Errors, near misses and adverse events in the emergency department: what can patients tell us?

PubMed

Friedman, Steven M; Provan, David; Moore, Shannon; Hanneman, Kate

2008-09-01

We sought to determine whether patients or their families could identify adverse events in the emergency department (ED), to characterize patient reports of errors and to compare patient reports to events recorded by health care providers. This was a prospective cohort study in a quaternary care inner city teaching hospital with approximately 40,000 annual visits. ED patients were recruited for participation in a standardized interview within 24 hours of ED discharge and a follow-up interview 3-7 days after discharge. Responses regarding events were tabulated and compared with physician and nurse notations in the medical record and hospital event reporting system. Of 292 eligible patients, 201 (69%) were interviewed within 24 hours of ED discharge, and 143 (71% of interviewees) underwent a follow-up interview 3-7 days after discharge. Interviewees did not differ from the base ED population in terms of age, sex or language. Analysis of patient interviews identified 10 adverse events (5% incident rate; 95% confidence interval [CI] 2.41%-8.96%), 8 near misses (4% incident rate; 95% CI 1.73%-7.69%) and no medical errors. Of the 10 adverse events, 6 (60%) were characterized as preventable (2 raters; kappa=0.78, standard error [SE] 0.20; 95% CI 0.39-1.00; p=0.01). Adverse events were primarily related to delayed or inadequate analgesia. Only 4 out of 8 (50%) near misses were intercepted by hospital personnel. The secondary interview elicited 2 out of 10 adverse events and 3 out of 8 near misses that had not been identified in the primary interview. No designation (0 out of 10) of an adverse event was recorded in the ED medical record or in the confidential hospital event reporting system. ED patients can identify adverse events affecting their care. Moreover, many of these events are not recorded in the medical record. Engaging patients and their family members in identification of errors may enhance patient safety.

Adverse events associated with meropenem versus imipenem/cilastatin therapy in a large retrospective cohort of hospitalized infants.

PubMed

Hornik, Christoph P; Herring, Amy H; Benjamin, Daniel K; Capparelli, Edmund V; Kearns, Gregory L; van den Anker, John; Cohen-Wolkowiez, Michael; Clark, Reese H; Smith, P Brian

2013-07-01

Carbapenems are commonly used in hospitalized infants despite a lack of complete safety data and associations with seizures in older children. We compared the incidence of adverse events in hospitalized infants receiving meropenem versus imipenem/cilastatin. We conducted a retrospective cohort study of 5566 infants treated with meropenem or imipenem/cilastatin in neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2010. Multivariable conditional logistic regression was performed to evaluate the association between carbapenem therapy and adverse events, controlling for infant factors and severity of illness. Adverse events were more common with use of meropenem compared with imipenem/cilastatin (62.8/1000 infant days versus 40.7/1000 infant days, P < 0.001). There was no difference in seizures with meropenem versus imipenem/cilastatin (adjusted odds ratio 0.96; 95% confidence interval: 0.68, 1.32). The incidence of death, as well as the combined outcome of death or seizure, was lower with meropenem use-odds ratio 0.68 (0.50, 0.88) and odds ratio 0.77 (0.62, 0.95), respectively. In this cohort of infants, meropenem was associated with more frequent but less severe adverse events when compared with imipenem/cilastatin.

Development of an online morbidity, mortality, and near-miss reporting system to identify patterns of adverse events in surgical patients.

PubMed

Bilimoria, Karl Y; Kmiecik, Thomas E; DaRosa, Debra A; Halverson, Amy; Eskandari, Mark K; Bell, Richard H; Soper, Nathaniel J; Wayne, Jeffrey D

2009-04-01

To design a Web-based system to track adverse and near-miss events, to establish an automated method to identify patterns of events, and to assess the adverse event reporting behavior of physicians. A Web-based system was designed to collect physician-reported adverse events including weekly Morbidity and Mortality (M&M) entries and anonymous adverse/near-miss events. An automated system was set up to help identify event patterns. Adverse event frequency was compared with hospital databases to assess reporting completeness. A metropolitan tertiary care center. Identification of adverse event patterns and completeness of reporting. From September 2005 to August 2007, 15,524 surgical patients were reported including 957 (6.2%) adverse events and 34 (0.2%) anonymous reports. The automated pattern recognition system helped identify 4 event patterns from M&M reports and 3 patterns from anonymous/near-miss reporting. After multidisciplinary meetings and expert reviews, the patterns were addressed with educational initiatives, correction of systems issues, and/or intensive quality monitoring. Only 25% of complications and 42% of inpatient deaths were reported. A total of 75.2% of adverse events resulting in permanent disability or death were attributed to the nature of the disease. Interventions to improve reporting were largely unsuccessful. We have developed a user-friendly Web-based system to track complications and identify patterns of adverse events. Underreporting of adverse events and attributing the complication to the nature of the disease represent a problem in reporting culture among surgeons at our institution. Similar systems should be used by surgery departments, particularly those affiliated with teaching hospitals, to identify quality improvement opportunities.

Development of a database and processing method for detecting hematotoxicity adverse drug events.

PubMed

Shimai, Yoshie; Takeda, Toshihiro; Manabe, Shirou; Teramoto, Kei; Mihara, Naoki; Matsumura, Yasushi

2015-01-01

Adverse events are detected by monitoring the patient's status, including blood test results. However, it is difficult to identify all adverse events based on recognition by individual doctors. We developed a system that can be used to detect hematotoxicity adverse events according to blood test results recorded in an electronic medical record system. The blood test results were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood test results (Up, Down, Flat) were assessed according to the variation in the grade. The changes in the blood test and injection data were stored in a database. By comparing the date of injection and start and end dates of the change in the blood test results, adverse events related to a designated drug were detected. Using this method, we searched for the occurrence of serious adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and 0.4%, respectively. This method is useful for detecting and estimating the rate of occurrence of hematotoxicity adverse drug events.

Acute adverse events associated with the administration of Crotalidae polyvalent immune Fab antivenom within the North American Snakebite Registry.

PubMed

Kleinschmidt, Kurt; Ruha, Anne-Michelle; Campleman, Sharan; Brent, Jeffrey; Wax, Paul

2018-04-24

Crotalidae Polyvalent Immune Fab (Fab Antivenom) is the primary Viperid antivenom used in the United States since 2000. Adverse event data associated with its use are limited. The purpose of this study is to describe the prevalence of acute adverse events associated with the use of Fab antivenom. The American College of Medical Toxicology's Toxicology Investigators Consortium maintains a prospective case registry of poisoned and envenomated patients managed by medical toxicologists at the bedside. This registry includes the North American Snakebite sub-registry. We performed a review of 438 cases entered into the Snakebite sub-registry. A total of 373 (85.2%) received at least one vial of Fab Antivenom. Forty percent were children. Adverse events occurred in 10 patients (2.7%) of whom six were adults. Rash was the most common adverse event. More severe adverse events (hypotension, bronchospasm, and/or angioedema) occurred in four (1.1%) patients. Prophylaxis was administered prior to Fab antivenom in 4.0%. Eight patients received various treatments for their adverse events. Neither the initial number of Fab antivenom vials, atopic history, nor prior envenomation correlated with the prevalence of adverse events. This prevalence of adverse events was lower than in previous studies and in a meta-analysis of 11 studies. The types of adverse events and treatments used are consistent with those in previous reports. There were no prior reports of prophylaxis use with which to compare. The prevalence of Fab antivenom adverse events in the North American Snakebite Registry was 2.7%.

ACCEPT: Introduction of the Adverse Condition and Critical Event Prediction Toolbox

NASA Technical Reports Server (NTRS)

Martin, Rodney A.; Santanu, Das; Janakiraman, Vijay Manikandan; Hosein, Stefan

2015-01-01

The prediction of anomalies or adverse events is a challenging task, and there are a variety of methods which can be used to address the problem. In this paper, we introduce a generic framework developed in MATLAB (sup registered mark) called ACCEPT (Adverse Condition and Critical Event Prediction Toolbox). ACCEPT is an architectural framework designed to compare and contrast the performance of a variety of machine learning and early warning algorithms, and tests the capability of these algorithms to robustly predict the onset of adverse events in any time-series data generating systems or processes.

Assessing stress-related treatment needs among girls at risk for poor functional outcomes: The impact of cumulative adversity, criterion traumas, and non-criterion events.

PubMed

Lansing, Amy E; Plante, Wendy Y; Beck, Audrey N

2017-05-01

Despite growing recognition that cumulative adversity (total stressor exposure, including complex trauma), increases the risk for psychopathology and impacts development, assessment strategies lag behind: Adversity-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A traumatic event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (separation from caregivers) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: (1) an average of 14 adverse Criterion-A and non-Criterion event exposures; (2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; (3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and (4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assignment of adverse event indexing terms in randomized clinical trials involving spinal manipulative therapy: an audit of records in MEDLINE and EMBASE databases.

PubMed

Gorrell, Lindsay M; Engel, Roger M; Lystad, Reidar P; Brown, Benjamin T

2017-03-14

Reporting of adverse events in randomized clinical trials (RCTs) is encouraged by the authors of The Consolidated Standards of Reporting Trials (CONSORT) statement. With robust methodological design and adequate reporting, RCTs have the potential to provide useful evidence on the incidence of adverse events associated with spinal manipulative therapy (SMT). During a previous investigation, it became apparent that comprehensive search strategies combining text words with indexing terms was not sufficiently sensitive for retrieving records that were known to contain reports on adverse events. The aim of this analysis was to compare the proportion of articles containing data on adverse events associated with SMT that were indexed in MEDLINE and/or EMBASE and the proportion of those that included adverse event-related words in their title or abstract. A sample of 140 RCT articles previously identified as containing data on adverse events associated with SMT was used. Articles were checked to determine if: (1) they had been indexed with relevant terms describing adverse events in the MEDLINE and EMBASE databases; and (2) they mentioned adverse events (or any related terms) in the title or abstract. Of the 140 papers, 91% were MEDLINE records, 85% were EMBASE records, 81% were found in both MEDLINE and EMBASE records, and 4% were not in either database. Only 19% mentioned adverse event-related text words in the title or abstract. There was no significant difference between MEDLINE and EMBASE records in the proportion of available papers (p = 0.078). Of the 113 papers that were found in both MEDLINE and EMBASE records, only 3% had adverse event-related indexing terms assigned to them in both databases, while 81% were not assigned an adverse event-related indexing term in either database. While there was effective indexing of RCTs involving SMT in the MEDLINE and EMBASE databases, there was a failure of allocation of adverse event indexing terms in both databases. We recommend the development of standardized definitions and reporting tools for adverse events associated with SMT. Adequate reporting of adverse events associated with SMT will facilitate accurate indexing of these types of manuscripts in the databases.

Mitigating adverse event reporting bias in spine surgery.

PubMed

Auerbach, Joshua D; McGowan, Kevin B; Halevi, Marci; Gerling, Michael C; Sharan, Alok D; Whang, Peter G; Maislin, Greg

2013-08-21

Recent articles in the lay press and literature have raised concerns about the ability to report honest adverse event data from industry-sponsored spine surgery studies. To address this, clinical trials may utilize an independent Clinical Events Committee (CEC) to review adverse events and readjudicate the severity and relatedness accordingly. We are aware of no prior study that has quantified either the degree to which investigator bias is present in adverse event reporting or the effect that an independent CEC has on mitigating this potential bias. The coflex Investigational Device Exemption study is a prospective randomized controlled trial comparing coflex (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis and spondylolisthesis. Investigators classified the severity of adverse events (mild, moderate, or severe) and their relationship to the surgery and device (unrelated, unlikely, possibly, probably, or definitely). An independent CEC, composed of three spine surgeons without affiliation to the study sponsor, reviewed and reclassified all adverse event reports submitted by the investigators. The CEC reclassified the level of severity, relation to the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported adverse events. The proportion of adverse events that underwent reclassification was similar in the coflex and fusion groups (37.9% compared with 36.0%, p = 0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1 to 10.6) times more likely to upgrade than downgrade the relationship to the surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than downgrade the relationship to the device. The status of the investigator's financial interest in the company had little effect on the reclassification of adverse events. Thirty-seven percent of adverse events were reclassified by the CEC; the large majority of the reclassifications were an upgrade in the level of severity or a designation of greater relatedness to the surgery or device. An independent CEC can identify and mitigate potential inherent investigator bias and facilitate an accurate assessment of the safety profile of an investigational device, and a CEC should be considered a requisite component of future clinical trials.

Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.

PubMed

Bhat, Amritha; Grote, Nancy K; Russo, Joan; Lohr, Mary Jane; Jung, Hyunzee; Rouse, Caroline E; Howell, Elaine C; Melville, Jennifer L; Carson, Kathy; Katon, Wayne

2017-01-01

The study examined the effectiveness of a perinatal collaborative care intervention in moderating the effects of adverse neonatal birth events on risks of postpartum depressive symptoms and impaired functioning among women of lower socioeconomic status with antenatal depression. A randomized controlled trial with blinded outcome assessments was conducted in ten public health centers, comparing MOMCare (choice of brief interpersonal psychotherapy, pharmacotherapy, or both) with intensive maternity support services (MSS-Plus). Participants had probable diagnoses of major depressive disorder or dysthymia during pregnancy. Generalized estimating equations estimated differences in depression and functioning measures between groups with and without adverse birth events within the treatment arms. A total of 160 women, 43% of whom experienced at least one adverse birth event, were included in the analyses. For women who received MOMCare, postpartum depression scores (measured with the Symptom Checklist-20) did not differ by whether or not they experienced an adverse birth event (mean±SD scores of .86±.51 for mothers with an adverse birth event and .83±.56 for mothers with no event; p=.78). For women who received MSS-Plus, having an adverse birth event was associated with persisting depression in the postpartum period (mean scores of 1.20±.0.61 for mothers with an adverse birth event and .93±.52 for mothers without adverse birth event; p=.04). Similar results were seen for depression response rates and functioning. MOMCare mitigated the risk of postpartum depressive symptoms and impaired functioning among women of low socioeconomic status who had antenatal depression and who experienced adverse birth events.

Adverse reactions to two intravenous antibiotics (Augmentin and Zinacef) used for surgical prophylaxis in dogs.

PubMed

Gosling, Mark James; Martínez-Taboada, Fernando

2018-01-20

Antibiotic prophylaxis in dogs undergoing surgical procedures frequently involves the administration of a product without a veterinary licence. Two drugs commonly used for this purpose are the clavulanate amoxicillin Augmentin and the cefuroxime Zinacef. This prospective observational study aims to compare the incidence of adverse events associated with these two antibiotics in a clinical setting. The authors hypothesised that a higher incidence of adverse effects would be observed with Augmentin. Sixty-five dogs were included in the study and adverse events were recorded using a modified scoring system. A significantly higher incidence of adverse events to Augmentin (8/22; 36 per cent) was observed compared with Zinacef (1/43; 2 per cent) (P=0.0003). The majority of these adverse events involved cutaneous signs and/or hypotension. These findings might be taken into consideration when selecting one of these intravenous antibiotics for prophylaxis in anaesthetised dogs undergoing surgery. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Filing Sources after Oral P2Y12 Platelet Inhibitors to the Food and Drug Administration Adverse Event Reporting System (FAERS).

PubMed

Serebruany, Victor L; Cherepanov, Vasily; Kim, Moo Hyun; Litvinov, Oleg; Cabrera-Fuentes, Hector A; Marciniak, Thomas A

The US Food and Drug Administration Adverse Event Reporting System (FAERS) is a global passive surveillance database that relies on voluntary reporting by health care professionals and consumers as well as required mandatory reporting by pharmaceutical manufacturers. However, the initial filers and comparative patterns for oral P2Y12 platelet inhibitor reporting are unknown. We assessed who generated original FAERS reports for clopidogrel, prasugrel, and ticagrelor in 2015. From the FAERS database we extracted and examined adverse event cases coreported with oral P2Y12 platelet inhibitors. All adverse event filing originating sources were dichotomized into consumers, lawyers, pharmacists, physicians, other health care professionals, and unknown. Overall, 2015 annual adverse events were more commonly coreported with clopidogrel (n = 13,234) with known source filers (n = 12,818, or 96.9%) than with prasugrel (2,896; 98.9% out of 2,927 cases) or ticagrelor (2,163, or 82.3%, out of 2,627 cases, respectively). Overall, most adverse events were filed by consumers (8,336, or 44.4%), followed by physicians (5,290, or 28.2%), other health care professionals (2,997, or 16.0%), pharmacists (1,125, or 6.0%), and finally by lawyers (129, or 0.7%). The origin of 811 (4.7%) initial reports remains unknown. The adverse event filing sources differ among drugs. While adverse events coreported with clopidogrel and prasugrel were commonly originated by patients (40.4 and 84.3%, respectively), most frequently ticagrelor reports (42.5%) were filed by physicians. The reporting quality and initial sources differ among oral P2Y12 platelet inhibitors in FAERS. The ticagrelor surveillance in 2015 was inadequate when compared to clopidogrel and prasugrel. Patients filed most adverse events for clopidogrel and prasugrel, while physicians originated most ticagrelor complaints. These differences justify stricter compliance control for ticagrelor manufacturers and may be attributed to the confusion of treating physicians with unexpected fatal, cardiac, and thrombotic adverse events linked to ticagrelor. © 2017 S. Karger AG, Basel.

Adverse Events Associated with Meropenem versus Imipenem/Cilastatin Therapy in a Large Retrospective Cohort of Hospitalized Infants

PubMed Central

Hornik, Christoph P.; Herring, Amy H.; Benjamin, Daniel K.; Capparelli, Edmund V.; Kearns, Gregory L.; van den Anker, John; Cohen-Wolkowiez, Michael; Clark, Reese H.; Smith, P. Brian

2013-01-01

Background Carbapenems are commonly used in hospitalized infants despite a lack of complete safety data and associations with seizures in older children. We compared the incidence of adverse events in hospitalized infants receiving meropenem versus imipenem/cilastatin. Methods We conducted a retrospective cohort study of 5566 infants treated with meropenem or imipenem/cilastatin in neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2010. Multivariable conditional logistic regression was performed to evaluate the association between carbapenem therapy and adverse events, controlling for infant factors and severity of illness. Results Adverse events were more common with use of meropenem compared with imipenem/cilastatin (62.8/1000 infant days vs. 40.7/1000 infant days, P<0.001). There was no difference in seizures with meropenem vs. imipenem/cilastatin (adjusted odds ratio [OR] 0.96; 95% confidence interval 0.68, 1.32). The incidence of death, as well as the combined outcome of death or seizure, was lower with meropenem use—OR 0.68 (0.50, 0.88) and OR 0.77 (0.62, 0.95), respectively. Conclusion In this cohort of infants, meropenem was associated with more frequent but less severe adverse events when compared with imipenem/cilastatin. PMID:23838776

Methodological Considerations for Comparison of Brand Versus Generic Versus Authorized Generic Adverse Event Reports in the US Food and Drug Administration Adverse Event Reporting System (FAERS).

PubMed

Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, David C; Hansen, Richard A

2017-12-01

The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

Adverse events associated with single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

PubMed

Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

2015-10-13

This is an update of a Cochrane overview published in Issue 9, 2011; that overview considered both efficacy and adverse events. This overview considers adverse events, with efficacy dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the adverse events associated with individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews. To provide an overview of adverse event rates associated with single-dose oral analgesics, compared with placebo, for acute postoperative pain in adults. We identified systematic reviews in The Cochrane Database of Systematic Reviews on The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group. We extracted information related to participants experiencing any adverse event, and reports of serious adverse events, and deaths from the individual reviews. Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth.For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events.Serious adverse events were rare, occurring a rate of about 1 in 3200 participants.Most reviews did not report specific adverse events. Despite ongoing problems with the measurement, recording, and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.

Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

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

Connor, Michael J.; Department of Radiation Oncology, University of California Irvine School of Medicine, Irvine, California; Marshall, Deborah C.

Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact).more » Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ{sup 2} test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance, improved software design, and manufacturer–user training may help mitigate these events.« less

Assessing Stress-Related Treatment Needs among Girls at Risk for Poor Functional Outcomes: The Impact of Cumulative Adversity, Criterion Traumas, and Non-Criterion Events

PubMed Central

Lansing, Amy E.; Plante, Wendy Y.; Beck, Audrey N.

2016-01-01

Despite growing recognition that cumulative adversity (total stressor exposure), including complex trauma, increases the risk for psychopathology and impacts development, assessment strategies lag behind: Trauma-related mental health needs (symptoms, functional impairment, maladaptive coping) are typically assessed in response to only one qualifying Criterion-A event. This is especially problematic for youth at-risk for health and academic disparities who experience cumulative adversity, including non-qualifying events (parental separations) which may produce more impairing symptomatology. Data from 118 delinquent girls demonstrate: 1) an average of 14 adverse Criterion-A and non-Criterion event exposures; 2) serious maladaptive coping strategies (self-injury) directly in response to cumulative adversity; 3) more cumulative adversity-related than worst-event related symptomatology and functional impairment; and 4) comparable symptomatology, but greater functional impairment, in response to non-Criterion events. These data support the evaluation of mental health needs in response to cumulative adversity for optimal identification and tailoring of services in high-risk populations to reduce disparities. PMID:27745922

Adverse event rates and classifications in medial opening wedge high tibial osteotomy.

PubMed

Martin, Robin; Birmingham, Trevor B; Willits, Kevin; Litchfield, Robert; Lebel, Marie-Eve; Giffin, J Robert

2014-05-01

Previously reported complications in medial opening wedge (MOW) high tibial osteotomy (HTO) vary considerably in both rate and severity. (1) To determine the rates of adverse events in MOW HTO classified into different grades of severity based on the treatments required and (2) to compare patient-reported outcomes between the different adverse event classifications. Case series; Level of evidence, 4. All patients receiving MOW HTO at a single medical center from 2005 to 2009 were included. Internal fixation was used in all cases, with either a nonlocking (Puddu) or locking (Tomofix) plate. Patients were evaluated at 2, 6, and 12 weeks; 6 and 12 months; and annually thereafter. Types of potential surgical and postoperative adverse events, categorized into 3 classes of severity based on the subsequent treatments, were defined a priori. Medical records and radiographs were then reviewed by an independent observer. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were compared in subgroups of patients based on the categories of adverse events observed. A total of 323 consecutive procedures (242 males) were evaluated (age, mean ± standard deviation, 46 ± 9 years; body mass index, mean ± standard deviation, 30 ± 5 kg/m(2)). Adverse events requiring no additional treatment (class 1) were undisplaced lateral cortical breaches (20%), displaced (>2 mm) lateral hinge fracture (6%), delayed wound healing (6%), undisplaced lateral tibial plateau fracture (3%), hematoma (3%), and increased tibial slope ≥10° (1%). Adverse events requiring additional or extended nonoperative management (class 2) were delayed union (12%), cellulitis (10%), limited hardware failure (1 broken screw; 4%), postoperative stiffness (1%), deep vein thrombosis (1%), and complex regional pain syndrome (CRPS) type 1 (1%). Adverse events requiring additional or revision surgery and/or long-term medical care (class 3) were aseptic nonunion (3%), deep infection (2%), CRPS type 2 (1%), and severe hardware failure with loss of correction (1%). Additional surgery rate was 3%. Class 1 and 2 adverse events did not affect patient-reported outcomes at 6, 12, or 24 months postoperatively. Patients with class 3 adverse events had significantly lower total WOMAC scores at 6 months but not at 12 or 24 months postoperatively. The most common adverse event in MOW HTO requiring extended nonoperative treatment (class 2) is delayed union (12%). The rate of severe adverse events requiring additional surgery and/or long-term medical care (class 3) is low (7%).

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

PubMed

Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

2017-10-01

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

Summarizing the incidence of adverse events using volcano plots and time intervals.

PubMed

Zink, Richard C; Wolfinger, Russell D; Mann, Geoffrey

2013-01-01

Adverse event incidence analyses are a critical component for describing the safety profile of any new intervention. The results typically are presented in lengthy summary tables. For therapeutic areas where patients have frequent adverse events, analysis and interpretation are made more difficult by the sheer number and variety of events that occur. Understanding the risk in these instances becomes even more crucial. We describe a space-saving graphical summary that overcomes the limitations of traditional presentations of adverse events and improves interpretability of the safety profile. We present incidence analyses of adverse events graphically using volcano plots to highlight treatment differences. Data from a clinical trial of patients experiencing an aneurysmal subarachnoid hemorrhage are used for illustration. Adjustments for multiplicity are illustrated. Color is used to indicate the treatment with higher incidence; bubble size represents the total number of events that occur in the treatment arms combined. Adjustments for multiple comparisons are displayed in a manner to indicate clearly those events for which the difference between treatment arms is statistically significant. Furthermore, adverse events can be displayed by time intervals, with multiple volcano plots or animation to appreciate changes in adverse event risk over time. Such presentations can emphasize early differences across treatments that may resolve later or highlight events for which treatment differences may become more substantial with longer follow-up. Treatment arms are compared in a pairwise fashion. Volcano plots are space-saving tools that emphasize important differences between the adverse event profiles of two treatment arms. They can incorporate multiplicity adjustments in a manner that is straightforward to interpret and, by using time intervals, can illustrate how adverse event risk changes over the course of a clinical trial.

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury.

Despite 2007 law requiring FDA hotline to be included in print drug ads, reporting of adverse events by consumers still low.

PubMed

Du, Dongyi; Goldsmith, John; Aikin, Kathryn J; Encinosa, William E; Nardinelli, Clark

2012-05-01

In 2007 the federal government began requiring drug makers to include in their print direct-to-consumer advertisements information for consumers on how to contact the Food and Drug Administration directly, either by phone or through the agency's website, to report any adverse events that they experienced after taking a prescription drug. Adverse events can range from minor skin problems like itching to serious injuries or illness that result in hospitalization, permanent disability, or even death. Even so, current rates of adverse event reporting are low. We studied adverse event reports about 123 drugs that came from patients before and after the enactment of the print advertising requirement and estimated that requirement's impact with model simulations. We found that if monthly spending on print direct-to-consumer advertising increased from zero to $7.7 million per drug, the presence of the Food and Drug Administration contact information tripled the increase in patient-reported adverse events, compared to what would have happened in the absence of the law. However, the absolute monthly increase was fewer than 0.24 reports per drug, suggesting that the public health impact of the increase was small and that the adverse event reporting rate would still be low. The study results suggest that additional measures, such as more publicity about the Adverse Event Reporting System or more consumer education, should be considered to promote patient reporting of adverse events.

Safety of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and Influenza Vaccinations in Pregnancy.

PubMed

Sukumaran, Lakshmi; McCarthy, Natalie L; Kharbanda, Elyse O; Weintraub, Eric S; Vazquez-Benitez, Gabriela; McNeil, Michael M; Li, Rongxia; Klein, Nicola P; Hambidge, Simon J; Naleway, Allison L; Lugg, Marlene M; Jackson, Michael L; King, Jennifer P; DeStefano, Frank; Omer, Saad B; Orenstein, Walter A

2015-11-01

To evaluate the safety of coadministering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination. We conducted a retrospective cohort study of pregnant women aged 14-49 years in the Vaccine Safety Datalink from January 1, 2007, to November 15, 2013. We compared medically attended acute events (fever, any acute reaction) and adverse birth outcomes (preterm delivery, low birth weight, small for gestational age) in women receiving concomitant Tdap and influenza vaccination and women receiving sequential vaccination. Among 36,844 pregnancies in which Tdap and influenza vaccines were administered, the vaccines were administered concomitantly in 8,464 (23%) pregnancies and sequentially in 28,380 (77%) pregnancies. Acute adverse events after vaccination were rare. We found no statistically significant increased risk of fever or any medically attended acute adverse event in pregnant women vaccinated concomitantly compared with sequentially. When analyzing women at 20 weeks of gestation or greater during periods of influenza vaccine administration, there were no differences in preterm delivery, low-birth-weight, or small-for-gestational-age neonates between women vaccinated concomitantly compared with sequentially in pregnancy. Concomitant administration of Tdap and influenza vaccines during pregnancy was not associated with a higher risk of medically attended adverse acute outcomes or birth outcomes compared with sequential vaccination. II.

Adverse events with bismuth salts for Helicobacter pylori eradication: Systematic review and meta-analysis

PubMed Central

Ford, Alexander C; Malfertheiner, Peter; Giguère, Monique; Santana, José; Khan, Mostafizur; Moayyedi, Paul

2008-01-01

AIM: To assess the safety of bismuth used in Helicobacter pylori (H pylori) eradication therapy regimens. METHODS: We conducted a systematic review and meta-analysis. MEDLINE and EMBASE were searched (up to October 2007) to identify randomised controlled trials comparing bismuth with placebo or no treatment, or bismuth salts in combination with antibiotics as part of eradication therapy with the same dose and duration of antibiotics alone or, in combination, with acid suppression. Total numbers of adverse events were recorded. Data were pooled and expressed as relative risks with 95% confidence intervals (CI). RESULTS: We identified 35 randomised controlled trials containing 4763 patients. There were no serious adverse events occurring with bismuth therapy. There was no statistically significant difference detected in total adverse events with bismuth [relative risk (RR) = 1.01; 95% CI: 0.87-1.16], specific individual adverse events, with the exception of dark stools (RR = 5.06; 95% CI: 1.59-16.12), or adverse events leading to withdrawal of therapy (RR = 0.86; 95% CI: 0.54-1.37). CONCLUSION: Bismuth for the treatment of H pylori is safe and well-tolerated. The only adverse event occurring significantly more commonly was dark stools. PMID:19109870

Hip fractures are risky business: an analysis of the NSQIP data.

PubMed

Sathiyakumar, Vasanth; Greenberg, Sarah E; Molina, Cesar S; Thakore, Rachel V; Obremskey, William T; Sethi, Manish K

2015-04-01

Hip fractures are one of the most common types of orthopaedic injury with high rates of morbidity. Currently, no study has compared risk factors and adverse events following the different types of hip fracture surgeries. The purpose of this paper is to investigate the major and minor adverse events and risk factors for complication development associated with five common surgeries for the treatment of hip fractures using the NSQIP database. Using the ACS-NSQIP database, complications for five forms of hip surgeries were selected and categorized into major and minor adverse events. Demographics and clinical variables were collected and an unadjusted bivariate logistic regression analyses was performed to determine significant risk factors for adverse events. Five multivariate regressions were run for each surgery as well as a combined regression analysis. A total of 9640 patients undergoing surgery for hip fracture were identified with an adverse events rate of 25.2% (n=2433). Open reduction and internal fixation of a femoral neck fracture had the greatest percentage of all major events (16.6%) and total adverse events (27.4%), whereas partial hip hemiarthroplasty had the greatest percentage of all minor events (11.6%). Mortality was the most common major adverse event (44.9-50.6%). For minor complications, urinary tract infections were the most common minor adverse event (52.7-62.6%). Significant risk factors for development of any adverse event included age, BMI, gender, race, active smoking status, history of COPD, history of CHF, ASA score, dyspnoea, and functional status, with various combinations of these factors significantly affecting complication development for the individual surgeries. Hip fractures are associated with significantly high numbers of adverse events. The type of surgery affects the type of complications developed and also has an effect on what risk factors significantly predict the development of a complication. Concerted efforts from orthopaedists should be made to identify higher risk patients and prevent the most common adverse events that occur postoperatively. Copyright © 2014 Elsevier Ltd. All rights reserved.

Assessing Adverse Events of Postprostatectomy Radiation Therapy for Prostate Cancer: Evaluation of Outcomes in the Regione Emilia-Romagna, Italy

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

Showalter, Timothy N., E-mail: tns3b@virginia.edu; Hegarty, Sarah E.; Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania

Purpose: Although the likelihood of radiation-related adverse events influences treatment decisions regarding radiation therapy after prostatectomy for eligible patients, the data available to inform decisions are limited. This study was designed to evaluate the genitourinary, gastrointestinal, and sexual adverse events associated with postprostatectomy radiation therapy and to assess the influence of radiation timing on the risk of adverse events. Methods: The Regione Emilia-Romagna Italian Longitudinal Health Care Utilization Database was queried to identify a cohort of men who received radical prostatectomy for prostate cancer during 2003 to 2009, including patients who received postprostatectomy radiation therapy. Patients with prior radiation therapymore » were excluded. Outcome measures were genitourinary, gastrointestinal, and sexual adverse events after prostatectomy. Rates of adverse events were compared between the cohorts who did and did not receive postoperative radiation therapy. Multivariable Cox proportional hazards models were developed for each class of adverse events, including models with radiation therapy as a time-varying covariate. Results: A total of 9876 men were included in the analyses: 2176 (22%) who received radiation therapy and 7700 (78%) treated with prostatectomy alone. In multivariable Cox proportional hazards models, the additional exposure to radiation therapy after prostatectomy was associated with increased rates of gastrointestinal (rate ratio [RR] 1.81; 95% confidence interval [CI] 1.44-2.27; P<.001) and urinary nonincontinence events (RR 1.83; 95% CI 1.83-2.80; P<.001) but not urinary incontinence events or erectile dysfunction. The addition of the time from prostatectomy to radiation therapy interaction term was not significant for any of the adverse event outcomes (P>.1 for all outcomes). Conclusion: Radiation therapy after prostatectomy is associated with an increase in gastrointestinal and genitourinary adverse events. However, the timing of radiation therapy did not influence the risk of radiation therapy–associated adverse events in this cohort, which contradicts the commonly held clinical tenet that delaying radiation therapy reduces the risk of adverse events.« less

Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life Events and Emotional and Behavioural Problems in Early Adolescence: The Importance of Moderator and Outcome Specificity

ERIC Educational Resources Information Center

Flouri, Eirini; Tzavidis, Nikos

2011-01-01

This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural…

Adverse Events During a Randomized Trial of Ketamine Versus Co-Administration of Ketamine and Propofol for Procedural Sedation in a Pediatric Emergency Department.

