The TS group’s claw pain threshold was found low. However, the claw pain thresholds of the ATS and ADR groups increased significantly. In the A-TS group, the pain threshold decreased compared with normal, and in the A-ATS and A-ADR groups, the pain threshold increased. TPS reduced the blood ADR levels in intact rats; however, no significant changes were observed in the NDR and DOP levels. #TPS provides hyperalgesia by reducing the production of ADR in rats. The present study shows that to achieve analgesic activity, TPS needs to be applied together with ADR. PMID:26211784

Adverse Drug Reactions to Antiretroviral Therapy in HIV-Infected Patients at the Largest Public Hospital in Nicaragua.

PubMed

Lorío, Marco; Colasanti, Jonathan; Moreira, Sumaya; Gutierrez, Gamaliel; Quant, Carlos

2014-01-01

Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are an important cause of hospitalization, treatment discontinuation, and regimen changes in both developed and developing countries. This study is the first to examine and understand ADRs in HIV-infected patients in Nicaragua. A retrospective descriptive study was conducted from May 2010 to March 2011, in a cohort of HIV-infected patients receiving ART at the largest public hospital in Managua, Nicaragua. Patients were identified based on ADRs reporting on a standardized antiretroviral pharmacotherapy form. Subsequently, chart reviews of these patients were performed in order to document the specific ADRs. Six hundred ninety-two patients on ART were included. The incidence of ADRs was 6.4% (95% confidence interval [CI] 4.5-8.2). Females demonstrated a higher incidence, that is, 10.2% (95% CI 5.3-15.1, P = .020). Patients treated with combinations of zidovudine (ZDV)/lamivudine (3TC) and emtricitabine (FTC)/tenofovir (TDF) had fewer ADRs (P < .01) than those using other combinations. Five patients were hospitalized or had a prolonged hospitalization secondary to ADRs, with no mortality attributed to ADR. The most common manifestations of ADRs were central nervous system (20 of 44), gastrointestinal (12 of 44), and dermatologic (8 of 44) reactions. Adverse drug reactions were classified as "likely ADRs" (25 of 44) and "possible ADRs" (19 of 44). No ADRs were preventable. Adverse drug reactions most frequently affected the central nervous system. No ADR was life threatening. The frequency of ADRs in this Nicaraguan patient population was less than that reported from other studies in resource-limited settings. © The Author(s) 2014.

Why Lumbar Artificial Disk Replacements (LADRs) Fail.

PubMed

Pettine, Kenneth; Ryu, Robert; Techy, Fernando

2017-07-01

A retrospective review of prospectively collected data. To determine why artificial disk replacements (ADRs) fail by examining results of 91 patients in FDA studies performed at a single investigational device exemption (IDE) site with minimum 2-year follow-up. Patients following lumbar ADR generally achieve their 24-month follow-up results at 3 months postoperatively. Every patient undergoing ADR at 1 IDE site by 2 surgeons was evaluated for clinical success. Failure was defined as <50% improvement in ODI and VAS or any additional surgery at index or adjacent spine motion segment. Three ADRs were evaluated: Maverick, 25 patients; Charité, 31 patients; and Kineflex, 35 patients. All procedures were 1-level operations performed at L4-L5 or L5-S1. Demographics and inclusion/exclusion criteria were similar and will be discussed. Overall clinical failure occurred in 26% (24 of 91 patients) at 2-year follow-up. Clinical failure occurred in: 28% (Maverick) (7 of 25 patients), 39% (Charité) (12 of 31 patients), and 14% (Kineflex) (5 of 35 patients). Causes of failure included facet pathology, 50% of failure patients (12 of 24). Implant complications occurred in 5% of total patients and 21% of failure patients (5 of 24). Only 5 patients went from a success to failure after 3 months. Only 1 patient went from a failure to success after a facet rhizotomy 1 year after ADR. Seventy-four percent of patients after ADR met strict clinical success after 2-year follow-up. The clinical success versus failure rate did not change from their 3-month follow-up in 85 of the 91 patients (93%). Overall clinical success may be improved most by patient selection and implant type.

Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study.

PubMed

Caldeira, Daniel; Rodrigues, Raquel; Abreu, Daisy; Anes, Ana Marta; Rosa, Mário M; Ferreira, Joaquim J

2018-04-01

In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals. We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation' (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications' (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98, 99%CI 1.50-10.53). Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.

Comparison of bacterial community structure and dynamics during the thermophilic composting of different types of solid wastes: anaerobic digestion residue, pig manure and chicken manure

PubMed Central

Song, Caihong; Li, Mingxiao; Jia, Xuan; Wei, Zimin; Zhao, Yue; Xi, Beidou; Zhu, Chaowei; Liu, Dongming

2014-01-01

This study investigated the impact of composting substrate types on the bacterial community structure and dynamics during composting processes. To this end, pig manure (PM), chicken manure (CM), a mixture of PM and CM (PM + CM), and a mixture of PM, CM and anaerobic digestion residue (ADR) (PM + CM + ADR) were selected for thermophilic composting. The bacterial community structure and dynamics during the composting process were detected and analysed by polymerase chain reaction–denaturing gradient gel electrophoresis (DGGE) coupled with a statistic analysis. The physical-chemical analyses indicated that compared to single-material composting (PM, CM), co-composting (PM + CM, PM + CM + ADR) could promote the degradation of organic matter and strengthen the ability of conserving nitrogen. A DGGE profile and statistical analysis demonstrated that co-composting, especially PM + CM + ADR, could improve the bacterial community structure and functional diversity, even in the thermophilic stage. Therefore, co-composting could weaken the screening effect of high temperature on bacterial communities. Dominant sequencing analyses indicated a dramatic shift in the dominant bacterial communities from single-material composting to co-composting. Notably, compared with PM, PM + CM increased the quantity of xylan-degrading bacteria and reduced the quantity of human pathogens. PMID:24963997

Longitudinal medical records as a complement to routine drug safety signal analysis†

PubMed Central

Watson, Sarah; Sandberg, Lovisa; Johansson, Jeanette; Edwards, I. Ralph

2015-01-01

Abstract Purpose To explore whether and how longitudinal medical records could be used as a source of reference in the early phases of signal detection and analysis of novel adverse drug reactions (ADRs) in a global pharmacovigilance database. Methods Drug and ADR combinations from the routine signal detection process of VigiBase® in 2011 were matched to combinations in The Health Improvement Network (THIN). The number and type of drugs and ADRs from the data sets were investigated. For unlabelled combinations, graphical display of longitudinal event patterns (chronographs) in THIN was inspected to determine if the pattern supported the VigiBase combination. Results Of 458 combinations in the VigiBase data set, 190 matched to corresponding combinations in THIN (after excluding drugs with less than 100 prescriptions in THIN). Eighteen percent of the VigiBase and 9% of the matched THIN combinations referred to new drugs reported with serious reactions. Of the 112 unlabelled combinations matched to THIN, 52 chronographs were inconclusive mainly because of lack of data; 34 lacked any outstanding pattern around the time of prescription; 24 had an elevation of events in the pre‐prescription period, hence weakened the suspicion of a drug relationship; two had an elevated pattern of events exclusively in the post‐prescription period that, after review of individual patient histories, did not support an association. Conclusions Longitudinal medical records were useful in understanding the clinical context around a drug and suspected ADR combination and the probability of a causal relationship. A drawback was the paucity of data for newly marketed drugs with serious reactions. © 2015 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd. PMID:25623045

Effect and mechanism of Qishen Yiqi Pills on adriamycin- induced cardiomyopathy in mice.

PubMed

Tong, Jia-Yi; Xu, Yan-Juan; Bian, Ye-Ping; Shen, Xiang-Bo; Yan, Lei; Zhu, Xin-Yi

2013-09-01

To study the effect and probable mechanism of Qishen Yiqi Pills on adriamycin (ADR)-induced cardiomyopathy in mice. Sixty-four mice were randomly divided into (1) the ADR group: saline (1 mL/100 g) administered every day by intragavage, ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks; (2) the ADR + Qishen Yiqi Pills I group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the beginning of the third week Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (3) the ADR + Qishen Yiqi Pills II group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the same time Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (4) the control group: saline (1 mL/100 g) administered every day by intragavage, saline (1 mL·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks. Six weeks later, cardiac function, myocardial pathology, and expression of Bcl-2 and Bax were evaluated. 1. The left ventricular diastolic diameter and the left ventricular systolic diameter were significantly increased (P < 0.05) and the left ventricular ejection fraction was significantly decreased (P < 0.05) in the ADR group, and the cardiac function of both the ADR + Qishen Yiqi Pills I group and the ADR + Qishen Yiqi Pills II group improved. 2. Myocardial morphologic observation showed that the myocardial fibers were disordered, there was cell edema, and gap widening in the ADR group. The degree of myocardial cell injury was reduced in the ADR + Qishen Yiqi Pills I group and ADR + Qishen Yiqi Pills II group compared with the ADR group. 3. The expression of Bax in the ADR group was significantly up-regulated, and the expression of Bcl-2 was significantly downregulated in the ADR group compared with the ADR + Qishen Yiqi Pills I group, the ADR + Qishen Yiqi Pills II group, and the control group (P < 0.05). Qishen Yiqi Pills can effectively improve the cardiac function of ADR-induced cardiomyopathy, and the earlier it is used is better. The probable mechanism of action may be the inhibition of the apoptosis of myocardial cells. Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

PubMed

Karp, J E; Humphrey, R L; Burke, P J

1981-03-01

Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two “challenging” case reports

PubMed Central

Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M.; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

2013-01-01

Introduction: Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. Materials and Methods: We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. Results: First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Discussion and Conclusion: Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health. PMID:24347986

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two "challenging" case reports.

PubMed

Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

2013-12-01

Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health.

Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries

PubMed Central

Lev-Ran, Shaul

2017-01-01

Background Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Objective Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. Methods We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration’s Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Results Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). Conclusions These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. PMID:29074469

Filtering Entities to Optimize Identification of Adverse Drug Reaction From Social Media: How Can the Number of Words Between Entities in the Messages Help?

PubMed

Abdellaoui, Redhouane; Schück, Stéphane; Texier, Nathalie; Burgun, Anita

2017-06-22

With the increasing popularity of Web 2.0 applications, social media has made it possible for individuals to post messages on adverse drug reactions. In such online conversations, patients discuss their symptoms, medical history, and diseases. These disorders may correspond to adverse drug reactions (ADRs) or any other medical condition. Therefore, methods must be developed to distinguish between false positives and true ADR declarations. The aim of this study was to investigate a method for filtering out disorder terms that did not correspond to adverse events by using the distance (as number of words) between the drug term and the disorder or symptom term in the post. We hypothesized that the shorter the distance between the disorder name and the drug, the higher the probability to be an ADR. We analyzed a corpus of 648 messages corresponding to a total of 1654 (drug and disorder) pairs from 5 French forums using Gaussian mixture models and an expectation-maximization (EM) algorithm . The distribution of the distances between the drug term and the disorder term enabled the filtering of 50.03% (733/1465) of the disorders that were not ADRs. Our filtering strategy achieved a precision of 95.8% and a recall of 50.0%. This study suggests that such distance between terms can be used for identifying false positives, thereby improving ADR detection in social media. ©Redhouane Abdellaoui, Stéphane Schück, Nathalie Texier, Anita Burgun. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 22.06.2017.

Reported time to onset of neurological adverse drug reactions among different age and gender groups using metoclopramide: an analysis of the global database Vigibase®.

PubMed

Svendsen, Kristian; Wood, Mollie; Olsson, Erika; Nordeng, Hedvig

2018-05-01

Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender. All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis. Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys). Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

Impact of reinforced education by telephone and short message service on the quality of bowel preparation: a randomized controlled study.

PubMed

Lee, Yoo Jin; Kim, Eun Soo; Choi, Jae Hyuk; Lee, Kyung In; Park, Kyung Sik; Cho, Kwang Bum; Jang, Byoung Kuk; Chung, Woo Jin; Hwang, Jae Seok

2015-11-01

High quality bowel preparation is essential for successful colonoscopy. This study aimed to assess the impact of reinforced education by telephone or short message service (SMS) on the quality of bowel preparation. A prospective, endoscopist-blinded, randomized, controlled study was conducted. Reinforced education groups received additional education via reminders by telephone or SMS 2 days before colonoscopy. The primary outcome was the quality of the bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The secondary outcomes included polyp detection rate (PDR), adenoma detection rate (ADR), tolerance, and subjective feelings of patients. A total of 390 patients were included. Total BBPS score was significantly higher in the reinforced education groups than in the control group (mean [SD] telephone vs. 7.1 [1.2] vs. 6.3 [1.4], P < 0.001; SMS vs. 6.8 [1.3] vs. 6.3 [1.4], P = 0.027). Between the two interventions, there was no significant difference in total BBPS score. PDR and ADR were not different among groups. Reinforced education groups showed lower anxiety and better tolerance compared with controls. A preparation-to-colonoscopy time of > 6 hours and < 80 % of the purgative ingested were independent factors associated with inadequate bowel preparation (BBPS < 5), whereas re-education by telephone was inversely related to inadequate bowel preparation. SMS was the optimal education modality, and was as effective as telephone reminders for the quality of bowel preparation. A reinforced educational approach via telephone or SMS should be individualized, depending on the resource availability of each clinical practice. ClinicalTrials.gov (NCT01911052). © Georg Thieme Verlag KG Stuttgart · New York.

Pattern of adverse drug reactions reported by the community pharmacists in Nepal

PubMed Central

Palaian, Subish; Ibrahim, Mohamed I.M.; Mishra, Pranaya

2010-01-01

The pharmacovigilance program in Nepal is less than a decade old, and is hospital centered. This study highlights the findings of a community based pharmacovigilance program involving the community pharmacists. Objectives: To collect the demographic details of the patients experiencing adverse drug reactions (ADR) reported by the community pharmacists; to identify the common drugs causing the ADRs, the common types of ADRs; and to carry out the causality, severity and preventability assessments of the reported ADRs. Methods: The baseline Knowledge-Attitude-Practices (KAP) of 116 community pharmacists from Pokhara valley towards drug safety was evaluated using a validated (Cronbach alpha=0.61) KAP questionnaire having 20 questions [(knowledge 11, attitude 5 and practice 4) maximum possible score 40]. Thirty community pharmacists with high scores were selected for three training sessions, each session lasting for one to two hours, covering the basic knowledge required for the community pharmacists for ADR reporting. Pharmacist from the regional pharmacovigilance center visited the trained community pharmacists every alternate day and collected the filled ADR reporting forms. Results: Altogether 71 ADRs, from 71 patients (37 males) were reported. Antibiotics/ antibacterials caused 42% (n=37) of the total ADRs followed by non steroidal anti-inflammatory drugs [25% (n=22)]. Ibuprofen/paracetamol combination accounted for ten ADRs. The most common type of ADR was itching [17.2 % (n=20), followed by generalized edema [8.6 % (n=10)]. In order to manage the ADRs, the patients needed medical treatment in 69% (n=49) of the cases. Over two third (69%) of the ADRs had a ‘possible’ association with the suspected drugs and a high percentage (70.4%) were of ‘mild (level 2)’ type. Nearly two third [64.7 % (n=46)] of the ADRs were ‘definitely preventable’. Conclusion: The common class of drugs known to cause ADRs was antibacterial/ antibiotics. Ibuprofen/ Paracetamol combination use of the drug was responsible for more number of ADRs and the most common ADRs were related to dermatological system. Strengthening this program might improve safe use of medicines in the community. PMID:25126141

Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia.

PubMed

Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd; Ming, Long Chiau; Manan, Mohamed Mansor

2017-01-01

Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% ( n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash ( n = 215), maculopapular rash ( n = 206), urticaria ( n = 169), erythematous rash ( n = 76), and pruritus ( n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children.

Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia

PubMed Central

Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd.; Ming, Long Chiau; Manan, Mohamed Mansor

2017-01-01

Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia’s national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia’s National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens–Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial for systemic use, with most of the ADRs manifesting in skin reactions. This study also reveals rare cutaneous ADRs experienced by Malaysian children under the age of 2, which constitutes a crucial cause of harm among children. PMID:28239351

14 CFR 17.27 - Submission of joint or separate statements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... either— (1) A joint request for ADR, and an executed ADR agreement, pursuant to § 17.33(d), specifying which ADR techniques will be employed; or (2) Written explanation(s) as to why ADR proceedings will not... Register. (d) The submission of a statement which indicates that ADR will not be utilized will not in any...

14 CFR 17.27 - Submission of joint or separate statements.

Code of Federal Regulations, 2011 CFR

2011-01-01

... either— (1) A joint request for ADR, and an executed ADR agreement, pursuant to § 17.33(d), specifying which ADR techniques will be employed; or (2) Written explanation(s) as to why ADR proceedings will not... Register. (d) The submission of a statement which indicates that ADR will not be utilized will not in any...

Monitoring adverse drug reactions in children using community pharmacies: a pilot study

PubMed Central

Stewart, Derek; Helms, Peter; McCaig, Dorothy; Bond, Christine; McLay, James

2005-01-01

Aims To determine the feasibility of a community pharmacy-based parental adverse drug reaction (ADR) reporting system for children. Design Prospective study of parent-reported ADRs using a questionnaire issued to the parent or guardians of children 0–11 years of age collecting prescribed medicine for amoxicillin, and/or salbutamol, and collecting prescribed medicine for, or purchasing, paracetamol or ibuprofen suspension. Setting Seven community pharmacies in Grampian, Scotland. Results During a 4-week period 360 prescriptions or purchases for the study medications occurred. Two hundred and sixty-seven parents (85.5%) agreed to participate in the study. One hundred and six participants (40%) returned a total of 122 questionnaires. The demographics of responders and nonresponders including medication, age of child, and social status as assessed by the Depcat score were similar. There was no evidence of under-representation of any socio-economic group. Possible adverse events were detected using a symptom tick list and perceived ADRs using free text entry. Using the symptom tick list approach the most commonly reported symptoms were diarrhoea (28.9%) and tiredness (31.6%) for amoxicillin. The levels of diarrhoea and tiredness reported for ibuprofen, paracetamol and salbutamol were 15% and 20%, 7.4% and 18.5%, and 20% and 0%, respectively. Using the freehand section of the questionnaire 15 specific ADRs were reported by parents (12.3%). Eight children (21.2%) reported ADRs attributed to amoxicilin [diarrhoea (n = 4), fever (n = 1), anorexia (n = 1), hyperactivity (n = 1) and nonspecific (n = 1)], five to paracetamol [diarrhoea (n = 3), anorexia, irritability, crying and very angry (n = 1) and not stated (n = 1)], two to ibuprofen [diarrhoea (n = 1), not stated (n =)]. Only one off-label prescription was identified and this was for salbutamol syrup prescribed to a child under 2 years of age. Conclusions The prospective monitoring of paediatric ADRs, using a questionnaire issued to parents or guardians in the community pharmacies, is feasible. PMID:15948932

A Deterministic Approach to Active Debris Removal Target Selection

NASA Astrophysics Data System (ADS)

Lidtke, A.; Lewis, H.; Armellin, R.

2014-09-01

Many decisions, with widespread economic, political and legal consequences, are being considered based on space debris simulations that show that Active Debris Removal (ADR) may be necessary as the concerns about the sustainability of spaceflight are increasing. The debris environment predictions are based on low-accuracy ephemerides and propagators. This raises doubts about the accuracy of those prognoses themselves but also the potential ADR target-lists that are produced. Target selection is considered highly important as removal of many objects will increase the overall mission cost. Selecting the most-likely candidates as soon as possible would be desirable as it would enable accurate mission design and allow thorough evaluation of in-orbit validations, which are likely to occur in the near-future, before any large investments are made and implementations realized. One of the primary factors that should be used in ADR target selection is the accumulated collision probability of every object. A conjunction detection algorithm, based on the smart sieve method, has been developed. Another algorithm is then applied to the found conjunctions to compute the maximum and true probabilities of collisions taking place. The entire framework has been verified against the Conjunction Analysis Tools in AGIs Systems Toolkit and relative probability error smaller than 1.5% has been achieved in the final maximum collision probability. Two target-lists are produced based on the ranking of the objects according to the probability they will take part in any collision over the simulated time window. These probabilities are computed using the maximum probability approach, that is time-invariant, and estimates of the true collision probability that were computed with covariance information. The top-priority targets are compared, and the impacts of the data accuracy and its decay are highlighted. General conclusions regarding the importance of Space Surveillance and Tracking for the purpose of ADR are also drawn and a deterministic method for ADR target selection, which could reduce the number of ADR missions to be performed, is proposed.

A Continuous Adiabatic Demagnetization Refrigerator for Use with Mechanical Coolers

NASA Technical Reports Server (NTRS)

Shirron, P.; Abbondante, N.; Canavan, E.; DiPirro, M.; Grabowski, M.; Hirsch, M.; Jackson, M.; Tuttle, J.

2000-01-01

We have begun developing an adiabatic demagnetization refrigerator (ADR) which can produce continuous cooling at temperatures of 50 mK or lower, with high cooling power (goal of 10 PW). The design uses multiple stages to cascade heat from a continuously-cooled stage up to a heat sink. The serial arrangement makes it possible to add stages to extend the operating range to lower temperature, or to raise the heat rejection temperature. Compared to conventional single-shot ADRS, this system achieves higher cooling power per unit mass and is able to reject its heat at a more uniform rate. For operation with a mechanical cryocooler, this latter feature stabilizes the heat sink temperature and allows both the ADR and cryocooler to operate more efficiently. The ADR is being designed to operate with a heat sink as warm as 10-12 K to make it compatible with a wide variety of mechanical coolers as part of a versatile, cryogen-free low temperature cooling system. A two-stage system has been constructed and a proof-of-principle demonstration was conducted at 100 mK. Details of the design and test results, as well as the direction of future work, are discussed.

Transcriptional profiling of NCI/ADR-RES cells unveils a complex network of signaling pathways and molecular mechanisms of drug resistance

PubMed Central

Vert, Anna; Castro, Jessica; Ribó, Marc; Vilanova, Maria; Benito, Antoni

2018-01-01

Background Ovarian cancer has the highest mortality rate among all the gynecological cancers. This is mostly due to the resistance of ovarian cancer to current chemotherapy regimens. Therefore, it is of crucial importance to identify the molecular mechanisms associated with chemoresistance. Methods NCI/ADR-RES is a multidrug-resistant cell line that is a model for the study of drug resistance in ovarian cancer. We carried out a microarray-derived transcriptional profiling analysis of NCI/ADR-RES to identify differentially expressed genes relative to its parental OVCAR-8. Results Gene-expression profiling has allowed the identification of genes and pathways that may be important for the development of drug resistance in ovarian cancer. The NCI/ADR-RES cell line has differential expression of genes involved in drug extrusion, inactivation, and efficacy, as well as genes involved in the architectural and functional reorganization of the extracellular matrix. These genes are controlled through different signaling pathways, including MAPK–Akt, Wnt, and Notch. Conclusion Our findings highlight the importance of using orthogonal therapies that target completely independent pathways to overcome mechanisms of resistance to both classical chemotherapeutic agents and molecularly targeted drugs. PMID:29379303

49 CFR 1109.3 - Confidentiality in ADR Matters

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Confidentiality in ADR Matters 1109.3 Section 1109... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.3 Confidentiality in ADR Matters In all ADR matters... provisions of that Act (5 U.S.C. 574) shall bind the Board and all parties and neutrals in those ADR matters...

49 CFR 1109.3 - Confidentiality in ADR Matters

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Confidentiality in ADR Matters 1109.3 Section 1109... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.3 Confidentiality in ADR Matters In all ADR matters... provisions of that Act (5 U.S.C. 574) shall bind the Board and all parties and neutrals in those ADR matters...

49 CFR 1109.3 - Confidentiality in ADR Matters

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 8 2012-10-01 2012-10-01 false Confidentiality in ADR Matters 1109.3 Section 1109... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.3 Confidentiality in ADR Matters In all ADR matters... provisions of that Act (5 U.S.C. 574) shall bind the Board and all parties and neutrals in those ADR matters...

Structures and processes in spontaneous ADR reporting systems: a comparative study of Australia and Denmark.

PubMed

Aagaard, Lise; Stenver, Doris Irene; Hansen, Ebba Holme

2008-10-01

To explore the organisational structure and processes of the Danish and Australian spontaneous ADR reporting systems with a view to how information is generated about new ADRs. The Danish and Australian spontaneous ADR reporting systems. Qualitative analyses of documentary material, descriptive interviews with key informants, and observations were made. We analysed the organisational structure of the Danish and Australian ADR reporting systems with respect to structures and processes, including information flow and exchange of ADR data. The analysis was made based on Scott's adapted version of Leavitt's diamond model, with the components: goals/tasks, social structure, technology and participants, within a surrounding environment. The main differences between the systems were: (1) PARTICIPANTS: Outsourcing of ADR assessments to the pharmaceutical companies complicates maintenance of scientific skills within the Danish Medicines Agency (DKMA), as it leaves the handling of spontaneous ADR reports purely administrative within the DKMA, and the knowledge creation process remains with the pharmaceutical companies, while in Australia senior scientific staff work with evaluation of the ADR report; (2) Goals/tasks: In Denmark, resources are targeted at evaluating Periodic Safety Update Reports (PSUR) submitted by the companies, while the resources in Australia are focused on single case assessment resulting in faster and more proactive medicine surveillance; (3) Social structure: Discussions between scientific staff about ADRs take place in Australia, while the Danish system primarily focuses on entering and forwarding ADR data to the relevant pharmaceutical companies; (4) Technology: The Danish system exchanges ADR data electronically with pharmaceutical companies and the other EU countries, while Australia does not have a system for electronic exchange of ADR data; and (5) ENVIRONMENT: The Danish ADR system is embedded in the routines of cooperation within European pharmacovigilance network while the Australian system is acting alone, although they communicate with other systems. The two systems differ with regard to reporting requirements, report handling, resources being spent and information exchange with the environment. In Denmark, learning about ADRs primarily takes place in the safety divisions of the pharmaceutical companies and the authorities have no control over the knowledge creation process. In Australia, more learning and control of the knowledge is present than in Denmark.

Mining Patients' Narratives in Social Media for Pharmacovigilance: Adverse Effects and Misuse of Methylphenidate.

PubMed

Chen, Xiaoyi; Faviez, Carole; Schuck, Stéphane; Lillo-Le-Louët, Agnès; Texier, Nathalie; Dahamna, Badisse; Huot, Charles; Foulquié, Pierre; Pereira, Suzanne; Leroux, Vincent; Karapetiantz, Pierre; Guenegou-Arnoux, Armelle; Katsahian, Sandrine; Bousquet, Cédric; Burgun, Anita

2018-01-01

Background: The Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) have recognized social media as a new data source to strengthen their activities regarding drug safety. Objective: Our objective in the ADR-PRISM project was to provide text mining and visualization tools to explore a corpus of posts extracted from social media. We evaluated this approach on a corpus of 21 million posts from five patient forums, and conducted a qualitative analysis of the data available on methylphenidate in this corpus. Methods: We applied text mining methods based on named entity recognition and relation extraction in the corpus, followed by signal detection using proportional reporting ratio (PRR). We also used topic modeling based on the Correlated Topic Model to obtain the list of the matics in the corpus and classify the messages based on their topics. Results: We automatically identified 3443 posts about methylphenidate published between 2007 and 2016, among which 61 adverse drug reactions (ADR) were automatically detected. Two pharmacovigilance experts evaluated manually the quality of automatic identification, and a f-measure of 0.57 was reached. Patient's reports were mainly neuro-psychiatric effects. Applying PRR, 67% of the ADRs were signals, including most of the neuro-psychiatric symptoms but also palpitations. Topic modeling showed that the most represented topics were related to Childhood and Treatment initiation , but also Side effects . Cases of misuse were also identified in this corpus, including recreational use and abuse. Conclusion: Named entity recognition combined with signal detection and topic modeling have demonstrated their complementarity in mining social media data. An in-depth analysis focused on methylphenidate showed that this approach was able to detect potential signals and to provide better understanding of patients' behaviors regarding drugs, including misuse.

The Canadian Pharmacogenomics Network for Drug Safety: a model for safety pharmacology.

PubMed

Ross, Colin J D; Visscher, Henk; Sistonen, Johanna; Brunham, Liam R; Pussegoda, Kusala; Loo, Tenneille T; Rieder, Michael J; Koren, Gideon; Carleton, Bruce C; Hayden, Michael R

2010-07-01

Adverse drug reactions (ADRs) rank as one of the top 10 leading causes of death in the developed world, and the direct medical costs of ADRs exceed $100 billion annually in the United States alone. Pharmacogenomics research seeks to identify genetic factors that are responsible for individual differences in drug efficacy and susceptibility to ADRs. This has led to several genetic tests that are currently being used to provide clinical recommendations. The Canadian Pharmacogenomics Network for Drug Safety is a nation-wide effort established in Canada to identify novel predictive genomic markers of severe ADRs in children and adults. A surveillance network has been established in 17 of Canada's major hospitals to identify patients experiencing specific ADRs and to collect biological samples and relevant clinical history for genetic association studies. To identify ADR-associated genetic markers that could be incorporated into predictive tests that will reduce the occurrence of serious ADRs, high-throughput genomic analyses are conducted with samples from patients that have suffered serious ADRs and matched control patients. ADRs represent a significant unmet medical problem with significant morbidity and mortality, and Canadian Pharmacogenomics Network for Drug Safety is a nation-wide network in Canada that seeks to identify genetic factors responsible for interindividual differences in susceptibility to serious ADRs. Active ADR surveillance is necessary to identify and recruit patients who suffer from serious ADRs. National and international collaborations are required to recruit sufficient patients for these studies. Several pharmacogenomics tests are currently in clinical use to provide dosing recommendations, and the number of pharmacogenomics tests is expected to significantly increase in the future.

Prevalence, clinical features and avoidability of adverse drug reactions as cause of admission to a geriatric unit: a prospective study of 1756 patients.

PubMed

Franceschi, Marilisa; Scarcelli, Carlo; Niro, Valeria; Seripa, Davide; Pazienza, Anna Maria; Pepe, Giovanni; Colusso, Anna Maria; Pacilli, Luigi; Pilotto, Alberto

2008-01-01

Drug use increases with advancing age, and in older patients it is associated with an increase in adverse drug reactions (ADRs). ADRs are a primary cause of morbidity and mortality worldwide. To evaluate the prevalence, clinical characteristics and avoidability of ADR-related hospital admissions in elderly patients. From November 2004 to December 2005, all patients aged >or=65 years consecutively admitted to the Geriatric Unit of the Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo in Italy, were evaluated for enrolment in the study. ADRs were defined according to the WHO Adverse Reaction Terminology system. Drugs were classified according to Anatomical Therapeutic Chemical classification system. The Naranjo algorithm was used to evaluate the relationship between drug use and the ADR (definite, probable, possible or doubtful) and Hallas criteria were used to evaluate the avoidability of the ADR (definitely avoidable, possibly avoidable or unavoidable). All cases of a suspected ADR were discussed by a team trained in drug safety, including three geriatricians, one clinical pharmacologist and one pharmacist. Only cases of an ADR with an agreement >or=80% were included. Of the 1756 patients observed, 102 (5.8%, 42 males, 60 females, mean age 76.5 +/- 7.4 years, range 65-93 years) showed certain (6.8%) or probable (91.2%) ADR-related hospitalization. Gastrointestinal disorders (48 patients, 47.1%); platelet, bleeding and clotting disorders (20 patients, 19.6%); and cardiovascular disorders (13 patients, 12.7%) were the most frequent ADRs. NSAIDs (23.5%), oral anticoagulants (20.6%), low-dose aspirin (acetylsalicylic acid) [13.7%] and digoxin (12.7%) were the drugs most frequently involved in ADRs. Of the ADRs, 45.1% were defined as definitely avoidable, 31.4% as possibly avoidable, 18.6% as unavoidable and 4.9% as unclassifiable. Of 78 patients with definitely or possibly avoidable ADRs, 17 patients (21.8%) had received an inappropriate prescription, 29 patients (37.2%) had not received a prescription for an effective gastroprotective drug concomitantly with NSAID or low-dose aspirin treatment and 32 patients (41%) were not monitored during drug treatment. In the elderly, almost 6% of hospitalizations are ADR related. Most of these ADRs are potentially avoidable. Strategies that reduce inappropriate prescriptions and monitoring errors, as well as improving active prevention of ADRs, are needed in elderly subjects.

Geographical variation in reporting Interstitial Lung Disease as an adverse drug reaction: findings from an European Medicines Agency analysis of reports in EudraVigilance.