PubMed

Weisz, Keith; Bajaj, Lalit; Deakyne, Sara J; Brou, Lina; Brent, Alison; Wathen, Joseph; Roosevelt, Genie E

2017-07-01

The co-administration of ketamine and propofol (CoKP) is thought to maximize the beneficial profile of each medication, while minimizing the respective adverse effects of each medication. Our objective was to compare adverse events between ketamine monotherapy (KM) and CoKP for procedural sedation and analgesia (PSA) in a pediatric emergency department (ED). This was a prospective, randomized, single-blinded, controlled trial of KM vs. CoKP in patients between 3 and 21 years of age. The attending physician administered either ketamine 1 mg/kg i.v. or ketamine 0.5 mg/kg and propofol 0.5 mg/kg i.v. The physician could administer up to three additional doses of ketamine (0.5 mg/kg/dose) or ketamine/propofol (0.25 mg/kg/dose of each). Adverse events (e.g., respiratory events, cardiovascular events, unpleasant emergence reactions) were recorded. Secondary outcomes included efficacy, recovery time, and satisfaction scores. Ninety-six patients were randomized to KM and 87 patients were randomized to CoKP. There was no difference in adverse events or type of adverse event, except nausea was more common in the KM group. Efficacy of PSA was higher in the KM group (99%) compared to the CoKP group (90%). Median recovery time was the same. Satisfaction scores by providers, including nurses, were higher for KM, although parents were equally satisfied with both sedation regimens. We found no significant differences in adverse events between the KM and CoKP groups. While CoKP is a reasonable choice for pediatric PSA, our study did not demonstrate an advantage of this combination over KM. Copyright © 2017 Elsevier Inc. All rights reserved.

Reporting of harms outcomes: a comparison of journal publications with unpublished clinical study reports of orlistat trials.

PubMed

Hodkinson, Alex; Gamble, Carrol; Smith, Catrin Tudur

2016-04-22

The quality of harms reporting in journal publications is often poor, which can impede the risk-benefit interpretation of a clinical trial. Clinical study reports can provide more reliable, complete, and informative data on harms compared to the corresponding journal publication. This case study compares the quality and quantity of harms data reported in journal publications and clinical study reports of orlistat trials. Publications related to clinical trials of orlistat were identified through comprehensive literature searches. A request was made to Roche (Genentech; South San Francisco, CA, USA) for clinical study reports related to the orlistat trials identified in our search. We compared adverse events, serious adverse events, and the reporting of 15 harms criteria in both document types and compared meta-analytic results using data from the clinical study reports against the journal publications. Five journal publications with matching clinical study reports were available for five independent clinical trials. Journal publications did not always report the complete list of identified adverse events and serious adverse events. We found some differences in the magnitude of the pooled risk difference between both document types with a statistically significant risk difference for three adverse events and two serious adverse events using data reported in the clinical study reports; these events were of mild intensity and unrelated to the orlistat. The CONSORT harms reporting criteria were often satisfied in the methods section of the clinical study reports (70-90 % of the methods section criteria satisfied in the clinical study reports compared to 10-50 % in the journal publications), but both document types satisfied 80-100 % of the results section criteria, albeit with greater detail being provided in the clinical study reports. In this case study, journal publications provided insufficient information on harms outcomes of clinical trials and did not specify that a subset of harms data were being presented. Clinical study reports often present data on harms, including serious adverse events, which are not reported or mentioned in the journal publications. Therefore, clinical study reports could support a more complete, accurate, and reliable investigation, and researchers undertaking evidence synthesis of harm outcomes should not rely only on incomplete published data that are presented in the journal publications.

Serious adverse events and compensation in registration trials: a review of data from a Japanese university hospital

PubMed Central

2014-01-01

Background Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials. PMID:24742228

Adverse events and comparison of systematic and voluntary reporting from a paediatric intensive care unit.

PubMed

Silas, Reshma; Tibballs, James

2010-12-01

Little is known of the incidence of adverse events in the paediatric intensive care unit (PICU). Perceived incidence may be dependent on data-collection methods. To determine the incidence of adverse events by voluntary reporting and systematic enquiry. Adverse events in PICU were recorded contemporaneously by systematic enquiry with bedside nurses and attending doctors, and compared with data submitted voluntarily to the hospital's quality and safety unit. Events were classified as insignificant, minor, moderate, major and catastrophic or lethal, and assigned origins as medical/surgical diagnosis or management, medical/surgical procedures, medication or miscellaneous. Among 740 patients, 524 adverse events (mean 0.71 per patient) occurred in 193 patients (26.1%). Systematic enquiry detected 405 (80%) among 165 patients and were classified by one investigator as insignificant 30 (7%); minor 100 (25%); moderate 160 (37%); major 103(25%) and catastrophic 12 (3%). The coefficient of agreement (kappa) of severity between the two investigators was 0.82 (95% CI 0.78-0.87). Voluntary reporting detected 166 (32%) adverse events among 100 patients, of which 119 were undetected by systematic reporting. Forty-nine events (9%) were detected by both methods. The number and severity of events reported by the two methods were significantly different (p<0.0001). Voluntary reporting, mainly by nurses, did not capture major, severe or catastrophic events related to medical/surgical diagnosis or management. Neither voluntary reporting nor systematic enquiry captures all adverse events. While the two methods both capture some events, systematic reporting captures serious events, while voluntary reporting captures mainly insignificant and minor events.

Recovery process and determinants of adverse event occurrence in bronchoscopic procedures performed under general anaesthesia.

PubMed

Özden Omaygenç, Derya; Ünal, Nermin; Edipoğlu, Saadet İpek; Barca Şeker, Tuğçe; Özgül, Mehmet Akif; Turan, Demet; Özdemir, Cengiz; Karaca, İbrahim Oğuz; Çetinkaya, Erdoğan

2018-04-16

Regarding the fact that rigid bronchoscopy is generally performed under general anaesthesia and this patient subgroup is remarkably morbid, encountering procedure and/or anaesthesia related complications are highly likely. Here, we aimed to assess factors influencing recovery and detect possible determinants of adverse event occurrence during these operations performed in a tertiary referral centre. Eighty-one consecutive ASA I-IV patients were recruited for this investigation. In the operating theatre after induction of anaesthesia and advancement of the device, maintenance was provided with total intravenous anaesthesia. Neuromuscular blockage was invariably administered, and patients were ventilated manually. In addition to preoperative demographic and procedural characteristics, perioperative hemodynamic variables, recovery times and observed adverse events were noted. Basic demographic properties, ASA and Mallampati scores, and procedure specific variables as lesion localization, lesion and procedure type were comparable among groups assembled with reference to event occurrence. Patients who had experienced adverse event had higher heart rates. Recovery times were comparable between Event (-) and Event (+) groups. Relationship of recovery process were individually tested with all variables and only lesion type was detected to have an effect on respiration and extubation times. Among all parameters only procedural time seemed to be associated with adverse event occurrence (mins, 22.9 ± 11.9 vs 41.6 ± 28.8, P < .001). Recovery times related with return of spontaneous respiration were significantly lower in procedures performed for treatment of tumoral diseases in this study and procedure length was determined to be the ultimate factor which had an impact on adverse event occurrence. © 2018 John Wiley & Sons Ltd.

Stent thrombosis with bioabsorbable polymer drug-eluting stents: insights from the Food and Drug Administration database.

PubMed

Khan, Abdur R; Tripathi, Avnish; Farid, Talha A; Abaid, Bilal; Bhatt, Deepak L; Resar, Jon R; Flaherty, Michael P

2017-11-01

SYNERGY, a bioabsorbable polymer-based, everolimus-eluting stent (BP-DES), recently received regulatory approval in the USA for use in percutaneous coronary interventions. Yet, information on the safety of BP-DES in routine clinical practice is limited. Our aim was to compare the safety of the recently approved BP-DES with current durable polymer drug-eluting stents (DP-DES) by analyzing adverse events, namely, stent thrombosis (ST), reported to the Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database requires nationwide mandatory notification for adverse events on devices approved for clinical use. This database was searched for adverse events reported between 1 October 2015 and 25 December 2016, encountered after the placement of either BP-DES or DP-DES. Only those adverse events were included where the exposure period to the stents was comparable after the index procedure. Of all the adverse events reported, the event of interest was ST. A total of 951 adverse events were reported. ST occurred in 48/951 of all events, 31/309 and 17/642 when BP-DES or DP-DES were used, respectively (P=0.00001). Of the 31 ST events with BP-DES, 68% (21/31) occurred within less than or equal to 24 h of the index procedure and 52% (16/31) occurred within less than or equal to 2 h. Our results raise the possibility of an increased risk of ST, particularly early ST (within 24 h), with the recently approved BP-DES. However, because of the inherent limitations of reporting within the MAUDE database, these data merely highlight a potential need for additional surveillance and randomized trials to assess further the safety of the bioabsorbable platform.

Differences in Antipsychotic-Related Adverse Events in Adult, Pediatric, and Geriatric Populations.

PubMed

Sagreiya, Hersh; Chen, Yi-Ren; Kumarasamy, Narmadan A; Ponnusamy, Karthik; Chen, Doris; Das, Amar K

2017-02-26

In recent years, antipsychotic medications have increasingly been used in pediatric and geriatric populations, despite the fact that many of these drugs were approved based on clinical trials in adult patients only. Preliminary studies have shown that the "off-label" use of these drugs in pediatric and geriatric populations may result in adverse events not found in adults. In this study, we utilized the large-scale U.S. Food and Drug Administration (FDA) Adverse Events Reporting System (AERS) database to look at differences in adverse events from antipsychotics among adult, pediatric, and geriatric populations. We performed a systematic analysis of the FDA AERS database using MySQL by standardizing the database using structured terminologies and ontologies. We compared adverse event profiles of atypical versus typical antipsychotic medications among adult (18-65), pediatric (age < 18), and geriatric (> 65) populations. We found statistically significant differences between the number of adverse events in the pediatric versus adult populations with aripiprazole, clozapine, fluphenazine, haloperidol, olanzapine, quetiapine, risperidone, and thiothixene, and between the geriatric versus adult populations with aripiprazole, chlorpromazine, clozapine, fluphenazine, haloperidol, paliperidone, promazine, risperidone, thiothixene, and ziprasidone (p < 0.05, with adjustment for multiple comparisons). Furthermore, the particular types of adverse events reported also varied significantly between each population for aripiprazole, clozapine, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone (Chi-square, p < 10 -6 ). Diabetes was the most commonly reported side effect in the adult population, compared to behavioral problems in the pediatric population and neurologic symptoms in the geriatric population. We also found discrepancies between the frequencies of reports in AERS and in the literature. Our analysis of the FDA AERS database shows that there are significant differences in both the numbers and types of adverse events among these age groups and between atypical and typical antipsychotics. It is important for clinicians to be mindful of these differences when prescribing antipsychotics, especially when prescribing medications off-label.

Blunt splenic injury: are early adverse events related to trauma, nonoperative management, or surgery?

PubMed Central

Frandon, Julien; Rodiere, Mathieu; Arvieux, Catherine; Vendrell, Anne; Boussat, Bastien; Sengel, Christian; Broux, Christophe; Bricault, Ivan; Ferretti, Gilbert; Thony, Frédéric

2015-01-01

PURPOSE We aimed to compare clinical outcomes and early adverse events of operative management (OM), nonoperative management (NOM), and NOM with splenic artery embolization (SAE) in blunt splenic injury (BSI) and identify the prognostic factors. METHODS Medical records of 136 consecutive patients with BSI admitted to a trauma center from 2005 to 2010 were retrospectively reviewed. Patients were separated into three groups: OM, NOM, and SAE. We focused on associated injuries and early adverse events. Multivariate analysis was performed on 23 prognostic factors to find predictors. RESULTS The total survival rate was 97.1%, with four deaths all occurred in the OM group. The spleen salvage rate was 91% in NOM and SAE. At least one adverse event was observed in 32.8%, 62%, and 96% of patients in NOM, SAE, and OM groups, respectively (P < 0.001). We found significantly more deaths, infectious complications, pleural drainage, acute renal failures, and pancreatitis in OM and more pseudocysts in SAE. Six prognostic factors were statistically significant for one or more adverse events: simplified acute physiology score 2 ≥25 for almost all adverse events, age ≥50 years for acute respiratory syndrome, limb fracture for secondary bleeding, thoracic injury for pleural drainage, and at least one associated injury for pseudocyst. Adverse events were not related to the type of BSI management. CONCLUSION Patients with BSI present worse outcome and more adverse events in OM, but this is related to the severity of injury. The main predictor of adverse events remains the severity of injury. PMID:26081719

Preterm Versus Term Children: Analysis of Sedation/Anesthesia Adverse Events and Longitudinal Risk.

PubMed

Havidich, Jeana E; Beach, Michael; Dierdorf, Stephen F; Onega, Tracy; Suresh, Gautham; Cravero, Joseph P

2016-03-01

Preterm and former preterm children frequently require sedation/anesthesia for diagnostic and therapeutic procedures. Our objective was to determine the age at which children who are born <37 weeks gestational age are no longer at increased risk for sedation/anesthesia adverse events. Our secondary objective was to describe the nature and incidence of adverse events. This is a prospective observational study of children receiving sedation/anesthesia for diagnostic and/or therapeutic procedures outside of the operating room by the Pediatric Sedation Research Consortium. A total of 57,227 patients 0 to 22 years of age were eligible for this study. All adverse events and descriptive terms were predefined. Logistic regression and locally weighted scatterplot regression were used for analysis. Preterm and former preterm children had higher adverse event rates (14.7% vs 8.5%) compared with children born at term. Our analysis revealed a biphasic pattern for the development of adverse sedation/anesthesia events. Airway and respiratory adverse events were most commonly reported. MRI scans were the most commonly performed procedures in both categories of patients. Patients born preterm are nearly twice as likely to develop sedation/anesthesia adverse events, and this risk continues up to 23 years of age. We recommend obtaining birth history during the formulation of an anesthetic/sedation plan, with heightened awareness that preterm and former preterm children may be at increased risk. Further prospective studies focusing on the etiology and prevention of adverse events in former preterm patients are warranted. Copyright © 2016 by the American Academy of Pediatrics.

Preparation for global introduction of inactivated poliovirus vaccine: safety evidence from the US Vaccine Adverse Event Reporting System, 2000-12.

PubMed

Iqbal, Shahed; Shi, Jing; Seib, Katherine; Lewis, Paige; Moro, Pedro L; Woo, Emily J; Shimabukuro, Tom; Orenstein, Walter A

2015-10-01

Safety data from countries with experience in the use of inactivated poliovirus vaccine (IPV) are important for the global polio eradication strategy to introduce IPV into the immunisation schedules of all countries. In the USA, IPV has been included in the routine immunisation schedule since 1997. We aimed to analyse adverse events after IPV administration reported to the US Vaccine Adverse Event Reporting System (VAERS). We analysed all VAERS data associated with IPV submitted between Jan 1, 2000, and Dec 31, 2012, either as individual or as combination vaccines, for all age and sex groups. We analysed the number and event type (non-serious, non-fatal serious, and death reports) of individual reports, and explored the most commonly coded event terms to describe the adverse event. We classified death reports according to previously published body-system categories (respiratory, cardiovascular, neurological, gastrointestinal, other infectious, and other non-infectious) and reviewed death reports to identify the cause of death. We classified sudden infant death syndrome as a separate cause of death considering previous concerns about sudden infant syndrome after vaccines. We used empirical Bayesian data mining methods to identify disproportionate reporting of adverse events for IPV compared with other vaccines. Additional VAERS data from 1991 to 2000 were analysed to compare the safety profiles of IPV and oral poliovirus vaccine (OPV). Of the 41,792 adverse event reports submitted, 39,568 (95%) were for children younger than 7 years. 38,381 of the reports for children in this age group (97%) were for simultaneous vaccination with IPV and other vaccines (most commonly pneumococcal and acellular pertussis vaccines), whereas standalone IPV vaccines accounted for 0·5% of all reports. 34,880 reports were for non-serious events (88%), 3905 reports were for non-fatal serious events (10%), and 783 reports were death reports (2%). Injection-site erythema was the most commonly coded term for non-serious events (29%), and pyrexia for non-fatal serious events (38%). Most deaths (96%) were in children aged 12 months or younger; most (52%) had sudden infant death syndrome as the reported cause of death. The safely profiles of combined IPV and whole-cell pertussis vaccines, OPV and whole-cell pertussis vaccines, and OPV and acellular pertussis vaccines were similar. We noted no indication of disproportionate reporting of adverse events after immunisation with IPV-containing vaccines compared with other vaccines between 1990 and 2013. Fairly few adverse events were reported for the more than 250 million IPV doses distributed between 2000 and 2012. Sudden infant death syndrome reports after IPV were consistent with reporting patterns for other vaccines. No new or unexpected vaccine safety problems were identified for fatal, non-fatal serious, and non-serious reports in this assessment of adverse events after IPV. None. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pediatric Patients Discharged from the Emergency Department with Abnormal Vital Signs.

PubMed

Winter, Josephine; Waxman, Michael J; Waterman, George; Ata, Ashar; Frisch, Adam; Collins, Kevin P; King, Christopher

2017-08-01

Children often present to the emergency department (ED) with minor conditions such as fever and have persistently abnormal vital signs. We hypothesized that a significant portion of children discharged from the ED would have abnormal vital signs and that those discharged with abnormal vital signs would experience very few adverse events. We performed a retrospective chart review encompassing a 44-month period of all pediatric patients (aged two months to 17 years) who were discharged from the ED with an abnormal pulse rate, respiratory rate, temperature, or oxygen saturation. We used a local quality assurance database to identify pre-defined adverse events after discharge in this population. Our primary aim was to determine the proportion of children discharged with abnormal vital signs and the frequency and nature of adverse events. Additionally, we performed a sub-analysis comparing the rate of adverse events in children discharged with normal vs. abnormal vital signs, as well as a standardized review of the nature of each adverse event. Of 33,185 children discharged during the study period, 5,540 (17%) of these patients had at least one abnormal vital sign. There were 24/5,540 (0.43%) adverse events in the children with at least one abnormal vital sign vs. 47/27,645 (0.17%) adverse events in the children with normal vital signs [relative risk = 2.5 (95% confidence interval, 1.6 to 2.4)].However, upon review of each adverse event we found only one case that was related to the index visit, was potentially preventable by a 23-hour hospital observation, and caused permanent disability. In our study population, 17% of the children were discharged with at least one abnormal vital sign, and there were very few adverse (0.43%) events associated with this practice. Heart rate was the most common abnormal vital sign leading to an adverse event. Severe adverse events that were potentially related to the abnormal vital sign(s) were exceedingly rare. Additional research is needed in broader populations to better determine the rate of adverse events and possible methods of avoiding them.

Severe Autoimmune Adverse Events Post Herpes Zoster Vaccine: A Case-Control Study of Adverse Events in a National Database.

PubMed

Lai, Yi Chun; Yew, Yik Weng

2015-07-01

Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases.

Cognition- and Dementia-Related Adverse Effects With Sacubitril-Valsartan: Analysis of the FDA Adverse Event Report System Database.

PubMed

Perlman, Amichai; Hirsh Raccah, Bruria; Matok, Ilan; Muszkat, Mordechai

2018-05-07

Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor sacubitril-valsartan could increase the risk for dementia. We analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Report System from July 2015 to March 2017. Cognition- and dementia-related adverse event cases were defined with the use of broad and narrow structured medical queries. During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan. Based on the broad definition, sacubitril-valsartan was associated with cognition- and dementia-related adverse events in 459 reports (5.1%), but this was lower than the proportion of these reports among other medications (6.6%, reporting odds ratio [ROR] 0.72, 95% confidence interval [CI] 0.65-0.79). Restricting the comparison to cases with age >60 years and with the use of a comparator group with heart failure resulted in no association between sacubitril-valsartan and dementia-related adverse events, with the use of both the broad and the narrow definitions (ROR 0.87, 95% CI 0.76-1.02, and ROR 1.06, 95% CI 0.4-3.16, respectively). Sacubitril-valsartan is not associated with a disproportionately high rate of short-term dementia-related adverse effect reports. Long-term studies assessing cognitive outcomes are required to better establish the medication's cognition effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Cardiovascular and Cerebrovascular Events Are Associated With Nontraumatic Osteonecrosis of the Femoral Head.

PubMed

Sung, Pei-Hsun; Yang, Yao-Hsu; Chiang, Hsin-Ju; Chiang, John Y; Chen, Chi-Jen; Yip, Hon-Kan; Lee, Mel S

2018-04-01

Endothelial dysfunction has been identified as an etiologic factor for osteonecrosis of the femoral head (ONFH) and major adverse cardiovascular and cerebrovascular events (defined as major cardiovascular disease [CVD] and cerebrovascular accident [CVA]). However, the incidence of major adverse cardiovascular and cerebrovascular events in patients with nontraumatic ONFH and any association between the two diagnoses remain unclear. We compared a large cohort of patients with nontraumatic ONFH and a matched control group without this diagnosis and (1) examined the frequency and hazard ratio (HR) of major adverse cardiovascular and cerebrovascular events in both groups adjusted for age, sex, socioeconomic status, and associated comorbidities (which we defined as the adjusted HR), (2) determined whether any association of ONFH and major adverse cardiovascular and cerebrovascular events was stable after adjusting for confounding variables, and (3) compared the occurrence of major adverse cardiovascular and cerebrovascular events with time in both groups. A population-based cohort with a 14-year dataset period (1997-2010) from the Taiwan National Health Insurance Research Database was used for this retrospective study. The database includes a greater than 99.5% Asian population randomly selected from more than 23 million citizens and foreigners residing in Taiwan for longer than 6 months. A total of 1562 patients with nontraumatic ONFH were identified from a population of one million patients in the database after excluding initially concomitant diagnoses of major CVD and CVA. The comparison group (n = 15,620) without ONFH was analyzed in a one-to-10 ratio by matching the study cohort based on age, sex, income, and urbanization. The patients with ONFH had a higher frequency of major adverse cardiovascular and cerebrovascular events than their counterparts without ONFH (19% versus 14%; p < 0.001). The patients with ONFH had 1.34- and 1.27-fold adjusted HRs for occurrence of major CVD and CVA as compared with the normal population (95% CI, 1.11-1.61, p = 0.002, and 95% CI, 1.09-1.47, p = 0.002, respectively). Sensitivity analysis showed a consistent association between ONFH and major adverse cardiovascular and cerebrovascular events after controlling for potentially relevant confounding variables such as hypertension and diabetes. After adjusting for potential confounders including surgery and medications, ONFH remained independently associated with major CVD (adjusted HR, 1.51, 95% CI 1.09-2.03, p = 0.026) and CVA (adjusted HR, 2.44, 95% CI 1.69-3.51, p < 0.001), apart from age older than 65 years and traditional atherosclerotic risk factors. The cumulative incidence of major adverse cardiovascular and cerebrovascular events also was higher in the ONFH group than the non-ONFH group (30.3% vs 23.1% at the end of followup, p < 0.001). Patients with ONFH have a strong association with major adverse cardiovascular and cerebrovascular events as compared with the normal population, suggesting a potential common pathway involving endothelial dysfunction. In view of this association in the relatively young population with ONFH, it is important to closely monitor these patients, treat relevant comorbidities early, and investigate preventative measures for these major adverse events. Level III, prognostic study.

A randomised crossover study comparing bimatoprost and latanoprost in subjects with primary angle closure glaucoma.

PubMed

How, A C S; Kumar, R S; Chen, Y-M; Su, D H; Gao, H; Oen, F T; Ho, C-L; Seah, S K; Aung, T

2009-06-01

To compare the intraocular pressure (IOP) lowering efficacy and side effects of latanoprost 0.005% and bimatoprost 0.03% in subjects with chronic primary angle closure glaucoma (PACG). This was an observer-masked randomised crossover study of 60 PACG subjects who received either latanoprost or bimatoprost for 6 weeks, after which they were crossed over to the other medication for another 6 weeks. The IOP-reducing effect of the medications was assessed by the reduction in IOP after 6 weeks of treatment compared with baseline. Fifty-four subjects (80 eyes) completed the study. Latanoprost reduced IOP (mean (SD)) by 8.4 (3.8) mm Hg and bimatoprost by 8.9 (3.9) mm Hg from a baseline of 25.2 (3.6) mm Hg and 25.2 (3.6) mm Hg respectively (p = 0.23). Adverse events were mild in both groups; however there were twice as many reports of an adverse event in the bimatoprost group (81%) compared with the latanoprost group (40%, p<0.01). Ocular irritation was the most frequently reported adverse event in both groups; 22 subjects (37.9%) treated with bimatoprost experienced ocular hyperaemia as compared with 13 subjects (22.4%) treated with latanoprost (p = 0.11). Bimatoprost once daily was similarly effective in reducing IOP compared with latanoprost once daily in subjects with chronic PACG. Both drugs were well tolerated with mild ocular adverse events.

Do time of birth, unit volume, and staff seniority affect neonatal outcome in deliveries at ≥34+0 weeks of gestation?

PubMed

Reif, P; Pichler, G; Griesbacher, A; Lehner, G; Schöll, W; Lang, U; Hofmann, H; Ulrich, D

2018-06-01

We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34 +0 weeks of gestation. Population-based prospective cohort study. Ten public hospitals in the Austrian province of Styria. A total of 87 065 neonates delivered in the period 2004-2015. Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. Neonatal composite adverse and severely adverse outcome measures. The odds ratio for severely adverse events during the night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500-1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. Deliveries during night time lead to a greater number of neonates experiencing severely adverse events. © 2017 Royal College of Obstetricians and Gynaecologists.

Comparison of the adverse event profiles of levofloxacin 500 mg and 750 mg in clinical trials for the treatment of respiratory infections.

PubMed

Khashab, Mohammed M; Xiang, Jim; Kahn, James B

2006-10-01

To compare safety data with levofloxacin 500 mg and 750 mg from clinical trials for the treatment of respiratory infections. We compared adverse event data for levofloxacin 500 mg and 750 mg from clinical trials in acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and community-acquired pneumonia. Adverse events occurring after the initiation of therapy were classified as treatment-emergent adverse events (TEAE); drug-related adverse events (DRAE) were TEAE assessed by the clinical investigator as definitely/very likely or probably related to levofloxacin therapy. Overall, the safety profile of the two doses was similar but not identical. TEAE occurred in 49.0% (1601/3268) of those treated with 500 mg and in 45.5% (519/1141) of those treated with 750 mg (p = 0.042); the corresponding rates of DRAE were 7.6% (248/3268) and 8.0% (91/1141) (p = 0.699). There was no statistically significant difference in terms of overall TEAE and DRAE rates within each of the three infectious conditions, but there were in specific events, all of which are expected with levofloxacin therapy. The limitations of this analysis include that it utilized a subset of available safety data, that it includes data only from clinical trials, and that we report primarily on events occurring in > or = 2% of patients. Given similar adverse event profiles and the advantages of higher dose therapy, including shorter courses of therapy and potential impact on preventing resistance, clinicians should consider utilizing the 750 mg dose of levofloxacin when choosing between dosage strengths for treatment of indicated infections.

Cost-effectiveness of oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin in the emergency department.

PubMed

Rudis, Maria I; Touchette, Daniel R; Swadron, Stuart P; Chiu, Amy P; Orlinsky, Michael

2004-03-01

Oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin are all commonly used for loading phenytoin in the emergency department (ED). The cost-effectiveness of each was compared for patients presenting with seizures and subtherapeutic phenytoin concentrations. A simple decision tree was developed to determine the treatment costs associated with each of 3 loading techniques. We determined effectiveness by comparing adverse event rates and by calculating the time to safe ED discharge. Time to safe ED discharge was defined as the time at which therapeutic concentrations of phenytoin (>or=10 mg/L) were achieved with an absence of any adverse events that precluded discharge. The comparative cost-effectiveness of alternatives to oral phenytoin was determined by combining net costs and number of adverse events, expressed as cost per adverse events avoided. Cost-effectiveness was also determined by comparing the net costs of each loading technique required to achieve the time to safe ED discharge, expressed as cost per hour of ED time saved. The outcomes and costs were primarily derived from a prospective, randomized controlled trial, augmented by time-motion studies and alternate-cost sources. Costs included the cost of drugs, supplies, and personnel. Analyses were also performed in scenarios incorporating labor costs and savings from using a lower-urgency area of the ED. The mean number of adverse events per patient for oral phenytoin, intravenous phenytoin, and intravenous fosphenytoin was 1.06, 1.93, and 2.13, respectively. Mean time to safe ED discharge in the 3 groups was 6.4 hours, 1.7 hours, and 1.3 hours. Cost per patient was 2.83 dollars, 21.16 dollars, and 175.19 dollars, respectively, and did not differ substantially in the Labor and Triage (lower-urgency area of ED) scenarios. When the measure of effectiveness was adverse events, oral phenytoin dominated intravenous phenytoin and intravenous fosphenytoin, with a lower cost and number of adverse events. With time to safe ED discharge as the outcome measure, the incremental cost-effectiveness ratios were 3.90 dollars and 387.27 dollars per hour of ED time saved for oral phenytoin versus intravenous phenytoin and for intravenous fosphenytoin versus intravenous phenytoin, respectively. Oral phenytoin is the most cost-effective loading method in most settings. Intravenous phenytoin is preferred if one is willing to pay an additional 20.65 dollars to 44.25 dollars per patient and willing to have more adverse events for a quicker average time to safe ED discharge. It is unlikely that intravenous fosphenytoin is justifiable in any setting.

Comparison of mesalazine and balsalazide in induction and maintenance of remission in patients with ulcerative colitis: a meta-analysis.

PubMed

Rahimi, Roja; Nikfar, Shekoufeh; Rezaie, Ali; Abdollahi, Mohammad

2009-04-01

5-Aminosalicylates are the standard treatment for induction and maintenance of remission in mild-to-moderate ulcerative colitis. In recent years, the 5-aminosalicylic acid-containing pro-drug balsalazide has been the focus of attention. To compare the efficacy and tolerance of balsalazide and mesalazine by meta-analysis. Pubmed, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for studies comparing the efficacy and/or tolerance of balsalazide with mesalazine in the management of UC. The search terms were: "mesalazine" or "5-aminosalicylic acid" and "balsalazide" and "ulcerative colitis." Data were collected from 1966 to 2007 (up to February). There was no language restriction. "Symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. Six randomized placebo-controlled clinical trials met our criteria and were included in the meta-analysis. In these "symptomatic remission," "complete remission," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were evaluated in three, three, two, five, and six of the trials, respectively. They included 653 patients consisting of 55.4% men and 44.6% women randomized to receive either balsalazide or mesalazine. Pooling of three trials for symptomatic remission yielded a significant relative risk (RR) of 1.23 (95% confidence interval of 1.03-1.47, P = 0.02). The summary RR for complete remission in three trials was 1.3 (95% CI of 1.002-1.68, P = 0.048). Pooling of two trials for the outcome of relapse yielded a non-significant RR of 0.77 (95% CI of 0.56-1.07, P = 0.12). Pooling five studies from which data for any adverse events were extracted, yielded a non-significant RR of 0.87 (95% CI of 0.75-1.001, P = 0.53). The summary RR for withdrawals because of adverse events in six trials was 0.69, a non-significant RR (95% CI of 0.37-1.29, P = 0.24). Balsalazide is more effective than mesalazine in induction of remission, but balsalazide has no benefit compared with mesalazine in preventing relapse in the population selected. The number of patients with any adverse events and withdrawals because of severe adverse events is similar for mesalazine and balsalazide.

Tolerability of sibutramine during a 6-week treatment period in high-risk patients with cardiovascular disease and/or diabetes: a preliminary analysis of the Sibutramine Cardiovascular Outcomes (SCOUT) Trial.