PubMed

Pinheiro, Luis; Blake, Kevin; Januskiene, Justina; Yue, Qun-Ying; Arlett, Peter

2016-06-01

Clinically, interstitial lung disease (ILD) is a heterogeneous group of over 150 respiratory disorders. In the context of its signal evaluation work, the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has seen geographic clustering of case reports of ILD from Japan. To explore this further, EudraVigilance (EV), the EMA's database of adverse drug reactions (ADRs), was analysed. The results have been used to inform on implications for pharmacovigilance including signal detection and evaluation activities. EV was queried for reports of respiratory ADRs coded using MedDRA for the period 1994-2014 for all medicinal products. Descriptive statistics and non-parametric (chi-square) independence tests were produced to compare reporting of ILD from Japan versus the rest of the world. As of 31 December 2014, there were 26 551 case reports of ILD in EV of which 17 526 (66%) originated in Japan. The reporting rate of ILD for Japan has been consistently higher over the period. The odds that a case report from Japan in EV refers to ILD is OR = 20.7, 95% CI 20.2, 21.3 (p < 0.001), compared to OR = 0.60, 95% CI 0.54, 0.67 (p < 0.001) for pulmonary fibrosis. A geographic imbalance between Japan and the rest of the world in reporting respiratory ADRs as ILD is confirmed. Consequently, the PRAC has developed approaches to address this in relation to signals of ILD it assesses to allow for more targeted risk minimisation including updates to the product information in the EU setting. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

First French experience of ADR reporting by patients after a mass immunization campaign with Influenza A (H1N1) pandemic vaccines: a comparison of reports submitted by patients and healthcare professionals.

PubMed

Durrieu, Geneviève; Palmaro, Aurore; Pourcel, Laure; Caillet, Céline; Faucher, Angeline; Jacquet, Alexis; Ouaret, Shéhérazade; Perault-Pochat, Marie Christine; Kreft-Jais, Carmen; Castot, Anne; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis

2012-10-01

Available data concerning the contribution of patient adverse drug reaction (ADR) reporting in practice are scarce. Few studies have compared patients' reports with reports from healthcare professionals (HCPs). During the 2009-10 mass immunization campaign with A (H1N1)v2009 pandemic influenza vaccines, a reinforced pharmacovigilance plan was introduced in France according to European Medicines Agency recommendations. For the first time, patients were offered the opportunity to report suspected ADRs to pandemic vaccines directly to regional pharmacovigilance centres. The aim of the study was to compare the characteristics of patient and HCP ADR reports in order to assess the qualitative and quantitative contribution of patient reporting to the French Pharmacovigilance System. All spontaneous ADRs registered into the French Pharmacovigilance Database from 21 October 2009 to 15 June 2010, in which either one of the most frequently administered pandemic vaccines (i.e. Panenza® or Pandemrix®) was involved, were analysed. ADRs were classified as 'serious', 'medically serious' and 'non-serious'. This study focused on 'serious' and 'medically serious' ADRs. An ADR was ranked as 'medically serious' when it required medical intervention or hospitalization within less than 24 hours. In each level of seriousness, frequency of 'unlabelled' ADRs, ADRs of 'special interest', imputability scores and category of ADRs according to Medical Dictionary for Regulatory Activitives (MedDRA®) primary System Organ Class were compared between patient and professional reports. Among the 4746 reports received during the study period, 1006 (21.2%) originated from patients. HCPs reported significantly more 'medically serious' or 'serious' ADRs than patients (15.1% [565/3740] vs 8.4% [85/1006], respectively; p < 0.001). No difference was found in 'unlabelled, serious' ADRs between patients and HCPs (56.5% [n = 13] vs 56.7% [n = 136], respectively). In this first French experience of formal patient participation to ADR reporting, patient contribution to the total number of ADRs reached 21.2%. This study revealed no major qualitative difference between patient and HCP reports. ADR profiles reported by patients appeared to be consistent with those from professionals. Further investigations are necessary to assess the intrinsic quality of notification forms coming from non-professional reporters. However, this study is of particular interest in the context of publication of the first governmental decree that will formally integrate patient participation to the current French ADR reporting scheme.

Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Kejian, E-mail: kejian.wang.bio@gmail.com; Weng, Zuquan; Sun, Liya

Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. Inmore » the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.« less

Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries.

PubMed

Yom-Tov, Elad; Lev-Ran, Shaul

2017-10-26

Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration's Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R 2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. ©Elad Yom-Tov, Shaul Lev-Ran. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.10.2017.

Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer.

PubMed

Wang, Xiaohong; Xu, Chengfeng; Hua, Yitong; Sun, Leitao; Cheng, Kai; Jia, Zhongming; Han, Yong; Dong, Jianli; Cui, Yuzhen; Yang, Zhenlin

2016-12-01

Release of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance. In this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo). Exosomes were characterized by morphology, exosomal markers and size distribution. The ability of ADR/exo to transfer multidrug resistance was assessed by MTT and real-time quantitative PCR. The different formation and secretion of exosomes were detected by immunofluorescence and transmission electron microscopy. Then we performed comparative transcriptomic analysis using RNA-Seq technology and real-time quantitative PCR to better understand the gene expression regulation in exosmes formation and release after psoralen treatment. Our data showed that exosomes derived from MCF-7/ADR cells were able to promote active sequestration of drugs and could induce a drug resistance phenotype by transferring drug-resistance-related gene MDR-1 and P-glycoprotein protein. Psoralen could reduce the formation and secretion of exosomes to overcome drug resistance. There were 21 differentially expressed genes. Gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most significantly expressed genes were linked to PPAR and P53 signaling pathways which were related to exosomes formation, secretion and cargo sorting. Psoralen can affect the exosomes and induce the reduction of resistance transmission via exosomes might through PPAR and P53 signaling pathways, which might provide a novel strategy for breast cancer resistance to chemotherapy in the future.

Adverse drug reactions and adverse events of 33 varieties of traditional Chinese medicine injections on National Essential medicines List (2004 edition) of China: an overview on published literatures.

PubMed

Wang, Li; Yuan, Qiang; Marshall, Gareth; Cui, Xiaohua; Cheng, Lan; Li, Yuanyuan; Shang, Hongcai; Zhang, Boli; Li, Youping

2010-05-01

We conducted a literature review on adverse drug reactions (ADRs) related to 33 kinds of traditional Chinese medicine injections (CMIs) on China's National Essential medicines List (2004 edition). We aimed to retrieve basic ADR information, identify trends related to CMIs, and provide evidence for the research, development, and application of CMIs. We electronically searched the Chinese Biomedical Literature Database (CBM, January 1978-April 2009), the China National Knowledge Infrastructure Database (CNKI, January 1979-April 2009), the Chinese Science and Technology Periodical Database (January 1989-April 2009) and the Traditional Chinese Medicine Database (January 1984-April 2009). We used the terms of 'adverse drug reaction', 'adverse event', 'side effects', 'side reaction', 'toxicity', and 'Chinese medicine injections', as well as the names of the 33 CMIs to search. We also collected CMI-related ADR reports and regulations from the Chinese Food and Drug Administration's 'Newsletter of Adverse Drug Reactions' (Issue 1 to 22). Then we descriptively analyzed all the articles by year published, periodical, and study design. We also analyzed regulations relevants to ADRs. (1) We found 5405 relevant citations, of which 1010 studies met the eligibility criteria. (2) The rate of publishing of research articles on CMI-linked ADRs has risen over time. (3) The included 1010 articles were scattered among 297 periodicals. Of these, 55 journals on pharmaceutical medicine accounted for 39.5% of the total (399/1010); the 64 journals on traditional Chinese medicine, accounted for only 19.5% (197/1010). Only 22 periodicals with relevant articles were included on the core journals of the Beijing University List (2008 edition); these published 129 articles (12.8% of the included articles). (4) The relevant articles consisted of 348 case reports (34.5%), 254 case series (25.2%), 119 reviews (11.8%), 116 randomized controlled trials (11.5%), 78 cross-sectional studies (7.7%), 61 literature analyses of ADR (6.0%), and 28 non-randomized controlled clinical studies (2.8%). (5) Three journals, Adverse Drug Reactions Journal, China Medical Herald, and Chinese Pharmaceuticals, together published 12.3% of the included literature. (6) The most commonly-reported CMI-related ADRs were to Shuanghuanglian, Qingkailing, and Yuxingcao injections, each of which had ADRs mentioned in more than 200 articles. Four of the five CMIs with the most ADR reports (Shuanghuanglian, Ciwujia, Yuxingcao, and Yinzhihuang injections) had been suspended use or sale in the market. (1) Articles published on CMI-related ADRs increased over time, but overall the research is of low quality and is scattered through a large number of sources. (2) Four CMIs (Shuanghuanglian, Ciwujia, Yuxingcao, and Yinzhihuang injections) had been suspended for clinical use or sale. (3) There is an urgent need for a clear standard to grade ADRs of CMIs in order to better risk manage. (4) It is necessary to continually re-evaluate the safety of CMIs and to promote rational use of CMIs. © 2010 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

45 CFR 74.91 - Alternative dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-10-01

... resolution (ADR) techniques. ADR often is effective in reducing the cost, delay and contentiousness involved in appeals and other traditional ways of handling disputes. ADR techniques include mediation, neutral evaluation and other consensual methods. Information about ADR is available from the HHS Dispute Resolution...

45 CFR 74.91 - Alternative dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-10-01

... resolution (ADR) techniques. ADR often is effective in reducing the cost, delay and contentiousness involved in appeals and other traditional ways of handling disputes. ADR techniques include mediation, neutral evaluation and other consensual methods. Information about ADR is available from the HHS Dispute Resolution...

Evaluation of patient reporting of adverse drug reactions to the UK 'Yellow Card Scheme': literature review, descriptive and qualitative analyses, and questionnaire surveys.

PubMed

Avery, A J; Anderson, C; Bond, C M; Fortnum, H; Gifford, A; Hannaford, P C; Hazell, L; Krska, J; Lee, A J; McLernon, D J; Murphy, E; Shakir, S; Watson, M C

2011-05-01

The monitoring of adverse drug reactions (ADRs) through pharmacovigilance is vital to patient safety. Spontaneous reporting of ADRs is one method of pharmacovigilance, and in the UK this is undertaken through the Yellow Card Scheme (YCS). Yellow Card reports are submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) by post, telephone or via the internet. The MHRA electronically records and reviews information submitted so that important safety issues can be detected. While previous studies have shown differences between patient and health-care professional (HCP) reports for the types of drugs and reactions reported, relatively little is known about the pharmacovigilance impact of patient reports. There have also been few studies on the views and experiences of patients/consumers on the reporting of suspected ADRs. To evaluate the pharmacovigilance impact of patient reporting of ADRs by analysing reports of suspected ADRs from the UK YCS and comparing reports from patients and HCPs. To elicit the views and experiences of patients and the public about patient reporting of ADRs. (1) Literature review and survey of international experiences of consumer reporting of ADRs; (2) descriptive analysis of Yellow Card reports; (3) signal generation analysis of Yellow Card reports; (4) qualitative analysis of Yellow Card reports; (5) questionnaire survey of patients reporting on Yellow Cards; (6) qualitative analysis of telephone interviews with patient reporters to the scheme; (7) qualitative analysis of focus groups and usability testing of the patient YCS; and (8) national omnibus telephone survey of public awareness of the YCS. Patients (n = 5180) and HCPs (n = 20,949) submitting Yellow Card reports from October 2005 to September 2007. Respondents to questionnaire survey (n = 1362). Participants at focus groups and usability testing sessions (n = 40). National omnibus telephone survey (n = 2028). The literature review included studies in English from across the world. All other components included populations from the UK; the omnibus survey was restricted to Great Britain. None. Characteristics of patient reports: types of drug and suspected ADR reported; seriousness of reports; and content of reports. The relative contributions of patient reports and of HCP reports to signal generation. Views and experiences of patient reporters. Views of members of the public about the YCS, including user-friendliness and usability of different ways of patient reporting. Public awareness of the YCS. Suggestions for improving patient reporting to the YCS. Compared with HCPs, patient reports to the YCS contained a higher median number of suspected ADRs per report, and described reactions in more detail. The proportions of reports categorised as 'serious' were similar; the patterns of drugs and reactions reported differed. Patient reports were richer in their descriptions of reactions than those from HCPs, and more often noted the effects of ADRs on patients' lives. Combining patient and HCP reports generated more potential signals than HCP reports alone; some potential signals in the 'HCP-only' data set were lost when combined with patient reports, but fewer than those gained; the addition of patient reports to HCP reports identified 47 new 'serious' reactions not previously included in 'Summaries of Product Characteristics'. Most patient reporters found it fairly easy to make reports, although improvements to the scheme were suggested, including greater publicity and the redesign of web- and paper-based reporting systems. Among members of the public, 8.5% were aware of the YCS in 2009. Patient reporting of suspected ADRs has the potential to add value to pharmacovigilance by reporting types of drugs and reactions different from those reported by HCPs; generating new potential signals; and describing suspected ADRs in enough detail to provide useful information on likely causality and impact on patients' lives. These findings suggest that further promotion of patient reporting to the YCS is justified, along with improvements to existing reporting systems. In order of priority, future work should include further investigation of (1) the pharmacovigilance impact of patient reporting in a longer-term study; (2) the optimum approach to signal generation analysis of patient and HCP reports; (3) the burden of ADRs in terms of impact on patients' lives; (4) the knowledge and attitudes of HCPs towards patient reporting of ADRs; (5) the value of using patient reports of ADRs to help other patients and HCPs who are seeking information on patient experiences of ADRs; and (6) the impact of increasing publicity and/or enhancements to reporting systems on the numbers and types of Yellow Card reports from patients. The National Institute for Health Research Health Technology Assessment programme.

Change in prescription pattern as a potential marker for adverse drug reactions of angiotensin converting enzyme inhibitors.

PubMed

Mahmoudpour, Seyed Hamidreza; Asselbergs, Folkert W; de Keyser, Catherine E; Souverein, Patrick C; Hofman, Albert; Stricker, Bruno H; de Boer, Anthonius; Maitland-van der Zee, Anke-Hilse

2015-12-01

Angiotensin converting enzyme inhibitors (ACEIs) are among the most frequently prescribed groups of medications. ACEI-induced adverse drug reactions (ADRs) are the main reason to discontinue or switch ACEI treatment. ADRs information is not available in prescription databases. OBJECTIVE :To identify a proxy for ACEI-induced ADRs in prescription databases. The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the Netherlands and has included 14,926 subjects aged 45 years or older. All ACEI starters from 2000 to 2011 were identified using prescription data within the Rotterdam Study. Participants were classified into 4 mutually exclusive groups: continuing, discontinuing, switching to angiotensin receptor blockers (ARBs), and switching to other antihypertensives. For categorization, the maximum time-interval between two prescription periods was set at 3 and 6 months. Subsequently, primary care physician files were searched and clinical events were classified as definite ADRs, probable ADRs, possible ADRs and definite non-ADRs. Finally the accuracy of different prescription patterns as indicators of ADRs was evaluated. Main outcome measure Positive predictive values (PPVs), negative predictive values (NPVs), sensitivity and specificity of the prescription patterns of the 4 groups were calculated. Totally, 1132 ACEI starters were included. The PPV for a definite ADR was 56.1 % for switchers to ARB, while the PPVs for switchers to other antihypertensives, and discontinuation were 39.5 and 19.5 %, respectively. After including probable ADRs and possible ADRs, PPVs for switchers to ARB increased to 68.3 and 90.5 %. A 6-month interval gave slightly higher PPVs compared to a 3-month interval (maximum 6.1 % higher). The differences in NPVs between 3 and 6-months interval groups were approximately 1.0 %. Switching ACEIs to ARBs is the best marker for ACEI-induced ADRs in prescription databases.

Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

PubMed

Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

2017-01-01

Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Using a capture–recapture method to assess the frequency of adverse drug reactions in a French university hospital

PubMed Central

Lugardon, Stephanie; Desboeuf, Karine; Fernet, Pierre; Montastruc, Jean-Louis; Lapeyre-Mestre, Maryse

2006-01-01

Aims There is evidence that different methods used to identify and quantify adverse drug reactions (ADR) in hospitals are not exhaustive (spontaneous reporting or computerized medical databases). The combination of these different sources of data could improve knowledge about ADR frequency in hospitals. The aim of this study was to estimate the incidence of serious ADRs handled in medical wards of a French university hospital using data from the Programme de Medicalization des Systemes d’Information (PMSI) and spontaneous reports recorded in the French Pharmacovigilance Database. Methods The study period was the first semester of 2001. From PMSI, all hospitalization summaries including an ICD-10th code related to a potential ADR were selected. From the French Pharmacovigilance Database, all serious ADRs which occurred during the study period and were reported by physicians working in the University Hospital were collected. After identification of common cases, the capture–recapture method was applied in order to estimate the real number of ADRs occurring during the first semester of 2001. Results From PMSI, we identified 274 different hospital stays related to an ADR. Out of 241 reports selected from the French Pharmacovigilance Database, we retained 151 ADRs for analysis. Fifty-two ADRs were common in the two databases, giving an estimated number of serious ADRs of 796 [95% confidence interval (CI) 638, 954], corresponding to 2.9% of inpatients (95% CI 2.3, 3.5). Conclusions This study shows the lack of exhaustiveness of ADR reporting whatever the sources of data and underlines the interest of merging data from different databases to identify fully the real impact of ADR in hospitals. PMID:16842398

Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography.

PubMed

Kim, S R; Lee, J H; Park, K H; Park, H J; Park, J W

2017-01-01

Low-osmolar non-ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar non-ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar non-ionic RCMs used in computed tomography (CT). Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM-contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day. Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%). The incidence of immediate ADRs varied according to the low-osmolar non-ionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations. © 2016 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Comparison of bacterial community structure and dynamics during the thermophilic composting of different types of solid wastes: anaerobic digestion residue, pig manure and chicken manure.

PubMed

Song, Caihong; Li, Mingxiao; Jia, Xuan; Wei, Zimin; Zhao, Yue; Xi, Beidou; Zhu, Chaowei; Liu, Dongming

2014-09-01

This study investigated the impact of composting substrate types on the bacterial community structure and dynamics during composting processes. To this end, pig manure (PM), chicken manure (CM), a mixture of PM and CM (PM + CM), and a mixture of PM, CM and anaerobic digestion residue (ADR) (PM + CM + ADR) were selected for thermophilic composting. The bacterial community structure and dynamics during the composting process were detected and analysed by polymerase chain reaction-denaturing gradient gel electrophoresis (DGGE) coupled with a statistic analysis. The physical-chemical analyses indicated that compared to single-material composting (PM, CM), co-composting (PM + CM, PM + CM + ADR) could promote the degradation of organic matter and strengthen the ability of conserving nitrogen. A DGGE profile and statistical analysis demonstrated that co-composting, especially PM + CM + ADR, could improve the bacterial community structure and functional diversity, even in the thermophilic stage. Therefore, co-composting could weaken the screening effect of high temperature on bacterial communities. Dominant sequencing analyses indicated a dramatic shift in the dominant bacterial communities from single-material composting to co-composting. Notably, compared with PM, PM + CM increased the quantity of xylan-degrading bacteria and reduced the quantity of human pathogens. © 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

14 CFR 17.39 - Confidentiality of ADR.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Confidentiality of ADR. 17.39 Section 17.39 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES... Evidence in deciding admissibility issues related to ADR communications. (c) ADR communications are not...

14 CFR 17.39 - Confidentiality of ADR.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Confidentiality of ADR. 17.39 Section 17.39 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES... Evidence in deciding admissibility issues related to ADR communications. (c) ADR communications are not...

14 CFR 17.39 - Confidentiality of ADR.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Confidentiality of ADR. 17.39 Section 17.39 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES... Evidence in deciding admissibility issues related to ADR communications. (c) ADR communications are not...

Adverse Drug Reactions Causing Admission to Medical Wards: A Cross-Sectional Survey at 4 Hospitals in South Africa.

PubMed

Mouton, Johannes P; Njuguna, Christine; Kramer, Nicole; Stewart, Annemie; Mehta, Ushma; Blockman, Marc; Fortuin-De Smidt, Melony; De Waal, Reneé; Parrish, Andy G; Wilson, Douglas P K; Igumbor, Ehimario U; Aynalem, Getahun; Dheda, Mukesh; Maartens, Gary; Cohen, Karen

2016-05-01

Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions.We prospectively followed patients admitted to 4 hospitals' medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission.There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34-65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06-2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09-1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07-1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17-3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable.In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect South Africa's high HIV and tuberculosis burden. Identification and management of these ADRs should be considered in HIV and tuberculosis care and treatment programs and should be emphasized in health care worker training programmes.

48 CFR 1233.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... resolution (ADR). 1233.214 Section 1233.214 Federal Acquisition Regulations System DEPARTMENT OF... Alternative dispute resolution (ADR). (c) The Administrative Dispute Resolution Act (ADRA) of 1990, Public Law... purposes. ADR procedures may be used when: (1) There is mutual consent by the parties to participate in the...

5 CFR 2423.2 - Alternative Dispute Resolution (ADR) services.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Alternative Dispute Resolution (ADR... Filing, Investigating, Resolving, and Acting on Charges § 2423.2 Alternative Dispute Resolution (ADR) services. The General Counsel provides ADR services under § 2423.12(a) after a Regional Director has...

48 CFR 3033.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... resolution (ADR). 3033.214 Section 3033.214 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND..., DISPUTES, AND APPEALS Disputes and Appeals 3033.214 Alternative dispute resolution (ADR). (c) The... informal resolution of disputes, and for other purposes. CBCA guidance on ADR may be obtained at http://www...

10 CFR 1023.3 - Principles of general applicability.

Code of Federal Regulations, 2011 CFR

2011-01-01

... functions or procedures, including ADR. (3) Decisions of the Board shall be final agency decisions and shall... (ADR) Functions. (1) Board judges and personnel shall perform ADR related functions impartially, with... judges limited to the nature, procedures, and availability of ADR through the Board are permitted and...

48 CFR 1233.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... resolution (ADR). 1233.214 Section 1233.214 Federal Acquisition Regulations System DEPARTMENT OF... Alternative dispute resolution (ADR). (c) The Administrative Dispute Resolution Act (ADRA) of 1990, Public Law... purposes. ADR procedures may be used when: (1) There is mutual consent by the parties to participate in the...

48 CFR 3033.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... resolution (ADR). 3033.214 Section 3033.214 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND..., DISPUTES, AND APPEALS Disputes and Appeals 3033.214 Alternative dispute resolution (ADR). (c) The... informal resolution of disputes, and for other purposes. CBCA guidance on ADR may be obtained at http://www...

Temporal trends in population-based death rates associated with chronic liver disease and liver cancer in the United States over the last 30 years.

PubMed

Kim, Yuhree; Ejaz, Aslam; Tayal, Amit; Spolverato, Gaya; Bridges, John F P; Anders, Robert A; Pawlik, Timothy M

2014-10-01

The health and economic burden from liver disease in the United States is substantial and rising. The objective of this study was to characterize temporal trends in mortality from chronic liver disease and liver cancer and the incidence of associated risk factors using population-based data over the past 30 years. Population-based mortality data were obtained from the National Vital Statistics System, and population estimates were derived from the national census for US adults (aged >45 years). Crude death rates (CDRs), age-adjusted death rates (ADRs), and average annual percentage change (AAPC) statistics were calculated. In total, 690,414 deaths (1.1%) were attributable to chronic liver disease, whereas 331,393 deaths (0.5%) were attributable to liver cancer between 1981 and 2010. The incidence of liver cancer was estimated at 7.1 cases per 100,000 population. Mortality rates from chronic liver disease and liver cancer increased substantially over the past 3 decades, with ADRs of 23.7 and 16.6 per 100,000 population in 2010, respectively. The AAPC from 2006 to 2010 demonstrated an increased ADR for chronic liver disease (AAPC, 1.5%; 95% confidence interval, 0.3%-2.8%) and liver cancer (AAPC, 2.6%; 95% confidence interval, 2.4%-2.7%). A comprehensive approach that involves primary and secondary prevention, increased access to treatment, and more funding for liver-related research is needed to address the high death rates associated with chronic liver disease and liver cancer in the United States. © 2014 American Cancer Society.

Incidence of adverse drug reactions in adult medical inpatients.

PubMed

Bowman, L; Carlstedt, B C; Black, C D

1994-10-01

This study was a prospective observational study of ADR occurrence and evaluation in adult internal medicine inpatients conducted over a 120-day period. Clinical pharmacists screened for ADRs at a county hospital in Indianapolis, IN. Patient information was reviewed on admission, every four days during hospitalization, and at discharge. ADRs occurring after hospital admission were assessed for causality, severity, pharmacological type (i.e., augmented pharmacology versus idiosyncratic reaction) and affected organ system. Nurse and pharmacist reports, incident reports, physician consults, patient transfers to critical care units, and serum drug concentration reports were additional means of ADR identification. Overall, 23.1% of patients experienced an ADR while 2.6% of the 11,702 drug exposures resulted in an ADR. Patients aged greater than 65 years (29.6% vs. 20.5% for younger patients) and females (26.2% vs. 20% for males) were at higher risk for ADR development (p < 0.05). Length of hospital stay was longer (13.3 days vs. 6.7 days; p < 0.05) and drug exposures more frequent for patients experiencing ADRs (p < 0.001). Furosemide elicited the most ADRs with 36 in 244 patient exposures (14.7%). Diltiazem, enalapril, heparin, trimterene/hydrochlorothiazide combination and captopril were also frequently implicated. ADRs were classified as mild (35.9%), moderate (52.6%), and severe (10.2%). Organ systems most commonly affected were the metabolic/hematologic (32.9%), gastrointestinal (17.8%), genitourinary (11.8%), and cardiovascular (10.5%). Over 30% of events were idiosyncratic reactions. ADR incidence was consistent with previous literature. Many frequently implicated medications were newer agents and the severity of events was less than previously reported.

Is gender still a predisposing factor in contrast-media associated adverse drug reactions? A systematic review and meta-analysis of randomized trials and observational studies.

PubMed

Lee, Heeyoung; Song, Seungyeon; Oh, Yun-Kyoung; Kang, WonKu; Kim, Eunyoung

2017-04-01

To evaluate the role of gender as a risk factor for developing contrast media-associated adverse drug reactions (CM-ADRs) by comparing the incidence of CM-ADR between male and female patients according to study design, ADR type, and computed tomography (CT) examination. We systematically searched three electronic databases for eligible studies. In the studies included (n=18), we assessed effect estimates of the relative incidence of CM-ADR, analysed by experimental design, ADR type and CT examination. This was calculated by using a random effects model if clinical conditions showed heterogeneity; otherwise, a fixed effects model was used. We identified 10,776 patients administered CM. According to the designs, studies were classified into randomised controlled trials (RCTs) and observational studies. Results were as follows: risk ratio (RR)=1.07 (95% confidence interval (CI): 0.79-1.46, P=0.66) for RCTs, and RR=0.77 (95% CI: 0.58-1.04, P=0.09) for observational studies. The results of analysis according to ADR type and for undergoing CT demonstrated that the incidence of CM-ADR did not differ between males and females. We found no significant difference in the incidence of CM-ADRs between male and female patients according to study design, ADR type, or CT examination. Future studies to determine why gender has shown different roles as a risk factor between CM-ADRs and non-CM ADRs are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey

PubMed Central

Mouton, Johannes P; Mehta, Ushma; Parrish, Andy G; Wilson, Douglas P K; Stewart, Annemie; Njuguna, Christine W; Kramer, Nicole; Maartens, Gary; Blockman, Marc; Cohen, Karen

2015-01-01

Aims Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status. Methods We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was ‘possible’, ‘probable’ or ‘certain’ using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria. Results ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7). Conclusions In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support. PMID:25475751

24 CFR 7.26 - EEO Alternative Dispute Resolution Program.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to participate in the EEO ADR Program or the traditional EEO counseling procedures. When ADR is... ADR process, the terms of the agreement must be in writing and signed by both the aggrieved person and the appropriate Department representative. The Director of EEO may execute ADR settlement agreements...

48 CFR 1433.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Alternative dispute resolution (ADR). 1433.214 Section 1433.214 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... dispute resolution (ADR). DOI strongly encourages the use of ADR in the resolution of disputes in lieu of...

48 CFR 1433.214 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Alternative dispute resolution (ADR). 1433.214 Section 1433.214 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR... dispute resolution (ADR). DOI strongly encourages the use of ADR in the resolution of disputes in lieu of...

24 CFR 7.26 - EEO Alternative Dispute Resolution Program.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to participate in the EEO ADR Program or the traditional EEO counseling procedures. When ADR is... ADR process, the terms of the agreement must be in writing and signed by both the aggrieved person and the appropriate Department representative. The Director of EEO may execute ADR settlement agreements...

In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model

NASA Astrophysics Data System (ADS)

Sun, Zhongchan; Song, Xinxing; Li, Xiujuan; Su, Tao; Qi, Shun; Qiao, Ruirui; Wang, Fu; Huan, Yi; Yang, Weidong; Wang, Jing; Nie, Yongzhan; Wu, Kaichun; Gao, Mingyuan; Cao, Feng

2014-11-01

miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADRfluc tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment.miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADRfluc tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03003f

Risk and association of HLA with oxcarbazepine-induced cutaneous adverse reactions in Asians.

PubMed

Chen, Chun-Bing; Hsiao, Yi-Hsin; Wu, Tony; Hsih, Mo-Song; Tassaneeyakul, Wichittra; Jorns, Teekayu P; Sukasem, Chonlaphat; Hsu, Chien-Ning; Su, Shih-Chi; Chang, Wan-Chun; Hui, Rosaline Chung-Yee; Chu, Chia-Yu; Chen, Yi-Ju; Wu, Ching-Ying; Hsu, Chao-Kai; Chiu, Tsu-Man; Sun, Pei-Lun; Lee, Hua-En; Yang, Chin-Yi; Kao, Pei-Han; Yang, Chih-Hsun; Ho, Hsin-Chun; Lin, Jing-Yi; Chang, Ya-Ching; Chen, Ming-Jing; Lu, Chun-Wei; Ng, Chau Yee; Kuo, Kang-Ling; Lin, Chien-Yio; Yang, Ching-Sheng; Chen, Ding-Ping; Chang, Pi-Yueh; Wu, Tsu-Lan; Lin, Yu-Jr; Weng, Yi-Ching; Kuo, Tseng-Tong; Hung, Shuen-Iu; Chung, Wen-Hung

2017-01-03

To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6  drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all ≦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10 -10 ; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further. © 2016 American Academy of Neurology.

A Meta-Analysis of Self-Administered vs Directly Observed Therapy Effect on Microbiologic Failure, Relapse, and Acquired Drug Resistance in Tuberculosis Patients

PubMed Central

Pasipanodya, Jotam G.; Gumbo, Tawanda

2013-01-01

Background Preclinical studies and Monte Carlo simulations have suggested that there is a relatively limited role of adherence in acquired drug resistance (ADR) and that very high levels of nonadherence are needed for therapy failure. We evaluated the superiority of directly observed therapy (DOT) for tuberculosis patients vs self-administered therapy (SAT) in decreasing ADR, microbiologic failure, and relapse in meta-analyses. Methods Prospective studies performed between 1965 and 2012 in which adult patients with microbiologically proven pulmonary Mycobacterium tuberculosis were separately assigned to either DOT or SAT as part of short-course chemotherapy were chosen. Endpoints were microbiologic failure, relapse, and ADR in patients on either DOT or SAT. Results Ten studies, 5 randomized and 5 observational, met selection criteria: 8774 patients were allocated to DOT and 3708 were allocated to SAT. For DOT vs SAT, the pooled risk difference for microbiologic failure was .0 (95% confidence interval [CI], −.01 to .01), for relapse .01 (95% CI, −.03 to .06), and for ADR 0.0 (95% CI, −0.01 to 0.01). The incidence rates for DOT vs SAT were 1.5% (95% CI, 1.3%–1.8%) vs 1.7% (95% CI, 1.2%–2.2%) for microbiologic failure, 3.7% (95% CI, 0.7%–17.6%) vs 2.3% (95% CI, 0.7%–7.2%) for relapse, and 1.5% (95% CI, 0.2%–9.90%) vs 0.9% (95% CI, 0.4%–2.3%) for ADR, respectively. There was no evidence of publication bias. Conclusions DOT was not significantly better than SAT in preventing microbiologic failure, relapse, or ADR, in evidence-based medicine. Resources should be shifted to identify other causes of poor microbiologic outcomes. PMID:23487389

Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus.

PubMed

Corsonello, Andrea; Pedone, Claudio; Corica, Francesco; Mazzei, Bruno; Di Iorio, Angelo; Carbonin, Pierugo; Incalzi, Raffaele Antonelli

2005-09-01

In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.

Cryogen-Free Ultra-Low Temperature Cooling using a Continuous ADR

NASA Technical Reports Server (NTRS)

Shirron, Peter; DiPirro, Michael; Jirmanus, Munir; Zhao, Zu-Yu; Shields, Bill

2003-01-01

The development of a continuous adiabatic demagnetization refrigerator (CADR) has progressed to the point where we have demonstrated a 4-stage system that provides continuous cooling at 50 mK and below, while rejecting heat to a 4.2 K helium bath. Since temperature control and cycling of the ADR is fully automated, the system is simple to operate and stable. Temperature fluctuations of the cold tip are typically less than 10 microKelvin rms (at 100 mK). The ADR s cooling power of 2 1 microwatts at 100 mK is comparable to that of small dilution refrigerators, but because its efficiency is so much higher (50% of Carnot), the peak heat rejection rate is less than 10 mW. This is significant in allowing the ADR to be cooled by relatively low-power cryocoolers. In addition to commercial pulse-tube and Gifford McMahon (GM) coolers, this potentially includes small GM systems that run on 120 V power and do not need water cooling. The present focus is to design and fabricate a small dewar to house the CADR and a cryocooler, in anticipation of making a cryogen-free, low cost CADR commercially available. Performance of the prototype CADR and the complete system will be discussed.

Inpatient paediatric use of intravenous immunoglobulin at an academic medical centre.

PubMed

Dashti-Khavidaki, S; Khalili, H; Farshadi, F; Aghamohammadi, A; Movahedi, M; Hajibabaei, M

2008-02-01

Intravenous immunoglobulin (IVIG) is an important research topic because of its efficacy in the management of an increasing number of diseases, its high cost and limited availability. This study was designed to evaluate the paediatric inpatient use of IVIG and identify strategies to reduce the drug expenditures. Over a six-month period, physician and nursing charts, and notes for subjects who were treated with IVIG, were reviewed to gather the required data. This included patient demographics, IVIG, indications, dosage regimen, adverse drug reactions (ADRs) and their management. 58.3 percent of IVIG infusions were ordered for labelled indications. Patients in the labelled group experienced more clinical improvement than subjects in the off-label group. Haematologists and neurologists were the most prevalent prescribers. ADRs were more prevalent in the off-label group. Hypotension, fever, headache and chills were the most common adverse effects. ADRs were managed with drugs in 22.9 percent of IVIG administrations and IVIG infusions were modified in 12.5 percent of infusions. ADRs were more prevalent in this hospital than those reported by other authors. This may be due to nursing negligence of the recommended infusion rate, higher sensitivity of our population or to the brands of IVIG which are used in the hospital. This shows the need for further evaluation of IVIG prescription and administration.

Design of the PIXIE Adiabatic Demagnetization Refrigerators

NASA Technical Reports Server (NTRS)

Shirron, Peter J.; Kimball, Mark Oliver; Fixsen, Dale J.; Kogut, Alan J.; Li, Xiaoyi; DiPirro, Michael

2012-01-01

The Primordial Inflation Explorer (PIXIE) is a proposed mission to densely map the polarization of the cosmic microwave background. It will operate in a scanning mode from a sun-synchronous orbit, using low temperature detectors (at 0.1 K) and located inside a teslescope that is cooled to approximately 2.73 K - to match the background temperature. A mechanical cryocooler operating at 4.5 K establishes a low base temperature from which two adiabatic demagnetization refrigerator (ADR) assemblies will cool the telescope and detectors. To achieve continuous scanning capability, the ADRs must operate continuously. Complicating the design are two factors: 1) the need to systematically vary the temperature of various telescope components in order to separate the small polarization signal variations from those that may arise from temperature drifts and changing gradients within the telescope, and 2) the orbital and monthly variations in lunar irradiance into the telescope barrels. These factors require the telescope ADR to reject quasi-continuous heat loads of 2-3 millwatts, while maintaining a peak heat reject rate of less than 12 milliwatts. The detector heat load at 0.1 K is comparatively small at 1-2 microwatts. This paper will describe the 3-stage and 2-stage continuous ADRs that will be used to meet the cooling power and temperature stability requirements of the PIXIE detectors and telescope.

HLA Association with Drug-Induced Adverse Reactions

PubMed Central

Fan, Wen-Lang; Shiao, Meng-Shin; Hui, Rosaline Chung-Yee; Wang, Chuang-Wei; Chang, Ya-Ching

2017-01-01

Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs. PMID:29333460

Trafficking Microenvironmental pHs of Polycationic Gene Vectors in Drug-Sensitive and Multidrug-Resistant MCF7 Breast Cancer Cells

PubMed Central

Kang, Han Chang; Samsonova, Olga; Bae, You Han

2010-01-01

While multidrug resistance (MDR) has been a significant issue in cancer chemotherapy, delivery resistance to various anticancer biotherapeutics, including genes, has not been widely recognized as a property of MDR. This study aims to provide a better understanding of the transfection characteristics of drug-sensitive and drug-resistant cells by tracing microenvironmental pHs of two representative polymer vectors: poly(l-lysine) and polyethyleneimine. Drug-sensitive breast MCF7 cells had four- to seven-times higher polymeric transfection efficiencies than their counterpart drug-resistant MCF7/ADR-RES cells. Polyplexes in MCF7/ADR-RES cells after endocytosis were exposed to a more acidic microenvironment than those in MCF7 cells; the MDR cells show faster acidification rates in endosomes/lysosomes than the drug-sensitive cells after endocytosis (in the case of PLL/pDNA complexes, ~ pH 5.1 for MCF7/ADR-RES cells vs. ~ pH 6.8 for MCF7 cells at 0.5 hr post-transfection). More polyplexes were identified trapped in acidic subcellular compartments of MCF7/ADR-RES cells than in MCF7 cells, suggesting that they lack endosomal escaping activity. These findings demonstrate that the design of polymer-based gene delivery therapeutics should take into account the pH of subcellular compartments. PMID:20092888

Difference in occurrence of heterotopic ossification according to prosthesis type in the cervical artificial disc replacement.

PubMed

Yi, Seong; Kim, Keung Nyun; Yang, Moon Sul; Yang, Joong Won; Kim, Hoon; Ha, Yoon; Yoon, Do Heum; Shin, Hyun Chul

2010-07-15

Retrospective study of the difference of heterotopic ossification (HO) occurrence according to 3 different types of prosthesis. This study was designed to investigate the difference of HO occurrence according to different type of prosthesis. HO is defined as formation of the bone outside the skeletal system. Reported HO occurrence rate in cervical artificial disc replacement (ADR) was unexpectedly high and varied. But the influencing factors of HO in cervical ADR have not been elucidated well. The prosthesis-related factors for making difference of HO occurrence were investigated in this study. A total of 170 patients undergoing cervical arthroplasty with the Bryan cervical disc prosthesis (Medtroic Sofamor Danek, Memphis, TN), Mobi-C disc prosthesis (LDR Medical, Troyes, France), and ProDisc-C (Synthes, Inc., West Chester, PA) were included. Cervical lateral radiographs obtained before and after surgery were used to identify HO. Occurrence rate, occurrence-free period, location, and grade of HOs were investigated according to the different prosthesis. Each prosthesis group included patients as follows: Bryan disc, 81 patients; Mobi-C, 61 patients; and ProDisc-C, 28 patients. Overall HO rate was 40.6% (69 of 170 patients). Each HO occurrence rate by prosthesis was as follows: the Bryan disc group, 21.0%; Mobi-C group, 52.5%; and the ProDisc-C group, 71.4%. In the survival analysis, all patients showed 27.1 +/- 3.7 months as the median survival. The Bryan disc group showed statistically longer survival (48.4 +/- 7.4 months) than the other groups. Occurrence of HO is an inevitable postoperative complication after cervical ADR. The occurrence rate of HO was higher than our expectation. Moreover, definite differences in occurrence rate according to the prosthesis type were identified by this study.

14 CFR Appendix A to Part 17 - Alternative Dispute Resolution (ADR)

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Alternative Dispute Resolution (ADR) A...—Alternative Dispute Resolution (ADR) A. The FAA dispute resolution procedures encourage the parties to protests and contract disputes to use ADR as the primary means to resolve protests and contract disputes...

14 CFR Appendix A to Part 17 - Alternative Dispute Resolution (ADR)

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Alternative Dispute Resolution (ADR) A...—Alternative Dispute Resolution (ADR) A. The FAA dispute resolution procedures encourage the parties to protests and contract disputes to use ADR as the primary means to resolve protests and contract disputes...

14 CFR 17.31 - Use of alternative dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-01-01

... parties to utilize ADR as their primary means to resolve protests and contract disputes. (b) The parties shall make a good faith effort to explore ADR possibilities in all cases and to employ ADR in every appropriate case. The Office of Dispute Resolution for Acquisition will encourage use of ADR techniques such...

48 CFR 5452.233-9001 - Disputes: Agreement To Use Alternative Dispute Resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... Alternative Dispute Resolution (ADR). 5452.233-9001 Section 5452.233-9001 Federal Acquisition Regulations... (ADR). As prescribed in 5433.214, insert the following provision: Disputes: Agreement To Use Alternative Dispute Resolution (ADR) (APR 2001)—DLAD (a) The parties agree to negotiate with each other to try...

14 CFR 17.33 - Election of alternative dispute resolution process.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Acquisition will make its personnel available to serve as Neutrals in ADR proceedings and, upon request by the...) The parties using an ADR process to resolve a protest shall submit an executed ADR agreement... this time for good cause. (c) The parties using an ADR process to resolve a contract dispute shall...

49 CFR 1109.1 - Invoking ADR in Board proceedings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 8 2011-10-01 2011-10-01 false Invoking ADR in Board proceedings. 1109.1 Section... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.1 Invoking ADR in Board proceedings. Any proceeding may be held in abeyance for 90 days while administrative dispute resolution (ADR) procedures (such as...

14 CFR 17.31 - Use of alternative dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-01-01

... parties to utilize ADR as their primary means to resolve protests and contract disputes. (b) The parties shall make a good faith effort to explore ADR possibilities in all cases and to employ ADR in every appropriate case. The Office of Dispute Resolution for Acquisition will encourage use of ADR techniques such...

14 CFR 17.33 - Election of alternative dispute resolution process.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Acquisition will make its personnel available to serve as Neutrals in ADR proceedings and, upon request by the...) The parties using an ADR process to resolve a protest shall submit an executed ADR agreement... this time for good cause. (c) The parties using an ADR process to resolve a contract dispute shall...

10 CFR 1023.8 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Alternative dispute resolution (ADR). 1023.8 Section 1023..., Functions and Authorities § 1023.8 Alternative dispute resolution (ADR). (a) Statement of Policy. It is the policy of the DOE and of the Board to facilitate consensual resolution of disputes and to employ ADR in...

7 CFR 11.5 - Informal review of adverse decisions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... participant also shall have the right to utilize any available alternative dispute resolution (ADR) or... prior to a NAD hearing. If a participant: (1) Requests mediation or ADR prior to filing an appeal with... once mediation or ADR has concluded. (2) Requests mediation or ADR after having filed an appeal to NAD...

10 CFR 1023.8 - Alternative dispute resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Alternative dispute resolution (ADR). 1023.8 Section 1023..., Functions and Authorities § 1023.8 Alternative dispute resolution (ADR). (a) Statement of Policy. It is the policy of the DOE and of the Board to facilitate consensual resolution of disputes and to employ ADR in...

49 CFR 1109.1 - Invoking ADR in Board proceedings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 8 2010-10-01 2010-10-01 false Invoking ADR in Board proceedings. 1109.1 Section... PROCEEDINGS AND THOSE IN WHICH THE BOARD IS A PARTY § 1109.1 Invoking ADR in Board proceedings. Any proceeding may be held in abeyance for 90 days while administrative dispute resolution (ADR) procedures (such as...

Alternative Dispute Resolution: A Business (and) Communication Strategy.

ERIC Educational Resources Information Center

Netzley, Michael

2001-01-01

Investigates Alternative Dispute Resolution (ADR) and its potential as a topic for business communication practice and research. Explores what ADR is; how mediation and ADR are used in business; how mediation and ADR are similar to and different from negotiating; and two or three essential learning points or skills to teach business students about…

Prevention and Management of Adverse Reactions Induced by Iodinated Contrast Media.

PubMed

Wu, Yi Wei; Leow, Kheng Song; Zhu, Yujin; Tan, Cher Heng

2016-04-01

Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM.

[Management of adverse drug effects].

PubMed

Schlienger, R G

2000-09-01

Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

Mechanical Design of a 4-Stage ADR for the PIPER mission

NASA Technical Reports Server (NTRS)

James, Bryan L.; Kimball, Mark O.; Shirron, Peter J.; Sampson, Michael A.; Letmate, Richard V.; Jackson, Michael L.

2017-01-01

The four 1,280 bolometer detector arrays that will fly on the balloon borne PIPER mission will be cooled by a 4-stage adiabatic demagnetization refrigerator (ADR). Two of the three mechanically independent ADR assemblies provide thermal isolation to their salt pills through Kevlar suspensions while the other provides thermal isolation to its salt pill through the use of bellows and Vespel material. The ADR integrates with the detector arrays and it sits in a large bucket Dewar containing superfluid liquid helium. This paper will describe the complex mechanical design of the PIPER ADR, and summarize the mechanical analysis done to validate the design.The four 1,280 bolometer detector arrays that will fly on the balloon borne PIPER mission will be cooled by a 4-stage adiabatic demagnetization refrigerator (ADR). Two of the three mechanically independent ADR assemblies provide thermal isolation to their salt pills through Kevlar suspensions while the other provides thermal isolation to its salt pill through the use of bellows and Vespel material. The ADR integrates with the detector arrays and it sits in a large bucket Dewar containing superfluid liquid helium. This paper will describe the complex mechanical design of the PIPER ADR, and summarize the mechanical analysis done to validate the design.

Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney.

PubMed

Mohebbati, Reza; Shafei, Mohammad Naser; Soukhtanloo, Mohammad; Mohammadian Roshan, Noema; Khajavi Rad, Abolfazl; Anaeigoudari, Akbar; Hosseinian, Sara; Karimi, Sareh; Beheshti, Farimah

2016-01-01

Inflammation and oxidative stress is considered to have a crucial role in induction of nephropathy. Curcuma longa (C. longa) and Nigella sativa (N. sativa) have anti-inflammatory and antioxidant effects. This study was designed to investigate the effect of mixed hydro-alcoholic extract of N.sativa and C. longa on the oxidative stress induced by Adriamycin (ADR) in rat kidney. The animals were divided into 6 groups: control (CO), ADR, Adriamycin+ Vitamin C (ADR+VIT C), C. longa extract+ Adriamycin (C.LE+ADR), N. sativa extract+ Adriamycin (N.SE+ADR) and C. longa extract+ N. sativa extract + Adriamycin (N.S+C.L+ADR). ADR (5mg/kg) was injected intravenously, whereas VITC (100mg/kg) and extract of C. longa (1000mg/kg) and N. sativa (200mg/kg) were administrated orally. Finally, the renal tissue, urine and blood samples were collected and submitted to measure of redox markers, osmolarity and renal index. The renal content of total thiol and superoxide dismutase (SOD) activity significantly decreased and Malondialdehyde (MDA) concentration increased in Adriamycin group compared to control group. The renal content of total thiol and SOD activity significantly enhanced and MDA concentration reduced in treated-mixed extract of C. longa and N. sativa along with ADR group compared to ADR group. The mixed extract did not restore increased renal index percentage induced by ADR. There also was no significant difference in urine and serum osmolarity between the groups. hydro-alcoholic extracts of N.sativa and C.longa led to an improvement in ADR-induced oxidative stress and mixed administration of the extracts enhanced the aforementioned therapeutic effect.

Adverse reactions associated with first-line regimens in patient initiating antiretroviral therapy.

PubMed

Mendes, Jullye Campos; Bonolo, Palmira de Fátima; Ceccato, Maria das Graças Braga; Costa, Juliana de Oliveira; Reis, Adriano Max Moreira; Dos Santos, Henrique; Silveira, Micheline Rosa

2018-05-08

To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment. This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22. We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm 3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively). The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.

An intervention to improve spontaneous adverse drug reaction reporting by hospital physicians: a time series analysis in Spain.

PubMed

Pedrós, Consuelo; Vallano, Antoni; Cereza, Gloria; Mendoza-Aran, Gemma; Agustí, Antònia; Aguilera, Cristina; Danés, Immaculada; Vidal, Xavier; Arnau, Josep M

2009-01-01

Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously. To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting. In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d'Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed. The median number of reported ADRs per year increased from 40 (range 23-55) in the first period to 224 (range 98-248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19). A continuous intervention based on healthcare management agreements with economic incentives and educational activities is associated with a quantitative and qualitative improvement of spontaneous reporting of ADRs by hospital physicians.

Zolpidem prescribing and adverse drug reactions in hospitalized general medicine patients at a Veterans Affairs hospital.

PubMed

Mahoney, Jane E; Webb, Melissa J; Gray, Shelly L

2004-03-01

Zolpidem is prescribed for sleep disruption in hospitalized patients, but data on the incidence of adverse drug reactions (ADRs) are based largely on outpatient studies. Thus, the incidence of ADRs in hospitalized patients may be much higher. The goal of this study was to describe prescribing patterns of zolpidem for hospitalized medical patients aged 50 years, the incidence of ADRs possibly and probably associated with its use, and the factors associated with central nervous system (CNS) ADRs. This case series was conducted in 4 general medicine wards at a Veterans Affairs hospital and was a consecutive sample of patients aged 50 years who were hospitalized between 1993 and 1997 and received zolpidem as a hypnotic during hospitalization, but had not received it in the previous 3 months. Chart review was conducted by 2 evaluators. Data extracted from the medical records included admission demographic characteristics, medications, comorbidities, and levels of function in performing basic and instrumental activities of daily living. The main outcome measure was ADRs possibly or probably related to zolpidem use. The association between zolpidem and the occurrence of CNS ADRs (eg, confusion, dizziness, daytime somnolence) was analyzed separately. The review included 119 medical patients aged > or =50 years who had newly received zolpidem for sleep disruption during hospitalization. The median age of the population was 70 years; 86 (72.3%) patients were aged 65 years. The initial zolpidem dose was 5 mg in 42 patients (35.3%) and 10 mg in 77 patients (64.7%). Twenty-three patients had a respective 16 and 10 ADRs possibly and probably related to zolpidem use (19.3% incidence). Of a total of 26 ADRs, 21 (80.8%) were CNS ADRs, occurring with both zolpidem 5 mg (10.8% of users) and 10 mg (18.3% of users). On univariate analyses, the only factor significantly associated with a CNS ADR was functional impairment at baseline (P = 0.003). Zolpidem was discontinued in 38.8% of patients experiencing a CNS ADR CONCLUSIONS: In this case series in medical inpatients, there was a high frequency of ADRs, particularly CNS ADRs, associated with zolpidem use. Zolpidem should be used cautiously in the hospital setting.

Adverse drug events resulting from use of drugs with sulphonamide-containing anti-malarials and artemisinin-based ingredients: findings on incidence and household costs from three districts with routine demographic surveillance systems in rural Tanzania

PubMed Central

2013-01-01

Background Anti-malarial regimens containing sulphonamide or artemisinin ingredients are widely used in malaria-endemic countries. However, evidence of the incidence of adverse drug reactions (ADR) to these drugs is limited, especially in Africa, and there is a complete absence of information on the economic burden such ADR place on patients. This study aimed to document ADR incidence and associated household costs in three high malaria transmission districts in rural Tanzania covered by demographic surveillance systems. Methods Active and passive surveillance methods were used to identify ADR from sulphadoxine-pyrimethamine (SP) and artemisinin (AS) use. ADR were identified by trained clinicians at health facilities (passive surveillance) and through cross-sectional household surveys (active surveillance). Potential cases were followed up at home, where a complete history and physical examination was undertaken, and household cost data collected. Patients were classified as having ‘possible’ or ‘probable’ ADR by a physician. Results A total of 95 suspected ADR were identified during a two-year period, of which 79 were traced, and 67 reported use of SP and/or AS prior to ADR onset. Thirty-four cases were classified as ‘probable’ and 33 as ‘possible’ ADRs. Most (53) cases were associated with SP monotherapy, 13 with the AS/SP combination (available in one of the two areas only), and one with AS monotherapy. Annual ADR incidence per 100,000 exposures was estimated based on ‘probable’ ADR only at 5.6 for AS/SP in combination, and 25.0 and 11.6 for SP monotherapy. Median ADR treatment costs per episode ranged from US$2.23 for those making a single provider visit to US$146.93 for patients with four visits. Seventy-three per cent of patients used out-of-pocket funds or sold part of their farm harvests to pay for treatment, and 19% borrowed money. Conclusion Both passive and active surveillance methods proved feasible methods for anti-malarial ADR surveillance, with active surveillance being an important complement to facility-based surveillance, given the widespread practice of self-medication. Household costs associated with ADR treatment were high and potentially catastrophic. Efforts should be made to both improve pharmacovigilance across Africa and to identify strategies to reduce the economic burden endured by households suffering from ADR. PMID:23844934

29 CFR 37.76 - What are the required elements of a recipient's discrimination complaint processing procedures?

Code of Federal Regulations, 2011 CFR

2011-07-01

... alternative dispute resolution (ADR), as described in paragraph (c) of this section (5) A written Notice of... procedures the recipient adopts must provide for alternative dispute resolution (ADR). The recipient's ADR procedures must provide that: (1) The choice whether to use ADR or the customary process rests with the...

Safety Profile of the Newest Antiepileptic Drugs: A Curated Literature Review.

PubMed

Palleria, Caterina; Cozza, Giuseppe; Khengar, Rajeshree; Libri, Vincenzo; De Sarro, Giovambattista

2017-01-01

Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remain unsatisfactory. In addition, whilst several antiepileptic drugs (AEDs) have been approved and consequently marketed in recent years, little is known about their long-term safety and tolerability. Availability of the newest AEDs, characterized by improved pharmacokinetic profiles, has positively impacted the treatment approach for patients with partial seizures in clinical practice. However, the main cause of treatment failure is still poor patient compliance due to the occurrence of adverse drug reactions (ADRs) that lead to treatment withdrawal in about 25% of cases before achieving maximal efficacy, and is associated with increasing health care costs. In this Review, we conducted an online database search using Medline, PubMed, Embase, and the Cochrane Online Library to review the available studies highlighting the clinical relevance of side effects, pharmacological interactions, safety and tolerability of the newest AEDs: Brivaracetam (BRV), Cannabidiol (CBD), Eslicarbazepine acetate (ESL), Lacosamide (LCM), and Perampanel (PER). The principal benefit of the newest AEDs, in addition to reduced frequency and seizure severity, is the low number and severity of ADRs reported compared to more historic drugs. Early detection of ADRs could lead to an improvement in patients' quality of life, therefore it is important to monitor ADRs and to adequately perform post marketing surveillance in the clinical practice setting. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Adiabatic Demagnetization Refrigerator Field Mapping and Shielding Models for a 70 mK Superconducting Transition Edge Sensor Array and Associated Electronics

NASA Astrophysics Data System (ADS)

Ladner, D. R.; Martinez-Galarce, D. S.; McCammon, D.

2006-04-01

An X-ray detection instrument to be flown on a sounding rocket experiment (the Advanced Technology Solar Spectroscopic Imager - ATSSI) for solar physics observations is being developed by the Lockheed Martin Solar and Astrophysics Laboratory (LMSAL). The detector is a novel class of microcalorimeter, a superconducting Transition-Edge Sensor (TES), that coupled with associated SQUID and feedback electronics requires high temperature stability at ~70 mK to resolve the energy of absorbed X-ray photons emitted from the solar corona. The cooling system incorporates an existing Adiabatic Demagnetization Refrigerator (ADR) developed at the University of Wisconsin (UW), which was previously flown to study the diffuse cosmic X-ray background. The Si thermistor detectors for that project required 130 K shielded JFET electronic components that are much less sensitive to the external field of the ADR solenoid than are the 1st (~70 mK) and 2nd (~2 K) SQUID stages used with TESs for solar observations. Modification of the Wisconsin ADR design, including TES focal plane and electronics re-positioning, therefore requires a tradeoff between the existing ADR solenoid nulling coil geometry and a low mass passive solenoid shield, while preserving the vibration isolation features of the existing design. We have developed models to accurately compute the magnetic field with and without shielding or nulling coils at critical locations to guide the re-design of the detector subsystem. The models and their application are described.

Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. A systematic review.

PubMed

Black, Corri; Tagiyeva-Milne, Nara; Helms, Peter; Moir, Dorothy

2015-10-01

A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children. MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keywords and abstracts were checked for age <18 years, potential ADRs and electronic healthcare data. Information extracted included age, data source, pharmacovigilance method, medicines and ADRs. Studies were quality assessed. From 14 804 titles, 314 had a full text review and 71 were included in the final review. Fifty were published in North America, 10 in Scandinavia. Study size ranged from less than 1000 children to more than 10 million. Sixty per cent of studies used data from one source. Comparative observational studies were most commonly reported (66.2%) with 15% using passive surveillance. Electronic healthcare data set linkage and the quality of the data source were poorly reported. ADRs were classified using the International Classification of Disease (ICD10). Multi-system reactions were most commonly studied, followed by central nervous system and mental and behavioural disorders. Vaccines were most frequently prescribed followed by corticosteroids, general anaesthetics and antidepressants. Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children. This growing and important health protection activity could be enhanced by consistent reporting of studies to improve the identification, interpretation and generalizability of the evidence base. © 2015 The British Pharmacological Society.

[Post-marketing safety surveillance of Diemailing Kudiezi injection: real world study in 30 233 cases].

PubMed

Liao, Xing; Yu, Dan-Dan; Xie, Yan-Ming; Zhang, Yun-Ling; He, Yan; Zhang, Yin; Liu, Yan; Yi, Dan-Hui; Wang, Yong-Yan

2017-08-01

This study was aimed to obtain the incidence of adverse drug reaction (ADR) of Diemailing Kudiezi injection, explore its characteristics, related risk factors and application in real world. A prospective single cohort study was conducted from 25 hospitals (including Chinese medicine hospitals and Western medicine hospitals) for 4 years. 30 233 consecutive inpatients using Diemailing Kudiezi injection were observed. Their general information was analyzed by using statistic frequency description. Association rules were used to analyze the correlation between comorbidities or drug combinations; the influential factors for ADRs were initially screened by using cross contingency method and Chi-square test, and then Group LASSAO method was used for further analysis. 54 patients with adverse drug events and 30 patients with ADRs were reported among 30 233 patients, with a total ADR incidence of 0.099%[95%CI (0.06%, 0.13%)]. There were 27 patients identified as the "general" ADR, one patients with "severe" ADR (anaphylactic shock) and two patients with new ADRs. ADR occurred most in 30 min after using Diemailing Kudiezi injection, in a total of 16 patients. The most ADRs were palpitation, vomiting, chills, pruritus and rash, 6 times for each symptom. Diemailing Kudiezi injection was well tolerated in the general population. The overall incidence of adverse reactions was rare, with high safety. However, the real incidence of ADRs may be underestimated in this study, and the blood samples were not obtained for the patients, so further mechanism studies shall be conducted. Copyright© by the Chinese Pharmaceutical Association.

Ophthalmic adverse drug reactions to systemic drugs: a systematic review.

PubMed

Miguel, Ana; Henriques, Filipe; Azevedo, Luís Filipe; Pereira, Altamiro Costa

2014-03-01

To perform a comprehensive and systematic review regarding ophthalmic adverse drug reactions (ADRs) to systemic drugs to: (i) systematically summarize existing evidence, (ii) identify areas, ophthalmic ADRs or drugs that lacked systematization or assessment (namely drugs with original studies characterizing specific ophthalmic ADRs but without causality assessment nor without meta-analysis). Systematic review of several electronic databases (last search 1/7/2012): Medline, SCOPUS, ISI web of knowledge, ISI Conference Proceedings, International Pharmaceutical Abstracts and Google scholar. Search query included: eye, ocular, ophthalmic, ophthalmology, adverse and reaction. Inclusion criteria were: (i) Primary purpose was to assess an ophthalmic ADR to a systemic medication; (ii) Patient evaluation performed by an ophthalmologist; (iii) Studies that specified diagnostic criteria for an ocular ADR. Different types of studies were included and analyzed separately. Two independent reviewers assessed eligibility criteria, extracted data and evaluated risk of bias. From 562 studies found, 32 were included (1 systematic review to sildenafil, 11 narrative reviews, 1 trial, 1 prospective study, 6 transversal studies, 6 spontaneous reports and 6 case series). Drugs frequently involved included amiodarone, sildenafil, hydroxychloroquine and biphosphonates. Frequent ophthalmic ADRs included: keratopathy, dry eye and retinopathy. To increase evidence about ophthalmic ADRs, there is a need for performing specific systematic reviews, applying strictly the World Health Organization's (WHO) definition of ADR and WHO causality assessment of ADRs. Some ophthalmic ADRs may be frequent, but require ophthalmological examination; therefore, ophthalmologists' education and protocols of collaboration between other specialties whenever they prescribe high-risk drugs are suggestions for the future. Copyright © 2014 John Wiley & Sons, Ltd.

25 CFR 170.935 - How does a direct service tribe begin the alternative dispute resolution process?

Code of Federal Regulations, 2011 CFR

2011-04-01

... ADR process, a direct service tribe must write to the BIA Regional Director or the Chief of BIA... (ADR) procedures in the Administrative Dispute Resolution Act of 1996, 5 U.S.C. 571-583 (ADR Act); and (2) Explain the factual and legal basis for the dispute. (b) ADR proceedings will be governed by...

Hyaluronan and calcium carbonate hybrid nanoparticles for colorectal cancer chemotherapy

NASA Astrophysics Data System (ADS)

Bai, Jinghui; Xu, Jian; Zhao, Jian; Zhang, Rui

2017-09-01

A hybrid drug delivery system (DDS) composed of hyaluronan and calcium carbonate (CC) was developed. By taking advantage of the tumor-targeting ability of hyaluronan and the drug-loading property of CC, the well-formed hyaluronan-CC nanoparticles were able to serve as a DDS targeting colorectal cancer with a decent drug loading content, which is beneficial in the chemotherapy of colorectal cancer. In this study, hyaluronan-CC nanoparticles smaller than 100 nm were successfully developed to load the wide-range anti-cancer drug adriamycin (Adr) to construct hyaluronan-CC/Adr nanoparticles. On the other hand, we also found that hyaluronan-CC/Adr nanoparticles can possibly increase the uptake ratio of Adr into HT29 colorectal cancer cells when compared with hyaluronan-free nanoparticles (CC/Adr) via the CD44 receptor-mediated endocytosis via competitive uptake and in vivo imaging assays. Note that both in vitro (CCK-8 assay on HT29 cells) and in vivo (anti-cancer assay on HT-29 tumor-bearing nude mice model) experiments revealed that hyaluronan-CC/Adr nanoparticles exhibited stronger anti-cancer activity than free Adr or CC/Adr nanoparticles with minimized toxic side effects and preferable cancer-suppression potential.

Semantic distance-based creation of clusters of pharmacovigilance terms and their evaluation.

PubMed

Dupuch, Marie; Grabar, Natalia

2015-04-01

Pharmacovigilance is the activity related to the collection, analysis and prevention of adverse drug reactions (ADRs) induced by drugs or biologics. The detection of adverse drug reactions is performed using statistical algorithms and groupings of ADR terms from the MedDRA (Medical Dictionary for Drug Regulatory Activities) terminology. Standardized MedDRA Queries (SMQs) are the groupings which become a standard for assisting the retrieval and evaluation of MedDRA-coded ADR reports worldwide. Currently 84 SMQs have been created, while several important safety topics are not yet covered. Creation of SMQs is a long and tedious process performed by the experts. It relies on manual analysis of MedDRA in order to find out all the relevant terms to be included in a SMQ. Our objective is to propose an automatic method for assisting the creation of SMQs using the clustering of terms which are semantically similar. The experimental method relies on a specific semantic resource, and also on the semantic distance algorithms and clustering approaches. We perform several experiments in order to define the optimal parameters. Our results show that the proposed method can assist the creation of SMQs and make this process faster and systematic. The average performance of the method is precision 59% and recall 26%. The correlation of the results obtained is 0.72 against the medical doctors judgments and 0.78 against the medical coders judgments. These results and additional evaluation indicate that the generated clusters can be efficiently used for the detection of pharmacovigilance signals, as they provide better signal detection than the existing SMQs. Copyright © 2014. Published by Elsevier Inc.

Study of adverse drug reactions in patients with diabetes attending a tertiary care hospital in New Delhi, India.

PubMed

Singh, Abhishank; Dwivedi, Shridhar

2017-02-01

The present prospective observational study was carried out in a tertiary care hospital in New Delhi, India from May 2014 to June 2015 to report adverse drug reactions (ADRs) in patients with type 2 diabetes mellitus (T2DM) using antidiabetic drugs. A total of 220 patients (121 males, 99 females) were enrolled. ADRs were recorded on the prescribed form. Causality and severity assessment was done using Naranjo's probability scale and modified Hartwig and Siegel's severity scale, respectively. Commonly prescribed drugs were biguanides, peptide hormone and sulphonylurea. A total of 26 ADRs were recorded (16 in males and 10 in females). Most commonly observed ADRs were related to endocrine and gastrointestinal system. Severity assessment of ADRs showed seven (26.9%) ADRs as moderate, and 19 (73.1%) as mild. No severe reactions were observed. ADRs were mostly related to endocrine and gastrointestinal system. More information on prescribed drugs and their side effects is required for ensuring patient safety.

[Adverse drug reactions of hydroxymethylglutaryl-CoA reductase inhibitors reported to agency for medicinal products and medical devices].

PubMed

Skvrce, Nikica Mirosević; Bozina, Nada; Sarinić, Viola Macolić; Tomić, Sinisa

2010-01-01

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are drugs used in the treatment of chronic diseases and frequently in concomitant therapy with many other drugs. Therefore, the risk of adverse drug reactions (ADRs), especially those caused by interactions is high. Aim of the study was to describe and analyze ADRs caused by statins reported to Croatian Agency from March 2005 to December 2008, and to emphasize reasons of their occurrence. 136 of statin ADRs were reported. 12 % of all reported statins' ADRs were caused by interactions, which is higher than percent (5.6%) of interactions caused by all other drugs in 2005 and 2006. Proportion of serious ADRs related to administered dose and thus preventable was higher than proportion of all ADRs caused by statins (p = 0.003). Most serious ADRs could have been prevented with better understanding of interactions and by use of pharmacogenomics in identifying patients that are because of genetic predisposition more sensitive to standard doses.