PubMed

Maggioni, Aldo P; Caterson, Ian; Coutinho, Walmir; Finer, Nick; Gaal, Luc Van; Sharma, Arya M; Torp-Pedersen, Christian; Bacher, Peter; Shepherd, Gillian; Sun, Rui; James, Philip

2008-11-01

Uncertainties about the cardiovascular safety of sibutramine led to the SCOUT trial that is investigating sibutramine plus weight management in high-risk, overweight/obese patients. A 6-week lead-in period during which all patients received sibutramine permitted an initial assessment of tolerability. A total of 10,742 patients received sibutramine and 3.1% of these discontinued due to an adverse event; issues affecting more than 10 patients were drug intolerance, headache, insomnia, nausea, dry mouth, and constipation-, tachycardia-, and hypertension-related events. Serious adverse events, most commonly associated with the System Organ Class, Cardiac disorders, were reported by 2.7% of patients; however, the majority was not considered sibutramine-related. Adverse events relating to high blood pressure and/or pulse rate, whether reported as adverse events leading to discontinuation, or serious adverse events were reported by less than 0.2% of patients. No serious or individual events leading to discontinuation occurred in more than 25 patients. There were 15 (0.1%) deaths; 10 were attributed to a cardiovascular cause. Discontinuations for adverse events were lower than anticipated. Serious adverse events generally reflected sibutramine's known pharmacology or were related to cardiac disorders already present in this high-risk population. When compared with epidemiological data, overall mortality rate was low and sibutramine was well tolerated in this mainly off-label population. No new safety issues were detected.

Combination pharmacotherapy for the treatment of fibromyalgia in adults.

PubMed

Thorpe, Joelle; Shum, Bonnie; Moore, R Andrew; Wiffen, Philip J; Gilron, Ian

2018-02-19

Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects. To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults. We searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries. Double-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain. From all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table. We identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination pharmacotherapy with each individual component but did not include an inactive placebo group; two studies compared the combination of two agents with only one of the agents alone; and three studies compared the combination of two or more agents only with inactive placebo.Heterogeneity among studies in terms of class of agents evaluated, specific combinations used, outcomes reported, and doses given prevented any meta-analysis. None of the combinations of drugs found provided sufficient data for analysis compared with placebo or other comparators for our preferred outcomes. We therefore provide a narrative description of results. There was no or inadequate evidence in any comparison for primary and secondary outcomes. Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item, only half or fewer of studies had unequivocal low risk of bias. Small size and selective reporting were common as high risk of bias.Our GRADE assessment was therefore very low for primary outcomes of pain relief of 30% or 50% or greater, PGIC much or very much improved or very much improved, any pain-related outcome, participants experiencing any adverse event, any serious adverse event, or withdrawing because of an adverse event.Three studies found some evidence that combination pharmacotherapy reduced pain compared to monotherapy; these trials tested three different combinations: melatonin and amitriptyline, fluoxetine and amitriptyline, and pregabalin and duloxetine. Adverse events experienced by participants were not serious, and where they were reported (in 12 out of 16 studies), all participants experienced them, regardless of treatment. Common adverse events were nausea, dizziness, somnolence, and headache. There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.

Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

PubMed

Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

2017-09-01

Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B.V. All rights reserved.

Proposal of a trigger tool to assess adverse events in dental care.

PubMed

Corrêa, Claudia Dolores Trierweiler Sampaio de Oliveira; Mendes, Walter

2017-11-21

The aim of this study was to propose a trigger tool for research of adverse events in outpatient dentistry in Brazil. The tool was elaborated in two stages: (i) to build a preliminary set of triggers, a literature review was conducted to identify the composition of trigger tools used in other areas of health and the principal adverse events found in dentistry; (ii) to validate the preliminarily constructed triggers a panel of experts was organized using the modified Delphi method. Fourteen triggers were elaborated in a tool with explicit criteria to identify potential adverse events in dental care, essential for retrospective patient chart reviews. Studies on patient safety in dental care are still incipient when compared to other areas of health care. This study intended to contribute to the research in this field. The contribution by the literature and guidance from the expert panel allowed elaborating a set of triggers to detect adverse events in dental care, but additional studies are needed to test the instrument's validity.

Vaxtracker: Active on-line surveillance for adverse events following inactivated influenza vaccine in children.

PubMed

Cashman, Patrick; Moberley, Sarah; Dalton, Craig; Stephenson, Jody; Elvidge, Elissa; Butler, Michelle; Durrheim, David N

2014-09-22

Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n=21), and piloted during the 2012 (n=200) and 2013 (n=477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n=113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

How Safe Are Common Analgesics for the Treatment of Acute Pain for Children? A Systematic Review.

PubMed

Hartling, Lisa; Ali, Samina; Dryden, Donna M; Chordiya, Pritam; Johnson, David W; Plint, Amy C; Stang, Antonia; McGrath, Patrick J; Drendel, Amy L

2016-01-01

Background . Fear of adverse events and occurrence of side effects are commonly cited by families and physicians as obstructive to appropriate use of pain medication in children. We examined evidence comparing the safety profiles of three groups of oral medications, acetaminophen, nonsteroidal anti-inflammatory drugs, and opioids, to manage acute nonsurgical pain in children (<18 years) treated in ambulatory settings. Methods . A comprehensive search was performed to July 2015, including review of national data registries. Two reviewers screened articles for inclusion, assessed methodological quality, and extracted data. Risks (incidence rates) were pooled using a random effects model. Results . Forty-four studies were included; 23 reported on adverse events. Based on limited current evidence, acetaminophen, ibuprofen, and opioids have similar nausea and vomiting profiles. Opioids have the greatest risk of central nervous system adverse events. Dual therapy with a nonopioid/opioid combination resulted in a lower risk of adverse events than opioids alone. Conclusions . Ibuprofen and acetaminophen have similar reported adverse effects and notably less adverse events than opioids. Dual therapy with a nonopioid/opioid combination confers a protective effect for adverse events over opioids alone. This research highlights challenges in assessing medication safety, including lack of more detailed information in registry data, and inconsistent reporting in trials.

Adverse Event Reporting: Harnessing Residents to Improve Patient Safety.

PubMed

Tevis, Sarah E; Schmocker, Ryan K; Wetterneck, Tosha B

2017-10-13

Reporting of adverse and near miss events are essential to identify system level targets to improve patient safety. Resident physicians historically report few events despite their role as front-line patient care providers. We sought to evaluate barriers to adverse event reporting in an effort to improve reporting. Our main outcomes were as follows: resident attitudes about event reporting and the frequency of event reporting before and after interventions to address reporting barriers. We surveyed first year residents regarding barriers to adverse event reporting and used this input to construct a fishbone diagram listing barriers to reporting. Barriers were addressed, and resident event reporting was compared before and after efforts were made to reduce obstacles to reporting. First year residents (97%) recognized the importance of submitting event reports; however, the majority (85%) had not submitted an event report in the first 6 months of residency. Only 7% of residents specified that they had not witnessed an adverse event in 6 months, whereas one third had witnessed 10 or more events. The main barriers were as follows: lack of knowledge about how to submit events (38%) and lack of time to submit reports (35%). After improving resident education around event reporting and simplifying the reporting process, resident event reporting increased 230% (68 to 154 annual reports, P = 0.025). We were able to significantly increase resident event reporting by educating residents about adverse events and near misses and addressing the primary barriers to event reporting. Moving forward, we will continue annual resident education about patient safety, focus on improving feedback to residents who submit reports, and empower senior residents to act as role models to junior residents in patient safety initiatives.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.

PubMed

Valgimigli, Marco; Frigoli, Enrico; Leonardi, Sergio; Rothenbühler, Martina; Gagnor, Andrea; Calabrò, Paolo; Garducci, Stefano; Rubartelli, Paolo; Briguori, Carlo; Andò, Giuseppe; Repetto, Alessandra; Limbruno, Ugo; Garbo, Roberto; Sganzerla, Paolo; Russo, Filippo; Lupi, Alessandro; Cortese, Bernardo; Ausiello, Arturo; Ierna, Salvatore; Esposito, Giovanni; Presbitero, Patrizia; Santarelli, Andrea; Sardella, Gennaro; Varbella, Ferdinando; Tresoldi, Simone; de Cesare, Nicoletta; Rigattieri, Stefano; Zingarelli, Antonio; Tosi, Paolo; van 't Hof, Arnoud; Boccuzzi, Giacomo; Omerovic, Elmir; Sabaté, Manel; Heg, Dik; Jüni, Peter; Vranckx, Pascal

2015-09-10

Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Adverse weather conditions for European wheat production will become more frequent with climate change

NASA Astrophysics Data System (ADS)

Trnka, Miroslav; Rötter, Reimund P.; Ruiz-Ramos, Margarita; Kersebaum, Kurt Christian; Olesen, Jørgen E.; Žalud, Zdeněk; Semenov, Mikhail A.

2014-07-01

Europe is the largest producer of wheat, the second most widely grown cereal crop after rice. The increased occurrence and magnitude of adverse and extreme agroclimatic events are considered a major threat for wheat production. We present an analysis that accounts for a range of adverse weather events that might significantly affect wheat yield in Europe. For this purpose we analysed changes in the frequency of the occurrence of 11 adverse weather events. Using climate scenarios based on the most recent ensemble of climate models and greenhouse gases emission estimates, we assessed the probability of single and multiple adverse events occurring within one season. We showed that the occurrence of adverse conditions for 14 sites representing the main European wheat-growing areas might substantially increase by 2060 compared to the present (1981-2010). This is likely to result in more frequent crop failure across Europe. This study provides essential information for developing adaptation strategies.

The added predictive value of biphasic events in ST analysis of the fetal electrocardiogram for intrapartum fetal monitoring.

PubMed

Becker, Jeroen H; Krikhaar, Anniek; Schuit, Ewoud; Mårtendal, Annika; Maršál, Karel; Kwee, Anneke; Visser, Gerard H A; Amer-Wåhlin, Isis

2015-02-01

To study the predictive value of biphasic ST-events for interventions for suspected fetal distress and adverse neonatal outcome, when using ST-analysis of the fetal electrocardiogram (FECG) for intrapartum fetal monitoring. Prospective cohort study. Three academic hospitals in Sweden. Women in labor with a high-risk singleton fetus in cephalic position beyond 36 weeks of gestation. In women in labor who were monitored with conventional cardiotocography, ST-waveform analysis was recorded and concealed. Traces with biphasic ST-events of the FECG (index) were compared with traces without biphasic events of the FECG. The ability of biphasic events to predict interventions for suspected fetal distress and adverse outcome was assessed using univariable and multivariable logistic regression analyses. Interventions for suspected fetal distress and adverse outcome (defined as presence of metabolic acidosis (i.e. umbilical cord pH <7.05 and base deficit in extracellular fluid >12 mmol), umbilical cord pH <7.00, 5-min Apgar score <7, admittance to neonatal intensive care unit or perinatal death). Although the presence of biphasic events of the FECG was associated with more interventions for fetal distress and an increased risk of adverse outcome compared with cases with no biphasic events, the presence of significant (i.e. intervention advised according to cardiotocography interpretation) biphasic events showed no independent association with interventions for fetal distress [odds ratio (OR) 1.71, 95% confidence interval (CI) 0.65-4.50] or adverse outcome (OR 1.96, 95% CI 0.74-5.24). The presence of significant biphasic events did not discriminate in the prediction of interventions for fetal distress or adverse outcome. Therefore, biphasic events in relation to ST-analysis monitoring during birth should be omitted if future studies confirm our findings. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

Adverse drug events in hospital: pilot study with trigger tool

PubMed Central

Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia

2013-01-01

OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for monitoring and evaluating patient care results. Psycothropic therapy should be critically appraised given the frequency of associated events, such as excessive sedation, lethargy, and hypotension. PMID:24626548

The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits.

PubMed

Ehrenpreis, Eli D; Deepak, Parakkal; Sifuentes, Humberto; Devi, Radha; Du, Hongyan; Leikin, Jerrold B

2013-06-01

We examined the effects of the black box warning about the risk of tardive dyskinesia (TD) with chronic use of metoclopramide on management of gastroparesis within a single clinical practice, and on reporting of adverse events. Medical records of gastroparesis patients were evaluated for physician management choices. The FDA Adverse Event Reporting System (FAERS) was analyzed for event reports, and for lawyer-initiated reports, with metoclopramide from 2004 to 2010. Google Scholar was searched for court opinions against metoclopramide manufacturers. Before the black box warning, 69.8% of patients received metoclopramide for gastroparesis, compared with 23.7% after the warning. Gastroenterologists prescribed domperidone more often after than before the warning. Metoclopramide prescriptions decreased after 2008. Adverse event reporting increased after the warning. Only 3.6% of all FAERS reports but 70% of TD reports were filed by lawyers, suggesting a distortion in signal. Forty-seven legal opinions were identified, 33 from 2009-2010. The black box warning for metoclopramide has decreased its usage and increased its rate of adverse event reporting. Lawyer-initiated reports of TD hinder pharmacovigilance.

[Comparison of the "Trigger" tool with the minimum basic data set for detecting adverse events in general surgery].

PubMed

Pérez Zapata, A I; Gutiérrez Samaniego, M; Rodríguez Cuéllar, E; Gómez de la Cámara, A; Ruiz López, P

Surgery is a high risk for the occurrence of adverse events (AE). The main objective of this study is to compare the effectiveness of the Trigger tool with the Hospital National Health System registration of Discharges, the minimum basic data set (MBDS), in detecting adverse events in patients admitted to General Surgery and undergoing surgery. Observational and descriptive retrospective study of patients admitted to general surgery of a tertiary hospital, and undergoing surgery in 2012. The identification of adverse events was made by reviewing the medical records, using an adaptation of "Global Trigger Tool" methodology, as well as the (MBDS) registered on the same patients. Once the AE were identified, they were classified according to damage and to the extent to which these could have been avoided. The area under the curve (ROC) were used to determine the discriminatory power of the tools. The Hanley and Mcneil test was used to compare both tools. AE prevalence was 36.8%. The TT detected 89.9% of all AE, while the MBDS detected 28.48%. The TT provides more information on the nature and characteristics of the AE. The area under the curve was 0.89 for the TT and 0.66 for the MBDS. These differences were statistically significant (P<.001). The Trigger tool detects three times more adverse events than the MBDS registry. The prevalence of adverse events in General Surgery is higher than that estimated in other studies. Copyright © 2017 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

[An efficient strategy to decrease the central venous catheter-related adverse events rate in haemodialysis patients].

PubMed

Jean, Guillaume; Vanel, Thierry; Bresson, Eric; Terrat, Jean-Claude; Hurot, Jean-Marc; Lorriaux, Christie; Mayor, Brice; Chazot, Charles

2009-07-01

Catheter-related adverse events (CAE) remain a major cause of mortality and morbidity. We aimed to compare the CAE prevalence and adverse events rate at 10 years interval in one centre using different devices, dressing procedures. We compared two periods, from 1994 to 1997 (period 1) and from 2004 to 2007 (period 2). We recorded all prevalent tunnelled CAE and their related adverse event rate: catheter-related bacteraemia (CRB), catheter local infection (CLI), catheter dysfunction leading to CAE exchange, thrombolytic use and spontaneous pulling up. In period 1, PermCath catheter (Quinton, N=63) and TwinCath catheter (MedComp, N=76) were used in 95 HD. BioFlex catheter (N=52) and ASPC split catheter (MedComp, N=52) were used in 72 HD in period 2. In period 1, we performed catheter dressing using povidone iodine versus alcoholic chlorexidine in period 2. Between period 1 and period 2, the CAE prevalence decreased from 15-18% to 9-6%, CRB from 1.1 to 0.23/1000 day-catheter (p<0.001), CLI from 1.1 to 0.28/1000 day-catheter (p<0.001), definitive dysfunction from 12 to 1.2% (p<0.001) and CAE pulling up from 4 to 0%. The annual urokinase consumption decreased from three to one unit per CAE. This study shows the dramatic decrease in CAE prevalence (-50%) and related-adverse events (approximately -200%) since 10 years. Switching povidone iodine to chlorexidine and using more recent catheter devices appear very efficient in decreasing catheter-related adverse events.

Platelet density per monocyte predicts adverse events in patients after percutaneous coronary intervention.

PubMed

Rutten, Bert; Roest, Mark; McClellan, Elizabeth A; Sels, Jan W; Stubbs, Andrew; Jukema, J Wouter; Doevendans, Pieter A; Waltenberger, Johannes; van Zonneveld, Anton-Jan; Pasterkamp, Gerard; De Groot, Philip G; Hoefer, Imo E

2016-01-01

Monocyte recruitment to damaged endothelium is enhanced by platelet binding to monocytes and contributes to vascular repair. Therefore, we studied whether the number of platelets per monocyte affects the recurrence of adverse events in patients after percutaneous coronary intervention (PCI). Platelet-monocytes complexes with high and low median fluorescence intensities (MFI) of the platelet marker CD42b were isolated using cell sorting. Microscopic analysis revealed that a high platelet marker MFI on monocytes corresponded with a high platelet density per monocyte while a low platelet marker MFI corresponded with a low platelet density per monocyte (3.4 ± 0.7 vs 1.4 ± 0.1 platelets per monocyte, P=0.01). Using real-time video microscopy, we observed increased recruitment of high platelet density monocytes to endothelial cells as compared with low platelet density monocytes (P=0.01). Next, we classified PCI scheduled patients (N=263) into groups with high, medium and low platelet densities per monocyte and assessed the recurrence of adverse events. After multivariate adjustment for potential confounders, we observed a 2.5-fold reduction in the recurrence of adverse events in patients with a high platelet density per monocyte as compared with a low platelet density per monocyte [hazard ratio=0.4 (95% confidence interval, 0.2-0.8), P=0.01]. We show that a high platelet density per monocyte increases monocyte recruitment to endothelial cells and predicts a reduction in the recurrence of adverse events in patients after PCI. These findings may imply that a high platelet density per monocyte protects against recurrence of adverse events.

Are measurements of patient safety culture and adverse events valid and reliable? Results from a cross sectional study.

PubMed

Farup, Per G

2015-05-02

The association between measurements of the patient safety culture and the "true" patient safety has been insufficiently documented, and the validity of the tools used for the measurements has been questioned. This study explored associations between the patient safety culture and adverse events, and evaluated the validity of the tools. In 2008/2009, a survey on patient safety culture was performed with Hospital Survey on Patient Safety Culture (HSOPSC) in two medical departments in two geographically separated hospitals of Innlandet Hospital Trust. Later, a retrospective analysis of adverse events during the same period was performed with the Global Trigger Tool (GTT). The safety culture and adverse events were compared between the departments. 185 employees participated in the study, and 272 patient records were analysed. The HSOPSC scores were lower and adverse events less prevalent in department 1 than in department 2. In departments 1 and 2 the mean HSOPSC scores (SD) were at the unit level 3.62 (0.42) and 3.90 (0.37) (p < 0.001), and at the hospital level 3.35 (1.53) and 3.67 (0.53) (ns, p = 0.19) respectively. The proportion of records with adverse events were 10/135 (7%) and 28/137 (20%) (p = 0.003) respectively. There was an inverse association between the patient safety culture and adverse events. Until the criterion validity of the tools for measuring patient safety culture and tracking of adverse events have been further evaluated, measurement of patient safety culture could not be used as a proxy for the "true" safety.

Completeness of serious adverse drug event reports received by the US Food and Drug Administration in 2014.

PubMed

Moore, Thomas J; Furberg, Curt D; Mattison, Donald R; Cohen, Michael R

2016-06-01

Adverse drug event reports to the US Food and Drug Administration (FDA) remain the primary tool for identifying serious drug adverse effects without adequate existing warnings. We assessed the completeness of reports the FDA received in 2014. Serious adverse drug event reports were evaluated for whether they included age, gender, event date, and at least one medical term describing the event in computer excerpts. Report sources were direct reports to the FDA, manufacturer expedited reports about events without adequate warnings, and manufacturer periodic reports about events with existing warnings. In 2014, the FDA received 528,192 new case reports indicating a serious or fatal outcome, 25,038 (4.7%) directly from health professionals and consumers, and 503,154 (95.3%) from drug manufacturers. Overall, 21,595 (86.2%) of serious reports submitted directly to the FDA provided data for all four completeness variables, compared with 271,022 (40.4%) of manufacturer expedited reports and 24,988 (51.3%) of periodic reports. Among manufacturer serious reports, 37.9% lacked age and 46.9% had no event date. Performance by 25 manufacturers submitting 5000 or more reports varied from 24.4% complete on all variables to 67% complete. Patient death cases had the lowest completeness scores in all categories. By these measures, report completeness from drug manufacturers was poor compared with direct submissions to the agency. The FDA needs to update reporting requirements and compliance policies to help industry capture better adverse event information from new forms of manufacturer interactions with health professionals and consumers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Assessing the interplay of childhood adversities with more recent stressful life events and conditions in predicting panic pathology among adults from the general population.

PubMed

Asselmann, E; Stender, J; Grabe, H J; König, J; Schmidt, C O; Hamm, A O; Pané-Farré, C A

2018-01-01

Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology. Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age). Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities. Data were assessed retrospectively and might be subject to recall biases. Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events. Copyright © 2017. Published by Elsevier B.V.

Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

PubMed

Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

2016-11-01

Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment modification. Occurrence of adverse drug events may be used as a predictor for possible therapy modification. We recommend the institution of active pharmacovigilance in HIV treatment programmes as it permits the proper identification and characterisation of drug-related adverse events. This can help develop approaches towards their management and also justify therapy modifications.

Admission hyperglycemia predicts inhospital mortality and major adverse cardiac events after primary percutaneous coronary intervention in patients without diabetes mellitus.

PubMed

Ekmekci, Ahmet; Cicek, Gokhan; Uluganyan, Mahmut; Gungor, Baris; Osman, Faizel; Ozcan, Kazim Serhan; Bozbay, Mehmet; Ertas, Gokhan; Zencirci, Aycan; Sayar, Nurten; Eren, Mehmet

2014-02-01

Admission hyperglycemia is associated with high inhospital and long-term adverse events in patients that undergo primary percutaneous coronary intervention (PCI). We aimed to evaluate whether hyperglycemia predicts inhospital mortality. We prospectively analyzed 503 consecutive patients. The patients were divided into tertiles according to the admission glucose levels. Tertile I: glucose <118 mg/dL (n = 166), tertile II: glucose 118 to 145 mg/dL (n = 168), and tertile III: glucose >145 mg/dL (n = 169). Inhospital mortality was 0 in tertile I, 2 in tertile II, and 9 in tertile III (P < .02). Cardiogenic shock occurred more frequently in tertile III compared to tertiles I and II (10% vs 4.1% and 0.6%, respectively, P = .01). Multivariate logistic regression analysis revealed that patients in tertile III had significantly higher risk of inhospital major adverse cardiac events compared to patients in tertile I (odds ratio: 9.55, P < .02). Admission hyperglycemia predicts inhospital adverse cardiac events in mortality and acute ST-segment elevation myocardial infarction in patients that underwent primary PCI.

Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem Cell Transplantation in Patients with Malignant Lymphoma

PubMed Central

Imataki, Osamu; Arai, Hidekazu; Kume, Tetsuo; Shiozaki, Hitomi; Katsumata, Naomi; Mori, Mariko; Ishide, Keiko; Ikeda, Takashi

2018-01-01

Background The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation. Material/Methods We enrolled patients who underwent autologous peripheral blood stem cell transplantation between 2007 and 2012. Outcomes were compared between ICE therapy (n=14) and MCEC therapy (n=14) in relation to nutrient balance, engraftment day, and length of hospital stay. In both groups, we compared the timing of nutrition-related adverse events with oral caloric intake, analyzed the correlation between length of hospital stay and duration of parenteral nutrition, and investigated the association between oral caloric intake and the proportion of parenteral nutrition energy in total calorie supply. Five-year survival was compared between the groups. Results Compared with the MCEC group, the ICE group showed significant improvement in oral caloric intake, length of hospital stay, and timing of nutrition-related adverse events and oral calorie intake, but a delay in engraftment. Both groups showed a correlation between duration of parenteral nutrition and length of hospital stay (P=0.0001) and between oral caloric intake (P=0.0017) and parenteral nutrition energy sufficiency rate (r=−0.73, P=0.003; r=−0.76, P=0.002). Five-year survival was not significantly different between the groups (P=0.1355). Conclusions Our findings suggest that compared with MCEC therapy, ICE therapy improves nutrition-related adverse events and reduces hospital stay, conserving medical resources, with no significant improvement in long-term survival. The nutritional pathway may serve as a tool for objective evaluation of pretreatment for autologous peripheral blood stem cell transplantation. PMID:29398693

US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.

PubMed

Shehab, Nadine; Lovegrove, Maribeth C; Geller, Andrew I; Rose, Kathleen O; Weidle, Nina J; Budnitz, Daniel S

2016-11-22

The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Drugs implicated in ED visits. National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Based on data from 42 585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated (56.4%; 95% CI, 51.8%-61.0%). Among children and adolescents aged 6 to 19 years, antibiotics also were the most common drug class implicated (31.8%; 95% CI, 28.7%-34.9%) in ED visits for adverse drug events, followed by antipsychotics (4.5%; 95% CI, 3.3%-5.6%). Among older adults (aged ≥65 years), 3 drug classes (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an estimated 59.9% (95% CI, 56.8%-62.9%) of ED visits for adverse drug events; 4 anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and 5 diabetes agents (insulin and 4 oral agents) were among the 15 most common drugs implicated. Medications to always avoid in older adults according to Beers criteria were implicated in 1.8% (95% CI, 1.5%-2.1%) of ED visits for adverse drug events. The prevalence of emergency department visits for adverse drug events in the United States was estimated to be 4 per 1000 individuals in 2013 and 2014. The most common drug classes implicated were anticoagulants, antibiotics, diabetes agents, and opioid analgesics.

Generic versus brand-name drugs used in cardiovascular diseases.

PubMed

Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A

2016-04-01

This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use.

Safety of diphtheria, tetanus, acellular pertussis and inactivated poliovirus (DTaP-IPV) vaccine.

PubMed

Daley, Matthew F; Yih, W Katherine; Glanz, Jason M; Hambidge, Simon J; Narwaney, Komal J; Yin, Ruihua; Li, Lingling; Nelson, Jennifer C; Nordin, James D; Klein, Nicola P; Jacobsen, Steven J; Weintraub, Eric

2014-05-23

In 2008, a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combined vaccine (DTaP-IPV) was licensed for use in children 4 through 6 years of age. While pre-licensure studies did not demonstrate significant safety concerns, the number vaccinated in these studies was not sufficient to examine the risk of uncommon but serious adverse events. To assess the risk of serious adverse events following DTaP-IPV vaccination. The study was conducted from January 2009 through September 2012 in the Vaccine Safety Datalink (VSD) project. In the VSD, electronic vaccination and encounter data are updated and aggregated weekly as part of ongoing surveillance activities. Based on previous reports and biologic plausibility, eight potential adverse events were monitored: meningitis/encephalitis; seizures; stroke; Guillain-Barré syndrome; Stevens-Johnson syndrome; anaphylaxis; serious allergic reactions other than anaphylaxis; and serious local reactions. Adverse event rates in DTaP-IPV recipients were compared to historical incidence rates in the VSD population prior to 2009. Sequential probability ratio testing was used to analyze the data on a weekly basis. During the study period, 201,116 children received DTaP-IPV vaccine. Ninety-seven percent of DTaP-IPV recipients also received other vaccines on the same day, typically measles-mumps-rubella and varicella vaccines. There was no statistically significant increased risk of any of the eight pre-specified adverse events among DTaP-IPV recipients when compared to historical incidence rates. In this safety surveillance study of more than 200,000 DTaP-IPV vaccine recipients, there was no evidence of increased risk for any of the pre-specified adverse events monitored. Continued surveillance of DTaP-IPV vaccine safety may be warranted to monitor for rare adverse events, such as Guillain-Barré syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.

PubMed

García-Doval, I; Hernández, M V; Vanaclocha, F; Sellas, A; de la Cueva, P; Montero, D

2017-03-01

Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. © 2016 British Association of Dermatologists.

Oral sildenafil citrate (viagra) for erectile dysfunction: a systematic review and meta-analysis of harms.

PubMed

Tsertsvadze, Alexander; Yazdi, Fatemeh; Fink, Howard A; MacDonald, Roderick; Wilt, Timothy J; Bella, Anthony J; Ansari, Mohammed T; Garritty, Chantelle; Soares-Weiser, Karla; Daniel, Raymond; Sampson, Margaret; Moher, David

2009-10-01

To summarize and compare evidence on harms in sildenafil- and placebo-treated men with erectile dysfunction (ED) in a systematic review and meta-analysis. Randomized placebo-controlled trials (RCTs) were identified using an electronic search in MEDLINE, EMBASE, PsycINFO, SCOPUS, and Cochrane CENTRAL. The rates of any adverse events (AEs), most commonly reported AEs, withdrawals because of adverse events, and serious adverse events were ascertained and compared between sildenafil and placebo groups. The results of men with ED were stratified by clinical condition(s). Statistical heterogeneity was explored. Meta-analyses based on random-effects model were also performed. A total of 49 RCTs were included. Sildenafil-treated men had a higher risk for all-cause AEs (RR = 1.56, 95% CI: 1.38, 1.76), headache, flushing, dyspepsia, and visual disturbances compared with placebo-treated men. The magnitude of excess risk was greater in fixed- than in flexible-dose trials. The rates of serious adverse events and withdrawals because of adverse events did not differ in sildenafil vs placebo groups. A higher dose of sildenafil corresponded to a greater risk of AEs. The increased risk of harms was observed within and across clinically defined specific groups of patients. There was a lack of RCTs reporting long-term (>6 months) harms data. In short-term trials, men with ED randomized to sildenafil had an increased risk of all-cause any AEs, headache, flushing, dyspepsia, and visual disturbances. The exploration of different modes of dose optimization of sildenafil may be warranted.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma.

PubMed

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-03-30

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration-time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters ( ABCB1 and ABCG2 ), UGT1A , and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate ( P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC ( P < 0.0001), and correctly predicted objective response rate ( P = 0.0044) as well as adverse events ( P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment ( P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC.

Pharmacogenetics-based area-under-curve model can predict efficacy and adverse events from axitinib in individual patients with advanced renal cell carcinoma

PubMed Central

Yamamoto, Yoshiaki; Tsunedomi, Ryouichi; Fujita, Yusuke; Otori, Toru; Ohba, Mitsuyoshi; Kawai, Yoshihisa; Hirata, Hiroshi; Matsumoto, Hiroaki; Haginaka, Jun; Suzuki, Shigeo; Dahiya, Rajvir; Hamamoto, Yoshihiko; Matsuyama, Kenji; Hazama, Shoichi; Nagano, Hiroaki; Matsuyama, Hideyasu

2018-01-01

We investigated the relationship between axitinib pharmacogenetics and clinical efficacy/adverse events in advanced renal cell carcinoma (RCC) and established a model to predict clinical efficacy and adverse events using pharmacokinetic and gene polymorphisms related to drug metabolism and efflux in a phase II trial. We prospectively evaluated the area under the plasma concentration–time curve (AUC) of axitinib, objective response rate, and adverse events in 44 consecutive advanced RCC patients treated with axitinib. To establish a model for predicting clinical efficacy and adverse events, polymorphisms in genes including ABC transporters (ABCB1 and ABCG2), UGT1A, and OR2B11 were analyzed by whole-exome sequencing, Sanger sequencing, and DNA microarray. To validate this prediction model, calculated AUC by 6 gene polymorphisms was compared with actual AUC in 16 additional consecutive patients prospectively. Actual AUC significantly correlated with the objective response rate (P = 0.0002) and adverse events (hand-foot syndrome, P = 0.0055; and hypothyroidism, P = 0.0381). Calculated AUC significantly correlated with actual AUC (P < 0.0001), and correctly predicted objective response rate (P = 0.0044) as well as adverse events (P = 0.0191 and 0.0082, respectively). In the validation study, calculated AUC prior to axitinib treatment precisely predicted actual AUC after axitinib treatment (P = 0.0066). Our pharmacogenetics-based AUC prediction model may determine the optimal initial dose of axitinib, and thus facilitate better treatment of patients with advanced RCC. PMID:29682213

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems.

PubMed

Brauchli Pernus, Yolanda; Nan, Cassandra; Verstraeten, Thomas; Pedenko, Mariia; Osokogu, Osemeke U; Weibel, Daniel; Sturkenboom, Miriam; Bonhoeffer, Jan

2016-12-12

Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population. Published by Elsevier Ltd.

A descriptive comparison of ultrasound-guided central venous cannulation of the internal jugular vein to landmark-based subclavian vein cannulation.