Safety profile of the direct oral anticoagulants: an analysis of the WHO database of adverse drug reactions.

PubMed

Monaco, Luca; Biagi, Chiara; Conti, Valentino; Melis, Mauro; Donati, Monia; Venegoni, Mauro; Vaccheri, Alberto; Motola, Domenico

2017-07-01

Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P ≤ 0.05 were statistically significant. We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P ≤ 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47-1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28-0.34)]. We identified other potential signals that have not been associated with DOACs previously. As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred. © 2017 The British Pharmacological Society.

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review.

PubMed

Pisano, Umberto; Deosaran, Jordanna; Leslie, Stephen J; Rushworth, Gordon F; Stewart, Derek; Ford, Ian; Watson, Angus J M

2016-03-01

Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location. The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant. Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001). Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established.

Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions: experience from two Australian tertiary hospitals.

PubMed

Fang, Wendy C; Adler, Nikki R; Graudins, Linda V; Goldblatt, Caitlin; Goh, Michelle S Y; Roberts, Stuart K; Trubiano, Jason A; Aung, Ar Kar

2018-05-01

Drug-induced liver injury (DILI) can be associated with certain cutaneous adverse drug reaction (cADR). To demonstrate the prevalence of DILI in patients with cADRs. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. A retrospective cohort study of patients with cADRs was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. One hundred and four patients with cADRs were identified. Of these, 33 (31.7%) had liver injury, representing 50% of patients with drug reaction with eosinophilia and systemic symptoms, and 30.2% of patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Most cases of liver injury (69.7%) were of a cholestatic/mixed pattern with severe disease in 18.2%. No significant risk factors for development of liver injury were noted, but peripheral lymphocytosis may represent a risk in patients with SJS (odds ratio, OR = 6.0, 95% confidence interval, CI: 1.8-19.7, P = 0.003). Antimicrobials were the most common class to be implicated in DILI. The median length of inpatient stay was longer in patients with liver injury compared to those without (19 vs 11 days, P = 0.002). The mortality rate in those with liver injury was 15.2% and 9.9% in those without. No patients required liver transplantation. DILI commonly occurs in patients with cADRs and is associated with longer inpatient stay. Patients with SJS/TEN and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury. © 2018 Royal Australasian College of Physicians.

Prescreening with FOBT Improves Yield and Is Cost-Effective in Colorectal Screening in the Elderly

PubMed Central

Changela, Kinesh; Mathur, Siddharth; Reddy, Sridhar; Momeni, Mojdeh; Krishnaiah, Mahesh; Anand, Sury

2014-01-01

Background. Utilization of colonoscopy for routine colorectal cancer (CRC) screening in the elderly (patients over 75) is controversial. This study was designed to evaluate if using fecal occult blood test (FOBT) to select patients for colonoscopy can improve yield and be a cost- effective approach for the elderly. Methods. Records of 10,908 subjects who had colonoscopy during the study period were reviewed. 1496 (13.7%) were ≥75 years. In 118 of these subjects, a colonoscopy was performed to evaluate a positive FOBT. Outcomes were compared between +FOBT group (F-Group) and the asymptomatic screening group (AS-Group). The cost-effectiveness was also calculated using a median estimated standardized worldwide colonoscopy and FOBT cost (rounded to closest whole numbers) of 1000 US $ and 10 US $, respectively. Results. 118/1496 (7.9%) colonoscopies were performed for evaluation of +FOBT. 464/1496 (31%) colonoscopies were performed in AS-Group. In F-Group, high risk adenoma detection rate (HR-ADR) was 15.2%, and 11.9% had 1-2 tubular adenomas. In comparison, the control AS-Group had HR-ADR of 19.2% and 17.7% had 1-2 tubular adenomas. In the FOBT+ group, CRC was detected in 5.1% which was significantly higher than the AS-Group in which CRC was detected in 1.7% (P = 0.03). On cost-effectiveness analysis, cost per CRC detected was significantly lower, that is, 19,666 US $ in F-Group in comparison to AS-Group 58,000 US $ (P < 0.05). There were no significant differences in other parameters among groups. Conclusion. Prescreening with FOBT to select elderly for colonoscopy seems to improve the yield and can be a cost-effective CRC screening approach in this subset. The benefit in the risk benefit analysis of screening the elderly appears improved by prescreening with an inexpensive tool. PMID:25101179

Prescreening with FOBT Improves Yield and Is Cost-Effective in Colorectal Screening in the Elderly.

PubMed

Singhal, Shashideep; Changela, Kinesh; Basi, Puneet; Mathur, Siddharth; Reddy, Sridhar; Momeni, Mojdeh; Krishnaiah, Mahesh; Anand, Sury

2014-01-01

Background. Utilization of colonoscopy for routine colorectal cancer (CRC) screening in the elderly (patients over 75) is controversial. This study was designed to evaluate if using fecal occult blood test (FOBT) to select patients for colonoscopy can improve yield and be a cost- effective approach for the elderly. Methods. Records of 10,908 subjects who had colonoscopy during the study period were reviewed. 1496 (13.7%) were ≥75 years. In 118 of these subjects, a colonoscopy was performed to evaluate a positive FOBT. Outcomes were compared between +FOBT group (F-Group) and the asymptomatic screening group (AS-Group). The cost-effectiveness was also calculated using a median estimated standardized worldwide colonoscopy and FOBT cost (rounded to closest whole numbers) of 1000 US $ and 10 US $, respectively. Results. 118/1496 (7.9%) colonoscopies were performed for evaluation of +FOBT. 464/1496 (31%) colonoscopies were performed in AS-Group. In F-Group, high risk adenoma detection rate (HR-ADR) was 15.2%, and 11.9% had 1-2 tubular adenomas. In comparison, the control AS-Group had HR-ADR of 19.2% and 17.7% had 1-2 tubular adenomas. In the FOBT+ group, CRC was detected in 5.1% which was significantly higher than the AS-Group in which CRC was detected in 1.7% (P = 0.03). On cost-effectiveness analysis, cost per CRC detected was significantly lower, that is, 19,666 US $ in F-Group in comparison to AS-Group 58,000 US $ (P < 0.05). There were no significant differences in other parameters among groups. Conclusion. Prescreening with FOBT to select elderly for colonoscopy seems to improve the yield and can be a cost-effective CRC screening approach in this subset. The benefit in the risk benefit analysis of screening the elderly appears improved by prescreening with an inexpensive tool.

25 CFR 42.5 - When can a school use ADR processes to address an alleged violation?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false When can a school use ADR processes to address an alleged... RIGHTS § 42.5 When can a school use ADR processes to address an alleged violation? (a) The school may address an alleged violation through the ADR processes described in § 42.4, unless one of the conditions...

25 CFR 42.5 - When can a school use ADR processes to address an alleged violation?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false When can a school use ADR processes to address an alleged... RIGHTS § 42.5 When can a school use ADR processes to address an alleged violation? (a) The school may address an alleged violation through the ADR processes described in § 42.4, unless one of the conditions...

My Car Is a Lemon! Use of the Better Business Bureau's Auto Line[R] Program as a Pedagogical Model of ADR

ERIC Educational Resources Information Center

Steslow, Donna M.

2010-01-01

Alternative dispute resolution (ADR) is normally included as part of an introductory business law/legal environment course. While some business schools offer stand-alone ADR courses, the majority do not. As a result, a business student's only exposure to ADR processes may be through a Legal Studies in Business course. Several scholars have created…

Performance of a fast response miniature Adiabatic Demagnetisation Refrigerator using a single crystal tungsten magnetoresistive heat switch

NASA Astrophysics Data System (ADS)

Bartlett, J.; Hardy, G.; Hepburn, I. D.

2015-12-01

The performance of a fast thermal response miniature Adiabatic Demagnetisation Refrigerator (ADR) is presented. The miniature ADR is comprised of a fast thermal response Chromium Potassium Alum (CPA) salt pill, two superconducting magnets and unconventionally, a single crystal tungsten magnetoresistive (MR) heat switch. The development of this ADR is a result of the ongoing development of a continuously operating millikelvin cryocooler (mKCC), which will use only magnetoresistive heat switches. The design and performance of the MR heat switch developed for the mKCC and used in the miniature ADR is presented in this paper; the heat switch has a measured Residual Resistivity Ratio of 32,000 ± 3000 and an estimated switching ratio (on thermal conductivity divided by the off thermal conductivity) of 15,200 at 3.6 K and 38,800 at 0.2 K when using a 3 T magnetic field. The performance of the miniature ADR operating from a 3.6 K bath is presented, demonstrating that a complete cycle (magnetisation, cooling to the bath and demagnetisation) can be accomplished in 82 s. A magnet current step test, conducted when the ADR is cold and fully demagnetised, has shown the thermal response of the ADR to be sub-second. The measured hold times of the ADR with just parasitic heat load are given, ranging from 3 min at 0.2 K with 13.14 μW of parasitics, to 924 min at 3 K with 4.55 μW of parasitics. The cooling power has been measured for operating temperatures in the range 0.25-3 K by applying an additional heat load to the ADR via a heater, in order to reduce the hold time to 3 min (i.e. approximately double the recycle time); the maximum cooling power of the miniature ADR (in addition to parasitic load) when operating at 250 mK is 20 μW, which increases to 45 μW at 300 mK and continues to increase linearly to nearly 1.1 mW at 3 K. To conclude, the predicted performance of a tandem continuous ADR utilising two of the miniature ADRs is presented.

Use and safety of intratumoral application of European mistletoe (Viscum album L) preparations in Oncology.

PubMed

Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2015-03-01

Intratumoral (IT) injection of European mistletoe (Viscum album L) preparations might induce local tumor response through combined cytotoxic and immunomodulatory actions of the preparations. Although promising in vitro and in vivo data, along with clinical case studies suggest the need for validation of this hypothesis in prospective trials, the safety of IT mistletoe injections has yet to be thoroughly assessed. The present study summarizes the practice and safety of off-label IT mistletoe therapy within the Network Oncology, a conjoint clinical registry of German hospitals and outpatients specialized in anthroposophic and integrative medicine. Demographic, diagnosis and treatment data of cancer patients who received IT mistletoe applications between 2007 and 2013 were assessed. Suspected adverse drug reactions (ADRs) were analyzed in terms of type, frequency, severity, seriousness and potential risk factors. A total of 123 cancer patients received 862 IT mistletoe injections (preparations from Abnoba, Helixor and Iscucin). The most commonly applied preparations were Abnoba viscum Fraxini (71 patients) and Helixor Mali (54 patients). Of the total patients, 26 patients (21.1%) experienced 74 ADRs. All ADRs were in response to either Abnoba viscum Fraxini (25.4% of exposed patients) or Helixor Mali (18.5% of exposed patients). ADRs were mostly body temperature or immune related and of mild (83.8%) or moderate (14.9%) intensity. Only one possible ADR was described as severe (hypertension) and no serious ADRs occurred. The frequency of ADRs to IT mistletoe injections was 3 times and 5 times higher than has previously been found for subcutaneous and intravenous applications of mistletoe, respectively. IT injection of mistletoe preparations resulted in a relatively high frequency of ADRs. Nearly all ADRs were mild to moderate however, and no serious ADRs occurred. Furthermore, it is possible that immune-related ADRs such as pyrexia and local inflammatory reactions might be critical for tumor response. In light of these results, IT mistletoe therapy seems to be safe and prospective trials are recommended. © The Author(s) 2014.

Longitudinal trends of HIV drug resistance in a large Canadian cohort, 1996-2016.

PubMed

Rocheleau, G; Brumme, C J; Shoveller, J; Lima, V D; Harrigan, P R

2018-02-01

We aim to identify long-term trends in HIV drug resistance before and after combined antiretroviral therapy (cART) initiation. IAS-USA (2015) mutations were identified in 23 271 HIV protease-reverse transcriptase sequences from 6543 treatment naïve adults in British Columbia. Participants who started cART between 1996 and 2014 were followed until April 2016. Equality of proportions test was used to compare the percentage of participants with acquired drug resistance (ADR) or transmitted drug resistance (TDR) in 1996, to those in 2014. Kaplan-Meier was used to estimate time to ADR in four drug resistance categories. Multivariable regression odds ratios (OR) of ADR for select clinical variables were determined by 5-year eras of cART initiation. The proportion of individuals with ADR declined from 39% (51/132) to 3% (8/322) in 1996-2014 (p <0.0001), while the proportion with TDR increased from 12% (16/132) to 18% (59/322) (p 0.14). The estimated proportions of individuals with ADR rose to 29% (NNRTI), 28% (3TC/FTC), 14% (other nRTI), and 7% (PI) after >16 years of therapy. After 5 years on therapy, participants initiating cART in 1996-2000 had 5.5-times more 3TC/FTC ADR, 5.3-times more other nRTI ADR, 4.7-times more NNRTI ADR, and 24-times more PI ADR than those starting in 2011-2014. The individuals with highest odds of developing ADR in 1996-2010 were adherent to regimens at levels between 60% and 80%, which shifted to <40% adherent in 2011-2014. HIV drug resistance transitioned from being primarily selected de-novo to being driven by TDR. Among those who started treatment in the past 5 years, ADR is rare and observed mostly in the lowest adherence strata. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents

PubMed Central

Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile

2016-01-01

Objective To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. Design A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. Setting For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Participants Individuals contributing ADR information to product information documents. Main outcomes measures All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Results Twelve brand drugs—24 paired documents—were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65–425) and 114 (range: 56–265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Conclusions Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information. PMID:26996819

The adverse drug reaction reporting assignment for specialist oncology nurses: a preliminary evaluation of quality, relevance and educational value in a prospective cohort study.

PubMed

Schutte, Tim; van Eekeren, Rike; Richir, Milan; van Staveren, Jojanneke; van Puijenbroek, Eugène; Tichelaar, Jelle; van Agtmael, Michiel

2018-01-01

In a new prescribing qualification course for specialist oncology nurses, we thought that it is important to emphasize pharmacovigilance and adverse drug reaction (ADR) reporting. We aimed to develop and evaluate an ADR reporting assignment for specialist oncology nurses. The quality of report documentation was assessed with the "Clinical Documentation tool to assess Individual Case Safety Reports" (ClinDoc). The relevance of the reports was evaluated in terms of ADR seriousness, the listing for additional monitoring of the drug by European Medicines Agency (EMA), and lack of labelling information about the ADR. Nurses' opinions of the assignment were evaluated using an E-survey. Thirty-three ADRs were reported, 32 (97%) of which were well documented according to ClinDoc. Thirteen ADRs (39%) were "serious" according to CIOMS criteria. In five cases (15%), the suspect drugs were listed for additional monitoring by EMA and in seven cases (21%), the ADR was not mentioned in the Summary of Product Characteristics. Twenty-five (78.1%) of the 32 enrolled nurses completed the E-survey. Most were > 45 years of age (68%), female (92%) and had extensive clinical experience (6-33 years). All agreed or completely agreed that the reporting assignment was useful, that it fitted in daily practice and that it increased their attention for medication/patient safety. A large majority (84.0%) agreed the assignment changed how they dealt with ADRs. Specialist oncology nurses are capable of reporting ADRs, and they considered the assignment useful. The assignment yielded valuable, relevant, and well-documented ADR reports for pharmacovigilance practice.

Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009-2013 French PharmacoVigilance assessment.

PubMed

Moulis, Guillaume; Bagheri, Haleh; Sailler, Laurent; Jonville-Bera, Annie-Pierre; Weber, Emmanuelle; Guy, Claire; Petitpain, Nadine; Laroche, Marie-Laure; Favrelière, Sylvie; Béné, Johana; Baldin, Bernadette; Villeval-Federici, Laure; Tebacher-Alt, Martine; Bres, Virginie; Veyrac, Gwenaëlle; Grandvuillemin, Aurélie; Mauprivez, Cédric; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis

2014-10-01

Romiplostim and eltrombopag, the two marketed thrombopoietin receptor agonists (TPO-RAs), have distinct binding sites and might have distinct pharmacodynamic mechanisms. The aim of this study was to compare their adverse drug reaction (ADR) patterns. We selected in the French PharmacoVigilance Database all ADRs associated with TPO-RAs from TPO-RA marketing until the 31st of December 2013. Medical charts were reviewed. We conducted disproportionality analyses comparing romiplostim exposure in the reports of a given ADR pattern (thrombosis, neurological, cutaneous, gastrointestinal or hematological) to romiplostim exposure in all other TPO-RA-related ADR reports. Reporting Odds Ratios (RORs) were adjusted for age and gender. We also compared the number of reports of a given ADR pattern per million daily defined doses (DDDs) dispensed in France during the study period. We described 45 reports (53 ADRs) with romiplostim and 26 reports (37 ADRs) with eltrombopag. There were 19 venous thromboses. At least one other risk factor was present in 83.3% of the cases. Ten (55.6%) patients had been splenectomized previously. There were eight arterial thromboses. Another risk factor was noticed in all cases. There was no signal for an excess risk of thrombosis with romiplostim versus eltrombopag (ROR: 1.45, 95% CI [0.48-4.45]). There was a signal for a higher risk of gastrointestinal ADRs with eltrombopag (ROR: 30.28, 95% CI [3.23-383.86]) and of hematological ADRs with romiplostim (ROR: 14.36, 95% CI [1.73-119.08]). Dispensing data-adjusted comparisons led to similar results. This study suggests different ADR patterns between romiplostim and eltrombopag. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Proactive Regional Pharmacovigilance System Versus National Spontaneous Reporting for Collecting Safety Data on Concerning Off-Label Prescribing Practices: An Example with Baclofen and Alcohol Dependence in France.

PubMed

Auffret, Marine; Labreuche, Julien; Duhamel, Alain; Deheul, Sylvie; Cottencin, Olivier; Bordet, Régis; Gautier, Sophie; Rolland, Benjamin

2017-03-01

Off-label prescribing (OLP) may raise serious safety concerns that traditional spontaneous reporting of adverse drug reactions (ADRs) may not identify in a timely manner. In France, the 'Multidisciplinary Consultation Service for Off-Label Prescribing in Addiction Medicine' (CAMTEA) is a proactive regional system established to identify ADRs associated with the OLP of baclofen for alcohol dependence. The aim was to demonstrate, using the French pharmacovigilance database (FPVD), that CAMTEA allowed for the reporting of a substantial amount of ADRs, comparable in nature to those provided via spontaneous reporting. The 2012-2013 FPVD notifications associated with baclofen OLP were extracted. The ten most frequent types of ADRs among 'serious' and 'non-serious' reports were listed. The frequency of each type of ADR was compared between CAMTEA and spontaneous reporting, and the magnitudes of the differences were assessed using standardized differences. A total of 428 baclofen reports (1043 ADRs) were identified, among which 221 (51.64%) originated from CAMTEA. The ten most frequent ADRs in 'serious' reports were (1) confusion (17.3%), (2) seizures (11.5%), (3) drowsiness/sedation (11.5%), (4) agitation (10.9%), (5) coma (9.6%), (6) hallucinations (7.7%), (7) falls (7.1%), (8) behavioral disorders (5.8%), (9) withdrawal syndrome (5.1%), and (10) space-time disorientation (5.1%). A standardized difference of <0.2 was identified for six out of the ten most frequent 'serious' ADRs, and eight of the ten 'non-serious' ADRs. A proactive regional pharmacovigilance system could collect a substantial amount of safety data on a specific OLP practice. The profile of the ADRs collected was similar to that seen in the nationwide spontaneous reporting system.

Analysis of spontaneous inquiries about suspected adverse drug reactions posted by the general public on the electronic Japanese bulletin board "Yahoo! Japan Chiebukuro".

PubMed

Dobashi, Akira; Kurata, Kaori; Okazaki, Mitsuhiro; Nishizawa, Mari

2016-01-01

Spontaneous inquiries about the development of adverse drug reactions (ADRs) to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board "Yahoo! Japan Chiebukuro". Our aim was to clarify the characteristics related to people's descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term "Fukusayō" (ADR in Japanese) that were posted from July 2004 to June 2009 were extracted from the site. Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s). Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525). Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms, suspected medicines, and the disease for which the medicine was used. However, they often did not describe the start time when the ADR appeared or when the suspected medicine was started.

Hypoglycaemic complications with diabetes mellitus management: the predominant adverse drug reaction presenting to the Accident and Emergency Department of The University Hospital of the West Indies.

PubMed

Gossell-Williams, M; Williams-Johnson, J; Francis, L

2010-10-01

Evaluation of adverse drug reactions (ADRs) is important to the assessment of risk factors in an aim to ensure maximum benefits of drug therapy. This study was done to assess the types of ADRs presenting to the Accident and Emergency department (A&E) of the University Hospital of the West Indies. Admissions to the A&E associated with drugs were followed on a weekly basis for 19 weeks from October 2007 to February 2008 using the patient logbook. Medical records of patients with suspected ADRs were collected and evaluated by an Emergency Medicine Consultant of A & E to confirm the occurrence of ADRs and the suspected drug. Of the 8170 admissions to A&E, 48 (0.6%) were related to ADRs, with most occurring in females and the mean age (+/- standard error) was 58.9 (+/- 3.4) years. Drug induced hypoglycaemia accounted for 28 (56.3%) cases of ADRs and included mainly patients on insulin, with or without a sulphonylurea therapy. Most of these diabetic patients also had co-morbidities and were on multi-drug therapy (18). Allergic reactions accounted for 10 (21%) of the ADR outcomes. Other drugs accounting for ADRs included cardiovascular drugs (10.4%), analgesic/anti-inflammatory medications (8.3%), drugs acting on the central nervous system (8.3%) and anti-infectives (8.3%). It is concluded that drug-induced hypoglycaemia is the major ADR presenting to the A&E of the University Hospital of the West Indies; it is a preventable ADR and therefore further investigation should evaluate possible factors attributed to the occurrences.

What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? Experiences from reports to a consumer association.

PubMed

Vilhelmsson, Andreas; Svensson, Tommy; Meeuwisse, Anna; Carlsten, Anders

2011-10-25

According to the World Health Organization (WHO) the cost of adverse drug reactions (ADRs) in the general population is high and under-reporting by health professionals is a well-recognized problem. Another way to increase ADR reporting is to let the consumers themselves report directly to the authorities. In Sweden it is mandatory for prescribers to report serious ADRs to the Medical Products Agency (MPA), but there are no such regulations for consumers. The non-profit and independent organization Consumer Association for Medicines and Health, KILEN has launched the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. This study aimed to analyze these consumer reports. All reports submitted from January 2002 to April 2009 to an open web site in Sweden where anyone could report their experience with the use of pharmaceuticals were analyzed with focus on common psychiatric side effects related to antidepressant usage. More than one ADR for a specific drug could be reported. In total 665 reports were made during the period. 442 reports concerned antidepressant medications and the individual antidepressant reports represented 2392 ADRs and 878 (37%) of these were psychiatric ADRs. 75% of the individual reports concerned serotonin-reuptake inhibitor (SSRI) and the rest serotonin-norepinephrine reuptake inhibitor (SNRI). Women reported more antidepressant psychiatric ADRs (71%) compared to men (24%). More potentially serious psychiatric ADRs were frequently reported to KILEN and withdrawal symptoms during discontinuation were also reported as a common issue. The present study indicates that consumer reports may contribute with important information regarding more serious psychiatric ADRs following antidepressant treatment. Consumer reporting may be considered a complement to traditional ADR reporting.

Documentation of penicillin adverse drug reactions in electronic health records: inconsistent use of allergy and intolerance labels.

PubMed

Inglis, Joshua M; Caughey, Gillian E; Smith, William; Shakib, Sepehr

2017-11-01

The majority of patients with penicillin allergy labels tolerate penicillins. Inappropriate avoidance of penicillin is associated with increased hospitalisation, infections and healthcare costs. To examine the documentation of penicillin adverse drug reactions (ADR) in a large-scale hospital-based electronic health record. Penicillin ADR were extracted from 96 708 patient records in the Enterprise Patient Administration System in South Australia. Expert criteria were used to determine consistency of ADR entry and suitability for further evaluation. Of 43 011 unique ADR reports, there were 5023 ADR to penicillins with most being entered as allergy (n = 4773, 95.0%) rather than intolerance (n = 250, 5.0%). A significant proportion did not include a reaction description (n = 1052, 20.9%). Using pre-set criteria, 10.1% of reports entered as allergy had a reaction description that was consistent with intolerance and 31.0% of the entered intolerances had descriptions consistent with allergy. Virtually all ADR (n = 4979, 99.1%) were appropriate for further evaluation by history taking or immunological testing and half (50.7%, n = 2549) had documented reactions suggesting low-risk of penicillin allergy. The frequency of penicillin allergy label in this data set is consistent with the known overdiagnosis of penicillin allergy in the hospital population. ADR documentation was poor with incomplete entries and inconsistent categorisation. The concepts of allergy and intolerance for ADR classification, whilst mechanistically valid, may not be useful at the point of ADR entry by generalist clinicians. Systematic evaluation of reported ADR is needed to improve the quality of information for future prescribers. © 2017 Royal Australasian College of Physicians.

Aviation Machinist's Mate R 1 and C: Rate Training Manual.

ERIC Educational Resources Information Center

Naval Education and Training Command, Pensacola, FL.

The profusely illustrated rate training manual is one of a series of training manuals prepared for enlisted personnel of the Navy and Naval Reserve who are studying for advancement in the Aviation Machinist's Mate R rating (ADR 1 and ADRC). Chapter one provides information helpful for use in advancement. Chapters two through ten consist of units…

Risk factors for the prescription of potentially inappropriate medication (PIM) in the elderly : an analysis of sickness fund routine claims data from Germany.

PubMed

Stock, Stephanie; Redaelli, Marcus; Simic, Dusan; Siegel, Martin; Henschel, Frank

2014-10-01

Elderly people are especially prone to suffer adverse drug reactions (ADR). Main reasons for the higher vulnerability of the elderly to ADR are changes in metabolism as i.e. slower renal clearance and polypharmacie which often results from multimorbidity. To prevent ADR careful prescription with special consideration of these aspects is warranted. To help physicians avoid drugs which are especially likely to cause ADR lists have been developed following the consensus method process. For Germany this list is called the PRISCUS list. It was developed based on a literature review, review of international lists such as the American Beers list, and a consensus process based on a Delphi survey. It contains 83 drugs from 18 classes which are classified as potentially inapropriate medication (PIM). It also lists alternatives for each PIM. If a drug is registered with the PRISCUS list this does not mean automatically that it is contraindicated in the elderly but that special caution should be excercised in prescribing the drug, alternatives should be considered and the patient carefully monitored.Prescription rates for PIMs in Germany in the elderly is pretty much stable at around 23% with only a small decline in the past years. Also, more than 5% of all prescriptions in the elderly are PIM prescriptions. Physicians specially trained in geriatrics tend to prescribe less PIMs compared to other physicians.

Traditional Chinese medicine pharmacovigilance in signal detection: decision tree-based data classification.

PubMed

Wei, Jian-Xiang; Wang, Jing; Zhu, Yun-Xia; Sun, Jun; Xu, Hou-Ming; Li, Ming

2018-03-09

Traditional Chinese Medicine (TCM) is a style of traditional medicine informed by modern medicine but built on a foundation of more than 2500 years of Chinese medical practice. According to statistics, TCM accounts for approximately 14% of total adverse drug reaction (ADR) spontaneous reporting data in China. Because of the complexity of the components in TCM formula, which makes it essentially different from Western medicine, it is critical to determine whether ADR reports of TCM should be analyzed independently. Reports in the Chinese spontaneous reporting database between 2010 and 2011 were selected. The dataset was processed and divided into the total sample (all data) and the subsample (including TCM data only). Four different ADR signal detection methods-PRR, ROR, MHRA and IC- currently widely used in China, were applied for signal detection on the two samples. By comparison of experimental results, three of them-PRR, MHRA and IC-were chosen to do the experiment. We designed several indicators for performance evaluation such as R (recall ratio), P (precision ratio), and D (discrepancy ratio) based on the reference database and then constructed a decision tree for data classification based on such indicators. For PRR: R 1 -R 2  = 0.72%, P 1 -P 2  = 0.16% and D = 0.92%; For MHRA: R 1 -R 2  = 0.97%, P 1 -P 2  = 0.20% and D = 1.18%; For IC: R 1 -R 2  = 1.44%, P 2 -P 1  = 4.06% and D = 4.72%. The threshold of R,Pand Dis set as 2%, 2% and 3% respectively. Based on the decision tree, the results are "separation" for PRR, MHRA and IC. In order to improve the efficiency and accuracy of signal detection, we suggest that TCM data should be separated from the total sample when conducting analyses.

Development of LC-MS/MS method for the simultaneous analysis of the cardioprotective drug dexrazoxane and its metabolite ADR-925 in isolated cardiomyocytes and cell culture medium.

PubMed

Kovarikova, Petra; Pasakova-Vrbatova, Ivana; Vavrova, Anna; Stariat, Jan; Klimes, Jiri; Simunek, Tomas

2013-03-25

Dexrazoxane (DEX) is the only clinically used drug effective against anthracycline-induced cardiotoxicity and extravasation injury. However, the mechanism of its cardioprotective action still remains elusive. This paucity of comprehensive data is at least partially caused by the analytical difficulties associated with selective and sensitive simultaneous determination of the parent drug and its putative active metabolite ADR-925 in the relevant biological material. The aim of this study was to develop and validate the first LC-MS/MS method for simultaneous determination of DEX and ADR-925 in the isolated rat neonatal ventricular cardiomyocytes (NVCMs) and the cell culture medium. The analysis was performed on a Synergi Polar-RP column using the gradient profile of the mobile phase composed of 2mM ammonium formate and methanol. Electrospray ionization and ion trap mass analyzer were used as ionization and detection techniques, respectively. NVCMs were precipitated with methanol and the cell culture medium samples were diluted with the same solvent prior the LC-MS/MS analysis. The method was validated within the range of 4-80pmol/10(6) NVCMs and 7-70pmol/10(6) NVCMs for DEX and ADR-925, respectively, and at the concentrations of 8-100μM for both compounds in the culture cell medium. The practical applicability of this method was confirmed by the pilot analysis of NVCMs and the corresponding cell medium samples from relevant in vitro experiment. Hence, the LC-MS/MS method developed in this study represents a modern analytical tool suitable for investigation of DEX bioactivation inside the cardiomyocytes. In addition, the basic utility of the method for the analysis of DEX and ADR-925 in plasma samples was proved in a pilot experiment. Copyright © 2013 Elsevier B.V. All rights reserved.

30 CFR 291.103 - May I use alternative dispute resolution to informally resolve an allegation that open and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... denied? You may ask to use ADR either before or after you file a complaint. To make a request, call the...-0001. (a) You may request that ADR be administered by: (1) A contracted ADR provider agreed to by all... staff trained in ADR and certified by the CADR. (b) Each party must pay its respective share of all...

Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program

PubMed Central

Chiu, Sherry Yueh-Hsia; Chuang, Shu-Ling; Chen, Sam Li-Sheng; Yen, Amy Ming-Fang; Fann, Jean Ching-Yuan; Chang, Dun-Cheng; Lee, Yi-Chia; Wu, Ming-Shiang; Chou, Chu-Kuang; Hsu, Wen-Feng; Chiou, Shu-Ti; Chiu, Han-Mo

2017-01-01

Objectives Interval colorectal cancer (CRC) after colonoscopy may affect effectiveness and cost-effectiveness of screening programmes. We aimed to investigate whether and how faecal haemoglobin concentration (FHbC) of faecal immunochemical testing (FIT) affected the risk prediction of interval cancer (IC) caused by inadequate colonoscopy quality in a FIT-based population screening programme. Design From 2004 to 2009, 29 969 subjects underwent complete colonoscopy after positive FIT in the Taiwanese Nationwide CRC Screening Program. The IC rate was traced until the end of 2012. The incidence of IC was calculated in relation to patient characteristics, endoscopy-related factors (such adenoma detection rate (ADR)) and FHbC. Poisson regression analysis was performed to assess the potential risk factors for colonoscopy IC. Results One hundred and sixty-two ICs developed after an index colonoscopy and the estimated incidence was 1.14 per 1000 person-years of observation for the entire cohort. Increased risk of IC was most remarkable in the uptake of colonoscopy in settings with ADR lower than 15% (adjusted relative risk (aRR)=3.09, 95% CI 1.55 to 6.18) and then higher FHbC (μg Hb/g faeces) (100–149: aRR=2.55, 95% CI 1.52 to 4.29, ≥150: aRR=2.74, 95% CI 1.84 to 4.09) with adjustment for older age and colorectal neoplasm detected at baseline colonoscopy. Similar findings were observed for subjects with negative index colonoscopy. Conclusions Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC. PMID:26515543

Comparison of carbon dioxide and air insufflation during consecutive EGD and colonoscopy in moderate-sedation patients: a prospective, double-blind, randomized controlled trial.

PubMed

Kim, Su Young; Chung, Jun-Won; Park, Dong Kyun; Kwon, Kwang An; Kim, Kyoung Oh; Kim, Yoon Jae; Kim, Jung Ho

2017-06-01

Endoscopy is performed with air insufflation and is usually associated with abdominal pain. It is well recognized that carbon dioxide (CO 2 ) is absorbed more quickly into the body than air; however, to date, few studies have investigated the use of CO 2 insufflation during consecutive EGD and colonoscopy (CEC). Thus, this study evaluated the efficacy of CO 2 insufflation compared with air insufflation in CEC. From March 2014 to April 2016, a total of 215 consecutive patients were randomly assigned to receive CO 2 insufflation (CO 2 group, n = 108) or air insufflation (air group, n = 107). Abdominal pain after CEC was recorded on a visual analogue scale (VAS). The amount of sedatives administered, use of analgesics, polyp detection rate (PDR), adenoma detection rate (ADR), abdominal circumference, and adverse events were also analyzed. Baseline patient characteristics were not significantly different between the groups. Abdominal pain on the VAS in the CO 2 group and air group 1 hour after CEC was, respectively, 13.8 and 20.1 (P = .010), 3 hours after CEC was 8.3 and 12.5 (P = .056), 6 hours after CEC was 3.5 and 5.3 (P = .246), and 1 day after CEC was 1.8 and 3.4 (P = .192). The dose of sedative administered, analgesic usage, PDR, ADR, and adverse events were not statistically different between the groups. However, the increase in abdominal circumference was significantly higher in the air group than in the CO 2 group. CO 2 insufflation was superior to air insufflation with regard to the pain score on the VAS in the hour after CEC. (Clinical trial registration number: KCT0001491.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

48 CFR 833.103 - Protests to VA.

Code of Federal Regulations, 2011 CFR

2011-10-01

... encouraged to use alternative dispute resolution (ADR) procedures to resolve protests at any stage in the protest process. If ADR is used, VA will not furnish any documentation in an ADR proceeding beyond what is...

A Parametric Study on Using Active Debris Removal for LEO Environment Remediation

NASA Technical Reports Server (NTRS)

2010-01-01

Recent analyses on the instability of the orbital debris population in the low Earth orbit (LEO) region and the collision between Iridium 33 and Cosmos 2251 have reignited the interest in using active debris removal (ADR) to remediate the environment. There are; however, monumental technical, resource, operational, legal, and political challenges in making economically viable ADR a reality. Before a consensus on the need for ADR can be reached, a careful analysis of its effectiveness must be conducted. The goal is to demonstrate the need and feasibility of using ADR to better preserve the future environment and to guide its implementation to maximize the benefit-to-cost ratio. This paper describes a new sensitivity study on using ADR to stabilize the future LEO debris environment. The NASA long-term orbital debris evolutionary model, LEGEND, is used to quantify the effects of several key parameters, including target selection criteria/constraints and the starting epoch of ADR implementation. Additional analyses on potential ADR targets among the currently existing satellites and the benefits of collision avoidance maneuvers are also included.

Mechanical design of a 3-stage ADR for the Astro-H mission

NASA Astrophysics Data System (ADS)

James, Bryan L.; Martinez, Raul M.; Shirron, Peter; Tuttle, Jim; Francis, John J.; San Sebastian, Marcelino; Wegel, Donald C.; Galassi, Nicholas M.; McGuinness, Daniel S.; Puckett, David; Flom, Yury

2012-04-01

The X-ray micro-calorimeter array in the Soft X-ray Spectrometer (SXS) instrument on Astro-H will be cooled by a 3-stage adiabatic demagnetization refrigerator (ADR). The ADR consists of two mechanically independent assemblies. When integrated with a mounting structure and the detector assembly, they form a self-contained unit that will be inserted into the top end of a liquid helium tank. The unique configuration requires many components and sub-assemblies to be thermally isolated from their structural mount. Normally in an ADR this is limited to suspending cold salt pills within their (much warmer) magnets, but in the case of SXS, it also involves one ADR stage being supported by, but thermally isolated from, the helium tank. This paper will describe the complex thermal and mechanical design of the SXS ADR, and summarize vibration and mechanical properties tests that have been performed to validate the design.

Thermodynamic Performance of the 3-Stage ADR for the Astro-H Soft X-Ray Spectrometer Instrument

NASA Technical Reports Server (NTRS)

Shirron, Peter J.; Kimball, Mark O.; James, Bryan L.; Muench, Theodore; DiPirro, Michael J.; Bialas, Thomas G.; Sneiderman, Gary A.; Porter, Frederick S.; Kelley, Richard L.

2015-01-01

The Soft X-ray Spectrometer (SXS) instrument[1] on Astro-H[2] will use a 3-stage ADR[3] to cool the microcalorimeter array to 50 mK. In the primary operating mode, two stages of the ADR cool the detectors using superfluid helium at =1.20 K as the heat sink[4]. In the secondary mode, which is activated when the liquid helium is depleted, the ADR uses a 4.5 K Joule-Thomson cooler as its heat sink. In this mode, all three stages operate together to continuously cool the (empty) helium tank and singleshot cool the detectors. The flight instrument - dewar, ADR, detectors and electronics - were integrated in 2014 and have since undergone extensive performance testing. This paper presents a thermodynamic analysis of the ADR's operation, including cooling capacity, heat rejection to the heat sinks, and various measures of efficiency.

Exploring New Zealand prescription data using sequence symmetry analyses for predicting adverse drug reactions.

PubMed

Nishtala, P S; Chyou, T-Y

2017-04-01

Prescription sequence symmetry analyses (PSSA) is a ubiquitous tool employed in pharmacoepidemiological research to predict adverse drug reactions (ADRs). Several studies have reported the advantage of PSSA as a method that can be applied to a large prescription database with computational ease. The objective of this study was to validate New Zealand (NZ) prescription database as a potential source for identifying ADRs using the PSSA method. We analysed de-identified individual-level prescription data for people aged 65 years and above for the period 2005 to 2014 from the pharmaceutical collections supplied by the NZ Ministry of Health. We selected six positive controls that have been previously investigated and reported for causing ADRs. The six positive controls identified were amiodarone (repeated twice), frusemide, simvastatin, lithium and fluticasone. Amiodarone and lithium have been reported to induce thyroid dysfunction. Simvastatin reported to cause muscle cramps while fluticasone is well documented to cause oral candidiasis. Thyroxine was identified as a marker drug to treat hypothyroidism associated with amiodarone and lithium. Carbimazole was identified as a marker drug to treat hyperthyroidism associated with amiodarone use. Quinine sulphate was identified as a marker drug to treat muscle cramps associated with statins. In addition, we also analysed six negative controls that are unlikely to be associated with ADRs. The main outcome measure is to determine associations with ADRs using adjusted sequence ratios (ASR), and 95% confidence intervals RESULTS AND DISCUSSION: Our analyses confirmed a significant signal for all six positive controls. Significant positive associations were noted for amiodarone [ASR = 3·57, 95% CI (3·17-4·02)], and lithium chloride induced hypothyroidism [ASR = 3·43, 95% CI (2·55-4·70)]. Amiodarone was also strongly associated with hyperthyroidism [ASR = 8·81 95% CI (5·86-13·77)]. Simvastatin was associated with muscle cramps [ASR = 1·69, 95% CI (1·61-1·77)]. Fluticasone was positively associated with oral candidiasis [ASR = 2·34, 95% CI (2·19-2·50)]. Frusemide was associated with hypokalaemia [ASR = 2·94, 95% CI (2·83-3·05]). No strong associations were noted for the negative pairs. It is important to highlight that PSSA automatically controls for all confounding factors including unknown and unmeasured confounding variables, plus the effect of temporal trend in prescriptions, and hence allows a more robust ADR detection especially when confounding factors are difficult to determine or measure. New Zealand prescription database can be a potential source to identify ADRs engaging the PSSA method, and this could complement pharmacovigilance surveillance in NZ. The PSSA can be an important method for post-marketing surveillance and monitoring of ADRs which have relatively short latency. However, the predictive validity of PSSA will be compromised in certain scenarios, particularly when sample size is small, when new drugs are in the market and data are sparse. © 2016 John Wiley & Sons Ltd.

A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

PubMed

Hoban, Claire L; Byard, Roger W; Musgrave, Ian F

2015-07-01

Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications. © 2015 Wiley Publishing Asia Pty Ltd.

47 CFR 90.699 - Transition of the upper 200 channels in the 800 MHz band to EA licensing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... over the amount of reimbursement required, will be encouraged to use expedited ADR procedures. ADR procedures provide several alternative methods such as binding arbitration, mediation, or other ADR...

Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.

PubMed

Matthews, Edwin J; Kruhlak, Naomi L; Weaver, James L; Benz, R Daniel; Contrera, Joseph F

2004-12-01

The FDA's Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (# ADR reports / # shipping units) x 1,000,000. MCASE/MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by > or = 4 ADR reports and > or = 20,000 shipping units during five years of marketing, and an RI > or = 4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects.

Therapeutic Drug Monitoring in Children and Adolescents Under Pharmacotherapy With Olanzapine in Daily Clinical Practice.

PubMed

Fekete, Stefanie; Wewetzer, Christoph; Mehler-Wex, Claudia; Holtkamp, Kristian; Burger, Rainer; Reichert, Susanne; Taurines, Regina; Romanos, Marcel; Gerlach, Manfred; Egberts, Karin

2017-06-01

The relationship between daily dose, serum concentrations, and clinical outcomes of olanzapine as well as the influencing factors thereof in children and adolescents treated for different psychiatric disorders were investigated in daily clinical practice. In addition, it was examined whether the current recommended therapeutic range (TR) for adult patients with psychotic disorders is valid for minors. The Competence Network for Therapeutic Drug Monitoring (www.tdm-kjp.com) routinely collects demographic and clinical outcome data as well as serum concentrations of children and adolescents treated with psychotropics. The therapeutic effect is documented using the Clinical Global Impression Scale subscale for Global Improvement. Adverse drug reactions (ADRs) are assessed using the Udvalg for Kliniske Undersogelser-Side Effect Rating Scale. One hundred fifteen patients (mean age = 15.9 years; range = 10.4-18.8 years; 40.9% male) were included. The majority (72.1%) was cotreated with other psychotropic drugs. A positive medium linear relationship (r = 0.619; P < 0.001) between olanzapine dose (mean = 11.64 mg/d) and serum concentration (mean = 35.65 ng/mL) was found with a marked interindividual variability of serum concentrations. Neither relationship between olanzapine serum concentration and treatment response (clinical benefit documented in 80%) nor ADRs (documented in 53.3%, in 7.5% judged as severe) was detected. Most of the patients with psychotic and eating disorders (68.8% and 71.8%, respectively) had an olanzapine serum concentration within the TR suggested for adults. There are several limitations of this study because of the naturalistic design, and our results should therefore be interpreted with caution. As most of the patients showed a clinical benefit under olanzapine concentrations within the TR for adults and only a minority had severe ADRs, it is reasonable to conclude a similar TR for children, adolescents, and adults.

Simethicone improves bowel cleansing with low-volume polyethylene glycol: a multicenter randomized trial.

PubMed

Zhang, Shenghong; Zheng, Danping; Wang, Jinping; Wu, Jianwei; Lei, Pingguang; Luo, Qi; Wang, Liping; Zhang, Beiping; Wang, Hong; Cui, Yi; Chen, Minhu

2018-04-01

 For bowel preparation, using a reduced volume of polyethylene glycol (PEG) solution without influencing its effectiveness would be preferable. While simethicone shows great potential as an adjunctive agent, data on its use are limited. We aimed to clarify whether simethicone added to low-volume PEG solution improved bowel cleansing. PATIENTS AND METHODS : Consecutive adult patients registered for colonoscopy were recruited from seven medical centers in South China between 15 April and 15 July 2015 and prospectively randomized into two groups: 2 L PEG (conventional group) and 2 L PEG plus simethicone (simethicone group). The primary endpoint was the effectiveness of bowel cleansing according to the Boston Bowel Preparation Scale (BBPS). Secondary endpoints included cecal intubation time, adenoma detection rate (ADR), patient safety and compliance, and adverse events. RESULTS : We included 290 and 289 patients in the conventional and simethicone groups, respectively, for analysis. The proportion with acceptable bowel cleansing (BBPS ≥ 6) was significantly higher in the simethicone group than in the conventional group (88.2 % vs. 76.6 %; P  < 0.001). The mean (SD) BBPS score was significantly lower in the conventional group (6.5 [1.8] vs. 7.3 [1.7]; P  < 0.001), as was the bubble score (2.5 [0.7] vs. 2.8 [0.5]; P  < 0.001). The average cecal intubation time was significantly shorter in the simethicone group (6.3 [3.1] vs. 7.5 [5.1] minutes; P  < 0.001). The ADR in the right colon was higher in the simethicone group than in the conventional group (16.6 % vs. 10.3 %; P  = 0.03). Safety and compliance, including the taste, smell, and dosage of PEG, were similar for both groups.  Simethicone added to low-volume PEG solution improves bowel-cleansing efficacy, with similar safety and compliance, shorter cecal intubation time, and higher ADR. © Georg Thieme Verlag KG Stuttgart · New York.

Safety and Effectiveness of Natalizumab: First Report of Interim Results of Post-Marketing Surveillance in Japan.

PubMed

Saida, Takahiko; Yokoyama, Kazumasa; Sato, Ryusuke; Makioka, Haruki; Iizuka, Yukihiko; Hase, Masakazu; Ling, Yan; Torii, Shinichi

2017-12-01

Natalizumab, a humanized anti-α4 integrin monoclonal antibody, received marketing approval in Japan in 2014 for the treatment of multiple sclerosis (MS). Because the previous large-scale clinical trials of natalizumab were mainly conducted in Europe and North American countries, and data in patients with MS from Japan were limited, we conducted an all-case post-marketing surveillance of natalizumab-treated MS patients from Japan to investigate the safety and effectiveness of natalizumab in a real-world clinical setting in Japan. Here, we report the results of an interim analysis. During the observation period of 2 years, all patients who were treated with natalizumab subsequent to its approval in Japan were followed. The effectiveness of natalizumab was assessed by examining the changes in expanded disability status scale (EDSS) score and annualized relapse rate (ARR) from baseline. Safety was assessed by analyzing the incidence of adverse drug reactions (ADRs). The safety analysis included 106 patients (mean age 39.3 years; women 62.3%) whose data were collected until the data lock point (February 7, 2016). The effectiveness analysis included 75 patients. The majority of patients had relapsing-remitting MS (93/106 patients; 87.7%). The mean length of treatment exposure in the present study was 6.6 months. During the 2-year observation period, no significant change in the EDSS was observed, while the ARR decreased significantly from baseline (72.9% reduction, p = 0.001). ADRs and serious ADRs were observed in 11.3% and 3.8% of patients, respectively; however, no new safety concerns were detected. No patient had progressive multifocal leukoencephalopathy (PML) during the present study period. The safety and effectiveness of natalizumab were confirmed in Japanese patients with MS in clinical practice. Nevertheless, potential risks including PML require continuous, careful observation. Biogen Japan Ltd (Tokyo, Japan).

Safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): Interim results of a post-marketing surveillance study.

PubMed

Terauchi, Yasuo; Yokote, Koutaro; Nakamura, Ichiro; Sugamori, Haruko

2016-01-01

To determine the incidence of adverse drug reactions (ADRs) associated with ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus. We report interim results of a postmarketing surveillance survey. Japanese physicians recorded ADRs in elderly patients (≥ 65 years old) who were first prescribed with ipragliflozin within 3 months of its launch (April 2014). Incidence of ADRs within 1 year of starting treatment with ipragliflozin. 898 ADRs occurred in 721/7,170 patients (10.06%). Skin complication-, volume depletion-, genital infection-, polyuria/pollakiuria-, urinary tract infection-, and hypoglycemia-related ADRs occurred in 2.23%, 1.90%, 1.45%, 1.32%, 0.77%, and 0.32%, respectively. ADRs were classified as serious in 44 (0.61%) patients. Half of the ADRs occurred within 30 days of starting treatment. There were no cases of Stevens-Johnson syndrome or toxic epidermal necrolysis. Most (92.1%) of the ADRs resolved or improved. Glycated hemoglobin, fasting blood glucose, body weight, and systolic blood pressure decreased by 0.6% (baseline 7.8%), 22.7 mg/dL (baseline 163.0 mg/dL), 2.3 kg (baseline 67.4 kg), and 3.1 mmHg (baseline 133.2 mmHg), respectively, from baseline to treatment discontinuation/last visit. Ipragliflozin is well tolerated and reduced surrogate endpoints in elderly Japanese patients with type 2 diabetes mellitus. Clinicaltrials.gov identifier: NCT02297620.

Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

PubMed

Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2012-09-01

Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

PubMed Central

Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

2016-01-01

Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

Combinatorial resveratrol and quercetin polymeric micelles mitigate doxorubicin induced cardiotoxicity in vitro and in vivo.

PubMed

Cote, Brianna; Carlson, Lisa Janssen; Rao, Deepa A; Alani, Adam W G

2015-09-10

Doxorubicin hydrochloride (ADR) is an anthracycline antibiotic used to treat various cancers. However, due to its extensive cardiotoxic side effects a lifetime cumulative dose limit of 450-550 mg/m2 exists. The postulated mechanism of the cardiotoxicity is generation of reactive oxygen and nitrogen species. Natural products like resveratrol (RES), and quercetin (QUE) are known free radical scavengers and have shown cardioprotective effects. However, concurrent dosing of these natural products with ADR is limited due to their low solubility, and low oral bioavailability. We hypothesize that the combination of RES and QUE in Pluronic® F127 micelles (mRQ) when co-administered with ADR, will be cardioprotective in vitro and in vivo, while maintaining or increasing the efficacy of ADR against cancer cell lines in vitro. We prepared mRQ micelles capable of retaining 1.1mg/mL and 1.42 mg/mL of RES and QUE respectively. The in vitro release of RES and QUE from the micelles followed first order kinetics over 48h. In vitro cell viability and combination index analysis studies in human ovarian cancer cells (SKOV-3) and rat cardiomyocytes (H9C2) showed that RES:QUE: ADR at 10:10:1 ratio was synergistic in SKOV-3 cells and antagonistic in H9C2 cells. Caspase 3/7 activity studies indicated that mRQ did not interfere with ADR caspase activity in SKOV-3 cells but significantly decreased it in H9C2 cells. The generation of reactive oxygen species (ROS) in SKOV-3 and H9C2 cells in the presence of mRQ also indicated no changes in ROS activity in SKOV-3 cells but significant scavenging in H9C2 cells. Healthy mice were exposed to acute doses of ADR and ADR with mRQ. Based on biochemical estimations the presence of mRQ with ADR conferred full cardioprotection in these mice. Concurrent administration of mRQ with ADR at 10:10:1 ratio provides a viable strategy to mitigate acute ADR induced cardiotoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents.

PubMed

Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile

2016-03-20

To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Individuals contributing ADR information to product information documents. All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Twelve brand drugs--24 paired documents--were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65-425) and 114 (range: 56-265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Privacy preserving data anonymization of spontaneous ADE reporting system dataset.

PubMed

Lin, Wen-Yang; Yang, Duen-Chuan; Wang, Jie-Teng

2016-07-18

To facilitate long-term safety surveillance of marketing drugs, many spontaneously reporting systems (SRSs) of ADR events have been established world-wide. Since the data collected by SRSs contain sensitive personal health information that should be protected to prevent the identification of individuals, it procures the issue of privacy preserving data publishing (PPDP), that is, how to sanitize (anonymize) raw data before publishing. Although much work has been done on PPDP, very few studies have focused on protecting privacy of SRS data and none of the anonymization methods is favorable for SRS datasets, due to which contain some characteristics such as rare events, multiple individual records, and multi-valued sensitive attributes. We propose a new privacy model called MS(k, θ (*) )-bounding for protecting published spontaneous ADE reporting data from privacy attacks. Our model has the flexibility of varying privacy thresholds, i.e., θ (*) , for different sensitive values and takes the characteristics of SRS data into consideration. We also propose an anonymization algorithm for sanitizing the raw data to meet the requirements specified through the proposed model. Our algorithm adopts a greedy-based clustering strategy to group the records into clusters, conforming to an innovative anonymization metric aiming to minimize the privacy risk as well as maintain the data utility for ADR detection. Empirical study was conducted using FAERS dataset from 2004Q1 to 2011Q4. We compared our model with four prevailing methods, including k-anonymity, (X, Y)-anonymity, Multi-sensitive l-diversity, and (α, k)-anonymity, evaluated via two measures, Danger Ratio (DR) and Information Loss (IL), and considered three different scenarios of threshold setting for θ (*) , including uniform setting, level-wise setting and frequency-based setting. We also conducted experiments to inspect the impact of anonymized data on the strengths of discovered ADR signals. With all three different threshold settings for sensitive value, our method can successively prevent the disclosure of sensitive values (nearly all observed DRs are zeros) without sacrificing too much of data utility. With non-uniform threshold setting, level-wise or frequency-based, our MS(k, θ (*))-bounding exhibits the best data utility and the least privacy risk among all the models. The experiments conducted on selected ADR signals from MedWatch show that only very small difference on signal strength (PRR or ROR) were observed. The results show that our method can effectively prevent the disclosure of patient sensitive information without sacrificing data utility for ADR signal detection. We propose a new privacy model for protecting SRS data that possess some characteristics overlooked by contemporary models and an anonymization algorithm to sanitize SRS data in accordance with the proposed model. Empirical evaluation on the real SRS dataset, i.e., FAERS, shows that our method can effectively solve the privacy problem in SRS data without influencing the ADR signal strength.

New initiatives for pharmacovigilance in South Korea: introducing the Korea Institute of Drug Safety and Risk Management (KIDS).

PubMed

Shin, Ju-Young; Jung, Sun-Young; Ahn, So-Hyeon; Lee, Shin Haeng; Kim, Su-Jin; Seong, Jong-Mi; Chung, Soo-Youn; Park, Byung-Joo

2014-11-01

Pharmacovigilance plays a vital role in ensuring that patients receive appropriate medical products that are safe and effective. This paper aims to describe the history of pharmacovigilance in Korea and introduce the establishment and goal of the KIDS. In Korea, the adverse drug reactions (ADR) reporting system was launched in 1988 by the Korea Ministry of Food and Drug Safety (MFDS) and spontaneous ADR reports have been collected from health care professionals and the general public. Although the ADR reporting system has begun, the reporting rate was very low in the first 10 years, and safety actions were done passively in response to the US Food and Drug Administration (FDA) or European Medicines Agency (EMA)'s safety alert and communications. Therefore, the Korea Institute of Drug Safety and Risk Management (KIDS) was established in April 2012 as a new initiative for pharmacovigilance. The KIDS will continue to contribute to the improvement of Korean pharmacovigilance by collecting, managing, and analyzing consumer-centered drug safety information. Copyright © 2014 John Wiley & Sons, Ltd.

Performance of probabilistic method to detect duplicate individual case safety reports.

PubMed

Tregunno, Philip Michael; Fink, Dorthe Bech; Fernandez-Fernandez, Cristina; Lázaro-Bengoa, Edurne; Norén, G Niklas

2014-04-01

Individual case reports of suspected harm from medicines are fundamental for signal detection in postmarketing surveillance. Their effective analysis requires reliable data and one challenge is report duplication. These are multiple unlinked records describing the same suspected adverse drug reaction (ADR) in a particular patient. They distort statistical screening and can mislead clinical assessment. Many organisations rely on rule-based detection, but probabilistic record matching is an alternative. The aim of this study was to evaluate probabilistic record matching for duplicate detection, and to characterise the main sources of duplicate reports within each data set. vigiMatch™, a published probabilistic record matching algorithm, was applied to the WHO global individual case safety reports database, VigiBase(®), for reports submitted between 2000 and 2010. Reported drugs, ADRs, patient age, sex, country of origin, and date of onset were considered in the matching. Suspected duplicates for the UK, Denmark, and Spain were reviewed and classified by the respective national centre. This included evaluation to determine whether confirmed duplicates had already been identified by in-house, rule-based screening. Furthermore, each confirmed duplicate was classified with respect to the likely source of duplication. For each country, the proportions of suspected duplicates classified as confirmed duplicates, likely duplicates, otherwise related, and unrelated were obtained. The proportions of confirmed or likely duplicates that were not previously known by the national organisation were determined, and variations in the rates of suspected duplicates across subsets of reports were characterised. Overall, 2.5 % of the reports with sufficient information to be evaluated by vigiMatch were classified as suspected duplicates. The rates for the three countries considered in this study were 1.4 % (UK), 1.0 % (Denmark), and 0.7 % (Spain). Higher rates of suspected duplicates were observed for literature reports (11 %) and reports with fatal outcome (5 %), whereas a lower rate was observed for reports from consumers and non-health professionals (0.5 %). The predictive value for confirmed or likely duplicates among reports flagged as suspected duplicates by vigiMatch ranged from 86 % for the UK, to 64 % for Denmark and 33 % for Spain. The proportions of confirmed duplicates that were previously unknown to national centres ranged from 89 % for Spain, to 60 % for the UK and 38 % for Denmark, despite in-house duplicate detection processes in routine use. The proportion of unrelated cases among suspected duplicates were below 10 % for each national centre in the study. Probabilistic record matching, as implemented in vigiMatch, achieved good predictive value for confirmed or likely duplicates in each data source. Most of the false positives corresponded to otherwise related reports; less than 10 % were altogether unrelated. A substantial proportion of the correctly identified duplicates had not previously been detected by national centre activity. On one hand, vigiMatch highlighted duplicates that had been missed by rule-based methods, and on the other hand its lower total number of suspected duplicates to review improved the accuracy of manual review.

Comprehensive Behavioral Phenotyping of Ts65Dn Mouse Model of Down Syndrome: Activation of β1-Adrenergic Receptor by Xamoterol as a Potential Cognitive Enhancer

PubMed Central

Faizi, Mehrdad; Bader, Patrick L.; Tun, Christine; Encarnacion, Angelo; Kleschevnikov, Alexander; Belichenko, Pavel; Saw, Nay; Priestley, Matthew; Tsien, Richard W; Mobley, William C; Shamloo, Mehrdad

2012-01-01

Down Syndrome (DS) is the most prevalent form of mental retardation caused by genetic abnormalities in humans. This has been successfully modeled in mice to generate the Ts65Dn mouse, a genetic model of DS. This transgenic mouse model shares a number of physical and functional abnormalities with people with DS, including changes in the structure and function of neuronal circuits. Significant abnormalities in noradrenergic (NE-ergic) afferents from the locus coeruleus to the hippocampus, as well as deficits in NE-ergic neurotransmission are detected in these animals. In the current study we characterized in detail the behavioral phenotype of Ts65Dn mice, in addition to using pharmacological tools for identification of target receptors mediating the learning and memory deficits observed in this model of DS. We undertook a comprehensive approach to mouse phenotyping using a battery of standard and novel tests encompassing: i) locomotion (Activity Chamber, PhenoTyper, and CatWalk), ii) learning and memory (spontaneous alternation, delayed matching-to-place water maze, fear conditioning, and Intellicage), and iii) social behavior. Ts65Dn mice showed increased locomotor activity in novel and home cage environments. There were significant and reproducible deficits in learning and memory tests including spontaneous alternation, delayed matching-to-place water maze, Intellicage place avoidance and contextual fear conditioning. Although Ts65Dn mice showed no deficit in sociability in the 3-chamber test, a marked impairment in social memory was detected. Xamoterol, a β1-adrenergic receptor (β1-ADR) agonist, effectively restored the memory deficit in contextual fear conditioning, spontaneous alternation and novel object recognition. These behavioral improvements were reversed by betaxolol, a selective β1-ADR antagonist. In conclusion, our results demonstrate that this mouse model of Down Syndrome display cognitive deficits which is mediated by imbalance in noradrenergic system. In this experimental model of Down Syndrome a selective activation of β1-ADR does restore some of these behavioral deficits. Further mechanistic studies will be needed to investigate the failure of noradrenergic system and the role of β1-ADR in cognitive deficit and pathogenesis of DS in people. Restoring NE neurotransmission or a selective activation of β1-ADR need to be further investigated for development of any potential therapeutic strategies for symptomatic relieve of memory deficit in DS. Furthermore, due to the significant involvement of noradrenergic system in the cardiovascular function further safety and translational studies will be needed to ensure the safety and efficacy of this approach. PMID:21527343

13-year overview of serious adverse drug reactions following subcutaneous specific immunotherapy with a chemically modified allergen preparation.

PubMed

Distler, Andreas; Pappelendam, Debbie

The Paul-Ehrlich-Institut (PEI) published an analysis of reports of adverse drug reactions (ADRs) in 2001 with test and therapy allergens from the period from 1991 to 2000. Possible risk factors were evaluated for the ADR reports classified as "serious". During the analyzed period, modified semi-depot preparations (allergoids) induced between 0.01 % and 0.0005 % serious systemic reactions, i. e. one serious ADR occurred in 10,000 to 200,000 injections. No information was provided regarding the respective incidences in relation to the individual companies or preparations. Within the scope of a 13-year analysis (2001-2013), the serious ADRs were analysed at HAL for the allergoid preparations PURETHAL® Pollen and Mites. As in the analysis of PEI, the frequency of serious ADRs was based on the estimated number of administered injections. A total of 46 cases with serious ADRs were received. In 26 % of the cases, a serious ADR occurred during initial treatment after the first injection. In 82.6 % of the cases, the serious ADR occurred within the 30-minute observation period in the practice. Adrenaline was administered as emergency treatment in seven cases. Hospitalisations were initiated by the treating physician or by patients themselves in 45 cases. The duration of the hospital stay varied from a few hours up to three days for further monitoring. Serious ADRs occurred in 11 cases with mites and in 35 cases with pollen. If it is assumed that there are six injections in each vial, this yields an incidence of 0.00061 % (1 : 164,000). The frequency with mites (0.00093 %) was slightly higher than with pollen (0.00055 %). The allergoid preparations (pollen and mite allergens) showed a very low risk of serious ADRs, which was close to the lower level of incidence of 0.0005 % for allergoid preparations published by the PEI.

Analysis of spontaneous inquiries about suspected adverse drug reactions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”

PubMed Central

Dobashi, Akira; Kurata, Kaori; Okazaki, Mitsuhiro; Nishizawa, Mari

2016-01-01

Purpose Spontaneous inquiries about the development of adverse drug reactions (ADRs) to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”. Our aim was to clarify the characteristics related to people’s descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Methods Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term “Fukusayō” (ADR in Japanese) that were posted from July 2004 to June 2009 were extracted from the site. Results Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s). Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525). Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Conclusion Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms, suspected medicines, and the disease for which the medicine was used. However, they often did not describe the start time when the ADR appeared or when the suspected medicine was started. PMID:27114703

48 CFR 5433.214. - Alternative Dispute Resolution (ADR).

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Alternative Dispute Resolution (ADR). 5433.214. Section 5433.214. Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE PROTESTS, DISPUTES AND APPEALS 5433.214. Alternative Dispute Resolution (ADR). The...

48 CFR 5433.214. - Alternative Dispute Resolution (ADR).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Alternative Dispute Resolution (ADR). 5433.214. Section 5433.214. Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE PROTESTS, DISPUTES AND APPEALS 5433.214. Alternative Dispute Resolution (ADR). The...

48 CFR 5433.214. - Alternative Dispute Resolution (ADR).

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Alternative Dispute Resolution (ADR). 5433.214. Section 5433.214. Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE PROTESTS, DISPUTES AND APPEALS 5433.214. Alternative Dispute Resolution (ADR). The...

48 CFR 5433.214. - Alternative Dispute Resolution (ADR).

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 7 2014-10-01 2014-10-01 false Alternative Dispute Resolution (ADR). 5433.214. Section 5433.214. Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE PROTESTS, DISPUTES AND APPEALS 5433.214. Alternative Dispute Resolution (ADR). The...

48 CFR 5433.214. - Alternative Dispute Resolution (ADR).

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 7 2013-10-01 2012-10-01 true Alternative Dispute Resolution (ADR). 5433.214. Section 5433.214. Federal Acquisition Regulations System DEFENSE LOGISTICS AGENCY, DEPARTMENT OF DEFENSE PROTESTS, DISPUTES AND APPEALS 5433.214. Alternative Dispute Resolution (ADR). The...

Adverse drug reactions in Germany: direct costs of internal medicine hospitalizations.