PubMed

Theodoro, Daniel; Bausano, Brian; Lewis, Lawrence; Evanoff, Bradley; Kollef, Marin

2010-04-01

The safest site for central venous cannulation (CVC) remains debated. Many emergency physicians (EPs) advocate the ultrasound-guided internal jugular (USIJ) approach because of data supporting its efficiency. However, a number of physicians prefer, and are most comfortable with, the subclavian (SC) vein approach. The purpose of this study was to describe adverse event rates among operators using the USIJ approach, and the landmark SC vein approach without US. This was a prospective observational trial of patients undergoing CVC of the SC or internal jugular veins in the emergency department (ED). Physicians performing the procedures did not undergo standardized training in either technique. The primary outcome was a composite of adverse events defined as hematoma, arterial cannulation, pneumothorax, and failure to cannulate. Physicians recorded the anatomical site of cannulation, US assistance, indications, and acute complications. Variables of interest were collected from the pharmacy and ED record. Physician experience was based on a self-reported survey. The authors followed outcomes of central line insertion until device removal or patient discharge. Physicians attempted 236 USIJ and 132 SC cannulations on 333 patients. The overall adverse event rate was 22% with failure to cannulate being the most common. Adverse events occurred in 19% of USIJ attempts, compared to 29% of non-US-guided SC attempts. Among highly experienced operators, CVCs placed at the SC site resulted in more adverse events than those performed using USIJ (relative risk [RR] = 1.89, 95% confidence interval [CI] = 1.05 to 3.39). While limited by observational design, our results suggest that the USIJ technique may result in fewer adverse events compared to the landmark SC approach.

Genetic associations with adverse events from anti-tumor necrosis factor therapy in inflammatory bowel disease patients.

PubMed

Lew, Daniel; Yoon, Soon Man; Yan, Xiaofei; Robbins, Lori; Haritunians, Talin; Liu, Zhenqiu; Li, Dalin; McGovern, Dermot Pb

2017-10-28

To study the type and frequency of adverse events associated with anti-tumor necrosis factor (TNF) therapy and evaluate for any serologic and genetic associations. This study was a retrospective review of patients attending the inflammatory bowel disease (IBD) centers at Cedars-Sinai IBD Center from 2005-2016. Adverse events were identified via chart review. IBD serologies were measured by ELISA. DNA samples were genotyped at Cedars-Sinai using Illumina Infinium Immunochipv1 array per manufacturer's protocol. SNPs underwent methodological review and were evaluated using several SNP statistic parameters to ensure optimal allele-calling. Standard and rigorous QC criteria were applied to the genetic data, which was generated using immunochip. Genetic association was assessed by logistic regression after correcting for population structure. Altogether we identified 1258 IBD subjects exposed to anti-TNF agents in whom Immunochip data were available. 269/1258 patients (21%) were found to have adverse events to an anti-TNF-α agent that required the therapy to be discontinued. 25% of women compared to 17% of men experienced an adverse event. All adverse events resolved after discontinuing the anti-TNF agent. In total: n = 66 (5%) infusion reactions; n = 49 (4%) allergic/serum sickness reactions; n = 19 (1.5%) lupus-like reactions, n = 52 (4%) rash, n = 18 (1.4%) infections. In Crohn's disease, IgA ASCA ( P = 0.04) and IgG-ASCA ( P = 0.02) levels were also lower in patients with any adverse events, and anti-I2 level in ulcerative colitis was significantly associated with infusion reactions ( P = 0.008). The logistic regression/human annotation and network analyses performed on the Immunochip data implicated the following five signaling pathways: JAK-STAT (Janus Kinase-signal transducer and activator of transcription), measles, IBD, cytokine-cytokine receptor interaction, and toxoplasmosis for any adverse event. Our study shows 1 in 5 IBD patients experience an adverse event to anti-TNF therapy with novel serologic, genetic , and pathways associations.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration: a meta-analysis of randomized controlled trials.

PubMed

Nguyen, Chu Luan; Oh, Lawrence J; Wong, Eugene; Wei, Joe; Chilov, Michael

2018-05-30

To evaluate the relative efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular age-related macular degeneration (AMD). Systematic literature review identifying RCTs comparing anti-VEGF agents to another treatment published before June 2016. Efficacy assessed by mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline at up to 2 years followup. Safety assessed by proportions of patients with death, arteriothrombotic and venous thrombotic events, and at least one serious systemic adverse event at up to 2 years of followup. Fifteen RCTs selected for meta-analysis (8320 patients). Two trials compared pegaptanib, and three trials compared ranibizumab versus control. Eight trials compared bevacizumab with ranibizumab. Two trials compared aflibercept with ranibizumab. There were no significant differences between bevacizumab and ranibizumab for BCVA at 1 or 2 years (weighted mean difference = - 0.57, 95% CI - 1.55 to 0.41, P = 0.25 and weighted mean difference = - 0.76, 95% CI - 2.25 to 0.73, P = 0.32, respectively). Ranibizumab was more effective in reducing CMT at 1 year (weighted mean difference = 4.49, 95% CI 1.13 to 7.84, P = 0.009). Risk ratios comparing rates of serious systemic adverse events at 1 and 2 years were slightly out of favour for bevacizumab. Aflibercept compared with ranibizumab demonstrated similar mean change in BCVA, reduction in CMT, and safety at 1 year. Bevacizumab and ranibizumab had equivalent efficacy for BCVA, while ranibizumab had greater reduction in CMT and less rate of serious systemic adverse events. Aflibercept and ranibizumab had comparable efficacy for BCVA and CMT. This provides information to balance comparable effects on vision and risk of adverse events between anti-VEGF agents.

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database

PubMed Central

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung-eun; Jin, Xue-mei; Lee, Joongyub; Yang, Bo Ram

2017-01-01

Purpose To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). Materials and Methods We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. Results There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. Conclusion We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. PMID:28332362

Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

PubMed

Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung Eun; Jin, Xue Mei; Lee, Joongyub; Yang, Bo Ram; Park, Byung Joo

2017-05-01

To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. © Copyright: Yonsei University College of Medicine 2017

Neurologic adverse events associated with smallpox vaccination in the United States – response and comment on reporting of headaches as adverse events after smallpox vaccination among military and civilian personnel

PubMed Central

Schumm, Walter R

2006-01-01

Background Accurate reporting of adverse events occurring after vaccination is an important component of determining risk-benefit ratios for vaccinations. Controversy has developed over alleged underreporting of adverse events within U.S. military samples. This report examines the accuracy of adverse event rates recently published for headaches, and examines the issue of underreporting of headaches as a function of civilian or military sources and as a function of passive versus active surveillance. Methods A report by Sejvar et al was examined closely for accuracy with respect to the reporting of neurologic adverse events associated with smallpox vaccination in the United States. Rates for headaches were reported by several scholarly sources, in addition to Sejvar et al, permitting a comparison of reporting rates as a function of source and type of surveillance. Results Several major errors or omissions were identified in Sejvar et al. The count of civilian subjects vaccinated and the totals of both civilians and military personnel vaccinated were reported incorrectly by Sejvar et al. Counts of headaches reported in VAERS were lower (n = 95) for Sejvar et al than for Casey et al (n = 111) even though the former allegedly used 665,000 subjects while the latter used fewer than 40,000 subjects, with both using approximately the same civilian sources. Consequently, rates of nearly 20 neurologic adverse events reported by Sejvar et al were also incorrectly calculated. Underreporting of headaches after smallpox vaccination appears to increase for military samples and for passive adverse event reporting systems. Conclusion Until revised or corrected, the rates of neurologic adverse events after smallpox vaccinated reported by Sejvar et al must be deemed invalid. The concept of determining overall rates of adverse events by combining small civilian samples with large military samples appears to be invalid. Reports of headaches as adverse events after smallpox vaccination appear to be have occurred much less frequently using passive surveillance systems and by members of the U.S. military compared to civilians, especially those employed in healthcare occupations. Such concerns impact risk-benefit ratios associated with vaccines and weigh against making vaccinations mandatory, without informed consent, even among military members. Because of the issues raised here, adverse event rates derived solely or primarily from U.S. Department of Defense reporting systems, especially passive surveillance systems, should not be used, given better alternatives, for making public health policy decisions. PMID:17096855

Risk assessment for respiratory complications in paediatric anaesthesia: a prospective cohort study.

PubMed

von Ungern-Sternberg, Britta S; Boda, Krisztina; Chambers, Neil A; Rebmann, Claudia; Johnson, Chris; Sly, Peter D; Habre, Walid

2010-09-04

Perioperative respiratory adverse events in children are one of the major causes of morbidity and mortality during paediatric anaesthesia. We aimed to identify associations between family history, anaesthesia management, and occurrence of perioperative respiratory adverse events. We prospectively included all children who had general anaesthesia for surgical or medical interventions, elective or urgent procedures at Princess Margaret Hospital for Children, Perth, Australia, from Feb 1, 2007, to Jan 31, 2008. On the day of surgery, anaesthetists in charge of paediatric patients completed an adapted version of the International Study Group for Asthma and Allergies in Childhood questionnaire. We collected data on family medical history of asthma, atopy, allergy, upper respiratory tract infection, and passive smoking. Anaesthesia management and all perioperative respiratory adverse events were recorded. 9297 questionnaires were available for analysis. A positive respiratory history (nocturnal dry cough, wheezing during exercise, wheezing more than three times in the past 12 months, or a history of present or past eczema) was associated with an increased risk for bronchospasm (relative risk [RR] 8.46, 95% CI 6.18-11.59; p<0.0001), laryngospasm (4.13, 3.37-5.08; p<0.0001), and perioperative cough, desaturation, or airway obstruction (3.05, 2.76-3.37; p<0.0001). Upper respiratory tract infection was associated with an increased risk for perioperative respiratory adverse events only when symptoms were present (RR 2.05, 95% CI 1.82-2.31; p<0.0001) or less than 2 weeks before the procedure (2.34, 2.07-2.66; p<0.0001), whereas symptoms of upper respiratory tract infection 2-4 weeks before the procedure significantly lowered the incidence of perioperative respiratory adverse events (0.66, 0.53-0.81; p<0.0001). A history of at least two family members having asthma, atopy, or smoking increased the risk for perioperative respiratory adverse events (all p<0.0001). Risk was lower with intravenous induction compared with inhalational induction (all p<0.0001), inhalational compared with intravenous maintenance of anaesthesia (all p<0.0001), airway management by a specialist paediatric anaesthetist compared with a registrar (all p<0.0001), and use of face mask compared with tracheal intubation (all p<0.0001). Children at high risk for perioperative respiratory adverse events could be systematically identified at the preanaesthetic assessment and thus can benefit from a specifically targeted anaesthesia management. Department of Anaesthesia, Princess Margaret Hospital for Children, Swiss Foundation for Grants in Biology and Medicine, and the Voluntary Academic Society Basel. Copyright 2010 Elsevier Ltd. All rights reserved.

Comparative risk of cerebrovascular adverse events in community-dwelling older adults using risperidone, olanzapine and quetiapine: a multiple propensity score-adjusted retrospective cohort study.

PubMed

Chatterjee, Satabdi; Chen, Hua; Johnson, Michael L; Aparasu, Rajender R

2012-10-01

Atypical antipsychotic agents have been associated with cerebrovascular adverse events, particularly in elderly dementia patients. However, limited evidence exists regarding comparative cerebrovascular profiles of individual atypical agents, particularly in community settings. The objective of this study was to evaluate the risk of cerebrovascular events associated with use of risperidone, olanzapine and quetiapine in community-dwelling older adults in the US. A propensity score-adjusted retrospective cohort design involving the IMS LifeLink™ Health Plan Claims Database was used for the study. The study population included all older adults (aged ≥50 years) who initiated risperidone, olanzapine or quetiapine anytime during 1 July 2000 to 30 June 2008. Patients were followed until hospitalization or an emergency room visit for a cerebrovascular event, or the end of the study period, whichever occurred earlier. The Cox proportional hazard regression model with time-varying covariates was used to evaluate the risk of cerebrovascular events during the follow-up period, using olanzapine as the reference. The covariates adjusted for in the final model included multiple propensity scores and exposure to other medications that could be associated with the risk of cerebrovascular events. A total of 2,458 cerebrovascular events were identified in the study cohort: 1,081 (21.38%) for risperidone users, 816 (18.75%) for olanzapine users and 561 (21.05%) for quetiapine users. After adjusting for propensity scores and other covariates, the Cox proportional hazard model revealed that use of quetiapine [hazard ratio (HR) 0.88; 95% CI 0.78, 0.99] but not risperidone (HR 1.05; 95% CI 0.95, 1.16) was associated with a decrease in the risk of cerebrovascular adverse events compared with olanzapine. The study suggested that quetiapine use may be associated with a moderately lower risk of cerebrovascular events than olanzapine in older adults. Prescribers should closely monitor the patients treated with atypical agents for the incidence of cerebrovascular adverse events.

Efficacy and Safety of Tacrolimus Therapy for Active Ulcerative Colitis; A Systematic Review and Meta-analysis

PubMed Central

Komaki, Yuga; Komaki, Fukiko; Ido, Akio

2016-01-01

Background: Approximately 25% of patients with ulcerative colitis [UC] experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus as a rescue therapy for active UC. Methods: Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short- and long-term clinical response, colectomy free rates, and rate of adverse events in randomised controlled trials [RCTs] and observational studies. Results: Two RCTs comparing high trough concentration [10–15ng/ml] versus placebo [n = 103] and 23 observational studies [n = 831] were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio [RR] = 4.61, 95% confidence interval [CI] = 2.09–10.17, p = 0.15 x 10-3] among RCTs. Rates of clinical response at 1 and 3 months were 0.73 [95% CI = 0.64–0.81] and 0.76 [95% CI = 0.59–0.87], and colectomy-free rates remained high at 1, 3, 6, and 12 months [0.86, 0.84, 0.78, and 0.69, respectively] among observational studies. Among RCTs, adverse events were more frequent compared with placebo [RR = 2.01, 95% CI = 1.20–3.37, p = 0.83 x 10-2], but there was no difference in severe adverse events [RR = 3.15, 95% CI = 0.14–72.9, p = 0.47]. Severe adverse events were rare among observational studies [0.11, 95% CI = 0.06–0.20]. Conclusions: In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC. PMID:26645641

Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines

PubMed Central

Sarntivijai, Sirarat; Xiang, Zuoshuang; Shedden, Kerby A.; Markel, Howard; Omenn, Gilbert S.; Athey, Brian D.; He, Yongqun

2012-01-01

Vaccine adverse events (VAEs) are adverse bodily changes occurring after vaccination. Understanding the adverse event (AE) profiles is a crucial step to identify serious AEs. Two different types of seasonal influenza vaccines have been used on the market: trivalent (killed) inactivated influenza vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). Different adverse event profiles induced by these two groups of seasonal influenza vaccines were studied based on the data drawn from the CDC Vaccine Adverse Event Report System (VAERS). Extracted from VAERS were 37,621 AE reports for four TIVs (Afluria, Fluarix, Fluvirin, and Fluzone) and 3,707 AE reports for the only LAIV (FluMist). The AE report data were analyzed by a novel combinatorial, ontology-based detection of AE method (CODAE). CODAE detects AEs using Proportional Reporting Ratio (PRR), Chi-square significance test, and base level filtration, and groups identified AEs by ontology-based hierarchical classification. In total, 48 TIV-enriched and 68 LAIV-enriched AEs were identified (PRR>2, Chi-square score >4, and the number of cases >0.2% of total reports). These AE terms were classified using the Ontology of Adverse Events (OAE), MedDRA, and SNOMED-CT. The OAE method provided better classification results than the two other methods. Thirteen out of 48 TIV-enriched AEs were related to neurological and muscular processing such as paralysis, movement disorders, and muscular weakness. In contrast, 15 out of 68 LAIV-enriched AEs were associated with inflammatory response and respiratory system disorders. There were evidences of two severe adverse events (Guillain-Barre Syndrome and paralysis) present in TIV. Although these severe adverse events were at low incidence rate, they were found to be more significantly enriched in TIV-vaccinated patients than LAIV-vaccinated patients. Therefore, our novel combinatorial bioinformatics analysis discovered that LAIV had lower chance of inducing these two severe adverse events than TIV. In addition, our meta-analysis found that all previously reported positive correlation between GBS and influenza vaccine immunization were based on trivalent influenza vaccines instead of monovalent influenza vaccines. PMID:23209624

Efficacy and adverse events of cold vs hot polypectomy: A meta-analysis.

PubMed

Fujiya, Mikihiro; Sato, Hiroki; Ueno, Nobuhiro; Sakatani, Aki; Tanaka, Kazuyuki; Dokoshi, Tatsuya; Fujibayashi, Shugo; Nomura, Yoshiki; Kashima, Shin; Gotoh, Takuma; Sasajima, Junpei; Moriichi, Kentaro; Watari, Jiro; Kohgo, Yutaka

2016-06-21

To compare previously reported randomized controlled studies (RCTs) of cold and hot polypectomy, we systematically reviewed and clarify the utility of cold polypectomy over hot with respect to efficacy and adverse events. A meta-analysis was conducted to evaluate the predominance of cold and hot polypectomy for removing colon polyps. Published articles and abstracts from worldwide conferences were searched using the keywords "cold polypectomy". RCTs that compared either or both the effects or adverse events of cold polypectomy with those of hot polypectomy were collected. The patients' demographics, endoscopic procedures, No. of examined lesions, lesion size, macroscopic and histologic findings, rates of incomplete resection, bleeding amount, perforation, and length of procedure were extracted from each study. A forest plot analysis was used to verify the relative strength of the effects and adverse events of each procedure. A funnel plot was generated to assess the possibility of publication bias. Ultimately, six RCTs were selected. No significant differences were noted in the average lesion size (less than 10 mm) between the cold and hot polypectomy groups in each study. Further, the rates of complete resection and adverse events, including delayed bleeding, did not differ markedly between cold and hot polypectomy. The average procedural time in the cold polypectomy group was significantly shorter than in the hot polypectomy group. Cold polypectomy is a time-saving procedure for removing small polyps with markedly similar curability and safety to hot polypectomy.

Cognitive complexity of the medical record is a risk factor for major adverse events.

PubMed

Roberson, David; Connell, Michael; Dillis, Shay; Gauvreau, Kimberlee; Gore, Rebecca; Heagerty, Elaina; Jenkins, Kathy; Ma, Lin; Maurer, Amy; Stephenson, Jessica; Schwartz, Margot

2014-01-01

Patients in tertiary care hospitals are more complex than in the past, but the implications of this are poorly understood as "patient complexity" has been difficult to quantify. We developed a tool, the Complexity Ruler, to quantify the amount of data (as bits) in the patient’s medical record. We designated the amount of data in the medical record as the cognitive complexity of the medical record (CCMR). We hypothesized that CCMR is a useful surrogate for true patient complexity and that higher CCMR correlates with risk of major adverse events. The Complexity Ruler was validated by comparing the measured CCMR with physician rankings of patient complexity on specific inpatient services. It was tested in a case-control model of all patients with major adverse events at a tertiary care pediatric hospital from 2005 to 2006. The main outcome measure was an externally reported major adverse event. We measured CCMR for 24 hours before the event, and we estimated lifetime CCMR. Above empirically derived cutoffs, 24-hour and lifetime CCMR were risk factors for major adverse events (odds ratios, 5.3 and 6.5, respectively). In a multivariate analysis, CCMR alone was essentially as predictive of risk as a model that started with 30-plus clinical factors. CCMR correlates with physician assessment of complexity and risk of adverse events. We hypothesize that increased CCMR increases the risk of physician cognitive overload. An automated version of the Complexity Ruler could allow identification of at-risk patients in real time.

Development, implementation and evaluation of a patient handoff tool to improve safety in orthopaedic surgery.

PubMed

Gagnier, Joel J; Derosier, Joseph M; Maratt, Joseph D; Hake, Mark E; Bagian, James P

2016-06-01

To develop, implement and test the effect of a handoff tool for orthopaedic trauma residents that reduces adverse events associated with the omission of critical information and the transfer of erroneous information. Components of this project included a literature review, resident surveys and observations, checklist development and refinement, implementation and evaluation of impact on adverse events through a chart review of a prospective cohort compared with a historical control group. Large teaching hospital. Findings of a literature review were presented to orthopaedic residents, epidemiologists, orthopaedic surgeons and patient safety experts in face-to-face meetings, during which we developed and refined the contents of a resident handoff tool. The tool was tested in an orthopaedic trauma service and its impact on adverse events was evaluated through a chart review. The handoff tool was developed and refined during the face-to-face meetings and a pilot implementation. Adverse event data were collected on 127 patients (n = 67 baseline period; n = 60 test period). A handoff tool for use by orthopaedic residents. Adverse events in patients handed off by orthopaedic trauma residents. After controlling for age, gender and comorbidities, testing resulted in fewer events per person (25-27% reduction; P < 0.10). Preliminary evidence suggests that our resident handoff tool may contribute to a decrease in adverse events in orthopaedic patients. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Development of a Classification Scheme for Examining Adverse Events Associated with Medical Devices, Specifically the DaVinci Surgical System as Reported in the FDA MAUDE Database.

PubMed

Gupta, Priyanka; Schomburg, John; Krishna, Suprita; Adejoro, Oluwakayode; Wang, Qi; Marsh, Benjamin; Nguyen, Andrew; Genere, Juan Reyes; Self, Patrick; Lund, Erik; Konety, Badrinath R

2017-01-01

To examine the Manufacturer and User Facility Device Experience Database (MAUDE) database to capture adverse events experienced with the Da Vinci Surgical System. In addition, to design a standardized classification system to categorize the complications and machine failures associated with the device. Overall, 1,057,000 DaVinci procedures were performed in the United States between 2009 and 2012. Currently, no system exists for classifying and comparing device-related errors and complications with which to evaluate adverse events associated with the Da Vinci Surgical System. The MAUDE database was queried for events reports related to the DaVinci Surgical System between the years 2009 and 2012. A classification system was developed and tested among 14 robotic surgeons to associate a level of severity with each event and its relationship to the DaVinci Surgical System. Events were then classified according to this system and examined by using Chi-square analysis. Two thousand eight hundred thirty-seven events were identified, of which 34% were obstetrics and gynecology (Ob/Gyn); 19%, urology; 11%, other; and 36%, not specified. Our classification system had moderate agreement with a Kappa score of 0.52. Using our classification system, we identified 75% of the events as mild, 18% as moderate, 4% as severe, and 3% as life threatening or resulting in death. Seventy-seven percent were classified as definitely related to the device, 15% as possibly related, and 8% as not related. Urology procedures compared with Ob/Gyn were associated with more severe events (38% vs 26%, p < 0.0001). Energy instruments were associated with less severe events compared with the surgical system (8% vs 87%, p < 0.0001). Events that were definitely associated with the device tended to be less severe (81% vs 19%, p < 0.0001). Our classification system is a valid tool with moderate inter-rater agreement that can be used to better understand device-related adverse events. The majority of robotic related events were mild but associated with the device.

Adverse cardiac events in 56,000 orthopaedic trauma patients: Does anatomic area make a difference?

PubMed

Lee, Adam K; Dodd, Ashley C; Lakomkin, Nikita; Yarlagadda, Mahesh; Jahangir, A Alex; Collinge, Cory A; Sethi, Manish K

2016-08-01

Postoperative cardiac events in orthopaedic trauma patients constitute severe morbidity and mortality. It is therefore increasingly important to determine patient risk factors that are predictive of postoperative myocardial infarctions and cardiac arrests. This study sought to assess if there is an association between anatomic area and cardiac complications in the orthopaedic trauma patient. From 2006-2013, a total of 361,402 orthopaedic patients were identified in the NSQIP database using Current Procedural Terminology (CPT) codes. Of these, 56,336 (15.6%) patients were identified as orthopaedic trauma patients broken down by anatomic region: 11,905 (21.1%) upper extremity patients (UE), 29,009 (51.5%) hip/pelvis patients (HP), and 15,422 (27.4%) lower extremity patients (LE) using CPT codes. Patients were defined as having adverse cardiac events if they developed myocardial infarctions or cardiac arrests within 30days after surgery. Chi-squared analysis was used to determine if there was an association between anatomic area and rates of cardiac events. Multivariate logistical analysis was used with over 40 patient characteristics including age, gender, history of cardiac disease, and anatomic region as independent predictors to determine whether anatomic area significantly predicted the development of cardiac complications. There were significant differences in baseline demographics among the three groups: HP patients had the greatest average age (77.6 years) compared to 54.8 years for UE patients and 54.1 years in LE patients (p<0.001). HP patients also had the highest average ASA score (3.0) (p<0.001). There was a significant difference in adverse cardiac events based on anatomic area: 0.27% (32/11,905) UE patients developed cardiac complications compared to 2.15% (623/29,009) HP patients and 0.61% (94/15,422) LE patients. After multivariate analysis, HP patients were significantly more likely to develop cardiac complications compared to both UE patients (OR: 6.377, p=0.014) and LE patients (OR: 2.766, p=0.009). There is a significant difference in adverse cardiac events following orthopaedic trauma based on anatomic region. Hip/Pelvis surgery appeared to be a significant risk factor in developing an adverse cardiac event. Further studies should investigate why hip/pelvic patients are at a higher risk of adverse cardiac events. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adverse events and adherence to HIV post-exposure prophylaxis: a cohort study at the Korle-Bu Teaching Hospital in Accra, Ghana.

PubMed

Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Nortey, Priscilla A; Dodoo, Alexander N O

2015-06-20

There is strong evidence that post-exposure prophylaxis (PEP) with antiretroviral drugs in the timely management of occupational exposures sustained by healthcare workers decreases the risk of HIV infection and PEP is now widely used. Antiretroviral drugs have well documented toxicities and produce adverse events in patients living with HIV/AIDS. In the era of "highly active antiretroviral therapy", non-adherence to treatment has been closely linked to the occurrence of adverse events in HIV patients and this ultimately influences treatment success but the influence of adverse events on adherence during PEP is less well studied. Following the introduction of a HIV post-exposure prophylaxis program in the Korle-Bu Teaching Hospital in January 2005, the incidence of adverse events and adherence were documented in occupationally-exposed healthcare workers (HCWs) and healthcare students (HCSs). Cohort event monitoring was used in following-up on exposed HCWs/HCSs for the two study outcomes; adverse events and adherence. All adverse events reported were grouped by MedDRA system organ classification and then by preferred term according to prophylaxis regimen. Adherence was determined by the completion of prophylaxis schedule. Cox proportional regression analysis was applied to determine the factors associated with the cohort study outcomes. Differences in frequencies were tested using the Chi square test and p < 0.05 was considered statistically significant. A total of 228 exposed HCWs/HCSs were followed up during the study, made up of 101 exposed HCWs/HCSs administered lamivudine/zidovudine (3TC/AZT) for 3 days; 75 exposed HCWs/HCSs administered lamivudine/zidovudine (3TC/AZT) for 28 days; and 52 exposed HCWs/HCSs administered lamivudine/zidovudine/lopinavir-ritonavir (3TC/AZT/LPV-RTV) for 28 days. The frequency of adverse events was 28% (n = 28) in exposed HCWs/HCSs administered 3TC/AZT for 3 days, 91% (n = 68) in exposed HCWs/HCSs administered 3TC/AZT for 28 days and 96% (n = 50) in exposed HCWs/HCSs administered 3TC/AZT/LPV-RTV for 28 days. Nausea was the most commonly reported adverse events in all three regimens. Adherence was complete in all exposed HCWs/HCSs administered 3TC/AZT for 3days, 56% (n = 42) in exposed HCWs/HCSs administered 3TC/AZT for 28 days and 62% (n = 32) in exposed HCWs/HCSs administered 3TC/AZT/LPV-RTV for 28 days. In the Cox regression multi-variate analysis, exposed HCWs/HCSs administered 3TC/AZT for 3 days were 70% less likely to report adverse events compared with exposed HCWs/HCSs administered 3TC/AZT for 28 days (Adjusted HR = 0.30 [95% CI, 0.18-0.48], p < 0.001). Exposed HCWs/HCSs administered 3TC/AZT for 3 days were 75% more likely to adhere to the schedule compared with exposed HCWs/HCSs administered 3TC/AZT for 28 days (Adjusted HR = 1.75 [95% CI, 1.16-2.66], p = 0.008). The intolerance to adverse events was cited as the sole reason for truncating PEP, thereby indicating the need for adequate, appropriate and effective counselling, education, active follow-up (possibly through mobile /phone contact) and management of adverse events. Education on the need to complete PEP schedule (especially for exposed HCWs/HCSs on 28-day schedule) can lead to increased adherence, which is very critical in minimizing the risk of HIV sero-conversion. The present results also indicate that cohort event monitoring could be an effective pharmacovigilance tool in monitoring adverse events in exposed HCWs/HCSs on HIV post-exposure prophylaxis.

Adverse event reporting in Czech long-term care facilities.

PubMed

Hěib, Zdenřk; Vychytil, Pavel; Marx, David

2013-04-01

To describe adverse event reporting processes in long-term care facilities in the Czech Republic. Prospective cohort study involving a written questionnaire followed by in-person structured interviews with selected respondents. Long-term care facilities located in the Czech Republic. Staff of 111 long-term care facilities (87% of long-term care facilities in the Czech Republic). None. Sixty-three percent of long-term health-care facilities in the Czech Republic have adverse event-reporting processes already established, but these were frequently very immature programs sometimes consisting only of paper recording of incidents. Compared to questionnaire responses, in-person interview responses only partially tended to confirm the results of the written survey. Twenty-one facilities (33%) had at most 1 unconfirmed response, 31 facilities (49%) had 2 or 3 unconfirmed responses and the remaining 11 facilities (17%) had 4 or more unconfirmed responses. In-person interviews suggest that use of a written questionnaire to assess the adverse event-reporting process may have limited validity. Staff of the facilities we studied expressed an understanding of the importance of adverse event reporting and prevention, but interviews also suggested a lack of knowledge necessary for establishing a good institutional reporting system in long-term care.

Initial Experience with Balloon-Occluded Trans-catheter Arterial Chemoembolization (B-TACE) for Hepatocellular Carcinoma

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

Maruyama, Mitsunari, E-mail: mitunari@med-shimane.u.ac.jp; Yoshizako, Takeshi, E-mail: yosizako@med.shimane-u.ac.jp; Nakamura, Tomonori, E-mail: t-naka@med.shimane-u.ac.jp

2016-03-15

PurposeThis study was performed to evaluate the accumulation of lipiodol emulsion (LE) and adverse events during our initial experience of balloon-occluded trans-catheter arterial chemoembolization (B-TACE) for hepatocellular carcinoma (HCC) compared with conventional TACE (C-TACE).MethodsB-TACE group (50 cases) was compared with C-TACE group (50 cases). The ratio of the LE concentration in the tumor to that in the surrounding embolized liver parenchyma (LE ratio) was calculated after each treatment. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Effects (CTCAE) version 4.0.ResultsThe LE ratio at the level of subsegmental showed a statistically significant difference between the groups (tmore » test: P < 0.05). Only elevation of alanine aminotransferase was more frequent in the B-TACE group, showing a statistically significant difference (Mann–Whitney test: P < 0.05). While B-TACE caused severe adverse events (liver abscess and infarction) in patients with bile duct dilatation, there was no statistically significant difference in incidence between the groups. Multivariate logistic regression analysis suggested that the significant risk factor for liver abscess/infarction was bile duct dilatation (P < 0.05).ConclusionThe LE ratio at the level of subsegmental showed a statistically significant difference between the groups (t test: P < 0.05). B-TACE caused severe adverse events (liver abscess and infarction) in patients with bile duct dilatation.« less

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Franco, Juan Va; Turk, Tarek; Jung, Jae Hung; Xiao, Yu-Tian; Iakhno, Stanislav; Garrote, Virginia; Vietto, Valeria

2018-01-26

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture reduces prostatitis symptoms in an appreciable number of participants compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference in adverse events (moderate QoE). It probably also decreases prostatitis symptoms compared with standard medical therapy in an appreciable number of participants (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2. Circumcision: (one study, 713 participants) based on short-term follow-up, early circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD -3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a greater incidence of adverse events compared with control (a waiting list to be circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants) based on short-term follow-up, we are uncertain of the effects of the use of an electromagnetic chair on prostatitis symptoms. It may be associated with a greater incidence of adverse events compared with sham procedure (low to very low QoE).4. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a greater improvement in prostatitis symptoms in an appreciable number of participants compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events.5. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events.7. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE).8. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events.9. Other interventions: there is uncertainty about the effects of other interventions included in this review. We found no information regarding psychological support or prostatic surgery. Some of the interventions can decrease prostatitis symptoms in an appreciable number without a greater incidence of adverse events. The QoE was mostly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

Adverse events in an integrated trauma-focused intervention for women in community substance abuse treatment.