PubMed

Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Farker, Katrin; Saljé, Karen; Mueller, Silke; Hippius, Marion; Thuermann, Petra A; Hasford, Joerg

2011-06-01

German hospital reimbursement modalities changed as a result of the introduction of Diagnosis Related Groups (DRG) in 2004. Therefore, no data on the direct costs of adverse drug reactions (ADRs) resulting in admissions to departments of internal medicine are available. The objective was to quantify the ADR-related economic burden (direct costs) of hospitalizations in internal medicine wards in Germany. Record-based study analyzing the patient records of about 57,000 hospitalizations between 2006 and 2007 of the Net of Regional Pharmacovigilance Centers (Germany). All ADRs were evaluated by a team of experts in pharmacovigilance for severity, causality, and preventability. The calculation of accurate person-related costs for ADRs relied on the German DRG system (G-DRG 2009). Descriptive and bootstrap statistical methods were applied for data analysis. The incidence of hospitalization due to at least 'possible' serious outpatient ADRs was estimated to be approximately 3.25%. Mean age of the 1834 patients was 71.0 years (SD 14.7). Most frequent ADRs were gastrointestinal hemorrhage (n = 336) and drug-induced hypoglycemia (n = 270). Average inpatient length-of-stay was 9.3 days (SD 7.1). Average treatment costs of a single ADR were estimated to be approximately €2250. The total costs sum to €434 million per year for Germany. Considering the proportion of preventable cases (20.1%), this equals a saving potential of €87 million per year. Preventing ADRs is advisable in order to realize significant nationwide savings potential. Our cost estimates provide a reliable benchmark as they were calculated based on an intensified ADR surveillance and an accurate person-related cost application. Copyright © 2011 John Wiley & Sons, Ltd.

A time series analysis of the effects of financial incentives and mandatory clinical applications as interventions to improve spontaneous adverse drug reaction reporting by hospital medical staff in China.

PubMed

Chang, Feng; Xi, Yue; Zhao, Jie; Zhang, Xiaojian; Lu, Yun

2017-12-01

Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is often under-reported, which may lead to problems in patient management. This study was aimed to assess the effectiveness of a financial intervention based on a fine and a bonus for improving spontaneous reporting of ADRs by physicians in a hospital setting. This study was conducted at the First Affiliated Hospital of Zhengzhou University (China). Starting in 2009, a bonus of 20 RMB (Chinese currency) was given for each spontaneous ADR report, and a fine of 50 RMB was given for any withheld ADR report. A time series analysis using autoregressive integrated moving average models was performed to assess the changes in the total number of spontaneous ADR reports between the preintervention period (2006-2008) and during the first (2009-2011) and second (2012-2014) intervention periods. The median number of reported ADRs per year increased from 29 (range 27-72) in the preintervention period to 277 (range 199-284) in the first intervention period and to 666 in the second (range 644-691). The monthly number of reported ADRs was stable during the 3 periods: 3.56 ± 3.60/month (95% confidence interval (CI), 2.42-4.75) during the preintervention period, 21 ± 13/month (95% CI, 16.97-25.80) in the first intervention period, and 56 ± 20/month (95% CI, 48.81-62.17) in the second intervention period. A financial incentive and ADR management regulations had a significant effect on the increase of reported ADRs. © 2017 John Wiley & Sons, Ltd.

Shenmai injection enhances the cytotoxicity of chemotherapeutic drugs against colorectal cancers via improving their subcellular distribution

PubMed Central

Liu, Wen-yue; Zhang, Jing-wei; Yao, Xue-quan; Jiang, Chao; He, Ji-chao; Ni, Pin; Liu, Jia-li; Chen, Qian-ying; Li, Qing-ran; Zang, Xiao-jie; Yao, Lan; Liu, Ya-zhong; Wang, Mu-lan; Shen, Pei-qiang; Wang, Guang-ji; Zhou, Fang

2017-01-01

Shenmai injection (SMI) is a Chinese patent-protected injection, which was mainly made of Red Ginseng and Radix Ophiopogonis and widely used for treating coronary heart disease and tumors by boosting Qi and nourishing Yin. In this study we examined whether SMI could produce direct synergetic effects on the cytoxicity of adriamycin (ADR) and paclitaxel (PTX) in colorectal cancers in vivo and in vitro, and explored the underlying pharmacokinetic mechanisms. BALB/c nude mice with LoVo colon cancer xenografts were intraperitoneally injected with ADR (2 mg·kg−1·3d−1) or PTX (7.5 mg·kg−1·3d−1) with or without SMI (0.01 mL·g−1·d−1) for 13 d. Co-administration of SMI significantly enhanced the chemotherapeutic efficacy of ADR and PTX, whereas administration of SMI alone at the given dosage did not produce visible anti-cancer effects, The chemosensitizing action of SMI was associated with increased concentrations of ADR and PTX in the plasma and tumors. In Caco-2 and LoVo cells in vitro, co-treatment with SMI (2 μL/mL) significantly enhanced the cytotoxicity of ADR and PTX, and resulted in some favorable pharmacokinetic changes in the subcellular distribution of ADR and PTX. In addition, SMI-induced intracellular accumulation of ADR was closely correlated with the increased expression levels of P-glycoprotein in 4 colon cancer cell lines (r2=+0.8558). SMI enhances the anti-cancer effects of ADR and PTX in colon cancers in vivo and in vitro by improving the subcellular distributions of ADR and PTX. PMID:27867186

Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

PubMed

Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique

2014-12-01

This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.

Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors

PubMed Central

Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei

2017-01-01

Objective: To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Methods: Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. Results: The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s−1; p < 0.01). Conclusion: The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population. PMID:27928926

Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors.

PubMed

Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei; Zhang, Weiguo

2017-02-01

To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s -1 ; p < 0.01). The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population.

Characteristics of adverse drug reactions in a vemurafenib early post-marketing phase vigilance study in Japan.

PubMed

Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N

2018-02-01

Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.

Research on Simulation Requirements and Business Architecture of Automated Demand Response in Power Sales Side Market Liberalization

NASA Astrophysics Data System (ADS)

Liu, Yiqun; Zhou, Pengcheng; Zeng, Ming; Chen, Songsong

2018-01-01

With the gradual reform of the electricity market, the power sale side liberalization has become the focus of attention as the key task of reform. The open power market provides a good environment for DR (Demand Response). It is of great significance to research the simulation requirements and business architecture of ADR (Automatic Demand Response) in power sale side market liberalization. Firstly, this paper analyzes the simulation requirements of ADR. Secondly, it analyzes the influence factors that the business development of ADR from five aspects after power sale side market liberalization. Finally, Based on ADR technology support system, the business architecture of ADR after power sale side market liberalization is constructed.

Baseline characteristics and interim (3-month) efficacy and safety data from STELLA-LONG TERM, a long-term post-marketing surveillance study of ipragliflozin in Japanese patients with type 2 diabetes in real-world clinical practice.

PubMed

Maegawa, Hiroshi; Tobe, Kazuyuki; Tabuchi, Hiromi; Nakamura, Ichiro

2016-10-01

To evaluate the efficacy and safety of ipragliflozin in real-world clinical practice in Japanese patients with type 2 diabetes. We conducted interim analyses at 3 months of a 3-year prospective study of patients who were first prescribed ipragliflozin between 17 July 2014 and 16 October 2015, and whose data were locked by 16 January 2016. Changes in glycemic control, blood pressure, and laboratory variables from baseline, and incidence of adverse drug reactions (ADRs). Of 11,412 patients initially registered, efficacy and safety data were available for 3481 (30.5%) and 4360 (38.2%) patients, respectively. Hemoglobin A1c and fasting plasma glucose decreased by 0.67% and 28.8 mg/dL, respectively, at 3 months/last assessment (both P < .001) from baseline (8.00% and 166.4 mg/dL, respectively). Blood pressure and lipid levels also improved significantly. There were 258 ADRs in 194 patients. The ADRs included 'renal and urinary disorders' (system organ class) in 110 patients (2.5%). These 3-month interim results indicate that ipragliflozin improved glycemic control, lipids, and blood pressure with low rates of ADRs in Japanese patients with type 2 diabetes in real-world clinical practice. The results were consistent with those of placebo-controlled, randomized clinical trials. Clinicaltrials.gov identifier: NCT02479399.

10 CFR 1023.5 - Duties and responsibilities of the Chair.

Code of Federal Regulations, 2011 CFR

2011-01-01

... cases, including alternative dispute resolution (ADR) proceedings, to administrative judges, hearing...) Authorizing and approving ADR arrangements for Board cases; obtaining non-Board personnel to serve as...-provided personnel and facilities in ADR capacities, for matters before the Board, and for other matters...

25 CFR 42.4 - What are alternative dispute resolution processes?

Code of Federal Regulations, 2010 CFR

2010-04-01

... What are alternative dispute resolution processes? Alternative dispute resolution (ADR) processes are... action. (a) ADR processes may: (1) Include peer adjudication, mediation, and conciliation; and (2... that these practices are readily identifiable. (b) For further information on ADR processes and how to...

14 CFR 17.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Administrator of the Federal Aviation Administration. (e) Alternative Dispute Resolution (ADR) is the primary... issuance of a Contracting Officer final decision. Contract disputes for purposes of ADR only may also... communication or the use of ADR. The Default Adjudicative Process is conducted by a DRO or Special Master...

25 CFR 42.4 - What are alternative dispute resolution processes?

Code of Federal Regulations, 2011 CFR

2011-04-01

... What are alternative dispute resolution processes? Alternative dispute resolution (ADR) processes are... action. (a) ADR processes may: (1) Include peer adjudication, mediation, and conciliation; and (2... that these practices are readily identifiable. (b) For further information on ADR processes and how to...

10 CFR 1023.5 - Duties and responsibilities of the Chair.

Code of Federal Regulations, 2010 CFR

2010-01-01

... cases, including alternative dispute resolution (ADR) proceedings, to administrative judges, hearing...) Authorizing and approving ADR arrangements for Board cases; obtaining non-Board personnel to serve as...-provided personnel and facilities in ADR capacities, for matters before the Board, and for other matters...

Operating Modes and Cooling Capabilities of the 3-Stage ADR Developed for the Soft-X-ray Spectrometer Instrument on Astro-H

PubMed Central

Shirron, Peter J; Kimball, Mark O; James, Bryan L; Muench, Theo; DiPirro, Michael J; Letmate, Richard V; Sampson, Michael A; Bialas, Tom G; Sneiderman, Gary A; Porter, Frederick S; Kelley, Richard L

2017-01-01

A 3-stage adiabatic demagnetization refrigerator (ADR)[1] is used on the Soft X-ray Spectrometer instrument[2] on Astro-H[3] to cool a 6×6 array of x-ray microcalorimeters to 50 mK. The ADR is supported by a cryogenic system[4] consisting of a superfluid helium tank, a 4.5 K Joule-Thomson (JT) cryocooler, and additional 2-stage Stirling cryocoolers that pre-cool the JT cooler and cool radiation shields within the cryostat. The ADR is configured so that it can use either the liquid helium or the JT cryocooler as its heat sink, giving the instrument an unusual degree of tolerance for component failures or degradation in the cryogenic system. The flight detector assembly, ADR and dewar were integrated into the flight dewar in early 2014, and have since been extensively characterized and calibrated. This paper summarizes the operation and performance of the ADR in all of its operating modes. PMID:28111478

Operating Modes and Cooling Capabilities of the 3-Stage ADR Developed for the Soft-X-ray Spectrometer Instrument on Astro-H.

PubMed

Shirron, Peter J; Kimball, Mark O; James, Bryan L; Muench, Theo; DiPirro, Michael J; Letmate, Richard V; Sampson, Michael A; Bialas, Tom G; Sneiderman, Gary A; Porter, Frederick S; Kelley, Richard L

2016-03-01

A 3-stage adiabatic demagnetization refrigerator (ADR)[1] is used on the Soft X-ray Spectrometer instrument[2] on Astro-H[3] to cool a 6×6 array of x-ray microcalorimeters to 50 mK. The ADR is supported by a cryogenic system[4] consisting of a superfluid helium tank, a 4.5 K Joule-Thomson (JT) cryocooler, and additional 2-stage Stirling cryocoolers that pre-cool the JT cooler and cool radiation shields within the cryostat. The ADR is configured so that it can use either the liquid helium or the JT cryocooler as its heat sink, giving the instrument an unusual degree of tolerance for component failures or degradation in the cryogenic system. The flight detector assembly, ADR and dewar were integrated into the flight dewar in early 2014, and have since been extensively characterized and calibrated. This paper summarizes the operation and performance of the ADR in all of its operating modes.

Operating Modes and Cooling Capabilities of the 3-Stage ADR Developed for the Soft-X-Ray Spectrometer Instrument on Astro-H

NASA Technical Reports Server (NTRS)

Shirron, Peter J.; Kimball, Mark O.; James, Bryan L.; Muench, Theo; DiPirro, Michael J.; Letmate, Richard V.; Sampson, Michael A.; Bialas, Tom G.; Sneiderman, Gary A.; Porter, Frederick S.;

Thermodynamic performance of the 3-stage ADR for the Astro-H Soft-X-ray Spectrometer instrument

NASA Astrophysics Data System (ADS)

Shirron, Peter J.; Kimball, Mark O.; James, Bryan L.; Muench, Theodore; DiPirro, Michael J.; Bialas, Thomas G.; Sneiderman, Gary A.; Porter, Frederick S.; Kelley, Richard L.

2016-03-01

The Soft X-ray Spectrometer (SXS) instrument (Mitsuda et al., 2010) [1] on Astro-H (Takahashi et al., 2010) [2] will use a 3-stage ADR (Shirron et al., 2012) to cool the microcalorimeter array to 50 mK. In the primary operating mode, two stages of the ADR cool the detectors using superfluid helium at ⩽1.20 K as the heat sink (Fujimoto et al., 2010). In the secondary mode, which is activated when the liquid helium is depleted, the ADR uses a 4.5 K Joule-Thomson cooler as its heat sink. In this mode, all three stages operate together to continuously cool the (empty) helium tank and single-shot cool the detectors. The flight instrument - dewar, ADR, detectors and electronics - were integrated in 2014 and have since undergone extensive performance testing. This paper presents a thermodynamic analysis of the ADR's operation, including cooling capacity, heat rejection to the heat sinks, and various measures of efficiency.

Adverse drug reactions: classification, susceptibility and reporting.

PubMed

Kaufman, Gerri

2016-08-10

Adverse drug reactions (ADRs) are increasingly common and are a significant cause of morbidity and mortality. Historically, ADRs have been classified as type A or type B. Type A reactions are predictable from the known pharmacology of a drug and are associated with high morbidity and low mortality. Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. These include type C (continuing), type D (delayed use), and type E (end of use) reactions. Susceptibility to ADRs is influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy. Drug safety is reliant on nurses and other healthcare professionals being alert to the possibility of ADRs, working with patients to optimise medicine use and exercising vigilance in the reporting of ADRs through the Yellow Card Scheme.

Analysis of the adverse reactions induced by natural product-derived drugs

PubMed Central

Zeng, Zhi-Ping; Jiang, Jian-Guo

2010-01-01

Compared with the therapeutic effects of established medicinal drugs, it is often considered that natural product-derived drugs are of a more benign nature in side-effects, which has made natural medicines become a popular form of therapy. Traditional Chinese medicine (TCM) is generally considered as being natural and harmless. TCM has been paid much more attention than before and widely used for the treatment nowadays. However, with the increasing cases of adverse drug reactions (ADRs), the ADRs induced by TCM are becoming more widely recognized. Some ADRs are sometimes even life-threatening. This article reviews literatures on ADRs induced by TCM which was published in the past 10 years. A total of 3122 cases including complete data are selected for the present analysis. From the data of the 3122 cases, statistics is carried out to the distribution of administration routes and time of the occurrence of ADRs, the prognosis of ADRs, sex and age factors, types and clinical symptoms of ADRs, and drugs involved in ADRs. In addition, occurrence and influencing factors of TCM-induced diseases are also analysed, which includes spices confusion, processing drugs improperly, toxic components, long-term medication, improper concerted application, interaction of TCM and Western medicine. It is concluded that the efficacy and toxicity of TCM, often using the compound prescription involving various plants and animals, resulted from a variety of chemical constituents, which lead to a comprehensive response in the human body. The ‘toxicity’ of TCM should be correctly recognized and reasonably utilized. PMID:20233209

[High activity antiretroviral therapy change associated to adverse drug reactions in a specialized center in Venezuela].

PubMed

Subiela, José D; Dapena, Elida

2016-03-01

Adverse drug reactions (ADRs) represent the first cause of change of the first-line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08±0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela.

Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis

PubMed Central

Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

2012-01-01

Background: Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results: Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Conclusions: Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region. PMID:23826016

Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions.

PubMed

Clarke, John D; Cherrington, Nathan J

2012-03-01

Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic factors include single nucleotide polymorphisms (SNPs) that change OATP activity and epigenetic regulation that modify OATP expression levels. SNPs in OATPs contribute to ADRs. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver diseases such as non-alcoholic fatty liver disease, cholestasis and hepatocellular carcinoma change the expression of multiple OATP isoforms. The role of liver diseases in the occurrence of ADRs is unknown. This article covers the roles OATPs play in ADRs when considered in the context of genetic or environmental factors. The reader will gain a greater appreciation for the current evidence regarding the salience and importance of each factor in OATP-mediated ADRs. A SNP in a single OATP transporter can cause changes in drug pharmacokinetics and contribute to ADRs but, because of overlap in substrate specificities, there is potential for compensatory transport by other OATP isoforms. By contrast, the expression of multiple OATP isoforms is decreased in liver diseases, reducing compensatory transport and thereby increasing the probability of ADRs. To date, most research has focused on the genetic factors in OATP-mediated ADRs while the impact of environmental factors has largely been ignored.

The predisposing factors for the heterotopic ossification after cervical artificial disc replacement.

PubMed

Yi, Seong; Shin, Dong Ah; Kim, Keung Nyun; Choi, Gwihyun; Shin, Hyun Chul; Kim, Keun Su; Yoon, Do Heum

2013-09-01

Heterotopic ossification (HO) is defined as a formation of bone outside the skeletal system. The reported HO occurrence rate in cervical artificial disc replacement (ADR) is unexpectedly high and is known to vary. However, the predisposing factors for HO in cervical ADR have not yet been elucidated. Investigation of the predisposing factors of HO in cervical arthroplasty and the relationship between degeneration of the cervical spine and HO occurrence. Retrospective study to discover predisposing factors of HO in cervical arthroplasty. A total of 170 patients who underwent cervical ADR were enrolled including full follow-up clinical and radiologic data. Radiologic outcomes were assessed by identification of HOs according to McAfee's classifications. This study enrolled a total of 170 patients who underwent cervical ADR. Pre-existing degenerative change included anterior or posterior osteophytes, ossification of the anterior longitudinal ligament, posterior longitudinal ligament, or ligamentum nuchae. The relationships between basic patient data, pre-existing degenerative change, and HO were investigated using linear logistic regression analysis. Among all 170 patients, HO was found in 69 patients (40.6%). Among the postulated predisposing factors, only male gender and artificial disc device type were shown to be statistically significant. Unexpectedly, preoperative degenerative changes in the cervical spine exerted no significant influence on the occurrence of HOs. The odds ratio of male gender compared with female gender was 2.117. With regard to device type, the odds ratios of Mobi-C (LDR medical, Troyes, France) and ProDisc-C (Synthes, Inc., West Chester, PA, USA) were 5.262 and 7.449, respectively, compared with the Bryan disc. Definite differences in occurrence rate according to the gender of patients and the prosthesis type were identified in this study. Moreover, factors indefinably expected to influence HO in the past were not shown to be risk factors thereof, the results of which may be meaningful to future studies. Copyright © 2013 Elsevier Inc. All rights reserved.

24 CFR 7.16 - Responsibilities of employees.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Department's EEO/ADR programs; (b) Adopting an attitude of full acceptance and respect for minorities... support for and participation in ADR; (c) Providing equality of treatment and service to all persons with... supervisors and managers in carrying out their responsibilities in the EEO/ADR programs; and (e) Cooperating...

76 FR 55136 - Implementation of the Alternative Dispute Resolution Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-06

... the NRC's ADR program. The ADR program is comprised of two entirely different sub- programs; the first... tends to preserve relationships and generally promotes a safety conscious work environment by... litigation and unnecessary expenses. The second sub-program (commonly referred to as ``Post-Investigation ADR...

48 CFR 852.233-70 - Protest content/alternative dispute resolution.

Code of Federal Regulations, 2011 CFR

2011-10-01

... encouraged to use alternative dispute resolution (ADR) procedures to resolve protests at any stage in the protest process. If ADR is used, the Department of Veterans Affairs will not furnish any documentation in an ADR proceeding beyond what is allowed by the Federal Acquisition Regulation. (End of provision) ...

48 CFR 33.204 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... Agencies are encouraged to use ADR procedures to the maximum extent practicable. Certain factors, however, may make the use of ADR inappropriate (see 5 U.S.C. 572(b)). Except for arbitration conducted pursuant... which is separate from that provided by the ADRA to use ADR procedures to resolve issues in controversy...

4 CFR 22.24 - Alternative Dispute Resolution [Rule 24].

Code of Federal Regulations, 2010 CFR

2010-01-01

...) Docketed appeals. The Board considers Alternative Dispute Resolution (ADR) to be an efficient way to timely resolve many contract disputes, and therefore encourages the parties to use ADR as an effective means to resolve their contract dispute. ADR with Board participation is available at the initiative of the Board...

48 CFR 33.204 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... Agencies are encouraged to use ADR procedures to the maximum extent practicable. Certain factors, however, may make the use of ADR inappropriate (see 5 U.S.C. 572(b)). Except for arbitration conducted pursuant... which is separate from that provided by the ADRA to use ADR procedures to resolve issues in controversy...

48 CFR 852.233-70 - Protest content/alternative dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-10-01

... encouraged to use alternative dispute resolution (ADR) procedures to resolve protests at any stage in the protest process. If ADR is used, the Department of Veterans Affairs will not furnish any documentation in an ADR proceeding beyond what is allowed by the Federal Acquisition Regulation. (End of provision) ...

24 CFR 7.5 - EEO Alternative Dispute Resolution Program.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Statement regarding Alternative Dispute Resolution (ADR) located on the Department's website and 29 CFR 1614.102(b)(2), the Department shall establish and maintain an ADR program that addresses, at a minimum, EEO matters at the pre-complaint and formal complaint stages of the EEO process. ADR is a non...

4 CFR 22.24 - Alternative Dispute Resolution [Rule 24].

Code of Federal Regulations, 2011 CFR

2011-01-01

...) Docketed appeals. The Board considers Alternative Dispute Resolution (ADR) to be an efficient way to timely resolve many contract disputes, and therefore encourages the parties to use ADR as an effective means to resolve their contract dispute. ADR with Board participation is available at the initiative of the Board...

Final Summary of On-Orbit ADR Operation on Hitomis Soft X-Ray Spectrometer Instrument

NASA Technical Reports Server (NTRS)

Shirron, Peter

2016-01-01

The Soft X-ray Spectrometer (SXS) on the Astro-H observatory contains a 6x6 array of x-ray microcalorimeters that are cooled to 50 mK by an adiabatic demagnetization refrigerator (ADR). The ADR consists of three stages in order to provide stable detector cooling using either a 1.2 K superfluid helium bath or a 4.5 K Joule-Thomson (JT) cryocooler as its heat sink. Astro-H was renamed Hitomi after it was successfully launched in February 2016. The SXS carried approximately 36 liters of helium into orbit, and by day 5 the helium had cooled sufficiently (1.4 K) to allow operation of the ADR. This paper summarizes the ADRs performance during the 38 days that the satellite was operational.

A Parametric Study on Using Active Debris Removal to Stabilize the Future LEO Debris Environment

NASA Technical Reports Server (NTRS)

Liou, J.C.

2010-01-01

Recent analyses of the instability of the orbital debris population in the low Earth orbit (LEO) region and the collision between Iridium 33 and Cosmos 2251 have reignited the interest in using active debris removal (ADR) to remediate the environment. There are; however, monumental technical, resources, operational, legal, and political challenges in making economically viable ADR a reality. Before a consensus on the need for ADR can be reached, a careful analysis of the effectiveness of ADR must be conducted. The goal is to demonstrate the feasibility of using ADR to preserve the future environment and to guide its implementation to maximize the benefit-cost ratio. This paper describes a comprehensive sensitivity study on using ADR to stabilize the future LEO debris environment. The NASA long-term, orbital debris evolutionary model, LEGEND, is used to quantify the effects of many key parameters. These parameters include (1) the starting epoch of ADR implementation, (2) various target selection criteria, (3) the benefits of collision avoidance maneuvers, (4) the consequence of targeting specific inclination or altitude regimes, (5) the consequence of targeting specific classes of vehicles, and (6) the timescale of removal. Additional analyses on the importance of postmission disposal and how future launches might affect the requirements to stabilize the environment are also included.

Adverse drug reactions in children: a ten-year review of reporting to the Portuguese Pharmacovigilance System.

PubMed

Nogueira Guerra, Leonor; Herdeiro, Maria Teresa; Ribeiro-Vaz, Inês; Clérigo, Maria Inês Pinto; Rocha, Cristina; Araújo, Ana; Pêgo, Alexandra; Rebelo Gomes, Eva

2015-01-01

Adverse drug reactions (ADR) are a public health problem. They cause significant morbidity, mortality and health costs. Less is known about pediatric ADR. Our goal was to characterize a pediatric case series of ADR reported to the Portuguese Pharmacovigilance System (PPS) during the past 10 years. Retrospective analysis of ADR reports concerning patients till 17 years old received by the PPS between 2003 and 2012. We evaluated patients' demographic data and involved drugs, as well as characteristics and seriousness of reactions, stratified by age groups. We found 1742 reports (50% females) corresponding to 9.7% of the total received. The age of the patients varied from 0 to 17 years (median: 5 years, interquartile range: 10.6), with 566 cases (32%) occurring in patients younger than 2y. Among the 1195 serious cases, 31% (370) episodes led to hospitalization. In 32 cases (2%) there was a fatal outcome. Most of the ADR reported referred to general disorders and administration site conditions, followed by skin and subcutaneous tissue reactions. Vaccines were the most represented group (42%) followed by antibacterials for systemic use (17%). Pediatric ADR represents about 10% of the reports received by the PPS. Most ADR were considered serious. Major findings varied according to age groups.

The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

PubMed

Carnovale, Carla; Brusadelli, Tatiana; Zuccotti, GianVincenzo; Beretta, Silvia; Sullo, Maria Giuseppa; Capuano, Annalisa; Rossi, Francesco; Moschini, Martina; Mugelli, Alessandro; Vannacci, Alfredo; Laterza, Marcella; Clementi, Emilio; Radice, Sonia

2014-09-01

To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

Safety of Intravenous Application of Mistletoe (Viscum album L.) Preparations in Oncology: An Observational Study

PubMed Central

Steele, Megan L.; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2014-01-01

Background. Traditional mistletoe therapy in cancer patients involves subcutaneous applications of Viscum album L. preparations, with doses slowly increasing based on patient responses. Intravenous infusion of high doses may improve therapeutic outcomes and is becoming more common. Little is known about the safety of this “off-label” application of mistletoe. Methods. An observational study was performed within the Network Oncology. Treatment with intravenous mistletoe applications is described. The frequency of adverse drug reactions (ADRs) to intravenous mistletoe applications was calculated and compared to ADR data from a study on subcutaneous applications. Results. Of 475 cancer patients who received intravenous infusions of Helixor, Abnoba viscum, or Iscador mistletoe preparations, 22 patients (4.6%) reported 32 ADRs of mild (59.4%) or moderate severity (40.6%). No serious ADRs occurred. ADRs were more frequently reported to i.v. mistletoe administered alone (4.3%), versus prior to chemotherapy (1.6%). ADR frequency differed with respect to preparation type, with Iscador preparations showing a higher relative frequency, compared to Abnoba viscum and Helixor. Overall, patients were almost two times less likely to experience an ADR to intravenous compared to subcutaneous application of mistletoe. Conclusion. Intravenous mistletoe therapy was found to be safe and prospective studies for efficacy are recommended. PMID:24955100

Suspected adverse reactions to contrast media in Campania Region (Italy): results from 14 years of post-marketing surveillance.

PubMed

Sessa, Maurizio; Rossi, Claudia; Mascolo, Annamaria; Grassi, Enrico; Fiorentino, Sonia; Scavone, Cristina; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

2015-01-01

During the last years in Italy, contrast media (CM) use increased. An increase of monitoring activities on CM-induced adverse drug reaction (ADR) is necessary, also in our regional territory. The main aim of this study was to give a preliminary evaluation of all Spontaneous Reports of ADRs (SRA) attributed to CM sent to Campania Pharmacovigilance Regional Center (CRFVC) from 01 January 2001 to 31 October 2014. For each SRA we evaluated: frequency and source, ADRs onset (time to event, seriousness and outcome), socio-demographic characteristics and risk factors of cases, the most reported CM (checking for pharmacodynamic and pharmacokinetic interactions). A total of 111 SRA were sent to CRFVC; specialist in radiology was the main source of reports. Ninety-seven SRA (87.3%) were referable to hypersensitivity reactions. Thirty-four SRA (30.6%) reported serious ADRs. The most reported CM were iopamidol, gadobenic acid and gadoteric acid. We identified two SRA induced by pharmacokinetic and/or pharmacodynamic interactions. During 14 years of post-marketing surveillance, only few SRA concerning CM-induced ADRs were sent to CRFVC probably due to underreporting. We aim to improve monitoring activity on CM-induced ADRs especially in hospitals. Most reported ADR and CM were in line with current body of literature.

Comparison of hybrid constructs with 2-level artificial disc replacement and 2-level anterior cervical discectomy and fusion for surgical reconstruction of the cervical spine: a kinematic study in whole cadavers.

PubMed

Liu, Baoge; Zeng, Zheng; Hoof, Tom Van; Kalala, Jean Pierre; Liu, Zhenyu; Wu, Bingxuan

2015-04-08

Multi-level cervical degeneration of the spine is a common clinical pathology that is often repaired by anterior cervical discectomy and fusion (ACDF). The aim of this study was to investigate the kinematics of the cervical spine after hybrid surgery compared with 2-level ACDF. Five freshly frozen, unembalmed whole human cadavers were used including 3 males and 2 females with a mean age of 51 ± 8 years. After evaluating the intact spine for range of motion (ROM), sagittal alignment and instantaneous center of rotation (ICR), each cadaver underwent 4 consecutive surgeries: 2-level artificial disc replacement (ADR) from C4 to C6 (ADR surgery); 2-level ACDF from C4 to C6 (ACDF surgery); hybrid C4-5 ACDF and C5-6 ADR (ACDF+ADR surgery); and hybrid C4-5 ADR and C5-6 ACDF (ADR+ACDF surgery). The ROM and ICR of adjacent intact segments (C3-4; C6-7), and whole sagittal alignment were revaluated. Two-level ACDF resulted in increased ROM at C3-4 and C6-7 compared with intact spine. ROM was significantly different to intact spine using ACDF surgery at C3-C4 and C6-C7 and ROM was increased with ACDF+ADR surgery at C6-C7 (all P<0.05). No improvement in sagittal alignment was observed with any approach. The localization of the ICR shifted upwards and anteriorly at C3-C4 after reconstruction. ICR changes at C3-C4 were greatest for ADR+ACDF surgery and were significantly different to ACDF surgery (P<0.05), but not between ADR surgery and ACDF+ADR surgery. At C6-C7, the ICR was more posterior and superior than in the intact condition. The greatest change in ICR was observed in ACDF surgery at the C6-C7 level, significantly different from the other groups (P<0.05). For 2-level reconstruction, hybrid surgery and ADR did not alter ROM and minimally changed ICR at the adjacent-level. The type of surgery had a significant impact on the ICR location. This suggests that hybrid surgery may be a viable option for 2-level cervical surgery.

Methodological approaches to developing and establishing the body of evidence on post-marketing Chinese medicine safety.

PubMed

Liao, Xing; Robinson, Nicola

2013-07-01

Evidence based medicine demands the highest form of scientific evidence to demonstrate the efficacy and clinical effectiveness for any therapeutic intervention in order to provide best care. It is however accepted that in the absence of scientific evidence, personal experience and expert opinion together with professional judgement are critical. Obtaining evidence for drug safety, postmarketing surveillance (PMS) has focussed on follow up of observational cohorts exposed to a particular drug in order to estimate the incidence of adverse drug reactions (ADRs). Evidence on PMS of Chinese herbal products is still limited, in particular for herbal injections. The aim of this article is to suggest a new model of ascertaining the safety of Chinese medicine using a more comprehensive approach for collecting data. To collect safety data on the Chinese herbal injection, Kudiezi, a mixed methods approach is proposed using 18 hospital information systems to detect ADRs in order to prospectively observe 30,000 patients over 3 years. Evidence will also be collected using a questionnaire survey and through a sample of semi structured interviews. This information based on the expert opinion and the experience of clinicians will produce additional data on the frequency and types of side effects in clinical practice. Furthermore semi structured interviews with a random sample of patients receiving the injection will be carried out to ascertain any potential side effects missed. It is hoped that this comprehensive approach to data collection will accumulate wider evidence based on individual traditional Chinese medicine care and treatment and provide important feedback to the national data collection system to ensure completeness of ADR data recording, monitoring and any potential wider effects through developing improved ADR guidelines.

A prediction model-based algorithm for computer-assisted database screening of adverse drug reactions in the Netherlands.

PubMed

Scholl, Joep H G; van Hunsel, Florence P A M; Hak, Eelko; van Puijenbroek, Eugène P

2018-02-01

The statistical screening of pharmacovigilance databases containing spontaneously reported adverse drug reactions (ADRs) is mainly based on disproportionality analysis. The aim of this study was to improve the efficiency of full database screening using a prediction model-based approach. A logistic regression-based prediction model containing 5 candidate predictors was developed and internally validated using the Summary of Product Characteristics as the gold standard for the outcome. All drug-ADR associations, with the exception of those related to vaccines, with a minimum of 3 reports formed the training data for the model. Performance was based on the area under the receiver operating characteristic curve (AUC). Results were compared with the current method of database screening based on the number of previously analyzed associations. A total of 25 026 unique drug-ADR associations formed the training data for the model. The final model contained all 5 candidate predictors (number of reports, disproportionality, reports from healthcare professionals, reports from marketing authorization holders, Naranjo score). The AUC for the full model was 0.740 (95% CI; 0.734-0.747). The internal validity was good based on the calibration curve and bootstrapping analysis (AUC after bootstrapping = 0.739). Compared with the old method, the AUC increased from 0.649 to 0.740, and the proportion of potential signals increased by approximately 50% (from 12.3% to 19.4%). A prediction model-based approach can be a useful tool to create priority-based listings for signal detection in databases consisting of spontaneous ADRs. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

Active pharmacovigilance in China: recent development and future perspectives.

PubMed

Li, Xinling; Li, Haona; Deng, Jianxiong; Zhu, Feng; Liu, Ying; Chen, Wenge; Yue, Zhihua; Ren, Xuequn; Xia, Jielai

2018-04-10

The effectiveness of active pharmacovigilance depends on the specific methods adopted and the work patterns put into place. Over the past few years, much attention has been paid to the importance of implementing such systems in China. However, less has been done to evaluate the state of implementation and future needs of such systems. This paper reviews China's recent approaches to active pharmacovigilance by examining: (1) information collected from scientific articles and the websites of the China Food and Drug Administration and the China National Center for Adverse Drug Reaction Monitoring, (2) information available on China's spontaneous reporting systems (SRS) and active pharmacovigilance system, and (3) annual reports and internal reports on this subject. Areas that improved most meaningfully for China's active pharmacovigilance in recent years appear to include: (1) quicker reporting and more intelligent scanning methods for adverse drug reactions (ADRs), (2) the use of pharmacovigilance approaches to mine electronic hospital records, and (3) the development of integrated systems including the China Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program. Not only has the national online SRS system provided a platform for passive pharmacovigilance, it has also become an important platform for various explorations of active pharmacovigilance in China. Quick reporting and intelligent scanning of ADRs, facilitated by automated ADR detection based on electronic hospital records, have accelerated to capabilities for active pharmacovigilance. The outcomes of the programs, such as the China Hospital Pharmacovigilance System and China Sentinel Hospital Alliance Program, usher in a new era for China's active pharmacovigilance. These are particularly important to bridge the information system of sentinel hospitals and ADR research centers, but gaps remain. Thus, much work needs to be done before a high-level active pharmacovigilance system is sufficiently mature to ensure drug safety in the country.

The anti-doping hot-line, a means to capture the abuse of doping agents in the Swedish society and a new service function in clinical pharmacology.

PubMed

Eklöf, Ann-Charlotte; Thurelius, Ann-Mari; Garle, Mats; Rane, Anders; Sjöqvist, Folke

2003-11-01

With the support of the Swedish National Institute of Health a national information service was started in 1993 aiming to capture the abuse of doping agents in the general public. It was organized as a telephone service, called the Anti-Doping Hot-Line, from our department and managed by trained nurses co-operating with clinical pharmacologists. Important information collected about all callers (anonymous) was: date of call, its origin, category of caller, doping experience and main question being asked. Abusers were asked about their age, sex, affiliation, abused drug(s), duration of abuse, habit of administration and adverse reactions (ADRs). Between October 1993 and December 2000 25,835 calls were received with a peak during spring and autumn. Most calls (12,400) came from non-abusers, 60% being males. Callers connected with gyms represented the largest group (30%). Most calls about specific drugs concerned anabolic androgenic steroids (AAS). Other drugs or products included ephedrine, clenbuterol and creatine. The most commonly abused anabolic steroids were testosterone, nandrolone-decanoate, methandienone and stanozolol. The ten most commonly reported ADRs of AAS were aggressiveness (835), depression (829), acne (770), gynecomastia (637), anxiousness (637), potency problems (413), testicular atrophy (404), sleep disorders (328), fluid retention (318) and mood disturbances (302). Female side effects included menstruation disturbances, hair growth in the face, lower voice and enlarged clitoris. During the period 1996-200, totally 4339 persons reported about 10,800 side effects. This figure should be compared with the very low number of ADRs (27) reported by prescribers to the Swedish ADR committee during the same period. Abuse of doping agents appears to be a new public health problem that needs detection, medical care and prevention.

Influence of Observed Diurnal Cycles of Aerosol Optical Depth on Aerosol Direct Radiative Effect

NASA Technical Reports Server (NTRS)

Arola, A.; Eck, T. F.; Huttunen, J.; Lehtinen, K. E. J.; Lindfors, A. V.; Myhre, G.; Smirinov, A.; Tripathi, S. N.; Yu, H.

2013-01-01

The diurnal variability of aerosol optical depth (AOD) can be significant, depending on location and dominant aerosol type. However, these diurnal cycles have rarely been taken into account in measurement-based estimates of aerosol direct radiative forcing (ADRF) or aerosol direct radiative effect (ADRE). The objective of our study was to estimate the influence of diurnal aerosol variability at the top of the atmosphere ADRE estimates. By including all the possible AERONET sites, we wanted to assess the influence on global ADRE estimates. While focusing also in more detail on some selected sites of strongest impact, our goal was to also see the possible impact regionally.We calculated ADRE with different assumptions about the daily AOD variability: taking the observed daily AOD cycle into account and assuming diurnally constant AOD. Moreover, we estimated the corresponding differences in ADREs, if the single AOD value for the daily mean was taken from the the Moderate Resolution Imaging Spectroradiometer (MODIS) Terra or Aqua overpass times, instead of accounting for the true observed daily variability. The mean impact of diurnal AOD variability on 24 h ADRE estimates, averaged over all AERONET sites, was rather small and it was relatively small even for the cases when AOD was chosen to correspond to the Terra or Aqua overpass time. This was true on average over all AERONET sites, while clearly there can be much stronger impact in individual sites. Examples of some selected sites demonstrated that the strongest observed AOD variability (the strongest morning afternoon contrast) does not typically result in a significant impact on 24 h ADRE. In those cases, the morning and afternoon AOD patterns are opposite and thus the impact on 24 h ADRE, when integrated over all solar zenith angles, is reduced. The most significant effect on daily ADRE was induced by AOD cycles with either maximum or minimum AOD close to local noon. In these cases, the impact on 24 h ADRE was typically around 0.1-0.2W/sq m (both positive and negative) in absolute values, 5-10% in relative ones.

Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients (The PADR-EC Score)

PubMed Central

Parameswaran Nair, Nibu; Chalmers, Leanne; Connolly, Michael; Bereznicki, Bonnie J.; Peterson, Gregory M.; Curtain, Colin; Castelino, Ronald L.; Bereznicki, Luke R.

2016-01-01

Background Adverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged ≥65 years. Methods ADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged ≥65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively. Results In the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65–0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients’ admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56–0.78). Conclusions This study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in clinical practice. PMID:27798708

Clinicians' Reports in Electronic Health Records Versus Patients' Concerns in Social Media: A Pilot Study of Adverse Drug Reactions of Aspirin and Atorvastatin.

PubMed

Topaz, Maxim; Lai, Kenneth; Dhopeshwarkar, Neil; Seger, Diane L; Sa'adon, Roee; Goss, Foster; Rozenblum, Ronen; Zhou, Li

2016-03-01

Large databases of clinician reported (e.g., allergy repositories) and patient reported (e.g., social media) adverse drug reactions (ADRs) exist; however, whether patients and clinicians report the same concerns is not clear. Our objective was to compare electronic health record data and social media data to better understand differences and similarities between clinician-reported ADRs and patients' concerns regarding aspirin and atorvastatin. This pilot study explored a large repository of electronic health record data and social media data for clinician-reported ADRs and patients concerns for two common medications: aspirin (n = 31,817 ADRs accessible in clinical data; n = 19,186 potential ADRs accessible in social media data) and atorvastatin (n = 15,047 ADRs accessible in clinical data; n = 23,408 potential ADRs accessible in social media data). We found that the most frequently reported ADRs matched the most frequent patients' concerns. However, several less frequently reported reactions were more prevalent on social media (i.e., aspirin-induced hypoglycemia was discussed only on social media). Overall, we found a relatively strong positive and statistically significant correlation between the frequency ranking of reactions and patients' concerns for atorvastatin (Pearson's r = 0.61, p < 0.001) but not for aspirin (Pearson's r = 0.1, p = 0.69). Future studies should develop further natural language methods for a more detailed data analysis (i.e., identifying causality and temporal aspects in the social media data).

C. elegans ADARs antagonize silencing of cellular dsRNAs by the antiviral RNAi pathway.

PubMed

Reich, Daniel P; Tyc, Katarzyna M; Bass, Brenda L

2018-02-01

Cellular dsRNAs are edited by adenosine deaminases that act on RNA (ADARs). While editing can alter mRNA-coding potential, most editing occurs in noncoding sequences, the function of which is poorly understood. Using dsRNA immunoprecipitation (dsRIP) and RNA sequencing (RNA-seq), we identified 1523 regions of clustered A-to-I editing, termed editing-enriched regions (EERs), in four stages of Caenorhabditis elegans development, often with highest expression in embryos. Analyses of small RNA-seq data revealed 22- to 23-nucleotide (nt) siRNAs, reminiscent of viral siRNAs, that mapped to EERs and were abundant in adr-1;adr-2 mutant animals. Consistent with roles for these siRNAs in silencing, EER-associated genes (EAGs) were down-regulated in adr-1;adr-2 embryos, and this was dependent on associated EERs and the RNAi factor RDE-4. We observed that ADARs genetically interact with the 26G endogenous siRNA (endo-siRNA) pathway, which likely competes for RNAi components; deletion of factors required for this pathway ( rrf-3 or ergo-1 ) in adr-1;adr-2 mutant strains caused a synthetic phenotype that was rescued by deleting antiviral RNAi factors. Poly(A) + RNA-seq revealed EAG down-regulation and antiviral gene induction in adr-1;adr-2;rrf-3 embryos, and these expression changes were dependent on rde-1 and rde-4 Our data suggest that ADARs restrict antiviral silencing of cellular dsRNAs. © 2018 Reich et al.; Published by Cold Spring Harbor Laboratory Press.

Design of a 3-Stage ADR for the Soft X-Ray Spectrometer Instrument on the Astro-H Mission

NASA Technical Reports Server (NTRS)

Shirron, Peter J.; Kimball, Mark O.; Wegel, Donald C.; Canavan, Edgar R.; DiPirro, Michael J.

2011-01-01

The Japanese Astro-H mission will include the Soft X-ray Spectrometer (SXS) instrument, whose 36-pixel detector array of ultra-sensitive x-ray microcalorimeters requires cooling to 50 mK. This will be accomplished using a 3-stage adiabatic demagnetization refrigerator (ADR). The design is dictated by the need to operate with full redundancy with both a superfluid helium dewar at 1.3 K or below, and with a 4.5 K Joule-Thomson (JT) cooler. The ADR is configured as a 2-stage unit that is located in a well in the helium tank, and a third stage that is mounted to the top of the helium tank. The third stage is directly connected through two heat switches to the JT cooler and the helium tank, and manages heat flow between the two. When liquid helium is present, the 2-stage ADR operates in a single-shot manner using the superfluid helium as a heat sink. The third stage may be used independently to reduce the time-average heat load on the liquid to extend its lifetime. When the liquid is depleted, the 2nd and 3rd stages operate as a continuous ADR to maintain the helium tank at as low a temperature as possible - expected to be 1.2 K - and the 1st stage cools from that temperature as a single-stage, single-shot ADR. The ADR s design and operating modes are discussed, along with test results of the prototype 3-stage ADR.

Enhanced antitumor efficacy on hepatoma-bearing rats with adriamycin-loaded nanoparticles administered into hepatic artery.

PubMed

Chen, Jiang-Hao; Ling, Rui; Yao, Qing; Wang, Ling; Ma, Zhong; Li, Yu; Wang, Zhe; Xu, Hu

2004-07-01

To investigate the antitumor activity of adriamycin (ADR) encapsulated in nanoparticles (NADR) and injected into the hepatic artery of hepatoma-bearing rats. NADR was prepared by the interfacial polymerization method. Walker-256 carcinosarcomas were surgically implanted into the left liver lobes of 60 male Wistar rats, which were divided into 4 groups at random (15 rats per group). On the 7th day after implantation, normal saline (NS), free ADR (FADR), NADR, or ADR mixed with unloaded nanoparticles (ADR+NP) was respectively injected via the hepatic artery (i.a.) of rats in different groups. The dose of ADR in each formulation was 2.0 mg/kg body weight and the concentration was 1.0 mg/mL. Survival time, tumor enlargement ratio, and tumor necrosis degree were compared between each group. Compared with the rats that received NS i.a., the rats that received FADR or ADR+NP acquired apparent inhibition on tumor growth, as well as prolonged their life span. Further significant anticancer efficacy was observed in rats that received i.a. administration of NADR. Statistics indicated that NADR brought on a more significant tumor inhibition and more extensive tumor necrosis, as compared to FADR or ADR+NP. The mean tumor enlargement ratio on the 7th day after NADR i.a. was 1.106. The mean tumor-bearing survival time was 39.50 days. Prolonged life span ratio was 109.22% as compared with rats that accepted NS. Therapeutic effect of ADR on liver malignancy can be significantly enhanced by its nanopaticle formulation and administration via hepatic artery.

14 CFR 17.17 - Initial protest procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... protected information and the issuance of any needed protective order; (4) Encourage the parties to use ADR... Resolution for Acquisition— (1) A joint statement that they have decided to pursue ADR proceedings in lieu of adjudication in order to resolve the protest; or (2) Joint or separate written explanations as to why ADR...

14 CFR 17.17 - Initial protest procedures.

Code of Federal Regulations, 2011 CFR

2011-01-01

... protected information and the issuance of any needed protective order; (4) Encourage the parties to use ADR... Resolution for Acquisition— (1) A joint statement that they have decided to pursue ADR proceedings in lieu of adjudication in order to resolve the protest; or (2) Joint or separate written explanations as to why ADR...

Alternative Dispute Resolution (ADR): A Different Framework for Conflict Resolution in Educational Settings.

ERIC Educational Resources Information Center

Turan, Selahattin; Taylor, Charles

This paper briefly introduces alternative dispute resolution (ADR) processes and their fundamental principles. The paper provides a review of the literature on ADR and discusses its applicability in educational settings. The concept of conflict is explained, along with analysis of the limitations of traditional conflict resolution processes. The…

Operating Modes and Cooling Capabilities of the Flight ADR for the SXS Instrument on Astro-H

NASA Technical Reports Server (NTRS)

Shirron, Peter; Kimball, Mark; DiPirro, Michael

2015-01-01

The microcalorimeter array on the Soft X-ray Spectrometer instrument on Astro-H requires cooling to 50 mK, which will be accomplished by a 3-stage adiabatic demagnetization refrigerator (ADR). The ADR is surrounded by a cryogenic system consisting of a superfluid helium tank, a 4.5 K Joule-Thomson (JT) cryocooler, and additional 2-stage Stirling cryocoolers that pre-cool the JT cooler and radiation shields within the cryostat. The unique ADR design allows the instrument to meet all of its science requirements using either the stored cryogen or the JT cryocooler as its heat sink, giving the instrument an unusual degree of tolerance for component failures or degradation in the cryogenic system. The flight detector assembly, ADR and dewar were integrated in early 2014, and have since been extensively characterized and calibrated. At present, the four instruments are being integrated with the spacecraft in preparation for an early 2016 launch. This presentation summarizes the operation and performance of the ADR in all of its operating modes.

Performance Testing of the Astro-H Flight Model 3-Stage ADR

NASA Technical Reports Server (NTRS)

Shirron, Peter J.; Kimball, Mark Oliver; DiPirro, Michael; Bialas, Tom G.

2014-01-01

The Soft X-ray Spectrometer (SXS) is one of four instruments that will be flown on the Japanese Astro-H satellite, planned for launch in late 2015early 2016. The SXS will perform imaging spectroscopy in the soft x-ray band using a 6x6 array of silicon micro calorimeters operated at 50 mK, cooled by an adiabatic demagnetization refrigerator (ADR). NASAGSFC is providing the detector array and ADR, and Sumitomo Heavy Industries, Inc. is providing the remainder of the cryogenic system (superfluid helium dewar (1.3 K), Stirling cryocoolers and a 4.5 K Joule-Thomson (JT) cryocooler). The ADR is unique in that it is designed to use both the liquid helium and the JT cryocooler as it heat sink. The flight detector and ADR assembly have successfully undergone vibration and performance testing at GSFC, and have now undergone initial performance testing with the flight dewar at Sumitomo Heavy Industries, Inc. in Japan. This presentation summarizes the performance of the flight ADR in both cryogen-based and cryogen-free operating modes.

Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study.

PubMed

Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Yamamoto, Kazuhiko; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao

2018-04-27

We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA). This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52. Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52. Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.

Performance Testing of the Astro-H Flight Model 3-stage ADR

NASA Astrophysics Data System (ADS)

Shirron, Peter J.; Kimball, Mark O.; DiPirro, Michael J.; Bialas, Thomas G.

The Soft X-ray Spectrometer (SXS) is one of four instruments that will be flown on the Japanese Astro-H satellite, planned for launch in late 2015/early 2016. The SXS will perform imaging spectroscopy in the soft x-ray band using a 6x6 array of silicon microcalorimeters operated at 50 mK, cooled by an adiabatic demagnetization refrigerator (ADR). NASA/GSFC is providing the detector array and ADR, and Sumitomo Heavy Industries, Inc. is providing the remainder of the cryogenic system (superfluid helium dewar (<1.3 K), Stirling cryocoolers and a 4.5 K Joule-Thomson (JT) cryocooler). The ADR is unique in that it is designed to use both the liquid helium and the JT cryocooler as it heat sink. The flight detector and ADR assembly have successfully undergone vibration and performance testing at GSFC, and have now undergone initial performance testing with the flight dewar at Sumitomo Heavy Industries, Inc. in Japan. This paper summaries the performance of the flight ADR in both cryogen-based and cryogen-free operating modes.

Operating modes and cooling capabilities of the 3-stage ADR developed for the Soft-X-ray Spectrometer instrument on Astro-H

NASA Astrophysics Data System (ADS)

Shirron, Peter J.; Kimball, Mark O.; James, Bryan L.; Muench, Theodore; DiPirro, Michael J.; Letmate, Richard V.; Sampson, Michael A.; Bialas, Tom G.; Sneiderman, Gary A.; Porter, Frederick S.; Kelley, Richard L.

2016-03-01

A 3-stage adiabatic demagnetization refrigerator (ADR) (Shirron et al., 2012) is used on the Soft X-ray Spectrometer instrument (Mitsuda et al., 2010) on Astro-H (Takahashi et al., 2010) [3] to cool a 6 × 6 array of X-ray microcalorimeters to 50 mK. The ADR is supported by a cryogenic system (Fujimoto et al., 2010) consisting of a superfluid helium tank, a 4.5 K Joule-Thomson (JT) cryocooler, and additional 2-stage Stirling cryocoolers that pre-cool the JT cooler and cool radiation shields within the cryostat. The ADR is configured so that it can use either the liquid helium or the JT cryocooler as its heat sink, giving the instrument an unusual degree of tolerance for component failures or degradation in the cryogenic system. The flight detector assembly, ADR and dewar were integrated into the flight dewar in early 2014, and have since been extensively characterized and calibrated. This paper summarizes the operation and performance of the ADR in all of its operating modes.

Matching colonoscopy and pathology data in population-based registries: development of a novel algorithm and the initial experience of the New Hampshire Colonoscopy Registry.

PubMed

Greene, Mary Ann; Butterly, Lynn F; Goodrich, Martha; Onega, Tracy; Baron, John A; Lieberman, David A; Dietrich, Allen J; Srivastava, Amitabh

2011-08-01

The quality of polyp-level data in a population-based registry depends on the ability to match each polypectomy recorded by the endoscopist to a specific diagnosis on the pathology report. To review impediments encountered in matching colonoscopy and pathology data in a population-based registry. New Hampshire Colonoscopy Registry data from August 2006 to November 2008 were analyzed for prevalence of missing reports, discrepancies between colonoscopy and pathology reports, and the proportion of polyps that could not be matched because of multiple polyps submitted in the same container. New Hampshire Colonoscopy Registry. This study involved all consenting patients during the study period. Develop an algorithm for capturing number, size, location, and histology of polyps and for defining and flagging discrepancies to ensure data quality. The proportion of polyps with no assumption or discrepancy, the proportion of patient records eligible for determining the adenoma detection rate (ADR), and the number of patients with ≥3 adenomas. Only 50% of polyps removed during this period were perfectly matched, with no assumption or discrepancy. Records from only 69.9% and 29.7% of eligible patients could be used to determine the ADR and the number of patients with ≥3 adenomas, respectively. Rates of missing reports may have been higher in the early phase of establishment of the registry. This study highlights the impediments in collecting polyp-level data in a population-based registry and provides useful parameters for evaluating the quality and accuracy of data obtained from such registries. Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

MicroRNA-29a contributes to drug-resistance of breast cancer cells to adriamycin through PTEN/AKT/GSK3β signaling pathway.

PubMed

Shen, Hongyu; Li, Liangpeng; Yang, Sujin; Wang, Dandan; Zhong, Shanliang; Zhao, Jianhua; Tang, Jinhai

2016-11-15

Acquisition of resistance to adriamycin (ADR) during the treatment of breast cancer is still a major clinical obstacle. MicroRNAs (miRNAs) are a class of short noncoding RNAs which associate with cancer chemoresistance through regulating gene expression by targeting mRNAs. Our previous microarray found that miR-29a may strongly confer the ADR resistance of breast cancer cells. Here, we aim to explore the possible mechanism by which miR-29a affects sensitivity to ADR. ADR-resistant MCF-7 breast cancer cell subline (MCF-7/ADR) was successfully established in vitro through a stepwise increase of ADR concentrations in the culture based on parental MCF-7 cell lines (MCF-7/S). We used TargetScan (a wide use of target prediction algorithms) in conjunction with pathway enrichment analyses to predict the mRNAs that were most likely to involve in miR-29a-mediated drug resistance in cancers. We confirmed the effects of miR-29a-mediated ADR resistance through MTT and apoptosis assays, and further investigated the activities of two target genes, PTEN and GSK3β, by RT-qPCR analyses and western blot assays. The expression level of miR-29a in MCF-7/ADR cells was remarkablely higher than in MCF-7/S cells. Further MTT and apoptosis assays revealed that transfection of miR-29a inhibitors into MCF-7/ADR cells resulted in prominent reduction of the drug resistance, in contrast, transfection of miR-29a mimics into MCF-7/S cells obviously increased their drug resistance. Through pathway enrichment analyses for miR-29a, we found that PTEN/AKT/GSK3β signaling pathway may be of importance. RT-qPCR and Western blot results showed that downregulation of miR-29a expression in MCF-7/ADR cells increased PTEN expression levels, resulting in decreased phospho-Akt (p-Akt) and phospho-GSK3β (p-GSK3β) expression. Conversely, upregulation of miR-29a expression in MCF-7/S cells is associated with decreasing PTEN expression and increasing p-Akt and p-GSK3β expression. PTEN and GSK3β are targeted by miR-29a, and miR-29a may contribute to ADR resistance through inhibition of the PTEN/AKT/GSK3β pathway in breast cancer cells. Thus, miR-29a may be a potential target for the patients who acquired ADR-resistance during the treatment of breast cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

A systematic investigation of computation models for predicting Adverse Drug Reactions (ADRs).

PubMed

Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

2014-01-01

Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.

Real-world evidence for the safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (STELLA-ELDER): final results of a post-marketing surveillance study.

PubMed

Yokote, Koutaro; Terauchi, Yasuo; Nakamura, Ichiro; Sugamori, Haruko

2016-10-01

To investigate the real-world safety of ipragliflozin in elderly Japanese patients with type 2 diabetes mellitus (T2DM). Japanese patients (≥65 years old) who were first prescribed ipragliflozin within 3 months after its launch in April 2014 were registered in this post-marketing surveillance (PMS). Final data collection was in July 2015. Survey items included demographics, treatments, adverse drug reactions (ADRs), vital signs, and laboratory variables. The PMS included 8505 patients (4181 males/4324 females). The mean age and diabetes duration were 72.3 years and 10.6 years, respectively. In 84.3% of patients, ipragliflozin was prescribed at 50 mg/day, which was continued unchanged. Overall, 16.91% of patients experienced 1880 ADRs, and 165 ADRs were classified as serious in 127 patients (1.49%). ADRs of special interest included skin complications, volume depletion, polyuria/pollakiuria, genital infection, urinary tract infection, renal disorders, hypoglycemia, cerebrovascular disease, cardiovascular disease, malignant tumor, fracture, and ketone body-related events. This 1-year PMS revealed probable ADRs in elderly Japanese patients with T2DM prescribed ipragliflozin in real-world settings, with no new safety concerns. The risk factors for ADRs varied but could be rationalized. The results should help physicians to identify possible treatment-emergent ADRs in ipragliflozin-treated patients.

Free radical mediated oxidative stress and toxic side effects in brain induced by the anti cancer drug adriamycin: insight into chemobrain.

PubMed

Joshi, Gururaj; Sultana, Rukhsana; Tangpong, Jitbanjong; Cole, Marsha Paulette; St Clair, Daret K; Vore, Mary; Estus, Steven; Butterfield, D Allan

2005-11-01

Adriamycin (ADR) is a chemotherapeutic agent useful in treating various cancers. ADR is a quinone-containing anthracycline chemotherapeutic and is known to produce reactive oxygen species (ROS) in heart. Application of this drug can have serious side effects in various tissues, including brain, apart from the known cardiotoxic side effects, which limit the successful use of this drug in treatment of cancer. Neurons treated with ADR demonstrate significant protein oxidation and lipid peroxidation. Patients under treatment with this drug often complain of forgetfulness, lack of concentration, dizziness (collectively called somnolence or sometimes called chemobrain). In this study, we tested the hypothesis that ADR induces oxidative stress in brain. Accordingly, we examined the in vivo levels of brain protein oxidation and lipid peroxidation induced by i.p. injection of ADR. We also measured levels of the multidrug resistance-associated protein (MRP1) in brain isolated from ADR- or saline-injected mice. MRP1 mediates ATP-dependent export of cytotoxic organic anions, glutathione S-conjugates and sulphates. The current results demonstrated a significant increase in levels of protein oxidation and lipid peroxidation and increased expression of MRP1 in brain isolated from mice, 72 h post i.p injection of ADR. These results are discussed with reference to potential use of this redox cycling chemotheraputic agent in the treatement of cancer and its chemobrain side effect in brain.

Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients

PubMed Central

Steele, Megan L.; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

2014-01-01

Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5 cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe. PMID:24672577

Geographical Detector-Based Identification of the Impact of Major Determinants on Aeolian Desertification Risk

PubMed Central

Du, Ziqiang; Xu, Xiaoming; Zhang, Hong; Wu, Zhitao; Liu, Yong

2016-01-01

Arid and semi-arid areas in North China are facing the challenge of a rising aeolian desertification risk (ADR) due to the intertwined effects of complex natural processes and intensified anthropogenic activities. An accurate quantitative assessment of the relationship between ADR and its determinants is beneficial for understanding the driving mechanisms of aeolian desertification and for controlling future desertification. Previous studies have failed to quantify the relative role of determinants driving ADR and have been limited in assessing their interactive impacts. In this study, a spatial variance analysis-based geographical detector methodology is used to quantify the effects of geological, physical, and human factors on the occurrence of ADR in an area characterized by mountains and hills in northern China. It is found that soil type, precipitation, and wind velocity are the major determinants of ADR, which implies that geological and physical elements (e.g., soil attribute) and climatic factors (e.g., precipitation and wind velocity) rather than human activities have played a greater role in the incidence of ADR. Particularly, the results show that the interaction of various determinants causes significant non-linearly enhanced impacts on the ADR. The findings of our study will assist local inhabitants and policy makers in developing measures for wind prevention and sand control to mitigate the effects of desertification in the region. PMID:26987114

Geographical Detector-Based Identification of the Impact of Major Determinants on Aeolian Desertification Risk.

PubMed

Du, Ziqiang; Xu, Xiaoming; Zhang, Hong; Wu, Zhitao; Liu, Yong

2016-01-01

Arid and semi-arid areas in North China are facing the challenge of a rising aeolian desertification risk (ADR) due to the intertwined effects of complex natural processes and intensified anthropogenic activities. An accurate quantitative assessment of the relationship between ADR and its determinants is beneficial for understanding the driving mechanisms of aeolian desertification and for controlling future desertification. Previous studies have failed to quantify the relative role of determinants driving ADR and have been limited in assessing their interactive impacts. In this study, a spatial variance analysis-based geographical detector methodology is used to quantify the effects of geological, physical, and human factors on the occurrence of ADR in an area characterized by mountains and hills in northern China. It is found that soil type, precipitation, and wind velocity are the major determinants of ADR, which implies that geological and physical elements (e.g., soil attribute) and climatic factors (e.g., precipitation and wind velocity) rather than human activities have played a greater role in the incidence of ADR. Particularly, the results show that the interaction of various determinants causes significant non-linearly enhanced impacts on the ADR. The findings of our study will assist local inhabitants and policy makers in developing measures for wind prevention and sand control to mitigate the effects of desertification in the region.

Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

PubMed

Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

2016-01-01

Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. © 2015 Wiley Periodicals, Inc.

HIV-1 Variants and Drug Resistance in Pregnant Women from Bata (Equatorial Guinea): 2012-2013.

PubMed

Alvarez, Patricia; Fernández McPhee, Carolina; Prieto, Luis; Martín, Leticia; Obiang, Jacinta; Avedillo, Pedro; Vargas, Antonio; Rojo, Pablo; Benito, Agustín; Ramos, José Tomás; Holguín, África

2016-01-01

This is the first study describing drug resistance mutations (DRM) and HIV-1 variants among infected pregnant women in Equatorial Guinea (GQ), a country with high (6.2%) and increasing HIV prevalence. Dried blood spots (DBS) were collected from November 2012 to December 2013 from 69 HIV-1 infected women participating in a prevention of mother-to-child transmission program in the Hospital Regional of Bata and Primary Health Care Centre María Rafols, Bata, GQ. The transmitted (TDR) or acquired (ADR) antiretroviral drug resistance mutations at partial pol sequence among naive or antiretroviral therapy (ART)-exposed women were defined following WHO or IAS USA 2015 lists, respectively. HIV-1 variants were identified by phylogenetic analyses. A total of 38 of 69 HIV-1 specimens were successfully amplified and sequenced. Thirty (79%) belonged to ART-experienced women: 15 exposed to nucleoside reverse transcriptase inhibitors (NRTI) monotherapy, and 15 to combined ART (cART) as first regimen including two NRTI and one non-NRTI (NNRTI) or one protease inhibitor (PI). The TDR rate was only found for PI (3.4%). The ADR rate was 37.5% for NNRTI, 8.7% for NRTI and absent for PI or NRTI+NNRTI. HIV-1 group M non-B variants caused most (97.4%) infections, mainly (78.9%) recombinants: CRF02_AG (55.2%), CRF22_A101 (10.5%), subtype C (10.5%), unique recombinants (5.3%), and A3, D, F2, G, CRF06_cpx and CRF11_cpx (2.6% each). The high rate of ADR to retrotranscriptase inhibitors (mainly to NNRTIs) observed among pretreated pregnant women reinforces the importance of systematic DRM monitoring in GQ to reduce HIV-1 resistance transmission and to optimize first and second-line ART regimens when DRM are present.

Imputation of adverse drug reactions: Causality assessment in hospitals

PubMed Central

Mastroianni, Patricia de Carvalho

2017-01-01

Background & objectives Different algorithms have been developed to standardize the causality assessment of adverse drug reactions (ADR). Although most share common characteristics, the results of the causality assessment are variable depending on the algorithm used. Therefore, using 10 different algorithms, the study aimed to compare inter-rater and multi-rater agreement for ADR causality assessment and identify the most consistent to hospitals. Methods Using ten causality algorithms, four judges independently assessed the first 44 cases of ADRs reported during the first year of implementation of a risk management service in a medium complexity hospital in the state of Sao Paulo (Brazil). Owing to variations in the terminology used for causality, the equivalent imputation terms were grouped into four categories: definite, probable, possible and unlikely. Inter-rater and multi-rater agreement analysis was performed by calculating the Cohen´s and Light´s kappa coefficients, respectively. Results None of the algorithms showed 100% reproducibility in the causal imputation. Fair inter-rater and multi-rater agreement was found. Emanuele (1984) and WHO-UMC (2010) algorithms showed a fair rate of agreement between the judges (k = 0.36). Interpretation & conclusions Although the ADR causality assessment algorithms were poorly reproducible, our data suggest that WHO-UMC algorithm is the most consistent for imputation in hospitals, since it allows evaluating the quality of the report. However, to improve the ability of assessing the causality using algorithms, it is necessary to include criteria for the evaluation of drug-related problems, which may be related to confounding variables that underestimate the causal association. PMID:28166274

Registered nurses' medication management of the elderly in aged care facilities.