PubMed

Killeen, Therese; Hien, Denise; Campbell, Aimee; Brown, Chanda; Hansen, Cheri; Jiang, Huiping; Kristman-Valente, Allison; Neuenfeldt, Christine; Rocz-de la Luz, Nicci; Sampson, Royce; Suarez-Morales, Lourdes; Wells, Elizabeth; Brigham, Greg; Nunes, Edward

2008-10-01

A substantial number of women who enter substance abuse treatment have a history of trauma and meet criteria for posttraumatic stress disorder (PTSD). Fear regarding the extent to which PTSD treatment can evoke negative consequences remains a research question. This study explored adverse events related to the implementation of an integrated treatment for women with trauma and substance use disorder (Seeking Safety) compared with a nontrauma-focused intervention (Women's Health Education). Three hundred fifty-three women enrolled in community substance abuse treatment were randomized to 1 of the 2 study groups and monitored weekly for adverse events. There were no differences between the two intervention groups in the number of women reporting study-related adverse events (28 [9.6%] for the Seeking Safety group and 21[7.2%] for the Women's Health Education group). Implementing PTSD treatment in substance abuse treatment programs appears to be safe, with minimal impact on intervention-related adverse psychiatric and substance abuse symptoms. More research is needed on the efficacy of such interventions to improve outcomes of PTSD and substance use.

Spontaneous Adverse Event Reports Associated with Zolpidem in the United States 2003–2012

PubMed Central

Wong, Carmen K.; Marshall, Nathaniel S.; Grunstein, Ronald R.; Ho, Samuel S.; Fois, Romano A.; Hibbs, David E.; Hanrahan, Jane R.; Saini, Bandana

2017-01-01

Study Objectives: Stimulated reporting occurs when patients and healthcare professionals are influenced or “stimulated” by media publicity to report specific drug-related adverse reactions, significantly biasing pharmacovigilance analyses. Among countries where the non-benzodiazepine hypnotic drug zolpidem is marketed, the United States experienced a comparable surge of media reporting during 2006–2009 linking the above drug with the development of complex neuropsychiatric sleep-related behaviors. However, the effect of this stimulated reporting in the United States Food and Drug Administration Adverse Event Reporting System has not been explored. Methods: Using disproportionality analyses, reporting odds ratios for zolpidem exposure and the following adverse events; parasomnia, movement-based parasomnia, nonmovement-based parasomnia, amnesia, hallucination, and suicidality were determined and compared to all other medications in the database, followed by specific comparison to the benzodiazepine hypnotic class, year-by-year from 2003 to 2012. Results: Odds ratios were increased significantly during and after the period of media publicity for parasomnias, movement-based parasomnias, amnesias and hallucinations. We also observed that zolpidem adverse drug reaction (ADR) reports have higher odds for parasomnias, movement-based parasomnias, amnesias, hallucinations, and suicidality compared to all other drugs, even before the media publicity cluster. Conclusions: Although our results indicate that zolpidem reports have higher odds for the ADR of interest even before the media publicity cluster, negative media coverage greatly exacerbated the reporting of these adverse reactions. The effect of such reporting must be borne in mind when decisions around drugs which have been the subject of intense media publicity are made by health professionals or regulatory bodies. Citation: Wong CK, Marshall NS, Grunstein RR, Ho SS, Fois RA, Hibbs DE, Hanrahan JR, Saini B. Spontaneous adverse event reports associated with zolpidem in the United States 2003–2012. J Clin Sleep Med. 2017;13(2):223–234. PMID:27784418

Active versus passive adverse event reporting after pediatric chiropractic manual therapy: study protocol for a cluster randomized controlled trial.

PubMed

Pohlman, Katherine A; Carroll, Linda; Tsuyuki, Ross T; Hartling, Lisa; Vohra, Sunita

2017-12-01

Patient safety performance can be assessed with several systems, including passive and active surveillance. Passive surveillance systems provide opportunity for health care personnel to confidentially and voluntarily report incidents, including adverse events, occurring in their work environment. Active surveillance systems systematically monitor patient encounters to seek detailed information about adverse events that occur in work environments; unlike passive surveillance, active surveillance allows for collection of both numerator (number of adverse events) and denominator (number of patients seen) data. Chiropractic manual therapy is commonly used in both adults and children, yet few studies have been done to evaluate the safety of chiropractic manual therapy for children. In an attempt to evaluate this, this study will compare adverse event reporting in passive versus active surveillance systems after chiropractic manual therapy in the pediatric population. This cluster randomized controlled trial aims to enroll 70 physicians of chiropractic (unit of randomization) to either passive or active surveillance system to report adverse events that occur after treatment for 60 consecutive pediatric (13 years of age and younger) patient visits (unit of analysis). A modified enrollment process with a two-phase consent procedure will be implemented to maintain provider blinding and minimize dropouts. The first phase of consent is for the provider to confirm their interest in a trial investigating the safety of chiropractic manual therapy. The second phase ensures that they understand the specific requirements for the group to which they were randomized. Percentages, incidence estimates, and 95% confidence intervals will be used to describe the count of reported adverse events in each group. The primary outcome will be the number and quality of the adverse event reports in the active versus the passive surveillance group. With 80% power and 5% one-sided significance level, the sample size was calculated to be 35 providers in each group, which includes an 11% lost to follow-up of chiropractors and 20% of patient visits. This study will be the first direct comparison of adverse event reporting using passive versus active surveillance. It is also the largest prospective evaluation of adverse events reported after chiropractic manual therapy in children, identified as a major gap in the academic literature. ClinicalTrials.gov, ID: NCT02268331 . Registered on 10 October 2014.

Percutaneous closure of patent foramen ovale and atrial septal defect in adults: the impact of clinical variables and hospital procedure volume on in-hospital adverse events.

PubMed

Opotowsky, Alexander R; Landzberg, Michael J; Kimmel, Stephen E; Webb, Gary D

2009-05-01

Percutaneous closure of patent foramen ovale/atrial septal defect (PFO/ASD) is an increasingly common procedure perceived as having minimal risk. There are no population-based estimates of in-hospital adverse event rates of percutaneous PFO/ASD closure. We used nationally representative data from the 2001-2005 Nationwide Inpatient Sample to identify patients >or-=20 years old admitted to an acute care hospital with an International Classification of Diseases, Ninth Revision code designating percutaneous PFO/ASD closure on the first or second hospital day. Variables analyzed included age, sex, number of comorbidities, year, same-day use of intracardiac or other echocardiography, same-day left heart catheterization, hospital size and teaching status, PFO/ASD procedural volume, and coronary intervention volume. Outcomes of interest included length of stay, charges, and adverse events. The study included 2,555 (weighted to United States population: 12,544 +/- 1,987) PFO/ASD closure procedures. Mean age was 52.0 +/- 0.4 years, and 57.3% +/- 1.0% were women. Annual hospital volume averaged 40.8 +/- 7.7 procedures (range, 1-114). Overall, 8.2 +/- 0.8% of admissions involved an adverse event. Older patients and those with comorbidities were more likely to sustain adverse events. Use of intracardiac echocardiography was associated with fewer adverse events. The risk of adverse events was inversely proportional to annual hospital volume (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.86-0.96, per 10 procedures), even after limiting the analysis to hospitals performing >or=10 procedures annually (OR 0.91, 95% CI 0.85-0.98). Adverse events were more frequent at hospitals in the lowest volume quintile as compared with the highest volume quintile (13.3% vs 5.4%, OR 2.42, 95% CI 1.55-3.78). The risk of adverse events of percutaneous PFO/ASD closure is inversely correlated with hospital volume. This relationship applies even to hospitals meeting the current guidelines, performing >or=10 procedures annually.

Adverse life events in elderly patients with major depression or dysthymic disorder and in healthy-control subjects.

PubMed

Devanand, D P; Kim, Min Kyung; Paykina, Natalya; Sackeim, Harold A

2002-01-01

The authors compared elderly outpatients (> or =60 years) with major depression or dysthymic disorder and healthy-control subjects on the type and subjective impact of adverse life events. The Geriatric Adverse Life Events Scale (GALES) was developed for this purpose. Fifty patients with major depression, 79 patients with dysthymic disorder, and 40 healthy controls completed the GALES. Adverse life events during two time periods were assessed: the year before the evaluation, and the year before onset of the index episode (patients only). During the year before evaluation, patients with major depression reported more life events with greater negative impact, particularly for interpersonal conflicts, and dysthymic patients scored intermediate between patients and controls. Sum scores for perceived stress and negative impact on mood differed significantly among the groups: highest for major depression, intermediate for dysthymic disorder, and lowest for controls. During the year before onset, patients with major depression reported significantly higher sum scores for negative impact on mood than patients with dysthymic disorder. On several measures, patients with major depression perceived greater negative impact of life events than patients with dysthymic disorder and healthy controls, particularly for interpersonal conflicts. The subjective impact of adverse life events may play an important role in the expression of depressive illness in elderly patients, particularly in major depression, and it needs to be considered in clinical management.

Traumas and other adverse life events in adolescents with alcohol abuse and dependence.

PubMed

Clark, D B; Lesnick, L; Hegedus, A M

1997-12-01

Clinical observation suggests that adolescents with alcohol use disorders often have complex histories that include childhood maltreatment and other traumas. The aim of this study was to determine the relationships among adolescent alcohol use disorders and a broad range of traumas and adverse life events. The subjects were 132 adolescents with alcohol dependence, 51 adolescents with alcohol abuse, and 73 adolescents recruited from the community as a control group. Trauma history was assessed by a semistructured interview and other adverse life events by questionnaire. Traumatic events reflecting interpersonal violence had occurred in many of the adolescents with alcohol dependence and abuse and few of the control adolescents. Adolescents with alcohol abuse or dependence, compared with control subjects, were 6 to 12 times more likely to have a physical abuse history and 18 to 21 times more likely to have a sexual abuse history. Sexual abuse was more common in females, and victimization by other violent acts was more common in males. Many other adverse life events were also significantly more common in the alcohol use disorder groups than in the control group, including having a close friend die, arguments within the family, and legal difficulties. These results demonstrate that trauma and other adverse life events are strongly associated with alcohol use disorders in adolescents. Clinical screening of adolescents with alcohol use disorders for a range of traumatic events is recommended.

Adverse Event Rates Associated with Transforaminal and Interlaminar Epidural Steroid Injections: A Multi-Institutional Study.

PubMed

El-Yahchouchi, Christine A; Plastaras, Christopher T; Maus, Timothy P; Carr, Carrie M; McCormick, Zachary L; Geske, Jennifer R; Smuck, Matthew; Pingree, Matthew J; Kennedy, David J

2016-02-01

Transforaminal epidural steroid injections (TFESI) have demonstrated efficacy and effectiveness in treatment of radicular pain. Despite little evidence of efficacy/effectiveness, interlaminar epidural steroid injections (ILESI) are advocated by some as primary therapy for radicular pain due to purported greater safety. To assess immediate and delayed adverse event rates of TFESI and ILESI injections at three academic medical centers utilizing International Spine Intervention Society practice guidelines. Quality assurance databases from a Radiology and two physical medicine and rehabilitation (PM&R) practices were interrogated. Medical records were reviewed, verifying immediate and delayed adverse events. There were no immediate major adverse events of neurologic injury or hemorrhage in 16,638 consecutive procedures in all spine segments (14,956 TFESI; 1,682 ILESI). Vasovagal reactions occurred in 1.2% of procedures, more frequently (P = 0.004) in TFESI (1.3%) than ILESI (0.5%). Dural punctures occurred in 0.06% of procedures, more commonly after ILESI (0.2% vs 0.04%, P = 0.006). Delayed follow up on PM&R patients (92.5% and 78.5, next business day) and radiology patients (63.1%, 2 weeks) identified no major adverse events of neurologic injury, hemorrhage, or infection. There were no significant differences in delayed minor adverse event rates. Central steroid response (sleeplessness, flushing, nonpositional headache) was seen in 2.6% of both TFESI and ILESI patients. 2.1% of TFESI and 1.8% of ILESI patients reported increased pain. No long-term sequelae were seen from any immediate or delayed minor adverse event. Both transforaminal and ILESI are safely performed with low immediate and delayed adverse event rates when informed by evidence-based procedural guidelines. By demonstrating comparable safety, this study suggests that the choice between ILESI and TFESIs can be based on documented efficacy and effectiveness and not driven by safety concerns.

Discriminative ability of commonly used indices to predict adverse outcomes after poster lumbar fusion: a comparison of demographics, ASA, the modified Charlson Comorbidity Index, and the modified Frailty Index.

PubMed

Ondeck, Nathaniel T; Bohl, Daniel D; Bovonratwet, Patawut; McLynn, Ryan P; Cui, Jonathan J; Shultz, Blake N; Lukasiewicz, Adam M; Grauer, Jonathan N

2018-01-01

As research tools, the American Society of Anesthesiologists (ASA) physical status classification system, the modified Charlson Comorbidity Index (mCCI), and the modified Frailty Index (mFI) have been associated with complications following spine procedures. However, with respect to clinical use for various adverse outcomes, no known study has compared the predictive performance of these indices specifically following posterior lumbar fusion (PLF). This study aimed to compare the discriminative ability of ASA, mCCI, and mFI, as well as demographic factors including age, body mass index, and gender for perioperative adverse outcomes following PLF. A retrospective review of prospectively collected data was performed. Patients undergoing elective PLF with or without interbody fusion were extracted from the 2011-2014 American College of Surgeons National Surgical Quality Improvement Program (NSQIP). Perioperative adverse outcome variables assessed included the occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, and discharge to higher-level care. Patient comorbidity indices and characteristics were delineated and assessed for discriminative ability in predicting perioperative adverse outcomes using an area under the curve analysis from the receiver operating characteristics curves. In total, 16,495 patients were identified who met the inclusion criteria. The most predictive comorbidity index was ASA and demographic factor was age. Of these two factors, age had the larger discriminative ability for three out of the six adverse outcomes and ASA was the most predictive for one out of six adverse outcomes. A combination of the most predictive demographic factor and comorbidity index resulted in improvements in discriminative ability over the individual components for five of the six outcome variables. For PLF, easily obtained patient ASA and age have overall similar or better discriminative abilities for perioperative adverse outcomes than numerically tabulated indices that have multiple inputs and are harder to implement in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Five-Year Safety Data for More than 55,000 Subjects following Breast Implantation: Comparison of Rare Adverse Event Rates with Silicone Implants versus National Norms and Saline Implants.

PubMed

Singh, Navin; Picha, George J; Hardas, Bhushan; Schumacher, Andrew; Murphy, Diane K

2017-10-01

The U.S. Food and Drug Administration has required postapproval studies of silicone breast implants to evaluate the incidence of rare adverse events over 10 years after implantation. The Breast Implant Follow-Up Study is a large 10-year study (>1000 U.S. sites) evaluating long-term safety following primary augmentation, revision-augmentation, primary reconstruction, or revision-reconstruction with Natrelle round silicone breast implants compared with national norms and outcomes with saline implants. Targeted adverse events in subjects followed for 5 to 8 years included connective tissue diseases, neurologic diseases, cancer, and suicide. The safety population comprised 55,279 women (primary augmentation, n = 42,873; revision-augmentation, n = 6837; primary reconstruction, n = 4828; and revision-reconstruction, n = 741). No targeted adverse events occurred at significantly greater rates in silicone implant groups versus national norms across all indications. The standardized incidence rate (observed/national norm) for all indications combined was 1.4 for cervical/vulvar cancer, 0.8 for brain cancer, 0.3 for multiple sclerosis, and 0.1 for lupus/lupus-like syndrome. Silicone implants did not significantly increase the risk for any targeted adverse events compared with saline implants. The risk of death was similar with silicone versus saline implants across all indications. The suicide rate (10.6 events per 100,000 person-years) was not significantly higher than the national norm. No implant-related deaths occurred. Results from 5 to 8 years of follow-up for a large number of subjects confirmed the safety of Natrelle round silicone implants, with no increased risk of systemic disease or suicide versus national norms or saline implants. Therapeutic, II.

Adaptation options for wheat in Europe will be limited by increased adverse weather events under climate change.

PubMed

Trnka, Miroslav; Hlavinka, Petr; Semenov, Mikhail A

2015-11-06

Ways of increasing the production of wheat, the most widely grown cereal crop, will need to be found to meet the increasing demand caused by human population growth in the coming decades. This increase must occur despite the decrease in yield gains now being reported in some regions, increased price volatility and the expected increase in the frequency of adverse weather events that can reduce yields. However, if and how the frequency of adverse weather events will change over Europe, the most important wheat-growing area, has not yet been analysed. Here, we show that the accumulated probability of 11 adverse weather events with the potential to significantly reduce yield will increase markedly across all of Europe. We found that by the end of the century, the exposure of the key European wheat-growing areas, where most wheat production is currently concentrated, may increase more than twofold. However, if we consider the entire arable land area of Europe, a greater than threefold increase in risk was predicted. Therefore, shifting wheat production to new producing regions to reduce the risk might not be possible as the risk of adverse events beyond the key wheat-growing areas increases even more. Furthermore, we found a marked increase in wheat exposure to high temperatures, severe droughts and field inaccessibility compared with other types of adverse events. Our results also showed the limitations of some of the presently debated adaptation options and demonstrated the need for development of region-specific strategies. Other regions of the world could be affected by adverse weather events in the future in a way different from that considered here for Europe. This observation emphasizes the importance of conducting similar analyses for other major wheat regions. © 2015 The Authors.

Adaptation options for wheat in Europe will be limited by increased adverse weather events under climate change

PubMed Central

Trnka, Miroslav; Hlavinka, Petr; Semenov, Mikhail A.

2015-01-01

Ways of increasing the production of wheat, the most widely grown cereal crop, will need to be found to meet the increasing demand caused by human population growth in the coming decades. This increase must occur despite the decrease in yield gains now being reported in some regions, increased price volatility and the expected increase in the frequency of adverse weather events that can reduce yields. However, if and how the frequency of adverse weather events will change over Europe, the most important wheat-growing area, has not yet been analysed. Here, we show that the accumulated probability of 11 adverse weather events with the potential to significantly reduce yield will increase markedly across all of Europe. We found that by the end of the century, the exposure of the key European wheat-growing areas, where most wheat production is currently concentrated, may increase more than twofold. However, if we consider the entire arable land area of Europe, a greater than threefold increase in risk was predicted. Therefore, shifting wheat production to new producing regions to reduce the risk might not be possible as the risk of adverse events beyond the key wheat-growing areas increases even more. Furthermore, we found a marked increase in wheat exposure to high temperatures, severe droughts and field inaccessibility compared with other types of adverse events. Our results also showed the limitations of some of the presently debated adaptation options and demonstrated the need for development of region-specific strategies. Other regions of the world could be affected by adverse weather events in the future in a way different from that considered here for Europe. This observation emphasizes the importance of conducting similar analyses for other major wheat regions. PMID:26577595

Adverse events in British hospitals: preliminary retrospective record review

PubMed Central

Vincent, Charles; Neale, Graham; Woloshynowych, Maria

2001-01-01

Objectives To examine the feasibility of detecting adverse events through record review in British hospitals and to make preliminary estimates of the incidence and costs of adverse events. Design Retrospective review of 1014 medical and nursing records. Setting Two acute hospitals in Greater London area. Main outcome measure Number of adverse events. Results 110 (10.8%) patients experienced an adverse event, with an overall rate of adverse events of 11.7% when multiple adverse events were included. About half of these events were judged preventable with ordinary standards of care. A third of adverse events led to moderate or greater disability or death. Conclusions These results suggest that adverse events are a serious source of harm to patients and a large drain on NHS resources. Some are major events; others are frequent, minor events that go unnoticed in routine clinical care but together have massive economic consequences. PMID:11230064

Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations

PubMed Central

Xie, Pingxing; Kranzler, Henry R.; Poling, James; Stein, Murray B.; Anton, Raymond F.; Brady, Kathleen; Weiss, Roger D.; Farrer, Lindsay; Gelernter, Joel

2010-01-01

Context: The 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) has been found to moderate several categories of emotional response after stressful life events. Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of post-traumatic stress disorder (PTSD). Objective: To examine the effects of childhood adversity, adult traumatic events, 5-HTTLPR genotypes, and gene×environment interactions on the etiology of PTSD. Design: A cross-sectional study in which participants in several studies investigating the genetics of substance dependence were also screened for lifetime PTSD. The triallelic system of 5-HTTLPR was genotyped. Logistic regression modeling was used in the analyses. Setting: General community. Participants: Five hundred eighty-two European American and 670 African American individuals who reported experiences of childhood adversity, adult traumatic events, or both. Main Outcome Measure: Diagnosis of PTSD, defined by DSM-IV diagnostic criteria and assessed through the Semi-Structured Assessment for Drug Dependence and Alcoholism interview. Results: Childhood adversity and adult traumatic events both predicted PTSD. Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure (European American: odds ratio [OR], 2.86; 95% confidence interval [CI], 1.50-5.45; P=.002; African American: OR, 1.88; 95% CI, 1.04-3.40; P=.04; pooled: OR, 2.31; 95% CI, 1.50-3.56; P<.001). Conclusions: Participants who had both childhood adversity and adult traumatic events were more likely to develop lifetime PTSD compared with those who experienced either type of adverse event. The risk was increased in individuals with 1 or 2 copies of the S′ (S) allele compared with the L′ (L) homozygotes. Our study provides additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors. PMID:19884608

Excessive Daytime Sleepiness is Associated with Longer Culprit Lesion and Adverse Outcomes in Patients with Coronary Artery Disease

PubMed Central

Lee, Chi-Hang; Ng, Wai-Yee; Hau, William; Ho, Hee-Hwa; Tai, Bee-Choo; Chan, Mark Y.; Richards, A. Mark; Tan, Huay-Cheem

2013-01-01

Study Objectives: We assessed whether excessive daytime sleepiness was associated with coronary plaque phenotype and subsequent adverse cardiovascular events. Methods: Prospective cohort study. Intravascular ultrasound (IVUS) examination of the culprit coronary stenosis was performed. The Epworth Sleepiness Scale (ESS) questionnaire was administered, and the patients were divided into 2 groups—(1) sleepier and (2) less sleepy—based on the ESS score. Adverse cardiovascular outcomes were defined as cardiac death, myocardial infarction, stroke, unplanned revascularization, or heart failure admission. Results: One hundred seventeen patients undergoing urgent or non-urgent coronary angiography were recruited. Compared with the less sleepy group (ESS ≤ 10, n = 87), the sleepier group (ESS > 10, n = 30) had higher serum levels of total cholesterol and of low-density-lipoprotein cholesterols (p < 0.05 for both). The IVUS examinations indicated coronary stenoses were longer in the sleepier group than in the less sleepy group (p = 0.011). The cumulative incidence of adverse cardiovascular events at 16-month follow-up was higher in the sleepier than the less sleepy group (12.5% versus 6.9%, p = 0.03). Cox regression analysis adjusting for age and smoking showed increased hazard of adverse cardiovascular events in sleepier group as compared to less sleepy group (HR = 3.44, 95% CI 1.01-11.72). Conclusion: In patients presenting with coronary artery disease, excessive daytime sleepiness based on ESS > 10 was associated with longer culprit lesions and future adverse cardiovascular events. Citation: Lee CH; Ng WY; Hau W; Ho HH; Tai BC; Chan MY; Richards AM; Tan HC. Excessive daytime sleepiness is associated with longer culprit lesion and adverse outcomes in patients with coronary artery disease. J Clin Sleep Med 2013;9(12):1267-1272. PMID:24340288

Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

PubMed

Kim, M H; Lin, J; Hussein, M; Battleman, D

2009-12-01

Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Twelve-week, multicenter, placebo-controlled, randomized, double-blind, parallel-group, comparative phase II/III study of benzoyl peroxide gel in patients with acne vulgaris: A secondary publication.

PubMed

Kawashima, Makoto; Sato, Shinichi; Furukawa, Fukumi; Matsunaga, Kayoko; Akamatsu, Hirohiko; Igarashi, Atsuyuki; Tsunemi, Yuichiro; Hayashi, Nobukazu; Yamamoto, Yuki; Nagare, Toshitaka; Katsuramaki, Tsuneo

2017-07-01

A placebo-controlled, randomized, double-blind, parallel-group, comparative, multicenter study was conducted to investigate the efficacy and safety of benzoyl peroxide (BPO) gel, administrated once daily for 12 weeks to Japanese patients with acne vulgaris. Efficacy was evaluated by counting all inflammatory and non-inflammatory lesions. Safety was evaluated based on adverse events, local skin tolerability scores and laboratory test values. All 609 subjects were randomly assigned to receive the study products (2.5% and 5% BPO and placebo), and 607 subjects were included in the full analysis set, 544 in the per protocol set and 609 in the safety analyses. The median rates of reduction from baseline to the last evaluation of the inflammatory lesion counts, the primary end-point, in the 2.5% and 5% BPO groups were 72.7% and 75.0%, respectively, and were significantly higher than that in the placebo group (41.7%). No deaths or other serious adverse events were observed. The incidences of adverse events in the 2.5% and 5% BPO groups were 56.4% and 58.8%, respectively; a higher incidence than in the placebo group, but there was no obvious difference between the 2.5% and 5% BPO groups. All adverse events were mild or moderate in severity. Most adverse events did not lead to study product discontinuation. The results suggested that both 2.5% and 5% BPO are useful for the treatment of acne vulgaris. © 2017 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd.

Adverse drug events and medication problems in "Hospital at Home" patients.

PubMed

Mann, Elizabeth; Zepeda, Orlando; Soones, Tacara; Federman, Alex; Leff, Bruce; Siu, Albert; Boockvar, Kenneth

2018-03-26

"Hospital at Home(HaH)" programs provide an alternative to traditional hospitalization. However, the incidence of adverse drug events in these programs is unknown. This study describes adverse drug events and potential adverse drug events in a new HaH program. We examined the charts of the first 50 patients admitted. We found 45 potential adverse drug events and 14 adverse drug events from admission to 30 days after HaH discharge. None of the adverse drug events were severe. Some events, like problems with medication administration, may be unique to the hospital at home setting. Monitoring for adverse drug events is feasible and important for hospital at home programs.

A systematic review of the extent, nature and likely causes of preventable adverse events arising from hospital care.

PubMed

Sari, A Akbari; Doshmangir, L; Sheldon, T

2010-01-01

Understanding the nature and causes of medical adverse events may help their prevention. This systematic review explores the types, risk factors, and likely causes of preventable adverse events in the hospital sector. MEDLINE (1970-2008), EMBASE, CINAHL (1970-2005) and the reference lists were used to identify the studies and a structured narrative method used to synthesise the data. Operative adverse events were more common but less preventable and diagnostic adverse events less common but more preventable than other adverse events. Preventable adverse events were often associated with more than one contributory factor. The majority of adverse events were linked to individual human error, and a significant proportion of these caused serious patient harm. Equipment failure was involved in a small proportion of adverse events and rarely caused patient harm. The proportion of system failures varied widely ranging from 3% to 85% depending on the data collection and classification methods used. Operative adverse events are more common but less preventable than diagnostic adverse events. Adverse events are usually associated with more than one contributory factor, the majority are linked to individual human error, and a proportion of these with system failure.

Who uses foodbanks and why? Exploring the impact of financial strain and adverse life events on food insecurity.

PubMed

Prayogo, E; Chater, A; Chapman, S; Barker, M; Rahmawati, N; Waterfall, T; Grimble, G

2017-11-14

Rising use of foodbanks highlights food insecurity in the UK. Adverse life events (e.g. unemployment, benefit delays or sanctions) and financial strains are thought to be the drivers of foodbank use. This research aimed to explore who uses foodbanks, and factors associated with increased food insecurity. We surveyed those seeking help from front line crisis providers from foodbanks (N = 270) and a comparison group from Advice Centres (ACs) (N = 245) in relation to demographics, adverse life events, financial strain and household food security. About 55.9% of foodbank users were women and the majority were in receipt of benefits (64.8%). Benefit delays (31.9%), changes (11.1%) and low income (19.6%) were the most common reasons given for referral. Compared to AC users, there were more foodbank users who were single men without children, unemployed, currently homeless, experiencing more financial strain and adverse life events (P = 0.001). Food insecurity was high in both populations, and more severe if they also reported financial strain and adverse life events. Benefit-related problems appear to be a key reason for foodbank referral. By comparison with other disadvantaged groups, foodbank users experienced more financial strain, adverse life events, both increased the severity of food insecurity. © The Author 2017. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Adverse events and treatment interruption in tuberculosis patients with and without HIV co‐infection

PubMed Central

Breen, R A M; Miller, R F; Gorsuch, T; Smith, C J; Schwenk, A; Holmes, W; Ballinger, J; Swaden, L; Johnson, M A; Cropley, I; Lipman, M C I

2006-01-01

Background Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co‐infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti‐TB treatment in the era of effective antiretroviral therapy. Methods The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co‐infected with HIV. Results 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti‐TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co‐infected patients (p<0.001; p = 0.006), although all cause interruption of anti‐TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re‐treatment. Conclusion Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti‐TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals. PMID:16844730

Pneumococcal pneumonia - Are the new severity scores more accurate in predicting adverse outcomes?

PubMed

Ribeiro, C; Ladeira, I; Gaio, A R; Brito, M C

2013-01-01

The site-of-care decision is one of the most important factors in the management of patients with community-acquired pneumonia. The severity scores are validated prognostic tools for community-acquired pneumonia mortality and treatment site decision. The aim of this paper was to compare the discriminatory power of four scores - the classic PSI and CURB65 ant the most recent SCAP and SMART-COP - in predicting major adverse events: death, ICU admission, need for invasive mechanical ventilation or vasopressor support in patients admitted with pneumococcal pneumonia. A five year retrospective study of patients admitted for pneumococcal pneumonia. Patients were stratified based on admission data and assigned to low-, intermediate-, and high-risk classes for each score. Results were obtained comparing low versus non-low risk classes. We studied 142 episodes of hospitalization with 2 deaths and 10 patients needing mechanical ventilation and vasopressor support. The majority of patients were classified as low risk by all scores - we found high negative predictive values for all adverse events studied, the most negative value corresponding to the SCAP score. The more recent scores showed better accuracy for predicting ICU admission and need for ventilation or vasopressor support (mostly for the SCAP score with higher AUC values for all adverse events). The rate of all adverse outcomes increased directly with increasing risk class in all scores. The new gravity scores appear to have a higher discriminatory power in all adverse events in our study, particularly, the SCAP score. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.

Cognitive Complexity of the Medical Record Is a Risk Factor for Major Adverse Events

PubMed Central

Roberson, David; Connell, Michael; Dillis, Shay; Gauvreau, Kimberlee; Gore, Rebecca; Heagerty, Elaina; Jenkins, Kathy; Ma, Lin; Maurer, Amy; Stephenson, Jessica; Schwartz, Margot

2014-01-01

Context: Patients in tertiary care hospitals are more complex than in the past, but the implications of this are poorly understood because “patient complexity” has been difficult to quantify. Objective: We developed a tool, the Complexity Ruler, to quantify the amount of data (as bits) in the patient’s medical record. We designated the amount of data in the medical record as the cognitive complexity of the medical record (CCMR). We hypothesized that CCMR is a useful surrogate for true patient complexity and that higher CCMR correlates with risk of major adverse events. Design: The Complexity Ruler was validated by comparing the measured CCMR with physician rankings of patient complexity on specific inpatient services. It was tested in a case-control model of all patients with major adverse events at a tertiary care pediatric hospital from 2005 to 2006. Main Outcome Measures: The main outcome measure was an externally reported major adverse event. We measured CCMR for 24 hours before the event, and we estimated lifetime CCMR. Results: Above empirically derived cutoffs, 24-hour and lifetime CCMR were risk factors for major adverse events (odds ratios, 5.3 and 6.5, respectively). In a multivariate analysis, CCMR alone was essentially as predictive of risk as a model that started with 30-plus clinical factors. Conclusions: CCMR correlates with physician assessment of complexity and risk of adverse events. We hypothesize that increased CCMR increases the risk of physician cognitive overload. An automated version of the Complexity Ruler could allow identification of at-risk patients in real time. PMID:24626065

Comparing data mining methods on the VAERS database.

PubMed

Banks, David; Woo, Emily Jane; Burwen, Dale R; Perucci, Phil; Braun, M Miles; Ball, Robert

2005-09-01

Data mining may enhance traditional surveillance of vaccine adverse events by identifying events that are reported more commonly after administering one vaccine than other vaccines. Data mining methods find signals as the proportion of times a condition or group of conditions is reported soon after the administration of a vaccine; thus it is a relative proportion compared across vaccines, and not an absolute rate for the condition. The Vaccine Adverse Event Reporting System (VAERS) contains approximately 150 000 reports of adverse events that are possibly associated with vaccine administration. We studied four data mining techniques: empirical Bayes geometric mean (EBGM), lower-bound of the EBGM's 90% confidence interval (EB05), proportional reporting ratio (PRR), and screened PRR (SPRR). We applied these to the VAERS database and compared the agreement among methods and other performance properties, particularly focusing on the vaccine-event combinations with the highest numerical scores in the various methods. The vaccine-event combinations with the highest numerical scores varied substantially among the methods. Not all combinations representing known associations appeared in the top 100 vaccine-event pairs for all methods. The four methods differ in their ranking of vaccine-COSTART pairs. A given method may be superior in certain situations but inferior in others. This paper examines the statistical relationships among the four estimators. Determining which method is best for public health will require additional analysis that focuses on the true alarm and false alarm rates using known vaccine-event associations. Evaluating the properties of these data mining methods will help determine the value of such methods in vaccine safety surveillance. (c) 2005 John Wiley & Sons, Ltd.

A meta-analysis of the efficacy of sulfasalazine in comparison with 5-aminosalicylates in the induction of improvement and maintenance of remission in patients with ulcerative colitis.

PubMed

Nikfar, Shekoufeh; Rahimi, Roja; Rezaie, Ali; Abdollahi, Mohammad

2009-06-01

Historically, sulfasalazine (SSZ) and 5-aminosalicylates (5-ASAs) have been a mainstay of mild-to-moderate ulcerative colitis (UC) remission induction and maintenance therapy. Considering the pivotal role of intestinal microbial flora in pathophysiology of UC and antimicrobial activity of sulfapyridine, we hypothesized that SSZ might be more effective than 5-ASAs in the management of UC. To compare the efficacy and tolerability of SSZ with each of the 5-ASAs (mesalamine, olsalazine, and balsalazide) by a meta-analysis technique. Pubmed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched for studies compared efficacy and/or tolerability of SSZ with 5-ASAs in the management of UC. The search terms were: "sulfasalazine" or "sulfasalazine" and "5-aminosalicylic acid," "mesalazine," "mesalamine," "olsalazine" or "balsalazide" and "ulcerative colitis." Data were collected from 1966 to April 2008. There was no language restriction. "Overall improvement," "relapse rate," "total adverse events," and "withdrawals because of adverse events" were the key outcomes of interest. Twenty randomized placebo controlled trials met our criteria and were included in the meta-analysis. Comparison of SSZ with mesalamine yielded a nonsignificant relative risk (RR) of 1.04 (95% confidence interval of 0.89-1.21, P = 0.63) for overall improvement, a nonsignificant RR of 0.98 (95% CI 0.78-1.23, P = 0.85) for relapse, a nonsignificant RR of 0.76 (95% CI 0.54-1.07, P = 0.11) for any adverse events, and a nonsignificant RR of 0.78 (95% CI 0.46-1.3, P = 0.33) for withdrawals due to adverse events. Comparison of SSZ with olsalazine yielded a nonsignificant RR of 1.14 (95% CI 0.91-1.43, P = 0.25) for overall improvement, a nonsignificant RR of 0.93 (95% CI 0.77-1.12, P = 0.42) for relapse, a nonsignificant RR of 1.21 (95% CI 0.9-1.61, P = 0.20) for any adverse events, and a nonsignificant RR of 1.53 (95% CI 0.93-2.52, P = 0.09) for withdrawals due to adverse events. Comparison of SSZ with balsalazide yielded a nonsignificant RR of 1.3 (95% CI 0.93-1.81, P = 0.12) for overall improvement, and a significant RR of 0.17 (95% CI 0.06-0.49, P = 0.001) for withdrawals because of adverse events. SSZ does not differ from mesalamine or olsalazine in terms of efficacy and tolerability in UC. Withdrawal from study due to adverse events was significantly lower for balsalazide compared with SSZ. Convincing conclusions on the comparison of effectiveness and safety of balsalazide and SSZ in UC remains to be elucidated by further clinical trials. Considering the lower cost of treatment with SSZ and the equal rate of adverse events with other 5-ASAa, it is not surprising to suggest SSZ as a first-choice treatment for UC and reserve 5-ASAs for when SSZ intolerability occurs.

Risks of Cardiovascular Adverse Events and Death in Patients with Previous Stroke Undergoing Emergency Noncardiac, Nonintracranial Surgery: The Importance of Operative Timing.

PubMed

Christiansen, Mia N; Andersson, Charlotte; Gislason, Gunnar H; Torp-Pedersen, Christian; Sanders, Robert D; Føge Jensen, Per; Jørgensen, Mads E

2017-07-01

The outcomes of emergent noncardiac, nonintracranial surgery in patients with previous stroke remain unknown. All emergency surgeries performed in Denmark (2005 to 2011) were analyzed according to time elapsed between previous ischemic stroke and surgery. The risks of 30-day mortality and major adverse cardiovascular events were estimated as odds ratios (ORs) and 95% CIs using adjusted logistic regression models in a priori defined groups (reference was no previous stroke). In patients undergoing surgery immediately (within 1 to 3 days) or early after stroke (within 4 to 14 days), propensity-score matching was performed. Of 146,694 nonvascular surgeries (composing 98% of all emergency surgeries), 5.3% had previous stroke (mean age, 75 yr [SD = 13]; 53% women, 50% major orthopedic surgery). Antithrombotic treatment and atrial fibrillation were more frequent and general anesthesia less frequent in patients with previous stroke (all P < 0.001). Risks of major adverse cardiovascular events and mortality were high for patients with stroke less than 3 months (20.7 and 16.4% events; OR = 4.71 [95% CI, 4.18 to 5.32] and 1.65 [95% CI, 1.45 to 1.88]), and remained increased for stroke within 3 to 9 months (10.3 and 12.3%; OR = 1.93 [95% CI, 1.55 to 2.40] and 1.20 [95% CI, 0.98 to 1.47]) and stroke more than 9 months (8.8 and 11.7%; OR = 1.62 [95% CI, 1.43 to 1.84] and 1.20 [95% CI, 1.08 to 1.34]) compared with no previous stroke (2.3 and 4.8% events). Major adverse cardiovascular events were significantly lower in 323 patients undergoing immediate surgery (21%) compared with 323 successfully propensity-matched early surgery patients (29%; P = 0.029). Adverse cardiovascular outcomes and mortality were greatly increased among patients with recent stroke. However, events were higher 4 to 14 days after stroke compared with 1 to 3 days after stroke.

The Impact of Adverse Child and Adult Experiences on Recovery from Serious Mental Illness

PubMed Central

Stumbo, Scott P.; Yarborough, Bobbi Jo H.; Paulson, Robert I.; Green, Carla A.

2015-01-01

Objective To compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. Methods As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a two-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Results Child and adult exposures to adverse experiences were high, at 91% and 82% respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning, social functioning, and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Conclusions and Implications for Practice Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. PMID:26053533

Spontaneous Adverse Event Reports Associated with Zolpidem in the United States 2003-2012.

PubMed

Wong, Carmen K; Marshall, Nathaniel S; Grunstein, Ronald R; Ho, Samuel S; Fois, Romano A; Hibbs, David E; Hanrahan, Jane R; Saini, Bandana

2017-02-15

Stimulated reporting occurs when patients and healthcare professionals are influenced or "stimulated" by media publicity to report specific drug-related adverse reactions, significantly biasing pharmacovigilance analyses. Among countries where the non-benzodiazepine hypnotic drug zolpidem is marketed, the United States experienced a comparable surge of media reporting during 2006-2009 linking the above drug with the development of complex neuropsychiatric sleep-related behaviors. However, the effect of this stimulated reporting in the United States Food and Drug Administration Adverse Event Reporting System has not been explored. Using disproportionality analyses, reporting odds ratios for zolpidem exposure and the following adverse events; parasomnia, movement-based parasomnia, nonmovement-based parasomnia, amnesia, hallucination, and suicidality were determined and compared to all other medications in the database, followed by specific comparison to the benzodiazepine hypnotic class, year-by-year from 2003 to 2012. Odds ratios were increased significantly during and after the period of media publicity for parasomnias, movement-based parasomnias, amnesias and hallucinations. We also observed that zolpidem adverse drug reaction (ADR) reports have higher odds for parasomnias, movement-based parasomnias, amnesias, hallucinations, and suicidality compared to all other drugs, even before the media publicity cluster. Although our results indicate that zolpidem reports have higher odds for the ADR of interest even before the media publicity cluster, negative media coverage greatly exacerbated the reporting of these adverse reactions. The effect of such reporting must be borne in mind when decisions around drugs which have been the subject of intense media publicity are made by health professionals or regulatory bodies. © 2017 American Academy of Sleep Medicine

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process.

PubMed

Whitstock, Margaret T; Pearce, Christopher M; Ridout, Stephen C; Eckermann, Elizabeth J

2011-05-21

The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Delayed Ileal Pouch Anal Anastomosis Has a Lower 30-Day Adverse Event Rate: Analysis From the National Surgical Quality Improvement Program.

PubMed

Kochar, Bharati; Barnes, Edward L; Peery, Anne F; Cools, Katherine S; Galanko, Joseph; Koruda, Mark; Herfarth, Hans H

2018-04-25

Ulcerative colitis (UC) patients requiring colectomy often have a staged ileal pouch anal anastomosis (IPAA). There are no prospective data comparing timing of pouch creation. We aimed to compare 30-day adverse event rates for pouch creation at the time of colectomy (PTC) with delayed pouch creation (DPC). Using prospectively collected data from 2011-2015 through the National Surgical Quality Improvement Program, we conducted a cohort study including subjects aged ≥18 years with a postoperative diagnosis of UC. We assessed 30-day postoperative rates of unplanned readmissions, reoperations, and major and minor adverse events (AEs), comparing the stage of the surgery where the pouch creation took place. Using a modified Poisson regression model, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) adjusting for age, sex, race, body mass index, smoking status, diabetes, albumin, and comorbidities. Of 2390 IPAA procedures, 1571 were PTC and 819 were DPC. In the PTC group, 51% were on chronic immunosuppression preoperatively, compared with 15% in the DPC group (P < 0.01). After controlling for confounders, patients who had DPC were significantly less likely to have unplanned reoperations (RR, 0.42; 95% CI, 0.24-0.75), major AEs (RR, 0.72; 95% CI, 0.52-0.99), and minor AEs (RR, 0.48; 95% CI, 0.32-0.73) than PTC. Patients undergoing delayed pouch creation were at lower risk for unplanned reoperations and major and minor adverse events compared with patients undergoing pouch creation at the time of colectomy. 10.1093/ibd/izy082_video1izy082.video15776112442001.

Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials

PubMed Central

Isomura, T; Suzuki, S; Origasa, H; Hosono, A; Suzuki, M; Sawada, T; Terao, S; Muto, Y; Koga, T

2016-01-01

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5–9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare. PMID:27188915

Safety in the operating room during orthopedic trauma surgery-incidence of adverse events related to technical equipment and logistics.

PubMed

van Delft, E A K; Schepers, T; Bonjer, H J; Kerkhoffs, G M M J; Goslings, J C; Schep, N W L

2018-04-01

Safety in the operating room is widely debated. Adverse events during surgery are potentially dangerous for the patient and staff. The incidence of adverse events during orthopedic trauma surgery is unknown. Therefore, we performed a study to quantify the incidence of these adverse events. Primary objective was to determine the incidence of adverse events related to technical equipment and logistics. The secondary objective was to evaluate the consequences of these adverse events. We completed a cross-sectional observational study to assess the incidence, consequences and preventability of adverse events related to technical equipment and logistics during orthopedic trauma surgery. During a 10 week period, all orthopedic trauma operations were evaluated by an observer. Six types of procedures were differentiated: osteosynthesis; arthroscopy; removal of hardware; joint replacement; bone grafting and other. Adverse events were divided in six categories: staff dependent factors; patient dependent factors; anaesthesia; imaging equipment; operation room equipment and instruments and implants. Adverse events were defined as any factor affecting the surgical procedure in a negative way. Hundred-fifty operative procedures were included. In 54% of the procedures, at least one adverse event occurred. In total, 147 adverse events occurred, with a range of 1-5 per procedure. Most adverse events occurred during joint replacement procedures. Thirty-seven percent of the incidents concerned defect, incorrect connected or absent instruments. In 36% of the procedures adverse events resulted in a prolonged operation time with a median prolongation of 10.0 min. In more than half of orthopedic trauma surgical procedures adverse events related to technical equipment and logistics occurred, most of them could easily be prevented. These adverse events could endanger the safety of the patient and staff and should therefore be reduced. 4.

Application of gene expression programming and neural networks to predict adverse events of radical hysterectomy in cervical cancer patients.

PubMed

Kusy, Maciej; Obrzut, Bogdan; Kluska, Jacek

2013-12-01

The aim of this article was to compare gene expression programming (GEP) method with three types of neural networks in the prediction of adverse events of radical hysterectomy in cervical cancer patients. One-hundred and seven patients treated by radical hysterectomy were analyzed. Each record representing a single patient consisted of 10 parameters. The occurrence and lack of perioperative complications imposed a two-class classification problem. In the simulations, GEP algorithm was compared to a multilayer perceptron (MLP), a radial basis function network neural, and a probabilistic neural network. The generalization ability of the models was assessed on the basis of their accuracy, the sensitivity, the specificity, and the area under the receiver operating characteristic curve (AUROC). The GEP classifier provided best results in the prediction of the adverse events with the accuracy of 71.96 %. Comparable but slightly worse outcomes were obtained using MLP, i.e., 71.87 %. For each of measured indices: accuracy, sensitivity, specificity, and the AUROC, the standard deviation was the smallest for the models generated by GEP classifier.

Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project

PubMed Central

Greene, Sharon K.; Kulldorff, Martin; Lewis, Edwin M.; Li, Rong; Yin, Ruihua; Weintraub, Eric S.; Fireman, Bruce H.; Lieu, Tracy A.; Nordin, James D.; Glanz, Jason M.; Baxter, Roger; Jacobsen, Steven J.; Broder, Karen R.; Lee, Grace M.

2010-01-01

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06–2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillian-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety. PMID:19965887

Adverse events associated with acupuncture: three multicentre randomized controlled trials of 1968 cases in China.

PubMed

Zhao, Ling; Zhang, Fu-wen; Li, Ying; Wu, Xi; Zheng, Hui; Cheng, Lin-hao; Liang, Fan-rong

2011-03-24

In order to evaluate the safety of acupuncture in China objectively, we investigated the adverse events associated with acupuncture based on three multicentre randomized controlled trials (RCTs) to assess the safety of acupuncture, identifying the common types of acupuncture adverse events, and analysing the related risk factors for their occurrence. This observational study included patients who received acupuncture from three multicentre RCTs respectively for migraine, functional dyspepsia and Bell's palsy. The 1968 patients and their acupuncturists documented adverse events associated with acupuncture after treatment. We collected data about adverse events due to acupuncture treatment from their case report forms. We analysed the incidence and details of the adverse effects, and studied the risk factors for acupuncture adverse events with non-conditional logistic regression analysis. Among the 1968 patients, 74 patients (3.76%) suffered at least one adverse event throughout the treatment period. We did not observe the occurrence of serious adverse events. 73 patients with adverse events recovered within 2 weeks through effective treatment such as physiotherapy or self-treatment. A total of 3 patients withdrew because of adverse events. There were 9 types of adverse events related to acupuncture, including subcutaneous haematoma, bleeding, skin bruising and needle site pain. Subcutaneous haematoma and haemorrhage in the needling points were the most common adverse events. Age and gender were related to the occurrence of acupuncture adverse events. The older the patients were, the higher the risk of adverse events was. In addition, male patients had slightly higher risk of an adverse event than female patients. Acupuncture is a safe therapy with low risk of adverse events in clinical practice. The risk factors for adverse events (AEs) were related to the patients' gender and age and the local anatomical structure of the acupoints. AEs could be reduced and mitigated by improving the medical environment, ensuring a high technical level of the acupuncture practitioners and establishing a good relationship of mutual trust between doctor and patient. ClinicalTrials.gov: NCT00599586, NCT00599677, NCT00608660.

The impact of endocrine supplementation on adverse events in septic shock.

PubMed

Bissell, Brittany D; Erdman, Michael J; Smotherman, Carmen; Kraemer, Dale F; Ferreira, Jason A

2015-12-01

The objective of this study was to compare the incidence of severe adverse events of vasopressin vs hydrocortisone for endocrine support therapy in patients with septic shock. This was a retrospective, propensity-matched cohort of patients admitted to the medical intensive care unit with septic shock between February 2012 and February 2015. Patients were included if vasopressin or hydrocortisone was administered for hemodynamic support secondary to norepinephrine. In the unmatched cohort of 124 patients, vasopressin was associated with a significant decrease in the number of severe adverse events (P=.03). In the matched cohort, severe adverse events occurred 3 times as often in patients receiving hydrocortisone; however, this difference was not statistically significant. (odds ratio, 3.33; 95% confidence interval, 0.92-12.11; P=.06). In the matched cohort, vasopressin was associated with a faster time to hemodynamic stability (P<.05) and discontinuation of hemodynamic support (P<.01) with an increased requirement for third-line therapy (P<.01). No statistical differences were seen in length of stay (intensive care unit and hospital), length of mechanical ventilation, and in-hospital mortality. Given the lower incidence of adverse events and faster time to hemodynamic stability, vasopressin appears to be the most advantageous endocrine agent for hemodynamic support in septic shock. Copyright © 2015 Elsevier Inc. All rights reserved.

Sodium-glucose co-transporter 2 inhibitors in addition to insulin therapy for management of type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

PubMed

Tang, Huilin; Cui, Wei; Li, Dandan; Wang, Tiansheng; Zhang, Jingjing; Zhai, Suodi; Song, Yiqing

2017-01-01

Given inconsistent trial results of sodium-glucose cotransporter 2 (SGLT2) inhibitors in addition to insulin therapy for treating type 2 diabetes mellitus (T2DM), a meta-analysis was performed to evaluate the efficacy and safety of this combination for T2DM by searching available randomized trials from PubMed, Embase, CENTRAL and ClinicalTrials.gov. Our meta-analysis included seven eligible placebo-controlled trials involving 4235 patients. Compared with placebo, SGLT2 inhibitor treatment was significantly associated with a mean reduction in HbA1c of -0.56%, fasting plasma glucose of -0.95 mmol/L, body weight of -2.63 kg and insulin dose of -8.79 IU, but an increased risk of drug-related adverse events by 36%, urinary tract infections by 29% and genital infections by 357%. No significant increase was observed in risk of overall adverse events [risk ratio (RR), 1.00], serious adverse events (RR, 0.90), adverse events leading to discontinuation (RR, 1.16), hypoglycaemia events (RR, 1.07) and severe hypoglycaemia events (RR, 1.24). No diabetic ketoacidosis events were reported. Further studies are needed to establish optimal combination type and dose. © 2016 John Wiley & Sons Ltd.

Perioperative outcomes and adverse events of minimally invasive versus open posterior lumbar fusion: meta-analysis and systematic review.

PubMed

Goldstein, Christina L; Macwan, Kevin; Sundararajan, Kala; Rampersaud, Y Raja

2016-03-01

The objective of this study was to determine the clinical comparative effectiveness and adverse event rates of posterior minimally invasive surgery (MIS) compared with open transforaminal or posterior lumbar interbody fusion (TLIF/PLIF). A systematic review of the Medline, EMBASE, PubMed, Web of Science, and Cochrane databases was performed. A hand search of reference lists was conducted. Studies were reviewed by 2 independent assessors to identify randomized controlled trials (RCTs) or comparative cohort studies including at least 10 patients undergoing MIS or open TLIF/PLIF for degenerative lumbar spinal disorders and reporting at least 1 of the following: clinical outcome measure, perioperative clinical or process measure, radiographic outcome, or adverse events. Study quality was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) protocol. When appropriate, a meta-analysis of outcomes data was conducted. The systematic review and reference list search identified 3301 articles, with 26 meeting study inclusion criteria. All studies, including 1 RCT, were of low or very low quality. No significant difference regarding age, sex, surgical levels, or diagnosis was identified between the 2 cohorts (856 patients in the MIS cohort, 806 patients in the open cohort). The meta-analysis revealed changes in the perioperative outcomes of mean estimated blood loss, time to ambulation, and length of stay favoring an MIS approach by 260 ml (p < 0.00001), 3.5 days (p = 0.0006), and 2.9 days (p < 0.00001), respectively. Operative time was not significantly different between the surgical techniques (p = 0.78). There was no significant difference in surgical adverse events (p = 0.97), but MIS cases were significantly less likely to experience medical adverse events (risk ratio [MIS vs open] = 0.39, 95% confidence interval 0.23-0.69, p = 0.001). No difference in nonunion (p = 0.97) or reoperation rates (p = 0.97) was observed. Mean Oswestry Disability Index scores were slightly better in the patients undergoing MIS (n = 346) versus open TLIF/PLIF (n = 346) at a median follow-up time of 24 months (mean difference [MIS - open] = 3.32, p = 0.001). The result of this quantitative systematic review of clinical comparative effectiveness research examining MIS versus open TLIF/PLIF for degenerative lumbar pathology suggests equipoise in patient-reported clinical outcomes. Furthermore, a meta-analysis of adverse event data suggests equivalent rates of surgical complications with lower rates of medical complications in patients undergoing minimally invasive TLIF/PLIF compared with open surgery. The quality of the current comparative evidence is low to very low, with significant inherent bias.

Adverse events following digital replantation in the elderly.

PubMed

Barzin, Ario; Hernandez-Boussard, Tina; Lee, Gordon K; Curtin, Catherine

2011-05-01

The decision to proceed with digital replantation in the elderly can be challenging. In addition to success of the replanted part, perioperative morbidity and mortality must be considered. The purpose of this study was to compare adverse events in patients less than 65 years of age compared with those 65 years and older after digital replantation. We hypothesize that there is an increased incidence of mortality and sentinel adverse events in patients aged 65 and older. We obtained data from the Nationwide Inpatient Sample over a 10-year period from 1998 to 2007. Replantation was identified using International Classification of Diseases-9 procedure codes for finger and thumb reattachment (84.21 and 84.22). Adverse events were identified using Patient Safety Indicators (PSI) to identify adverse events occurring during hospitalization. We used the Charlson index to study medical comorbidities and bivariate statistics. During the study period 15,413 finger and thumb replantations were performed in the United States, with 616 performed on patients age 65 and older. The overall in-hospital mortality was 0.04% with no statistical difference when factoring age. For the entire group, the percentage of PSI was 0.6%, the most common being postoperative deep venous thrombosis and pulmonary embolus. Overall, there was no difference in PSI between the 2 groups. The older group had a higher rate of transfusion, 4% versus 8% (p < .05) and were more likely to have a nonroutine disposition (ie, nursing home) (p < .001). We found no correlation between the Charlson index and PSI. This study found no difference in sentinel perioperative complications or mortality when comparing replantation patients under 65 years of age and those age 65 and older. Age alone should not be an absolute contraindication to finger replantation. Instead, the patient's functional demands, type of injury, general state of health, and rehabilitative potential should drive the decision of whether to proceed with replantation. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Efficacy and Safety of Tacrolimus Therapy for Active Ulcerative Colitis; A Systematic Review and Meta-analysis.

PubMed

Komaki, Yuga; Komaki, Fukiko; Ido, Akio; Sakuraba, Atsushi

2016-04-01

Approximately 25% of patients with ulcerative colitis [UC] experience a severe flare requiring steroid therapy to avoid colectomy. We performed a systematic review and meta-analysis to assess the efficacy of tacrolimus as a rescue therapy for active UC. Electronic databases were searched for relevant studies assessing the efficacy of tacrolimus for active UC. Outcomes included short- and long-term clinical response, colectomy free rates, and rate of adverse events in randomised controlled trials [RCTs] and observational studies. Two RCTs comparing high trough concentration [10-15ng/ml] versus placebo [n = 103] and 23 observational studies [n = 831] were identified. Clinical response at 2 weeks was significantly higher with tacrolimus compared with placebo (risk ratio [RR] = 4.61, 95% confidence interval [CI] = 2.09-10.17, p = 0.15 x 10(-3)] among RCTs. Rates of clinical response at 1 and 3 months were 0.73 [95% CI = 0.64-0.81] and 0.76 [95% CI = 0.59-0.87], and colectomy-free rates remained high at 1, 3, 6, and 12 months [0.86, 0.84, 0.78, and 0.69, respectively] among observational studies. Among RCTs, adverse events were more frequent compared with placebo [RR = 2.01, 95% CI = 1.20-3.37, p = 0.83 x 10(-2)], but there was no difference in severe adverse events [RR = 3.15, 95% CI = 0.14-72.9, p = 0.47]. Severe adverse events were rare among observational studies [0.11, 95% CI = 0.06-0.20]. In the present meta-analysis, tacrolimus was associated with high clinical response and colectomy-free rates without increased risk of severe adverse events for active UC. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Control charts for monitoring accumulating adverse event count frequencies from single and multiple blinded trials.

PubMed

Gould, A Lawrence

2016-12-30

Conventional practice monitors accumulating information about drug safety in terms of the numbers of adverse events reported from trials in a drug development program. Estimates of between-treatment adverse event risk differences can be obtained readily from unblinded trials with adjustment for differences among trials using conventional statistical methods. Recent regulatory guidelines require monitoring the cumulative frequency of adverse event reports to identify possible between-treatment adverse event risk differences without unblinding ongoing trials. Conventional statistical methods for assessing between-treatment adverse event risks cannot be applied when the trials are blinded. However, CUSUM charts can be used to monitor the accumulation of adverse event occurrences. CUSUM charts for monitoring adverse event occurrence in a Bayesian paradigm are based on assumptions about the process generating the adverse event counts in a trial as expressed by informative prior distributions. This article describes the construction of control charts for monitoring adverse event occurrence based on statistical models for the processes, characterizes their statistical properties, and describes how to construct useful prior distributions. Application of the approach to two adverse events of interest in a real trial gave nearly identical results for binomial and Poisson observed event count likelihoods. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of Aspirin Coadministration on the Safety of Celecoxib, Naproxen, or Ibuprofen.

PubMed

Reed, Grant W; Abdallah, Mouin S; Shao, Mingyuan; Wolski, Kathy; Wisniewski, Lisa; Yeomans, Neville; Lüscher, Thomas F; Borer, Jeffrey S; Graham, David Y; Husni, M Elaine; Solomon, Daniel H; Libby, Peter; Menon, Venu; Lincoff, A Michael; Nissen, Steven E

2018-04-24

The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain. The aim of this study was to compare the safety of combining NSAIDs with low-dose aspirin. This analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) trial included 23,953 patients with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk randomized to celecoxib, ibuprofen, or naproxen. The on-treatment population was used for this study. Outcomes included composite major adverse cardiovascular events, noncardiovascular death, gastrointestinal or renal events, and components of the composite. Cox proportional hazards models compared outcomes among NSAIDs stratified by aspirin use following propensity score adjustment. Kaplan-Meier analysis was used to compare the cumulative probability of events. When taken without aspirin, naproxen or ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.22 to 1.90, p <0.001; and HR: 1.81; 95% CI: 1.46 to 2.26; p <0.001, respectively). Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events. Taken with aspirin, ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (HR: 1.27; 95% CI: 1.06 to 1.51; p < 0.01); this was not significantly higher with naproxen (HR: 1.18; 95% CI: 0.98 to 1.41; p = 0.08). Among patients on aspirin, major adverse cardiovascular events were similar among NSAIDs, and compared with celecoxib, ibuprofen had more gastrointestinal and renal events (p < 0.05), while naproxen had more gastrointestinal events (p < 0.05), without a difference in renal events. Similar results were seen on adjusted Kaplan-Meier analysis. Celecoxib has a more favorable overall safety profile than naproxen or ibuprofen when taken without aspirin. Adding aspirin attenuates the safety advantage of celecoxib, although celecoxib is still associated with fewer gastrointestinal events than ibuprofen or naproxen and fewer renal events than ibuprofen. (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen [PRECISION]; NCT00346216). Copyright © 2018 American College of Cardiology Foundation. All rights reserved.

Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors.

PubMed

Thomas, Mark R; Storey, Robert F

2016-09-01

Platelet P2Y12 inhibitors have become an essential component of the treatment strategy for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. It is now well-established that approximately 30% of patients treated with the P2Y12 inhibitor clopidogrel display high residual platelet reactivity despite treatment. Patients with high on-treatment platelet reactivity have approximately 2-3-fold greater risk of adverse cardiovascular events and stent thrombosis than those without high platelet reactivity. Conversely, clopidogrel-treated patients with low platelet reactivity display approximately 1.7-fold increased risk of major bleeding. High platelet reactivity is uncommon during treatment with prasugrel and ticagrelor, which achieve a greater reduction in adverse cardiovascular events compared to clopidogrel in ACS patients treated with PCI. This is at the expense of an increase in spontaneous bleeding, however. Minor bleeding events, such as skin haematomas, are more common in prasugrel- and ticagrelor-treated patients that have particularly low platelet reactivity values. These minor bleeding events may occasionally prompt discontinuation of therapy, but their overall prognostic impact is uncertain. However, risk factors for bleeding tend to overlap with risk factors for adverse cardiovascular events. Therefore, patients with these minor bleeding events may also be at higher risk of adverse cardiovascular events, conferring a benefit from low platelet reactivity. Further work is needed to determine the optimal level of platelet reactivity in individuals by taking into account their risk of subsequent adverse cardiovascular events and bleeding. Copyright © 2016 Elsevier Inc. All rights reserved.

Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

PubMed

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-12-01

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

PubMed

Chlibek, Roman; Bayas, José M; Collins, Harry; de la Pinta, Maria Luisa Rodriguez; Ledent, Edouard; Mols, Johann F; Heineman, Thomas C

2013-12-15

An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. NCT00802464.

Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation.

PubMed

Meng, Kang; Lü, Shu-Zheng; Zhu, Hua-Gang; Chen, Xin; Ge, Chang-Jiang; Song, Xian-Tao

2010-12-01

Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention. A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months. Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred. An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Tolerability of buprenorphine transdermal system in nursing home patients with advanced dementia: a randomized, placebo-controlled trial (DEP.PAIN.DEM).

PubMed

Erdal, Ane; Flo, Elisabeth; Aarsland, Dag; Selbaek, Geir; Ballard, Clive; Slettebo, Dagrun D; Husebo, Bettina S

2018-01-01

Buprenorphine transdermal system is increasingly prescribed in people with advanced dementia, but no clinical trial has investigated the safety and factors associated with discontinuation due to adverse events in this population. One hundred sixty-two people with advanced dementia and significant depression from 47 nursing homes were included and randomized to active analgesic treatment (acetaminophen/buprenorphine) or identical placebo for 13 weeks. In this secondary analysis, the main outcomes were time to and reasons for discontinuation of buprenorphine due to adverse events. Change in daytime activity as measured by actigraphy was a secondary outcome. Of the 44 patients who received active buprenorphine 5 µg/hour, 52.3% (n=23) discontinued treatment due to adverse events compared to 13.3% (6 of 45) in the placebo group ( p <0.001). Psychiatric and neurological adverse events were the most frequently reported causes of discontinuation (69.6%, n=16). Concomitant use of antidepressants significantly increased the risk of discontinuation (HR 23.2, 95% CI: 2.95-182, p =0.003). Adjusted for age, sex, cognitive function, pain and depression at baseline, active buprenorphine was associated with 24.0 times increased risk of discontinuation (Cox model, 95% CI: 2.45-235, p =0.006). Daytime activity dropped significantly during the second day of active treatment (-21.4%, p =0.005) and decreased by 12.9% during the first week ( p =0.053). Active buprenorphine had significantly higher risk of discontinuation compared with placebo in people with advanced dementia and depression, mainly due to psychiatric and neurological adverse events. Daytime activity dropped significantly during the first week of treatment. Concomitant use of antidepressants further reduced the tolerability of buprenorphine.

Single Intravenous Dose of Oritavancin for Treatment of Acute Skin and Skin Structure Infections Caused by Gram-Positive Bacteria: Summary of Safety Analysis from the Phase 3 SOLO Studies.