PubMed

Lim, L M; Chiu, L H; Dohrmann, J; Tan, K-L

2010-03-01

Data on adverse drug reactions (ADRs) showed a rising trend in the elderly over 65 years using multiple medications. To identify registered nurses' (RNs) knowledge of medication management and ADRs in the elderly in aged care facilities; evaluate an education programme to increase pharmacology knowledge and prevent ADRs in the elderly; and develop a learning programme with a view to extending provision, if successful. This exploratory study used a non-randomized pre- and post-test one group quasi-experimental design without comparators. It comprised a 23-item knowledge-based test questionnaire, one-hour teaching session and a self-directed learning package. The volunteer sample was RNs from residential aged care facilities, involved in medication management. Participants sat a pre-test immediately before the education, and post-test 4 weeks later (same questionnaire). Participants' perceptions obtained. Pre-test sample n = 58, post-test n = 40, attrition rate of 31%. Using Microsoft Excel 2000, descriptive statistical data analysis of overall pre- and post-test incorrect responses showed: pre-test proportion of incorrect responses = 0.40; post-test proportion of incorrect responses = 0.27; Z-test comparing pre- and post-tests scores of incorrect responses = 6.55 and one-sided P-value = 2.8E-11 (P < 0.001). Pre-test showed knowledge deficits in medication management and ADRs in the elderly; post-test showed statistically significant improvement in RNs' knowledge. It highlighted a need for continuing professional education. Further studies are required on a larger sample of RNs in other aged care facilities, and on the clinical impact of education by investigating nursing practice and elderly residents' outcomes.

Magnitude of Antiretroviral Drug Toxicity in Adult HIV Patients in Ethiopia: A cohort study at seven teaching hospitals.

PubMed

Gudina, Esayas Kebede; Teklu, Alula M; Berhan, Asres; Gebreegziabhier, Atsbeha; Seyoum, Teshome; Nega, Abiy; Medhin, Girmay; Kebede, Amha; Assefa, Yibeltal

2017-02-01

The introduction of antiretroviral therapy (ART) has resulted in significant mortality reduction and improvement in the quality of life. However, this has come at a cost of increased drug toxicity. The objective of this study was to assess the patterns and predictors of ART toxicity in adult HIV patients in Ethiopia. This is a prospective cohort study conducted at seven teaching hospitals between September 2009 and December 2013 involving 3921 HIV patients on ART. Adverse drug reactions (ADR) due to ART were identified based on clinical assessment and/or laboratory parameters. Multivariable random effects Poisson regression analysis was used to identify factors independently associated with toxicity. ADR due to ART drugs was reported in 867 (22.1 %) of the participants; 374 (9.5%) had severe forms. About 87% of reported toxicities were limited to three organ systems - the skin, nervous system and blood. The overall incidence of ADR was 9 per 100 person years. About a third of toxicities occurred during the first six months after ART initiation with the incidence rate of 22.4 per 100 person years. Concomitant anti-tuberculosis treatment was the strongest independent predictor of toxicity. ADR was found to be highly prevalent in HIV patients on ART at tertiary hospitals in Ethiopia. Most of these conditions occurred early after ART initiation and in those with concomitant anti-tuberculosis treatment. Thus, routine monitoring of patients on ART should be strengthened with particular emphasis in the first 6 months. Strategies should also be devised to replace older and more toxic agents with newer and safer drugs available.

Comparative study on drug safety surveillance between medical students of Malaysia and Nigeria.

PubMed

Abubakar, Abdullahi Rabiu; Ismail, Salwani; Rahman, Nor Iza A; Haque, Mainul

2015-01-01

Internationally, there is a remarkable achievement in the areas of drug discovery, drug design, and clinical trials. New and efficient drug formulation techniques are widely available which have led to success in treatment of several diseases. Despite these achievements, large number of patients continue to experience adverse drug reactions (ADRs), and majority of them are yet to be on record. The purpose of this survey is to compare knowledge, attitude, and practice with respect to ADRs and pharmacovigilance (PV) between medical students of Malaysia and Nigeria and to determine if there is a relationship between their knowledge and practice. A cross-sectional, questionnaire-based survey involving year IV and year V medical students of the Department of Medicine, Universiti Sultan Zainal Abidin and Bayero University Kano was carried out. The questionnaire which comprised 25 questions on knowledge, attitude, and practice was adopted, modified, validated, and administered to them. The response was analyzed using SPSS version 20. The response rate from each country was 74%. There was a statistically significant difference in mean knowledge and practice score on ADRs and PV between medical students of Malaysia and Nigeria, both at P<0.000. No significance difference in attitude was observed at P=0.389. Also, a statistically significant relationship was recorded between their knowledge and practice (r=0.229, P=0.001), although the relationship was weak. Nigerian medical students have better knowledge and practice than those of Malaysia, although they need improvement. Imparting knowledge of ADRs and PV among medical students will upgrade their practice and enhance health care delivery services in the future.

More than skin deep. Ten year follow‐up of delayed cutaneous adverse drug reactions (CADR)

PubMed Central

Ly, Jenny; Trubiano, Jason; Aung, Ar Kar

2016-01-01

Abstract Aims To determine the gaps in practice regarding appropriate ADR documentation and risk communication for patients diagnosed with severe cutaneous adverse drug reactions (CADR). Methods This was a retrospective observational cohort study conducted using hospital coding and databases to identify inpatients diagnosed with CADR from January 2004 to August 2014. Hospital discharge summaries, ADR reports and pharmacy dispensing records were reviewed for ADR documentation. Patients still living in Australia and who did not opt out of being contacted were invited to be surveyed by telephone to determine their understanding of recommendations, re‐exposure rates and long‐term effects. Results Of 85 patients identified, median age was 59 (IQR 44–72) years and 47.1% were male. The most common diagnosis was TENS (49.4%). Ten patients (11.8%) died as inpatients. Of the 81 patients with a drug‐related causality, 47 (58%) had appropriate documentation in all three required medical record platforms. Of the 56 eligible patients, 38 (67.9%) were surveyed; 13% had no information provided upon discharge and 26.3% patients had a mismatch in knowledge of implicated medications. No surveyed patient had a relapse of CADR, but 23.7% had a subsequent unrelated allergic reaction. Thirteen patients (34.2%) reported long‐term effects. Conclusions We found gaps in the accuracy of ADR documentation and communication of risk at discharge, which indicated risks to patient safety. Electronic systems are being developed to improve documentation. Written information about CADR is being provided at discharge to improve patient understanding and knowledge. PMID:27265387

10 CFR Appendix to Part 719 - Guidance for Legal Resource Management

Code of Federal Regulations, 2011 CFR

2011-01-01

... resolution (ADR) at various stages of an issue in dispute, e.g., before a case is filed, pre-discovery, after initial discovery and pre-trial. This evaluation should be done in coordination with the Department's ADR liaison if one has been established or appointed or the Department counsel if an ADR liaison has not been...

39 CFR 601.108 - SDR Official disagreement resolution.

Code of Federal Regulations, 2011 CFR

2011-07-01

... was lodged with the contracting officer, if the use of ADR fails to resolve it at any time, if the... contracting officer (unless ADR had been used to attempt to resolve them); (2) Disagreements under § 601.107 for which ADR had been agreed to be used must be lodged with the SDR Official within 10 days after the...

26 CFR 12.4 - Election of Class Life Asset Depreciation Range System (ADR).

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 14 2011-04-01 2010-04-01 true Election of Class Life Asset Depreciation Range... Election of Class Life Asset Depreciation Range System (ADR). (a) Elections filed before February 1, 1972... election will be treated as an election under the Class Life Asset Depreciation Range System (ADR) as...

26 CFR 12.4 - Election of Class Life Asset Depreciation Range System (ADR).

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Election of Class Life Asset Depreciation Range... Election of Class Life Asset Depreciation Range System (ADR). (a) Elections filed before February 1, 1972... election will be treated as an election under the Class Life Asset Depreciation Range System (ADR) as...

Pyridine Nucleotide Complexes with Bacillus anthracis Coenzyme A-Disulfide Reductase: A Structural Analysis of Dual NAD(P)H Specificity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wallen,J.; Paige, C.; Mallett, T.

2008-01-01

We have recently reported that CoASH is the major low-molecular weight thiol in Bacillus anthracis, and we have now characterized the kinetic and redox properties of the B. anthracis coenzyme A-disulfide reductase (CoADR, BACoADR) and determined the crystal structure at 2.30 Angstroms resolution. While the Staphylococcus aureus and Borrelia burgdorferi CoADRs exhibit strong preferences for NADPH and NADH, respectively, B. anthracis CoADR can use either pyridine nucleotide equally well. Sequence elements within the respective NAD(P)H-binding motifs correctly reflect the preferences for S. aureus and Bo. burgdorferi CoADRs, but leave questions as to how BACoADR can interact with both pyridine nucleotides.more » The structures of the NADH and NADPH complexes at ca. 2.3 Angstroms resolution reveal that a loop consisting of residues Glu180-Thr187 becomes ordered and changes conformation on NAD(P)H binding. NADH and NADPH interact with nearly identical conformations of this loop; the latter interaction, however, involves a novel binding mode in which the 2'-phosphate of NADPH points out toward solvent. In addition, the NAD(P)H-reduced BACoADR structures provide the first view of the reduced form (Cys42-SH/CoASH) of the Cys42-SSCoA redox center. The Cys42-SH side chain adopts a new conformation in which the conserved Tyr367'-OH and Tyr425'-OH interact with the nascent thiol(ate) on the flavin si-face. Kinetic data with Y367F, Y425F, and Y367, 425F BACoADR mutants indicate that Tyr425' is the primary proton donor in catalysis, with Tyr367' functioning as a cryptic alternate donor in the absence of Tyr425'.« less

Design of the Anti-tuberculosis Drugs induced Adverse Reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS)

PubMed Central

2010-01-01

Background More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. Methods/Design Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. Discussion ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy. PMID:20492672

The contribution of direct patient reported ADRs to drug safety signals in the Netherlands from 2010 to 2015.

PubMed

van Hunsel, Florence; de Waal, Susan; Härmark, Linda

2017-08-01

The purpose of this study was to investigate the contribution of patient reports to signals sent by the Netherlands Pharmacovigilance Centre Lareb to the Dutch Medicines Evaluation Board and to determine if there are certain types of signals where patient report add a distinct contribution. All signals from 2010 until 2015 were included. First, we investigated how many patient reports were present in the signals and the characteristics of these reports compared to the health care professional and marketing authorization holders' reports. In addition to source, the analysis included ATC code of the drug, MedDRA® system organ class and preferred term for the adverse drug reaction (ADR), seriousness of the ADR, and 7 other factors like reports on over-the-counter medication, and how often an ADR listed in the important medical event terms list was present. Secondly, we determined the proportion of reports submitted by the individual groups to signals, in a cross-sectional manner. A total of 150 signals were included, including 1691 ADR reports. Our results show that 26.3% of all ADR reports in Dutch drug safety signals were reported by patients, and 30.5% of the patient reports in the signals contained one or more terms listed as important medical events. The proportion of reports by patients which were included the signals was 2% and 3.9% for health care professional reports and 0.2% for marketing authorization holders reports. Patients had an important contribution to signals overall, but especially for ADRs related to generic drug substitution and psychiatric ADRs. Copyright © 2017 John Wiley & Sons, Ltd.

A pragmatic randomized controlled trial of thiopurine methyltransferase genotyping prior to azathioprine treatment: the TARGET study.

PubMed

Newman, William G; Payne, Katherine; Tricker, Karen; Roberts, Stephen A; Fargher, Emily; Pushpakom, Sudeep; Alder, Jane E; Sidgwick, Gary P; Payne, Debbie; Elliott, Rachel A; Heise, Marco; Elles, Robert; Ramsden, Simon C; Andrews, Julie; Houston, J Brian; Qasim, Faeiza; Shaffer, Jon; Griffiths, Christopher E M; Ray, David W; Bruce, Ian; Ollier, William E R

2011-06-01

To conduct a pragmatic, randomized controlled trial to assess whether thiopurine methyltransferase (TPMT) genotyping prior to azathioprine reduces adverse drug reactions (ADRs). A total of 333 participants were randomized 1:1 to undergo TPMT genotyping prior to azathioprine or to commence treatment without genotyping. There was no difference in the primary outcome of stopping azathioprine due to an adverse reaction (ADR, p = 0.59) between the two study arms. ADRs were more common in older patients (p = 0.01). There was no increase in stopping azathioprine due to ADRs in TPMT heterozygotes compared with wild-type individuals. The single individual with TPMT variant homozygosity experienced severe neutropenia. Our work supports the strong evidence that individuals with TPMT variant homozygosity are at high risk of severe neutropenia, whereas TPMT heterozygotes are not at increased risk of ADRs at standard doses of azathioprine.

Detecting signals of drug-drug interactions in a spontaneous reports database.

PubMed

Thakrar, Bharat T; Grundschober, Sabine Borel; Doessegger, Lucette

2007-10-01

The spontaneous reports database is widely used for detecting signals of ADRs. We have extended the methodology to include the detection of signals of ADRs that are associated with drug-drug interactions (DDI). In particular, we have investigated two different statistical assumptions for detecting signals of DDI. Using the FDA's spontaneous reports database, we investigated two models, a multiplicative and an additive model, to detect signals of DDI. We applied the models to four known DDIs (methotrexate-diclofenac and bone marrow depression, simvastatin-ciclosporin and myopathy, ketoconazole-terfenadine and torsades de pointes, and cisapride-erythromycin and torsades de pointes) and to four drug-event combinations where there is currently no evidence of a DDI (fexofenadine-ketoconazole and torsades de pointes, methotrexade-rofecoxib and bone marrow depression, fluvastatin-ciclosporin and myopathy, and cisapride-azithromycine and torsade de pointes) and estimated the measure of interaction on the two scales. The additive model correctly identified all four known DDIs by giving a statistically significant (P < 0.05) positive measure of interaction. The multiplicative model identified the first two of the known DDIs as having a statistically significant or borderline significant (P < 0.1) positive measure of interaction term, gave a nonsignificant positive trend for the third interaction (P = 0.27), and a negative trend for the last interaction. Both models correctly identified the four known non interactions by estimating a negative measure of interaction. The spontaneous reports database is a valuable resource for detecting signals of DDIs. In particular, the additive model is more sensitive in detecting such signals. The multiplicative model may further help qualify the strength of the signal detected by the additive model.

Detecting signals of drug–drug interactions in a spontaneous reports database

PubMed Central

Thakrar, Bharat T; Grundschober, Sabine Borel; Doessegger, Lucette

2007-01-01

Aims The spontaneous reports database is widely used for detecting signals of ADRs. We have extended the methodology to include the detection of signals of ADRs that are associated with drug–drug interactions (DDI). In particular, we have investigated two different statistical assumptions for detecting signals of DDI. Methods Using the FDA's spontaneous reports database, we investigated two models, a multiplicative and an additive model, to detect signals of DDI. We applied the models to four known DDIs (methotrexate-diclofenac and bone marrow depression, simvastatin-ciclosporin and myopathy, ketoconazole-terfenadine and torsades de pointes, and cisapride-erythromycin and torsades de pointes) and to four drug-event combinations where there is currently no evidence of a DDI (fexofenadine-ketoconazole and torsades de pointes, methotrexade-rofecoxib and bone marrow depression, fluvastatin-ciclosporin and myopathy, and cisapride-azithromycine and torsade de pointes) and estimated the measure of interaction on the two scales. Results The additive model correctly identified all four known DDIs by giving a statistically significant (P< 0.05) positive measure of interaction. The multiplicative model identified the first two of the known DDIs as having a statistically significant or borderline significant (P< 0.1) positive measure of interaction term, gave a nonsignificant positive trend for the third interaction (P= 0.27), and a negative trend for the last interaction. Both models correctly identified the four known non interactions by estimating a negative measure of interaction. Conclusions The spontaneous reports database is a valuable resource for detecting signals of DDIs. In particular, the additive model is more sensitive in detecting such signals. The multiplicative model may further help qualify the strength of the signal detected by the additive model. PMID:17506784

30 CFR 291.103 - May I use alternative dispute resolution to informally resolve an allegation that open and...

Code of Federal Regulations, 2011 CFR

2011-07-01

... that open and nondiscriminatory access was denied? You may ask to use ADR either before or after you..., NW., Mail Stop 5438, Washington, DC 20240-0001. (a) You may request that ADR be administered by: (1) A contracted ADR provider agreed to by all parties; (2) The Department's Office of Collaborative...

77 FR 3010 - In the Matter of Mr. Francis Guilbeau; Order Prohibiting Involvement in NRC-Licensed Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-20

... request a predecisional enforcement conference or request alternative dispute resolution (ADR) with the... the absence of any request for hearing or ADR, or written approval of an extension of time in which to... hearing or ADR is requested, the effective date of this Order shall be determined in accordance with the...

Indian College of Physicians (ICP) Position Statement on Pharmacovigilance.

PubMed

Dhamija, Puneet; Kalra, Sanjay; Sharma, Pramod Kumar; Kalaiselvan, V; Muruganathan, A; Balhara, Yatan Pal Singh; Badani, Rajesh; Bantwal, Ganapathi; Das, A K; Dhorepatil, Bharati; Ghosh, Sujoy; Jeloka, Tarun; Khandelwal, Deepak; Nadkar, Milind Y; Patnaik, Kuppili Pooja; Saboo, Banshi; Sahay, Manisha; Sahay, Rakesh; Tiwaskar, Mangesh; Unnikrishnan, A G

2017-03-01

Pharmacovigilance is the art and science of detection, understanding and prevention of adverse drug reactions and not merely a critical analysis of prescriptions and errors. This field starts with reporting by clinicians of a suspected adverse drug reaction (ADR) to the pharmacologist followed by joint causality analysis and ends at the application of new information by a clinician for benefit of patients. There are a number of ways, which can be utilised for reporting adverse effects using pen and paper format to software applications for smart phones. Varied types of activities spreading from systematic reviews to the mechanistic evaluation of ADR can be performed under the umbrella of pharmacovigilance. It is of utmost importance for clinicians to understand how to identify, communicate and understand adverse effects of drugs with an aim to prevent harm to patients. © Journal of the Association of Physicians of India 2011.

Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance.

PubMed

Fornasier, G; Taborelli, M; Francescon, S; Polesel, J; Aliberti, M; De Paoli, P; Baldo, P

2018-05-21

Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥ 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.

A Systematic Investigation of Computation Models for Predicting Adverse Drug Reactions (ADRs)

PubMed Central

Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

2014-01-01

Background Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. Principal Findings In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Conclusion Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms. PMID:25180585

Pharmacogenetics of adverse reactions to antiepileptic drugs.

PubMed

Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M

2018-04-01

Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

25 CFR 42.5 - When can a school use ADR processes to address an alleged violation?

Code of Federal Regulations, 2013 CFR

2013-04-01

... school must address alleged violations through the formal disciplinary proceeding described in § 42.8. ... 25 Indians 1 2013-04-01 2013-04-01 false When can a school use ADR processes to address an alleged... RIGHTS § 42.5 When can a school use ADR processes to address an alleged violation? (a) The school may...

25 CFR 42.5 - When can a school use ADR processes to address an alleged violation?

Code of Federal Regulations, 2014 CFR

2014-04-01

... school must address alleged violations through the formal disciplinary proceeding described in § 42.8. ... 25 Indians 1 2014-04-01 2014-04-01 false When can a school use ADR processes to address an alleged... RIGHTS § 42.5 When can a school use ADR processes to address an alleged violation? (a) The school may...

25 CFR 42.5 - When can a school use ADR processes to address an alleged violation?

Code of Federal Regulations, 2012 CFR

2012-04-01

... school must address alleged violations through the formal disciplinary proceeding described in § 42.8. ... 25 Indians 1 2012-04-01 2011-04-01 true When can a school use ADR processes to address an alleged... RIGHTS § 42.5 When can a school use ADR processes to address an alleged violation? (a) The school may...

Heat Switches for ADRs

NASA Technical Reports Server (NTRS)

DiPirro, M. J.; Shirron, P. J.

2014-01-01

Heat switches are key elements in the cyclic operation of Adiabatic Demagnetization Refrigerators (ADRs). Several of the types of heat switches that have been used for ADRs are described in this paper. Key elements in selection and design of these switches include not only ON/OFF switching ratio, but also method of actuation, size, weight, and structural soundness. Some of the trade-off are detailed in this paper.

Partnering

DTIC Science & Technology

1991-12-01

pamplet is one in a series of pamplets describing applications of Alternative Dispute Resolution (ADR). The pamplet is part of a Corps program to...stages, or settle them prior to formal litigation. ADR is a new field, and additional techniques are being developed all the time. These pamplets are a...means of providing Corps managers with examples of how other managers have employed ADR techniques. The information in this pamplet is designed to

[Data-mining characteristics of adverse drug reactions and pharmacovi-gilance of Chinese patent drugs including Aconitum herbs].

PubMed

Zhang, Xiao-Meng; Li, Fan; Zhang, Bing; Chen, Xiao-Fen; Piao, Jing-Zhu

2018-01-01

The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication education to public, and avoid misuse or abuse to ensure rational drug use. Copyright© by the Chinese Pharmaceutical Association.

Data Analysis of Airborne Electromagnetic Bathymetry.

DTIC Science & Technology

1985-04-01

7 AD-R 58 889 DATA ANALYSIS OF AIRBORNE ELECTROMAGNETIC BRTHYMETRY i/i (U) NAVAL OCEAN RESEARCH AND DEVELOPMENT ACTIVITY NSTL STRTION MS R ZOLLINGER...Naval Ocean Research and Development Activity NSTL, Mississippi 39529 NORDA Report 93 April 1985 AD-A158 809 - Data Analysis of Airborne Electromagnetic ...8217 - Foreword CI Airborne electromagnetic (AEM) systems have traditionally been used for detecting anomalous conductors in the

Pharmacogenetics and Predictive Testing of Drug Hypersensitivity Reactions.

PubMed

Böhm, Ruwen; Cascorbi, Ingolf

2016-01-01

Adverse drug reactions adverse drug reaction (ADR) occur in approximately 17% of patients. Avoiding ADR is thus mandatory from both an ethical and an economic point of view. Whereas, pharmacogenetics changes of the pharmacokinetics may contribute to the explanation of some type A reactions, strong relationships of genetic markers has also been shown for drug hypersensitivity belonging to type B reactions. We present the classifications of ADR, discuss genetic influences and focus on delayed-onset hypersensitivity reactions, i.e., drug-induced liver injury, drug-induced agranulocytosis, and severe cutaneous ADR. A guidance how to read and interpret the contingency table is provided as well as an algorithm whether and how a test for a pharmacogenetic biomarker should be conducted.

Diversity in cell motility reveals the dynamic nature of the formation of zebrafish taste sensory organs.

PubMed

Soulika, Marina; Kaushik, Anna-Lila; Mathieu, Benjamin; Lourenço, Raquel; Komisarczuk, Anna Z; Romano, Sebastian Alejo; Jouary, Adrien; Lardennois, Alicia; Tissot, Nicolas; Okada, Shinji; Abe, Keiko; Becker, Thomas S; Kapsimali, Marika

2016-06-01

Taste buds are sensory organs in jawed vertebrates, composed of distinct cell types that detect and transduce specific taste qualities. Taste bud cells differentiate from oropharyngeal epithelial progenitors, which are localized mainly in proximity to the forming organs. Despite recent progress in elucidating the molecular interactions required for taste bud cell development and function, the cell behavior underlying the organ assembly is poorly defined. Here, we used time-lapse imaging to observe the formation of taste buds in live zebrafish larvae. We found that tg(fgf8a.dr17)-expressing cells form taste buds and get rearranged within the forming organs. In addition, differentiating cells move from the epithelium to the forming organs and can be displaced between developing organs. During organ formation, tg(fgf8a.dr17) and type II taste bud cells are displaced in random, directed or confined mode relative to the taste bud they join or by which they are maintained. Finally, ascl1a activity in the 5-HT/type III cell is required to direct and maintain tg(fgf8a.dr17)-expressing cells into the taste bud. We propose that diversity in displacement modes of differentiating cells acts as a key mechanism for the highly dynamic process of taste bud assembly. © 2016. Published by The Company of Biologists Ltd.

Post-authorisation passive enhanced safety surveillance of seasonal influenza vaccines: protocol of a pilot study in England.

PubMed

de Lusignan, Simon; Dos Santos, Gaël; Correa, Ana; Haguinet, François; Yonova, Ivelina; Lair, Florence; Byford, Rachel; Ferreira, Filipa; Stuttard, Karen; Chan, Tom

2017-05-17

To pilot enhanced safety surveillance of seasonal influenza vaccine meeting the European Medicines Agency (EMA) requirement to rapidly detect a significant increase in the frequency or severity of adverse events of interest (AEIs), which may indicate risk from the new season's vaccine. A prospective passive enhanced safety surveillance combining data collection from adverse drug reaction (ADR) cards with automated collection of pseudonymised routinely collected electronic health record (EHR) data. This study builds on a feasibility study carried out at the start of the 2015/2016 influenza season. We will report influenza vaccine exposure and any AEIs reported via ADR card or recorded directly into the EHR, from the commencement of influenza vaccination and ends as specified by EMA (30 November 2016). Ten volunteer English general practices, primarily using the GSK influenza vaccines. They had selected this vaccine in advance of the study. People who receive a seasonal influenza vaccine, in each age group defined in EMA interim guidance: 6 months to 5 years, 6-12 years, 13-17 years, 18-65 years and >65 years. The primary outcome measure is the rate of AEIs occurring within 7 days postvaccination, using passive surveillance of general practitioner (GP) EHR systems enhanced by a card-based ADR reporting system. Extracted data will be presented overall by brand (Fluarix Tetra vs others), by age strata and risk groups. The secondary outcome measure is the vaccine uptake among the subjects registered in the enrolled general practices. Ethical approval was granted by the Proportionate Review Sub-committee of the North East-Newcastle & North Tyneside 2 on 5 August 2016. The study received approval from the Health Research Authority on 1 September 2016. We will produce an interim analysis within 8 weeks, and an end-of-study report, which will be submitted to peer-reviewed journals. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Application of anaerobic digested residues on safe food production.

PubMed

Shi, Ya-juan; Lu, Yong-long; Liang, Dan

2002-01-01

Experiments were conducted in pot culture and field plots to study the effects of Anaerobic Digested Residues (ADR) on nitrate accumulation in leaf vegetables, which is critical for the safety of food. The results showed that compared to chemical fertilizer, ADR could decrease the nitrate accumulation in rape and spinach. Furthermore, nitrate content in plant tissue was increased with the increase of percentage of chemical nitrogen in the mixture of chemical fertilizer and ADR. A comparison of spraying digested slurry with irrigation showed that spraying method could reduce the nitrate content of rape, however, a reverse result was found in spinach. The nitrate accumulation in rape affected by ADR was more apparent in high fertility soil than that in low fertility one. To regulate the nitrate accumulation in plant, it was more apparent in rape under greenhouse cultivation, while more apparent in spinach under open-air cultivation. The results demonstrated that the ADR was effective in the safe food production and it may convert the technology to be more profitable.

Impact of high-risk conjunctions on Active Debris Removal target selection

NASA Astrophysics Data System (ADS)

Lidtke, Aleksander A.; Lewis, Hugh G.; Armellin, Roberto

2015-10-01

Space debris simulations show that if current space launches continue unchanged, spacecraft operations might become difficult in the congested space environment. It has been suggested that Active Debris Removal (ADR) might be necessary in order to prevent such a situation. Selection of objects to be targeted by ADR is considered important because removal of non-relevant objects will unnecessarily increase the cost of ADR. One of the factors to be used in this ADR target selection is the collision probability accumulated by every object. This paper shows the impact of high-probability conjunctions on the collision probability accumulated by individual objects as well as the probability of any collision occurring in orbit. Such conjunctions cannot be predicted far in advance and, consequently, not all the objects that will be involved in such dangerous conjunctions can be removed through ADR. Therefore, a debris remediation method that would address such events at short notice, and thus help prevent likely collisions, is suggested.

Post-marketing surveillance of quinolones 1988-1990.

PubMed

Davey, P G; McDonald, T; Lindsay, G

1991-04-01

It has been much easier to obtain original data on adverse drug reactions (ADR) of quinolones from the pharmaceutical industry than it was two years ago. This is to be welcomed and, as anticipated, the new data continue to suggest that the new 4-quinolones have an ADR profile which is very similar to that of other antimicrobials. Visual disturbance is not a prominent feature, in contrast to the ADR profile of nalidixic acid. Better definition of quinolone ADRs requires prospective study, and the results of a newly completed prescription event monitoring study are awaited with interest. The potential use of computerised databases and record linkage is examined, but at present the number of quinolone prescriptions is too small to assess documentation of serious but rare events such as convulsions. Physicians need to be aware of the limitations of current data on suspected ADRs. Further investment in computerised databases is required to satisfy the requirements for attributing causality of an event to a drug.

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

PubMed

Castleden, C M; Pickles, H

1988-10-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

PubMed Central

Castleden, C M; Pickles, H

1988-01-01

1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age. PMID:3263875

Expanded functions for a family of plant intracellular immune receptors beyond specific recognition of pathogen effectors

PubMed Central

Bonardi, Vera; Tang, Saijun; Stallmann, Anna; Roberts, Melinda; Cherkis, Karen; Dangl, Jeffery L.

2011-01-01

Plants and animals deploy intracellular immune receptors that perceive specific pathogen effector proteins and microbial products delivered into the host cell. We demonstrate that the ADR1 family of Arabidopsis nucleotide-binding leucine-rich repeat (NB-LRR) receptors regulates accumulation of the defense hormone salicylic acid during three different types of immune response: (i) ADRs are required as “helper NB-LRRs” to transduce signals downstream of specific NB-LRR receptor activation during effector-triggered immunity; (ii) ADRs are required for basal defense against virulent pathogens; and (iii) ADRs regulate microbial-associated molecular pattern-dependent salicylic acid accumulation induced by infection with a disarmed pathogen. Remarkably, these functions do not require an intact P-loop motif for at least one ADR1 family member. Our results suggest that some NB-LRR proteins can serve additional functions beyond canonical, P-loop–dependent activation by specific virulence effectors, extending analogies between intracellular innate immune receptor function from plants and animals. PMID:21911370

Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

PubMed

O'Callaghan, J; Griffin, B T; Morris, J M; Bermingham, Margaret

2018-06-01

In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines. The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland. Hospital doctors (n = 88), general practitioners (GPs) (n = 197), nurses (n = 104) and pharmacists (n = 309) completed an online questionnaire. There were differences in mean knowledge scores relating to ADR reporting and the pharmacovigilance of biologicals among the HCP groups. The majority of HCPs who use biological medicines in their practice generally record biologicals by brand name but practice behaviours relating to batch number recording differed between some professions. HCPs consider batch number recording to be valuable but also regard it as being more difficult than brand name recording. Most respondents were aware of the concept of additional monitoring but awareness rates differed between some groups. Among those who knew about additional monitoring, there was higher awareness of the inverted black triangle symbol among pharmacists (> 86.4%) compared with hospital doctors (35.1%), GPs (35.6%), and nurses (14.9%). Hospital pharmacists had more experience and knowledge of ADR reporting than other practising HCPs. This study highlights the important role hospital pharmacists play in post-marketing surveillance. There is a need to increase pharmacovigilance awareness of biological medicines and improve systems to support their batch traceability.

Comparative study on drug safety surveillance between medical students of Malaysia and Nigeria

PubMed Central

Abubakar, Abdullahi Rabiu; Ismail, Salwani; Rahman, Nor Iza A; Haque, Mainul

2015-01-01

Background Internationally, there is a remarkable achievement in the areas of drug discovery, drug design, and clinical trials. New and efficient drug formulation techniques are widely available which have led to success in treatment of several diseases. Despite these achievements, large number of patients continue to experience adverse drug reactions (ADRs), and majority of them are yet to be on record. Objectives The purpose of this survey is to compare knowledge, attitude, and practice with respect to ADRs and pharmacovigilance (PV) between medical students of Malaysia and Nigeria and to determine if there is a relationship between their knowledge and practice. Method A cross-sectional, questionnaire-based survey involving year IV and year V medical students of the Department of Medicine, Universiti Sultan Zainal Abidin and Bayero University Kano was carried out. The questionnaire which comprised 25 questions on knowledge, attitude, and practice was adopted, modified, validated, and administered to them. The response was analyzed using SPSS version 20. Results The response rate from each country was 74%. There was a statistically significant difference in mean knowledge and practice score on ADRs and PV between medical students of Malaysia and Nigeria, both at P<0.000. No significance difference in attitude was observed at P=0.389. Also, a statistically significant relationship was recorded between their knowledge and practice (r=0.229, P=0.001), although the relationship was weak. Conclusion Nigerian medical students have better knowledge and practice than those of Malaysia, although they need improvement. Imparting knowledge of ADRs and PV among medical students will upgrade their practice and enhance health care delivery services in the future. PMID:26170680