PubMed

Corey, G Ralph; Loutit, Jeffery; Moeck, Greg; Wikler, Matthew; Dudley, Michael N; O'Riordan, William

2018-04-01

Oritavancin is a lipoglycopeptide with bactericidal activity against Gram-positive organisms. Its rapid concentration-dependent bactericidal activity and long elimination half-life allow single-dose treatment of acute bacterial skin and skin structure infections (ABSSSI). SOLO I and SOLO II were randomized, double-blind studies evaluating the efficacy and safety of a single 1,200-mg intravenous (i.v.) dose of oritavancin versus twice-daily i.v. vancomycin for 7 to 10 days in ABSSSI patients. Safety data from both studies were pooled for safety analysis. The database comprised pooled safety data for 976 oritavancin-treated patients and 983 vancomycin-treated patients. The incidences of adverse events, serious adverse events, and discontinuations due to adverse events were similar for oritavancin (55.3, 5.8, and 3.7%, respectively) and vancomycin (56.9, 5.9, and 4.2%, respectively). The median time to onset (3.8 days versus 3.1 days, respectively) and the duration (3.0 days for both groups) of adverse events were also similar between the two groups. The most frequently reported events were nausea, headache, and vomiting. Greater than 90% of all events were mild or moderate in severity. There were slightly more infections and infestations, abscesses or cellulitis, and hepatic and cardiac adverse events in the oritavancin group; however, more than 80% of these events were mild or moderate. Subgroup analyses did not identify clinically meaningful differences in the incidence of adverse events attributed to oritavancin. A single 1,200-mg dose of oritavancin was well tolerated and had a safety profile similar to that of twice-daily vancomycin. The long elimination half-life of oritavancin compared to that of vancomycin did not result in a clinically meaningful delay to the onset or prolongation of adverse events. (This study has been registered at ClinicalTrials.gov under registration no. NCT01252719 and NCT01252732.). Copyright © 2018 American Society for Microbiology.

Risk Associated with Bee Venom Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Park, Jeong Hwan; Yim, Bo Kyung; Lee, Jun-Hwan; Lee, Sanghun; Kim, Tae-Hun

2015-01-01

Objective The safety of bee venom as a therapeutic compound has been extensively studied, resulting in the identification of potential adverse events, which range from trivial skin reactions that usually resolve over several days to life-threating severe immunological responses such as anaphylaxis. In this systematic review, we provide a summary of the types and prevalence of adverse events associated with bee venom therapy. Methods We searched the literature using 12 databases from their inception to June 2014, without language restrictions. We included all types of clinical studies in which bee venom was used as a key intervention and adverse events that may have been causally related to bee venom therapy were reported. Results A total of 145 studies, including 20 randomized controlled trials, 79 audits and cohort studies, 33 single-case studies, and 13 case series, were evaluated in this review. The median frequency of patients who experienced adverse events related to venom immunotherapy was 28.87% (interquartile range, 14.57–39.74) in the audit studies. Compared with normal saline injection, bee venom acupuncture showed a 261% increased relative risk for the occurrence of adverse events (relative risk, 3.61; 95% confidence interval, 2.10 to 6.20) in the randomized controlled trials, which might be overestimated or underestimated owing to the poor reporting quality of the included studies. Conclusions Adverse events related to bee venom therapy are frequent; therefore, practitioners of bee venom therapy should be cautious when applying it in daily clinical practice, and the practitioner’s education and qualifications regarding the use of bee venom therapy should be ensured. PMID:25996493

Evaluating Facility-Based Decision-Making in Women with a Prior Cesarean Delivery and Association with Maternal and Perinatal Outcomes.

PubMed

Boatin, Adeline Adwoa; Adu-Bonsaffoh, Kwame; Wylie, Blair Johnson; Obed, Samuel A

2017-09-01

Objective To describe facility-based decision-making for women with one prior cesarean delivery (CD) in a resource-limited setting and to characterize maternal and perinatal outcomes in these groups. Methods One year retrospective study of women with one prior CD delivering at Korle-Bu Teaching Hospital (KBTH), Ghana. Women were categorized into three groups based on initial plan of management on admission [trial of labor after cesarean (TOLAC), emergency repeat CD (EMCD) or non-emergent repeat CD (RCD)]. Characteristics and outcomes across these groups were then compared. Results During the study period, 1247 women with one prior CD delivered at KBTH, of which 377 (30.2%) were triaged to RCD, 439 (35.2%) to EMCD and 431 (34.6%) to TOLAC. Twelve uterine ruptures and no maternal deaths occurred. Perinatal mortality was 4.2% (n = 52). Compared to the RCD group, the TOLAC group had a lower risk for maternal adverse events (aOR 0.3, 95% CI 0.1-1.0; p = 0.04) and non-significant higher risk of perinatal adverse events (aOR 1.6, 95% CI 0.7-3.3; p = 0.25). Compared to women triaged to RCD, the EMCD group had a non-significant increase in risk of maternal adverse events (aOR 1.6, 95% CI 0.8-3.5; p = 0.2) and a significantly higher rate of perinatal adverse events (aOR 2.4, 95% CI 1.2-4.9; p = 0.01). Conclusions for Practice Women triaged to EMCD at admission are different when compared to women allowed a TOLAC or offered a non-emergent RCD. These women bear increased rates of adverse outcomes and should be considered as a separate group for analysis in future studies conducted in similar settings.

Minimizing adverse events while maintaining clinical improvement in a pediatric attention-deficit/hyperactivity disorder crossover trial with dextroamphetamine and methylphenidate.

PubMed

Ramtvedt, Bjørn E; Aabech, Henning S; Sundet, Kjetil

2014-04-01

The purpose of this study was to investigate whether the availability of both dextroamphetamine and methylphenidate provides an opportunity to minimize adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD) stimulant trial. Thirty-six medication-naïve children 9-14 years of age, diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned, counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by parents, was used to assess adverse events. SERS were available for 34 children, and data were analyzed both at the group and the single-subject level. The side-effect profiles of dextroamphetamine and methylphenidate appeared similar at the group level. Overall, insomnia and decreased appetite were the only adverse events associated with the stimulants as compared with placebo. No significant increase from placebo to stimulant conditions was detected on SERS items reflecting emotional symptoms. Furthermore, dextroamphetamine and methylphenidate did not differ from each other on any SERS item, except that dextroamphetamine was associated with higher severity of "insomnia" and a higher prevalence of "unusually happy." Single-subject analyses showed that one or more adverse events were reported in 14 children (41%), and were evenly distributed between those with dextroamphetamine as the drug that showed the greatest reduction in their ADHD symptoms ("best drug") and those with methylphenidate as their best drug. Among children in whom both stimulants were associated with a decrease in ADHD symptoms, a clinically valid difference between the two stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In these children, the availability of both stimulants provided an opportunity to minimize adverse events, while maintaining a reduction in ADHD symptoms. The availability of both dextroamphetamine and methylphenidate may contribute to minimize adverse events in a subsample of children in pediatric ADHD stimulant trials. The study was first registered in clinical trials September 28, 2010. Clinical Trials.gov Identifier: NCT01220440.

Minimizing Adverse Events While Maintaining Clinical Improvement in a Pediatric Attention-Deficit/Hyperactivity Disorder Crossover Trial with Dextroamphetamine and Methylphenidate

PubMed Central

Aabech, Henning S.; Sundet, Kjetil

2014-01-01

Abstract Objective: The purpose of this study was to investigate whether the availability of both dextroamphetamine and methylphenidate provides an opportunity to minimize adverse events in a pediatric attention-deficit/hyperactivity disorder (ADHD) stimulant trial. Methods: Thirty-six medication-naïve children 9–14 years of age, diagnosed with ADHD, were enrolled for 6 weeks in a crossover trial, with 2 weeks of methylphenidate, dextroamphetamine, and a placebo in a randomly assigned, counterbalanced sequence. Barkley's Side-Effect Rating Scale (SERS), rated by parents, was used to assess adverse events. SERS were available for 34 children, and data were analyzed both at the group and the single-subject level. Results: The side-effect profiles of dextroamphetamine and methylphenidate appeared similar at the group level. Overall, insomnia and decreased appetite were the only adverse events associated with the stimulants as compared with placebo. No significant increase from placebo to stimulant conditions was detected on SERS items reflecting emotional symptoms. Furthermore, dextroamphetamine and methylphenidate did not differ from each other on any SERS item, except that dextroamphetamine was associated with higher severity of “insomnia” and a higher prevalence of “unusually happy.” Single-subject analyses showed that one or more adverse events were reported in 14 children (41%), and were evenly distributed between those with dextroamphetamine as the drug that showed the greatest reduction in their ADHD symptoms (“best drug”) and those with methylphenidate as their best drug. Among children in whom both stimulants were associated with a decrease in ADHD symptoms, a clinically valid difference between the two stimulants in total adverse events score was found in 7 (39%) of the 18 cases. In these children, the availability of both stimulants provided an opportunity to minimize adverse events, while maintaining a reduction in ADHD symptoms. Conclusions: The availability of both dextroamphetamine and methylphenidate may contribute to minimize adverse events in a subsample of children in pediatric ADHD stimulant trials. Clinical Trials Registry: The study was first registered in clinical trials September 28, 2010. Clinical Trials.gov Identifier: NCT01220440. PMID:24666268

Number needed to treat to harm for discontinuation due to adverse events in the treatment of bipolar depression, major depressive disorder, and generalized anxiety disorder with atypical antipsychotics.

PubMed

Gao, Keming; Kemp, David E; Fein, Elizabeth; Wang, Zuowei; Fang, Yiru; Ganocy, Stephen J; Calabrese, Joseph R

2011-08-01

To estimate the number needed to treat to harm (NNTH) for discontinuation due to adverse events with atypical antipsychotics relative to placebo during the treatment of bipolar depression, major depressive disorder (MDD), and generalized anxiety disorder (GAD). English-language literature published and cited in MEDLINE from January 1966 to May 2009 was searched with the terms antipsychotic, atypical antipsychotic, generic and brand names of atypical antipsychotics, safety, tolerability, discontinuation due to adverse events, somnolence, sedation, weight gain, akathisia, or extrapyramidal side effect; and bipolar depression, major depressive disorder, or generalized anxiety disorder; and randomized, placebo-controlled clinical trial. This search was augmented with a manual search. Studies with a cumulative sample of ≥ 100 patients were included. The NNTHs for discontinuation due to adverse events, somnolence, sedation, ≥ 7% weight gain, and akathisia relative to placebo were estimated with 95% confidence intervals to reflect the magnitude of variance. Five studies in bipolar depression, 10 studies in MDD, and 4 studies in GAD were identified. Aripiprazole and olanzapine have been studied in bipolar depression and refractory MDD. Only quetiapine extended release (quetiapine-XR) has been studied in 3 psychiatric conditions with different fixed dosing schedules. For aripiprazole, the mean NNTH for discontinuation due to adverse events was 14 in bipolar depression, but was not significantly different from placebo in MDD. For olanzapine, the mean NNTHs were 24 in bipolar depression and 9 in MDD. The risk for discontinuation due to adverse events during quetiapine-XR treatment appeared to be associated with dose. For quetiapine-XR 300 mg/d, the NNTHs for discontinuation due to adverse events were 9 for bipolar depression, 8 for refractory MDD, 9 for MDD, and 5 for GAD. At the same dose of quetiapine-XR, patients with GAD appeared to have a lower tolerability than those with bipolar depression or MDD. Due to flexible dosing, the risk for discontinuation due to adverse events in the treatment of bipolar depression, MDD, or GAD with other atypical antipsychotics could not be compared. © Copyright 2011 Physicians Postgraduate Press, Inc.

The impact of adverse child and adult experiences on recovery from serious mental illness.

PubMed

Stumbo, Scott P; Yarborough, Bobbi Jo H; Paulson, Robert I; Green, Carla A

2015-12-01

The purpose of this study was to compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a 2-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia, or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Child and adult exposures to adverse experiences were high, at 91% and 82%, respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning and social functioning and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. (c) 2015 APA, all rights reserved).

Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population.

PubMed

Kishi, Taro; Ikuta, Toshikazu; Matsunaga, Shinji; Matsuda, Yuki; Oya, Kazuto; Iwata, Nakao

2017-01-01

The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was relatively limited. Additional efficacy and safety data are required to fully obtain a conclusive understanding.

Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population

PubMed Central

Kishi, Taro; Ikuta, Toshikazu; Matsunaga, Shinji; Matsuda, Yuki; Oya, Kazuto; Iwata, Nakao

2017-01-01

Background The relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability. Methods Bayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events. Results Eighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics. Conclusion Although the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was relatively limited. Additional efficacy and safety data are required to fully obtain a conclusive understanding. PMID:28553116

Comparative coronary risks of apixaban, rivaroxaban and dabigatran: a meta-analysis and adjusted indirect comparison

PubMed Central

Loke, Yoon K; Pradhan, Shiva; Yeong, Jessica Ka-yan; Kwok, Chun Shing

2014-01-01

Aims There are concerns regarding increased risk of acute coronary syndrome with dabigatran. We aimed to assess whether alternative treatment options such as rivaroxaban or apixaban carry a similar risk as compared with dabigatran. Methods We searched MEDLINE and EMBASE for randomized controlled trials of apixaban, dabigatran or rivaroxaban against control (placebo, heparin or vitamin K antagonist). We pooled odds ratios (OR) for adverse coronary events (acute coronary syndrome or myocardial infarction) using fixed effect meta-analysis and assessed heterogeneity with I2. We conducted adjusted indirect comparisons to compare risk of adverse coronary events with apixaban or rivaroxaban vs. dabigatran. Results Twenty-seven randomized controlled trials met the inclusion criteria. Dabigatran was associated with a significantly increased risk of adverse coronary events in pooled analysis of nine trials (OR 1.45, 95% CI 1.14, 1.86). There was no signal for coronary risk with apixaban from nine trials (pooled OR 0.89, 95% CI 0.78, 1.03) or rivaroxaban from nine trials (pooled OR 0.81, 95% CI 0.72, 0.93). Overall, adjusted indirect comparison suggested that both apixaban (OR 0.61, 95% CI 0.44, 0.85) and rivaroxaban (OR 0.54; 95% CI 0.39, 0.76) were associated with lower coronary risk than dabigatran. Restricting the indirect comparison to a vitamin K antagonist as a common control, yielded similar findings, OR 0.57 (95% CI 0.39, 0.85) for apixaban vs. dabigatran and 0.53 (95% CI 0.37, 0.77) for rivaroxaban vs. dabigatran. Conclusions There are significant differences in the comparative safety of apixaban, rivaroxaban and dabigatran with regards to acute coronary adverse events. PMID:24617578

Normal saline solution versus other viscous solutions for submucosal injection during endoscopic mucosal resection: a systematic review and meta-analysis.

PubMed

Yandrapu, Harathi; Desai, Madhav; Siddique, Sameer; Vennalganti, Prashanth; Vennalaganti, Sreekar; Parasa, Sravanthi; Rai, Tarun; Kanakadandi, Vijay; Bansal, Ajay; Titi, Mohammad; Repici, Alessandro; Bechtold, Matthew L; Sharma, Prateek; Choudhary, Abhishek

2017-04-01

EMR is being increasingly practiced for the removal of large colorectal polyps. A variety of solutions such as normal saline solution (NS) and other viscous and hypertonic solutions (VS) have been used as submucosal injections for EMR. A systematic review and meta-analysis is presented comparing the efficacy and adverse events of EMR performed using NS versus VS. Two independent reviewers conducted a search of all databases for human, randomized controlled trials that compared NS with VS for EMR of colorectal polyps. Data on complete en bloc resection, presence of residual lesions, and adverse events were extracted using a standardized protocol. Pooled odds ratio (OR) estimates along with 95% confidence intervals (CI) were calculated using fixed effect or random effects models. Five prospective, randomized controlled trials (504 patients) met the inclusion criteria. The mean polyp sizes were 20.84 mm with NS and 21.44 mm with VS. On pooled analysis, a significant increase in en bloc resection (OR, 1.91; 95% CI, 1.11-3.29; P = .02; I 2  = 0%) and decrease in residual lesions (OR, 0.54; 95% CI, 0.32-0.91; P = .02; I 2  = 0%) were noted in VS compared with NS. There was no significant difference in the rate of overall adverse events between the 2 groups. Use of VS during EMR leads to higher rates of en bloc resection and lower rates of residual lesions compared with NS, without any significant difference in adverse events. Endoscopists could consider using VS for EMR of large colorectal polyps and NS for smaller polyps because there is no significant difference in the outcomes with lesions <2 cm. Published by Elsevier Inc.

Pharmacy student perceptions of adverse event reporting.

PubMed

Kalari, Sirisha; Dormarunno, Matthew; Zvenigorodsky, Oleg; Mohan, Aparna

2011-09-10

To assess US pharmacy students' knowledge and perceptions of adverse event reporting. To gauge pharmacy students' impressions of adverse event reporting, a 10-question survey instrument was administered that addressed student perceptions of the reporting procedures of the Food and Drug Administration (FDA) and pharmaceutical manufacturers, as well as student understanding of the Health Insurance Portability and Accountability Act (HIPAA) and its relationship to adverse event reporting. Two hundred twenty-eight pharmacy students responded to the survey. The majority of respondents believed that the FDA is more likely than a pharmaceutical company to take action regarding an adverse event. There were misconceptions relating to the way adverse event reports are handled and the influence of HIPAA regulations on reporting. Communication between the FDA and pharmaceutical manufacturers regarding adverse event reports is not well understood by pharmacy students. Education about adverse event reporting should evolve so that by the time pharmacy students become practitioners, they are well acquainted with the relevance and importance of adverse event reporting.

Comparison of adverse events of laser and light-assisted hair removal systems in skin types IV-VI.

PubMed

Breadon, Jonith Y; Barnes, Chad A

2007-01-01

Photoepilation, utilizing lasers and noncoherent light sources, is designed to irradiate as much of the follicular unit as possible, with melanin as the target chromophore. Wavelength absorption should generate energy sufficient to heat and destroy the hair follicle, while preserving the surrounding tissue. When performing photoepilation on African-American skin (Fitzpatrick skin types IV-VI) a greater risk of potential epidermal adverse events, such as dyspigmentation, blistering, crusting, edema, and subsequent scarring, is possible. To reduce epidermal melanin absorption of energy longer wavelengths are considered safer for use on Fitzpatrick skin types IV to VI. This article reviews and compares the reported incidences of adverse events in African-American skin, utilizing lasers and noncoherent light sources for assisted hair removal.

Vaccine Adverse Events

MedlinePlus

... use in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA (800) 835- ... back to top Popular Content Home Latest Recalls Report an Adverse Event MedWatch Safety Alerts News Releases ...

Detecting, Monitoring, and Reporting Possible Adverse Drug Events Using an Arden-Syntax-based Rule Engine.

PubMed

Fehre, Karsten; Plössnig, Manuela; Schuler, Jochen; Hofer-Dückelmann, Christina; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

2015-01-01

The detection of adverse drug events (ADEs) is an important aspect of improving patient safety. The iMedication system employs predefined triggers associated with significant events in a patient's clinical data to automatically detect possible ADEs. We defined four clinically relevant conditions: hyperkalemia, hyponatremia, renal failure, and over-anticoagulation. These are some of the most relevant ADEs in internal medical and geriatric wards. For each patient, ADE risk scores for all four situations are calculated, compared against a threshold, and judged to be monitored, or reported. A ward-based cockpit view summarizes the results.

Comfort eating, psychological stress, and depressive symptoms in young adult women.

PubMed

Finch, Laura E; Tomiyama, A Janet

2015-12-01

Little is known about whether comfort eating actually functions to reduce psychological stress. In addition, the effectiveness of comfort eating may be particularly relevant in the context of depression, but no study has tested whether comfort eating processes might depend on severity of depressive symptomology. This study tested 1) whether greater comfort eating statistically buffers the relationship between adverse life events and perceived psychological stress at age 18-19, and 2) whether potential stress-buffering effects may differ by level of depressive symptoms. These relationships were examined in the NHLBI Growth and Health Study, comprising 2379 young adult women. Participants self-reported experiences with adverse life events, their perceived psychological stress, and whether they tended to eat more while experiencing certain negative emotions. As hypothesized, the relationship between adverse life events and perceived stress depended on comfort eating status (p = .033). The effect of adverse events on perceived stress was attenuated among comfort eaters compared to non-comfort eaters (p = .004), but this buffering effect was not shown in participants with an elevated level of depressive symptoms. In conclusion, among young adult women without high depressive symptoms, comfort eaters may experience reduced perceived stress compared to those who do not engage in this behavior. Intervention researchers should also consider the possible benefits of comfort eating. Copyright © 2015 Elsevier Ltd. All rights reserved.

The safety of flavocoxid, a medical food, in the dietary management of knee osteoarthritis.

PubMed

Morgan, Sarah L; Baggott, Joseph E; Moreland, Larry; Desmond, Renee; Kendrach, Angela C

2009-10-01

This study was designed to determine the safety of a medical food, flavocoxid, a proprietary blend of free-B ring flavonoids and flavans from the root of Scutellaria baicalensis (Chinese skullcap) and the bark of Acacia catechu in the dietary management of knee osteoarthritis. The 12-week, randomized, double-blind, placebo-controlled trial in an academic medical center enrolled 59 patients with moderate osteoarthritis of at least one knee who were recruited who were classified as having "below average" to "a moderately above average cardiovascular risk" with a Framingham-based scoring tool. Subjects were randomized to flavocoxid 250 mg twice a day versus identical placebo. Safety measures, including recording of adverse events, incidence of serious adverse events, and results of routine laboratory values, were compared between the two groups. There were no major differences in the baseline demographic characteristics of the placebo and flavocoxid groups. With one exception no significant differences were found between the two groups with respect to adverse events by body system, blood pressure, or laboratory values. There was a significantly higher incidence of upper respiratory adverse events in the placebo group (35.4% vs. 5.8%, P = .0003). There were no intra- or inter-group differences in any of the laboratory parameters from study baseline to completion. Thus, flavocoxid is safe when used in a population with "below average" to "moderately above average cardiovascular risk" compared to placebo.

OAE: The Ontology of Adverse Events.

PubMed

He, Yongqun; Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Guo, Abra; Zhang, Shelley; Jagannathan, Desikan; Toldo, Luca; Tao, Cui; Smith, Barry

2014-01-01

A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e.g., vaccinee age) important for determining their clinical outcomes.

Outcomes in advanced heart failure patients with left ventricular assist devices for destination therapy.

PubMed

Park, Soon J; Milano, Carmelo A; Tatooles, Antone J; Rogers, Joseph G; Adamson, Robert M; Steidley, D Eric; Ewald, Gregory A; Sundareswaran, Kartik S; Farrar, David J; Slaughter, Mark S

2012-03-01

The HeartMate II (HMII) destination therapy (DT) trial demonstrated significant improvements in outcomes in continuous-flow left ventricular assist devices compared with patients implanted with the pulsatile-flow HeartMate XVE. The primary hypothesis of the current study is that trial patients enrolled after the initial data cohort would have better clinical outcomes. Two hundred eighty-one patients who underwent HMII for DT from May 2007 to March 2009 (Mid Trial [MT] group) were compared with the initial 133 HMII patients from March 2005 to May 2007 (Early Trial [ET] group). Patient entry criteria were the same during the 2 time periods. Survival, adverse events, and quality of life were compared between the 2 groups. Baseline characteristics were similar between the groups. Compared with the ET group, patients in the MT group had reduced adverse event rates for bleeding requiring transfusions (1.66 versus 1.13 events per patient-year, P<0.001), sepsis (0.38 versus 0.27, P=0.025), device-related infections (0.47 versus 0.27, P<0.001), and hemorrhagic stroke (0.07 versus 0.03, P=0.01). Other event rates were similar between groups including ischemic stroke (0.06 versus 0.05 events per patient-year, P=0.57). Survival at 1 year in the MT group was 73% versus 68% in the ET group (P=0.21). Additionally, there was a significant reduction in deaths caused by hemorrhagic stroke (P=0.01). Quality of life improvements were significant in both the groups (P<0.001). The benefit of DT therapy with the HMII is confirmed in subsequent trial patients, with improved adverse event rates and a strong trend for improvements in survival. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00121485.

Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

PubMed

Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

2016-01-01

Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

The Incidence, Nature and Consequences of Adverse Events in Iranian Hospitals.

PubMed

Akbari Sari, Ali; Doshmangir, Leila; Torabi, Fereshteh; Rashidian, Arash; Sedaghat, Mojtaba; Ghomi, Robabeh; Prasopa-Plaizier, Nittita

2015-12-01

Adverse events are relatively common in healthcare, leading to extensive harm to patients and a significant drain on healthcare resources. Identifying the extent, nature and consequences of adverse events is an important step in preventing adverse events and their consequences which is the subject of this study. This is a retrospective review of medical records randomly selected from patients admitted to 4 general hospitals, staying more than 24 hours and discharged between April and September 2012. We randomly selected 1200 records and completed the record review for 1162 of these records. Standard forms (RF1 and RF2) were used to review medical records in two stages by nurses and medical doctors. Eighty-five (7.3%) of the 1162 records had an adverse event during the admission; and in 43 (3.7%) of the 1162 records, the patient was admitted to the hospital due to an adverse event that occurred before the admission. Therefore, a total of 128 (11.0%) adverse events occurred in 126 (10.9) records as two patients had more than one adverse event. Forty-four (34.3%) of these 128 adverse events were considered preventable. This study confirms that adverse events, particularly adverse drug reactions, post-operative infections, bedsore and hospital acquired infections are common and potentially preventable sources of harm to patients in Iranian hospitals.

A systematic review of yoga for major depressive disorder.

PubMed

Cramer, Holger; Anheyer, Dennis; Lauche, Romy; Dobos, Gustav

2017-04-15

The purpose of this review was to investigate the efficacy and safety of yoga interventions in treating patients with major depressive disorder. MEDLINE, Scopus, and the Cochrane Library were screened through December 2016. Randomized controlled trials (RCTs) comparing yoga to inactive or active comparators in patients with major depressive disorder were eligible. Primary outcomes included remission rates and severity of depression. Anxiety and adverse events were secondary outcomes. Risk of bias was assessed using the Cochrane tool. Seven RCTs with 240 participants were included. Risk of bias was unclear for most RCTs. Compared to aerobic exercise, no short- or medium-term group differences in depression severity was found. Higher short-term depression severity was found for yoga compared to electro-convulsive therapy; remission rates did not differ between groups. No short-term group differences occurred when yoga was compared to antidepressant medication. Conflicting evidence was found when yoga was compared to attention-control interventions, or when yoga as an add-on to antidepressant medication was compared to medication alone. Only two RCTs assessed adverse events and reported that no treatment-related adverse events were reported. Few RCTs with low sample size. This review found some evidence for positive effects beyond placebo and comparable effects compared to evidence-based interventions. However, methodological problems and the unclear risk-benefit ratio preclude definitive recommendations for or against yoga as an adjunct treatment for major depressive disorder. Larger and adequately powered RCTs using non-inferiority designs are needed. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of adjunctive lacosamide in patients with seizures: a systematic review and meta-analysis.

PubMed

Liu, Hongju; Xu, Xiaoli

2018-07-01

Adjunctive lacosamide treatment might be promising to treat seizures. However, the results remained controversial. We conducted a systematic review and meta-analysis to compare the efficacy and safety of adjunctive lacosamide versus placebo in patients with seizures. PubMed, EMbase, Web of science, EBSCO and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of adjunctive lacosamide versus placebo on seizures were included. Two investigators independently searched articles, extracted data and assessed the quality of included studies. The primary outcomes were 50% responder rate and seizure freedom. Four RCTs involving 1199 patients were included in the meta-analysis. Overall, compared with placebo treatment, adjunctive lacosamide treatment was associated with a significantly increased 50% responder rate (RR = 1.89; 95% CI = 1.51-2.36; P < 0.00001) and seizure freedom (RR = 4.97; 95% CI = 1.78-13.91; P = 0.002), but improved dizziness (RR = 3.97; 95% CI = 2.91-5.42; P < 0.00001), nausea (RR = 2.85; 95% CI = 1.75-4.66; P < 0.0001), vomiting (RR = 4.11; 95% CI = 2.23-7.57; P < 0.00001), diplopia (RR = 6.85; 95% CI = 3.36-13.94; P < 0.00001), treatment-emergent adverse events (RR = 2.29; 95% CI = 1.93-2.71; P < 0.00001) and serious adverse events (RR = 2.52; 95% CI = 1.33-4.78; P = 0.005). Compared to placebo, adjunctive lacosamide resulted in a significantly improved 50% responder rate and seizure freedom, but with increased dizziness, nausea, vomiting, diplopia, treatment-emergent adverse events and serious adverse events.

Oral and sublingual immunotherapy for egg allergy.

PubMed

Romantsik, Olga; Tosca, Maria Angela; Zappettini, Simona; Calevo, Maria Grazia

2018-04-20

Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen. To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017). We included randomized controlled trials (RCTs) comparing oral immunotherapy or sublingual immunotherapy administered by any protocol with placebo or an elimination diet. Participants were children or adults with clinical egg allergy. We retrieved 97 studies from the electronic searches. We selected studies, extracted data and assessed the methodological quality. We attempted to contact the study investigators to obtain the unpublished data, wherever possible. We used the I² statistic to assess statistical heterogeneity. We estimated a pooled risk ratio (RR) with 95% confidence interval (CI) for each outcome using a Mantel-Haenzel fixed-effect model if statistical heterogeneity was low (I² value less than 50%). We rated the quality of evidence for all outcomes using GRADE. We included 10 RCTs that met our inclusion criteria, that involved a total of 439 children (oral immunotherapy 249; control intervention 190), aged 1 year to 18 years. Each study used a different oral immunotherapy protocol; none used sublingual immunotherapy. Three studies used placebo and seven used an egg avoidance diet as the control. Primary outcomes were: an increased amount of egg that can be ingested and tolerated without adverse events while receiving allergen-specific oral immunotherapy or sublingual immunotherapy, compared to control; and a complete recovery from egg allergy after completion of oral immunotherapy or sublingual immunotherapy, compared to control. Most children (82%) in the oral immunotherapy group could ingest a partial serving of egg (1 g to 7.5 g) compared to 10% of control group children (RR 7.48, 95% CI 4.91 to 11.38; RD 0.73, 95% CI 0.67 to 0.80). Fewer than half (45%) of children receiving oral immunotherapy were able to tolerate a full serving of egg compared to 10% of the control group (RR 4.25, 95% CI 2.77 to 6.53; RD 0.35, 95% CI 0.28 to 0.43). All 10 trials reported numbers of children with serious adverse events (SAEs) and numbers of children with mild-to-severe adverse events. SAEs requiring epinephrine/adrenaline presented in 21/249 (8.4%) of children in the oral immunotherapy group, and none in the control group. Mild-to-severe adverse events were frequent; 75% of children presented mild-to-severe adverse events during oral immunotherapy treatment versus 6.8% of the control group (RR 8.35, 95% CI 5.31 to 13.12). Of note, seven studies used an egg avoidance diet as the control. Adverse events occurred in 4.2% of children, which may relate to accidental ingestion of egg-containing food. Three studies used a placebo control with adverse events present in 2.6% of children. Overall, there was inconsistent methodological rigour in the trials. All studies enrolled small numbers of children and used different methods to provide oral immunotherapy. Eight included studies were judged to be at high risk of bias in at least one domain. Furthermore, the quality of evidence was judged to be low due to small numbers of participants and events, and possible biases. Frequent and increasing exposure to egg over one to two years in people who are allergic to egg builds tolerance, with almost everyone becoming more tolerant compared with a minority in the control group and almost half of people being totally tolerant of egg by the end of treatment compared with 1 in 10 people who avoid egg. However, nearly all who received treatment experienced adverse events, mainly allergy-related. We found that 1 in 12 children had serious allergic reactions requiring adrenaline, and some people gave up oral immunotherapy. It appears that oral immunotherapy for egg allergy is effective, but confidence in the trade-off between benefits and harms is low; because there was a small number of trials with few participants, and methodological problems with some trials.

Comparative Effectiveness of Tacrolimus-Based Steroid Sparing versus Steroid Maintenance Regimens in Kidney Transplantation: Results from Discrete Event Simulation.

PubMed

Desai, Vibha C A; Ferrand, Yann; Cavanaugh, Teresa M; Kelton, Christina M L; Caro, J Jaime; Goebel, Jens; Heaton, Pamela C

2017-10-01

Corticosteroids used as immunosuppressants to prevent acute rejection (AR) and graft loss (GL) following kidney transplantation are associated with serious cardiovascular and other adverse events. Evidence from short-term randomized controlled trials suggests that many patients on a tacrolimus-based immunosuppressant regimen can withdraw from steroids without increased AR or GL risk. To measure the long-term tradeoff between GL and adverse events for a heterogeneous-risk population and determine the optimal timing of steroid withdrawal. A discrete event simulation was developed including, as events, AR, GL, myocardial infarction (MI), stroke, cytomegalovirus, and new onset diabetes mellitus (NODM), among others. Data from the United States Renal Data System were used to estimate event-specific parametric regressions, which accounted for steroid-sparing regimen (avoidance, early 7-d withdrawal, 6-mo withdrawal, 12-mo withdrawal, and maintenance) as well as patients' demographics, immunologic risks, and comorbidities. Regression-equation results were used to derive individual time-to-event Weibull distributions, used, in turn, to simulate the course of patients over 20 y. Patients on steroid avoidance or an early-withdrawal regimen were more likely to experience AR (45.9% to 55.0% v. 33.6%, P < 0.05) and GL (51.5% to 68.8% v. 37.8%, P < 0.05) compared to patients on steroid maintenance. Patients in 6-mo and 12-mo steroid withdrawal groups were less likely to experience MI (11.1% v. 13.3%, P < 0.05), NODM (30.7% to 34.4% v. 37.7%, P < 0.05), and cardiac death (29.9% to 30.5% v. 32.4%, P < 0.05), compared to steroid maintenance. Strategies of 6- and 12-mo steroid withdrawal post-kidney transplantation are expected to reduce the rates of adverse cardiovascular events and other outcomes with no worsening of AR or GL rates compared with steroid maintenance.

Complications and Adverse Events of a Randomized Clinical Trial Comparing 3 Graft Types for ACL Reconstruction.

PubMed

Mohtadi, Nicholas; Barber, Rhamona; Chan, Denise; Paolucci, Elizabeth Oddone

2016-05-01

Complications/adverse events of anterior cruciate ligament (ACL) surgery are underreported, despite pooled level 1 data in systematic reviews. All adverse events/complications occurring within a 2-year postoperative period after primary ACL reconstruction, as part of a large randomized clinical trial (RCT), were identified and described. Prospective, double-blind randomized clinical trial. Patients and the independent trained examiner were blinded to treatment allocation. University-based orthopedic referral practice. Three hundred thirty patients (14-50 years; 183 males) with isolated ACL deficiency were intraoperatively randomized to ACL reconstruction with 1 autograft type. Graft harvest and arthroscopic portal incisions were identical. Patients were equally distributed to patellar tendon (PT), quadruple-stranded hamstring tendon (HT), and double-bundle (DB) hamstring autograft ACL reconstruction. Adverse events/complications were patient reported, documented, and diagnoses confirmed. Two major complications occurred: pulmonary embolism and septic arthritis. Twenty-four patients (7.3%) required repeat surgery, including 25 separate operations: PT = 7 (6.4%), HT = 9 (8.2%), and DB = 8 (7.3%). Repeat surgery was performed for meniscal tears (3.6%; n = 12), intra-articular scarring (2.7%; n = 9), chondral pathology (0.6%; n = 2), and wound dehiscence (0.3%; n = 1). Other complications included wound problems, sensory nerve damage, muscle tendon injury, tibial periostitis, and suspected meniscal tears and chondral lesions. Overall, more complications occurred in the HT/DB groups (PT = 24; HT = 31; DB = 45), but more PT patients complained of moderate or severe kneeling pain (PT = 17; HT = 9; DB = 4) at 2 years. Overall, ACL reconstructive surgery is safe. Major complications were uncommon. Secondary surgery was necessary 7.3% of the time for complications/adverse events (excluding graft reinjury or revisions) within the first 2 years. Level 1 (therapeutic studies). This article reports on the complications/adverse events that were prospectively identified up to 2 years postoperatively, in a defined patient population participating in a large double-blind randomized clinical trial comparing PT, single-bundle hamstring, and DB hamstring reconstructions for ACL rupture.

Short-term effect and adverse events of adalimumab versus placebo in inducing remission for moderate-to-severe ulcerative colitis: a meta-analysis.

PubMed

Yang, Zheng; Ye, Xiao-Qing; Zhu, Yu-Zhen; Liu, Zhou; Zou, Ying; Deng, Ying; Guo, Can-Can; Garg, Sushil Kumar; Feng, Jin-Shan

2015-01-01

Adalimumab is used in an attempt to maintain remission for Ulcerative colitis. This study was to evaluate the efficacy and adverse events of adalimumab compared with placebo in inducing remission of Ulcerative colitis. MEDLINE, EMBASE, the Cochrane Controlled Trials Register, OVID, BIOSIS, CNKI, and Google were searched. All randomized trials comparing adalimumab with placebo in inducing remission of moderate-to-severe ulcerative colitis were included. Two randomized controlled trials with a total of 754 participants met the inclusion criteria. The pooled risk ratio (RR) of clinical remission was 1.85 (95% confidence interval (CI) 1.26 to 2.72) following adalimumab treatment. RR of clinical response was 1.40 (95% CI 1.19 to 1.65) while that of mucosal healing was 1.23 (95% CI 1.03 to 1.47). RR of any adverse events was 1.00 (95% CI 0.93 to 1.09). Compared with placebo, administration of adalimumab may increase the proportion of patients with moderate-to-severe ulcerative colitis attaining clinical remission, clinical response and mucosal healing. Adalimumab is also tolerated well in these patients.

The reasons for Chinese nursing staff to report adverse events: a questionnaire survey.

PubMed

Hong, Su; Li, QiuJie

2017-04-01

To investigate the impact of nurses' perception of patient safety culture and adverse event reporting, and demographic factors on adverse event reporting in Chinese hospitals. Accurate and timely adverse event reporting is integral in promoting patient safety and professional learning around the incident. In a cross-sectional survey, a sample of 919 nurses completed a structured questionnaire composed of two validated instruments measuring nurses' perception of patient safety culture and adverse event reporting. Associations between the variables were examined using multiple linear regression analysis. The positive response rates of five dimensions of the Patient Safety Culture Assessment Scale varied from 47.55% to 80.62%. The accuracy rate of Adverse Event Reporting Perception Scale was 63.16%. Five hundred and thirty-one (58.03%) nurses did not report adverse event in past 12 months. Six variables were found to be associated with nurses' adverse event reporting: total work experience (P = 0.003), overall patient safety culture score (P < 0.001), safety climate (P < 0.001), teamwork climate (P < 0.001), overall the adverse event reporting perception scale score (P = 0.003) and importance or reporting (P = 0.002). The results confirmed that improvements in the patient safety culture and nurses' perception of adverse event reporting were related to an increase in voluntary adverse event reporting. The knowledge of adverse event reporting should be integrated into the patient safety curriculum. Interventions that target a specific domain are necessary to improve the safety culture. © 2017 John Wiley & Sons Ltd.

The safety of yellow fever vaccine 17D or 17DD in children, pregnant women, HIV+ individuals, and older persons: systematic review.

PubMed

Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

2012-02-01

Yellow fever vaccine provides long-lasting immunity. Rare serious adverse events after vaccination include neurologic or viscerotropic syndromes or anaphylaxis. We conducted a systematic review of adverse events associated with yellow fever vaccination in vulnerable populations. Nine electronic bibliographic databases and reference lists of included articles were searched. Electronic databases identified 2,415 abstracts for review, and 32 abstracts were included in this review. We identified nine studies of adverse events in infants and children, eight studies of adverse events in pregnant women, nine studies of adverse events in human immunodeficiency virus-positive patients, five studies of adverse events in persons 60 years and older, and one study of adverse events in individuals taking immunosuppressive medications. Two case studies of maternal-neonate transmission resulted in serious adverse events, and the five passive surveillance databases identified very small numbers of cases of yellow fever vaccine-associated viscerotropic disease, yellow fever vaccine-associated neurotropic disease, and anaphylaxis in persons ≥ 60 years. No other serious adverse events were identified in the other studies of vulnerable groups.

Patients use an internet technology to report when things go wrong.

PubMed

Wasson, John H; MacKenzie, Todd A; Hall, Michael

2007-06-01

As patients directly experience harm from adverse events, investigators have proposed patient-report to complement professional reporting of adverse events. To investigate how an automated health assessment system can be used to identify adverse events. Internet survey responses from April 2003 to April 2005 involving communities and clinical practices across the USA. 44,860 adults aged 19-69 years. Patient perceptions of adverse events experienced during the previous year. Independent legal review was also used to estimate how many patient-reports were serious enough to be potentially compensable. Although patient reports of possible adverse events was low (1.4%), the percentage of adverse events was eight times higher for patients with the greatest burden of illness than for those with the least (3.4% vs 0.4%). Two expert malpractice attorneys agreed that 9% of the adverse events seemed to be serious. PATIENTS will use internet technology to report their perceptions of health-related adverse events. Some of the patient-reported events reported will be serious.

The Evaluation of a Pulmonary Display to Detect Adverse Respiratory Events Using High Resolution Human Simulator

PubMed Central

Wachter, S. Blake; Johnson, Ken; Albert, Robert; Syroid, Noah; Drews, Frank; Westenskow, Dwayne

2006-01-01

Objective Authors developed a picture-graphics display for pulmonary function to present typical respiratory data used in perioperative and intensive care environments. The display utilizes color, shape and emergent alerting to highlight abnormal pulmonary physiology. The display serves as an adjunct to traditional operating room displays and monitors. Design To evaluate the prototype, nineteen clinician volunteers each managed four adverse respiratory events and one normal event using a high-resolution patient simulator which included the new displays (intervention subjects) and traditional displays (control subjects). Between-group comparisons included (i) time to diagnosis and treatment for each adverse respiratory event; (ii) the number of unnecessary treatments during the normal scenario; and (iii) self-reported workload estimates while managing study events. Measurements Two expert anesthesiologists reviewed video-taped transcriptions of the volunteers to determine time to treat and time to diagnosis. Time values were then compared between groups using a Mann-Whitney-U Test. Estimated workload for both groups was assessed using the NASA-TLX and compared between groups using an ANOVA. P-values < 0.05 were considered significant. Results Clinician volunteers detected and treated obstructed endotracheal tubes and intrinsic PEEP problems faster with graphical rather than conventional displays (p < 0.05). During the normal scenario simulation, 3 clinicians using the graphical display, and 5 clinicians using the conventional display gave unnecessary treatments. Clinician-volunteers reported significantly lower subjective workloads using the graphical display for the obstructed endotracheal tube scenario (p < 0.001) and the intrinsic PEEP scenario (p < 0.03). Conclusion Authors conclude that the graphical pulmonary display may serve as a useful adjunct to traditional displays in identifying adverse respiratory events. PMID:16929038

Prevalence and impact of high platelet reactivity in chronic kidney disease: results from the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents registry.

PubMed

Baber, Usman; Mehran, Roxana; Kirtane, Ajay J; Gurbel, Paul A; Christodoulidis, Georgios; Maehara, Akiko; Witzenbichler, Bernhard; Weisz, Giora; Rinaldi, Michael J; Metzger, D Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Mazzaferri, Ernest L; Xu, Ke; Parise, Helen; Brodie, Bruce R; Stuckey, Thomas D; Stone, Gregg W

2015-06-01

Chronic kidney disease (CKD) is associated with increased rates of adverse events after percutaneous coronary intervention. We sought to determine the impact of CKD on platelet reactivity in clopidogrel-treated patients and whether high platelet reactivity (HPR) confers a similar or differential risk for adverse events among patients with CKD and non-CKD. We performed a post hoc analysis of the Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) registry, which included 8582 patients undergoing percutaneous coronary intervention with drug-eluting stents and platelet function testing using the VerifyNow assay. We compared HPR and its impact on ischemic and bleeding events >2 years among patients with CKD and non-CKD. Patients with CKD (n=1367) were older, more often female, diabetic, and had lower ejection fraction compared with their non-CKD counterparts (n=7043). Although HPR prevalence increased with worsening renal function in unadjusted analyses, these associations were no longer present after adjustment. Major adverse cardiac event rates at 2 years among those without CKD or HPR, HPR alone, CKD alone, and both CKD and HPR were 9.0%, 11.2%, 13.3%, and 17.5%, respectively (P<0.001). Associations between HPR and adverse events were uniform across CKD strata without evidence of interaction. HPR is more common among those with versus without CKD, an association that is attributable to confounding risk factors that are more prevalent in CKD. The impact of HPR on ischemic and bleeding events is similar irrespective of CKD status. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794. © 2015 American Heart Association, Inc.

Outcome and risk factors assessment for adverse events in advanced esophageal cancer patients after self-expanding metal stents placement.

PubMed

Rodrigues-Pinto, E; Pereira, P; Coelho, R; Andrade, P; Ribeiro, A; Lopes, S; Moutinho-Ribeiro, P; Macedo, G

2017-02-01

Self-expanding metal stents (SEMS) are the treatment of choice for advanced esophageal cancers. Literature is scarce on risk factors predictors for adverse events after SEMS placement. Assess risk factors for adverse events after SEMS placement in advanced esophageal cancer and evaluate survival after SEMS placement. Cross-sectional study of patients with advanced esophageal cancer referred for SEMS placement, during a period of 3 years. Ninety-seven patients with advanced esophageal cancer placed SEMS. Adverse events were more common when tumors were located at the level of the distal esophagus/cardia (47% vs 23%, P = 0.011, OR 3.1), with statistical significance being kept in the multivariate analysis (OR 3.1, P = 0.018). Time until adverse events was lower in the tumors located at the level of the distal esophagus/cardia (P = 0.036). Survival was higher in patients who placed SEMS with curative intent (327 days [126-528] vs. 119 days [91-147], P = 0.002) and in patients submitted subsequently to surgery compared with those who did just chemo/radiotherapy or who did not do further treatment (563 days [378-748] vs. 154 days [133-175] vs. 46 days [20-72], P < 0.001). Subsequent treatment kept statistical significance in the multivariate analysis (HR 3.4, P < 0.001). SEMS allow palliation of dysphagia in advanced esophageal cancer and are associated with an increased out-of-hospital survival, as long as there are conditions for further treatments. Tumors located at the level of the distal esophagus/cardia are associated with a greater number of adverse events, which also occur earlier. © 2016 International Society for Diseases of the Esophagus.

Pirfenidone in idiopathic pulmonary fibrosis: real-life experience from a German tertiary referral center for interstitial lung diseases.

PubMed

Oltmanns, Ute; Kahn, Nicolas; Palmowski, Karin; Träger, Annette; Wenz, Heinrich; Heussel, Claus Peter; Schnabel, Philipp A; Puderbach, Michael; Wiebel, Matthias; Ehlers-Tenenbaum, Svenja; Warth, Arne; Herth, Felix J F; Kreuter, Michael

2014-01-01

Pirfenidone is a novel antifibrotic drug for the treatment of mild-to-moderate idiopathic pulmonary fibrosis (IPF). However, adverse events may offset treatment benefits and compliance. To assess recent course of disease, adverse events and compliance in patients who started pirfenidone. In an observational cohort study, 63 patients with mild-to-moderate IPF who started pirfenidone between May 2011 and June 2013 were reviewed. Pulmonary function, adverse events and treatment compliance were recorded at each clinic visit. Disease progression was defined as a reduction of vital capacity ≥10% and/or diffusion capacity (DLCO) ≥15%. Follow-up time on pirfenidone treatment was 11 (±7) months. Sixty-six percent of the patients continued with pirfenidone monotherapy and 34% of the patients received pirfenidone combined with corticosteroids (CCS) and/or N-acetylcysteine (NAC). There was a nonsignificant reduction in mean decline of percent predicted forced vital capacity after treatment start (0.7 ± 10.9%) compared to the pretreatment period (6.6 ± 6.7%, p = 0.098). Sixty-two percent of the patients had stable disease on pirfenidone treatment. Adverse events affected 85% of the patients, leading to discontinuation of pirfenidone in 20%. Adverse events and treatment discontinuation were seen more frequently in patients with concomitant CCS and/or NAC treatment. Adverse events affect the majority of patients treated with pirfenidone, but are mostly manageable with supportive measures. In this heterogeneous patient group, a nonsignificant effect of pirfenidone treatment on pulmonary function was seen, underlining the need for more data on patient selection criteria and efficacy of pirfenidone, particularly in patients with coexistent emphysema and concomitant NAC/CCS treatment.

Opioid Utilization and Opioid-Related Adverse Events in Non-Surgical Patients in U.S. Hospitals

PubMed Central

Herzig, Shoshana J.; Rothberg, Michael B.; Cheung, Michael; Ngo, Long H.; Marcantonio, Edward R.

2014-01-01

Background Recent studies in the outpatient setting have demonstrated high rates of opioid prescribing and overdose-related deaths. Prescribing practices in hospitalized patients are unexamined. Objective To investigate patterns and predictors of opioid utilization in non-surgical admissions to U.S. hospitals, variation in use, and the association between hospital-level use and rates of severe opioid-related adverse events. Design, Setting, and Patients Adult non-surgical admissions to 286 U.S. hospitals. Measurements Opioid exposure and severe opioid-related adverse events during hospitalization, defined using hospital charges and ICD-9-CM codes. Results Of 1.14 million admissions, opioids were used in 51%. The mean ± s.d. daily dose received in oral morphine equivalents (OME) was 68 ± 185 mg; 23% of exposed received a total daily dose of ≥ 100 mg OME. Opioid prescribing rates ranged from 5% in the lowest to 72% in the highest prescribing hospital (mean 51% ± 10%). After adjusting for patient characteristics, the adjusted opioid prescribing rates ranged from 33–64% (mean 50% ± s.d. 4%). Among exposed, 0.97% experienced severe opioid-related adverse events. Hospitals with higher opioid prescribing rates had higher adjusted relative risk of a severe opioid-related adverse event per patient exposed (RR 1.23 [1.14–1.33] for highest compared to lowest prescribing quartile). Conclusions The majority of hospitalized non-surgical patients were exposed to opioids, often at high doses. Hospitals that used opioids most frequently had increased adjusted risk of a severe opioid-related adverse event per patient exposed. Interventions to standardize and enhance the safety of opioid prescribing in hospitalized patients should be investigated. PMID:24227700

Parental satisfaction, efficacy, and adverse events in 54 patients treated with cantharidin for molluscum contagiosum infection.

PubMed

Cathcart, Shelley; Coloe, Jacqueline; Morrell, Dean S

2009-03-01

To study the efficacy, tolerability, and parental satisfaction of cantharidin in a patient population at a pediatric dermatology referral center. Chart review was completed for 110 patients who presented with molluscum infection and were treated with cantharidin. A total of 54 were available for follow-up by telephone interview regarding adverse effects, parental satisfaction, and overall clearance of the infection. Of those who were reachable, 96% improved after treatment with cantharidin. Parental satisfaction was 78%. Patients received an average of 2.2 treatments irrespective of outcome. Overall, 46% of patients experienced adverse events, including pain, pruritus, secondary infection, brisk immune response, and temporary hypopigmentation and 9% experienced an adverse event that they classified as severe. The results contribute to the data supporting cantharidin as a safe and effective treatment of molluscum contagiosum. Compared with other treatments, it appears to be equally effective and well-tolerated and should be considered a potential front-line treatment.

Adverse reactions to methylphenidate treatment for attention-deficit/hyperactivity disorder: structure and associations with clinical characteristics and symptom control.

PubMed

Sonuga-Barke, Edmund J S; Coghill, David; Wigal, Timothy; DeBacker, Marc; Swanson, James

2009-12-01

Methylphenidate (MPH)-related adverse events are well characterized. Their predictors and their relationship with therapeutic effects are less well understood. Here we examine these issues in relation to two long-acting formulations. Comparison of Methylphenidates in the Analog Classroom Setting (COMACS) was made in a large (n = 184) placebo-controlled trial comparing Equasym XL/Metadate CD, Concerta, and placebo (PLA) using a Laboratory School protocol. Therapeutic effects were measured using direct observation, scores on a simple math productivity task and parent ratings. Parents also completed the Barkley Stimulant Side Effect Rating Scale (BSSERS). The BSSERS had six factors: Emotionality, sleep/appetite, disengaged, dizzy, uninterested, and aches. Treatment effects were seen only for emotionality (which improved) and sleep and appetite (which worsened). Adverse events were not predictable from personal and clinical characteristics of patients. Sleep/appetite adverse events were not associated with therapeutic effects. Improvements in attention-deficit/hyperactivity disorder (ADHD) and emotionality were correlated. The results support a narrow conceptualization of MPH adverse events with problems restricted to appetite and sleep. These effects were not predictable on the basis of available information and may be due to an underlying mechanism rather distinct from those determining therapeutic effects.

Adverse childhood events, substance abuse, and measures of affiliation.

PubMed

Zlotnick, Cheryl; Tam, Tammy; Robertson, Marjorie J

2004-08-01

Adverse childhood events may influence later behaviors, including adulthood substance use and social affiliation. Studies have noted high prevalence rates of adverse childhood experiences and adulthood substance abuse among homeless adults. Using an existing longitudinal, countywide probability sample of 397 homeless adults, we examine the relationships among adverse childhood events on adulthood substance use, and the relationship of these variables to affiliation. Almost 75% of the sample had experienced an adverse childhood event. Path analysis indicated adulthood substance abuse mediated the inverse relationship between adverse childhood events and two measures of adulthood affiliation. Thus, although there is a relationship between adverse childhood events and adulthood substance use, it is adulthood substance use that determines most aspects of affiliation.

Comparison of adverse events with daily disposable hydrogels and spectacle wear: results from a 12-month prospective clinical trial.

PubMed

Sankaridurg, Padmaja R; Sweeney, Deborah F; Holden, Brien A; Naduvilath, Thomas; Velala, Indira; Gora, Rashmi; Krishnamachary, Murali; Rao, Gullapalli N

2003-12-01

To evaluate the type and incidence of adverse events seen with daily disposable hydrogel contact lens wear compared with a control (spectacle) group over 12 months. Prospective, randomized, observer-masked, comparative clinical trial. Two hundred eighty-one myopes with no prior contact lens wear experience were enrolled from August to December 1996. Subjects were 16 to 35 years old and had refractive errors ranging from a -0.75-diopter (D) sphere to a -6.00-D sphere with a cylinder less than -1.00 D. Each subject was randomly assigned to wear either bilateral disposable hydrogels on a daily disposable wear schedule or spectacles. Type and incidence of adverse events from each group. Adverse events were categorized as serious, significant, and nonsignificant based on the potential to cause vision impairment, severity at event, and level of clinical concern. At baseline, 1.6% of eyes had asymptomatic infiltrates that were nonsignificant. During the study, asymptomatic infiltrates were seen in both contact lens and spectacle groups at 20.5 events versus 11.3 events per 100 eyes per year of wear. No significant events were seen with the spectacle group. With the contact lens group, the type and incidence of significant events per 100 eyes per year of lens wear were corneal peripheral ulcer, 2.5 events; infiltrative keratitis, 1.5 events; and papillary conjunctivitis, 1 event. The incidence of both significant and nonsignificant events was greater with the contact lens group (P<0.05). No serious events (i.e., microbial keratitis) were seen in either group. A greater number of subjects were lost to follow-up or permanently discontinued from the contact lens group relative to the spectacle group (33% vs. 17%, P = 0.002). Lens-related problems such as dryness, discomfort, and difficulty with insertion and removal accounted for 27% of discontinuations from the contact lens group. Poor compliance (40%) was the greatest reason for discontinuations from the spectacle group. No clinically serious events were seen with either group. Only a small percentage of contact lens-wearing eyes presented with significant events, which is promising for daily disposable lens wear. Far more contact lens subjects were lost to follow-up or discontinued. Small, asymptomatic, subepithelial corneal infiltrates of unknown significance were seen in both contact lens- and spectacle-wearing eyes.

Incidence and risk factors of intraoperative adverse events during donor lobectomy for living-donor liver transplantation: a retrospective analysis.

PubMed

Araz, Coskun; Pirat, Arash; Unlukaplan, Aytekin; Torgay, Adnan; Karakayali, Hamdi; Arslan, Gulnaz; Moray, Gokhan; Haberal, Mehmet

2012-04-01

To evaluate the frequency, type, and predictors of intraoperative adverse events during donor hepatectomy for living-donor liver transplant. Retrospective analyses of the data from 182 consecutive living-donor liver transplant donors between May 2002 and September 2008. Ninety-one patients (50%) had at least 1 intraoperative adverse event including hypothermia (39%), hypotension (26%), need for transfusions (17%), and hypertension (7%). Patients with an adverse event were older (P = .001), had a larger graft weight (P = .023), more frequently underwent a right hepatectomy (P = .019), and were more frequently classified as American Society of Anesthesiologists physical status class II (P = .027) than those who did not have these adverse events. Logistic regression analysis revealed that only age (95% confidence interval 1.018-1.099; P = .001) was a risk factor for intraoperative adverse events. Patients with these adverse events more frequently required admission to the intensive care unit and were hospitalized longer postoperatively. A before and after analysis showed that after introduction of in-line fluid warmers and more frequent use of acute normovolemic hemodilution, the frequency of intraoperative adverse events was significantly lower (80% vs 29%; P < .001). Intraoperative adverse events such as hypothermia and hypotension were common in living-donor liver transplant donors, and older age was associated with an increased risk of these adverse events. However, the effect of these adverse events on postoperative recovery is not clear.

Non-verbal reasoning ability and academic achievement as moderators of the relation between adverse life events and emotional and behavioural problems in early adolescence: the importance of moderator and outcome specificity.

PubMed

Flouri, Eirini; Tzavidis, Nikos

2011-02-01

This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural problems was non-quadratic. Intelligence rather than academic achievement moderated the association between contextual risk and children's emotional and behavioural problems. However, the interaction effect was significant only on peer problems. These findings suggest that both moderator and outcome specificity should be considered when evaluating the role of intellectual competence in the association between contextual risk and children's emotional and behavioural problems.

Vedolizumab for induction and maintenance of remission in ulcerative colitis.

PubMed

Bickston, Stephen J; Behm, Brian W; Tsoulis, David J; Cheng, Jianfeng; MacDonald, John K; Khanna, Reena; Feagan, Brian G

2014-08-08

Cellular adhesion molecules play an important role in the pathogenesis of ulcerative colitis, making selective blockade of these molecules a promising therapeutic strategy. Vedolizumab, a recombinant humanized IgG1 monoclonal antibody, inhibits adhesion and migration of leukocytes into the gastrointestinal tract by binding the alpha4beta7 integrin. Animal studies have suggested that vedolizumab may be a useful therapy for ulcerative colitis. This updated systematic review summarizes the current evidence on the use of vedolizumab for induction and maintenance of remission in ulcerative colitis. The primary objectives were to determine the efficacy and safety of vedolizumab used for induction and maintenance of remission in ulcerative colitis. A computer-assisted search for relevant studies (inception to 15 June 2014) was performed using PubMed, MEDLINE, EMBASE and CENTRAL. References from published articles and conference proceedings were searched to identify additional citations. Randomized controlled trials comparing vedolizumab to placebo or a control therapy for induction or maintenance of remission in ulcerative colitis were included. Two authors independently extracted data and assessed the risk of bias for each trial. The primary outcomes were failure to induce clinical remission and relapse. Secondary outcomes included failure to induce a clinical response, failure to induce endoscopic remission, failure to induce an endoscopic response, quality of life, adverse events, serious adverse events and withdrawal due to adverse events. We calculated the relative risk (RR) and 95% confidence intervals (CI) for each outcome. Data were analyzed on an intention-to-treat basis. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Four studies (606 patients) were included. All of the studies were rated as having a low risk of bias. Pooled analyses revealed that vedolizumab was significantly superior to placebo for induction of remission, clinical response, and endoscopic remission and prevention of relapse. After 4 to 6 weeks of therapy 77% (293/382) of vedolizumab patients failed to enter clinical remission compared to 92% (205/224) of placebo patients (RR 0.86, 95% CI 0.80 to 0.91; 4 studies 606 patients). After 6 weeks of therapy 48% of vedolizumab patients failed to have a clinical response compared to 72% of placebo patients (RR 0.68, 95% CI 0.59 to 0.78; 3 studies 601 patients). After 4 to 6 weeks of therapy 68% of vedolizumab patients failed to enter endoscopic remission compared to 81% of placebo patients (RR 0.82, 95% CI 0.75 to 0.91; 3 studies, b583 patients). After 52 weeks of therapy, 54% of vedolizumab patients had a clinical relapse compared to 84% of placebo patients (RR 0.67, 95% CI 0.59 to 0.77; 1 study, 373 patients). One small study (28 patients) found no statistically significant difference in endoscopic response (RR 1.00, 95% CI 0.62 to 1.61). GRADE analyses indicated that the overall quality of the evidence for the primary outcomes was high for induction of remission and moderate for relapse (due to sparse data 246 events). There was no statistically significant difference between vedolizumab and placebo in terms of the risk of any adverse event (RR 0.99, 95% CI 0.93 to 1.07), or serious adverse events (RR 1.01, 95% CI 0.72 to 1.42). There was a statistically significant difference in withdrawals due to adverse events. Six per cent of vedolizumab patients withdrew due to an adverse event compared to 11% of placebo patients (RR 0.55, 95% CI 0.35 to 0.87; 2 studies, 941 patients). Adverse events commonly reported across the studies included: worsening ulcerative colitis, headache, nasopharyngitis, upper respiratory tract infection, nausea, and abdominal pain. Moderate to high quality data from four studies shows that vedolizumab is superior to placebo for induction of clinical remission and response and endoscopic remission in patients with moderate to severely active ulcerative colitis and prevention of relapse in patients with quiescent ulcerative colitis. Moderate quality data from one study suggests that vedolizumab is superior to placebo for prevention of relapse in patients with quiescent ulcerative colitis. Adverse events appear to be similar to placebo. Future trials are needed to define the optimal dose, frequency of administration and long-term efficacy and safety of vedolizumab used for induction and maintenance therapy of ulcerative colitis. Vedolizumab should be compared to other currently approved therapies for ulcerative colitis in these trials.

Detection and prevention of medication misadventures in general practice.

PubMed

Tam, Ka Wae Tammy; Kwok, Kon Hung; Fan, Yuen Man Cecilia; Tsui, Kwok Biu; Ng, Kwok Keung; Ho, King Yip Anthony; Lau, Kam Tong; Chan, Yuk Chun; Tse, Ching Wan Charmaine; Lau, Cheuk Man

2008-06-01

Adverse drug events are leading categories of iatrogenic patient injury. Development of preventive strategies for general practice setting depends on effective detection of events. The aim of the study is to compare the strengths and weaknesses of voluntary reporting, chart review and patient survey in measuring medication misadventures in general practice and to analyze the events by severity and preventability, drug groups and patients' and doctors' characteristics, for the formulation of preventive strategies. In the 2-month study period, we applied voluntary report, chart review and patient survey to collect data related to medication misadventures and compared their detection rate. The chart review demonstrated the highest yield for detecting overall medication misadventures (2.03% medication orders), followed by patient survey (1.46% medication orders) and voluntary reporting (0.52% medication orders). Chart review and patient survey were better than voluntary reporting in uncovering preventable adverse drug events. However, voluntary reporting was pivotal in capturing sentinel events. Beta-blocker, diuretic, angiotensin-converting enzyme inhibitor, aspirin and non-steroidal anti-inflammatory drugs had caused 82.0% of all adverse drug events. These events were more common with advanced age of patients, greater number of consultation problems and prescribed drug items. Additional resources implicated were minimal. We suggested a complementary approach using chart review and voluntary reporting in measuring and monitoring medication misadventures in general practice. Close monitoring of the events was necessary for older patients, multiple medical problems and poly-pharmacy and for patients using beta-blocker, diuretic, angiotensin-converting enzyme inhibitor, aspirin or non-steroidal anti-inflammatory drugs on a long-term basis.

French national survey of inpatient adverse events prospectively assessed with ward staff.

PubMed

Michel, Philippe; Quenon, Jean Luc; Djihoud, Ahmed; Tricaud-Vialle, Sophie; de Sarasqueta, Anne Marie

2007-10-01

To estimate the incidence of adverse events in medical and surgical activity in public and private hospitals, and to assess the clinical situation of patients and the active errors. Prospective assessment of adverse events by external senior nursing and doctor investigators with ward staff. Random three-stage stratified cluster sampling of stays or fractions of stay in a 7-day observation period for each ward. 8754 patients observed in 292 wards in 71 hospitals, over 35,234 hospitalisation days. Number of adverse events in relation to number of days of hospitalisation. The incidence density of adverse events was 6.6 per 1000 days of hospitalisation (95% CI 5.7 to 7.5), of which 35% were preventable. Invasive procedures were the source of half the adverse events, of which 20% were preventable. Adverse events related to the psychological sphere and pain were mostly considered as preventable. Ward staff found it difficult to assess the role of care management in the occurrence of adverse events: 41% of adverse events were expected because of the disease itself, and could have occurred in the absence of the related medical management. At the national level in France, every year 120,000-190,000 adverse events during hospitalisation can be considered as preventable. Areas such as perioperative period and geriatric units should receive closer attention. As adverse events occurred more commonly in vulnerable patients, who are not specifically targeted by clinical guidance, practising evidence-based medicine is not likely to prevent all cases. Therefore clinical risk management should prioritize empowerment of local staff, provision of favourable conditions within the organisation, and staff training based on simple tools appropriate for ward-level identification and analysis of adverse events.

Association of nutritional status-related indices and chemotherapy-induced adverse events in gastric cancer patients.

PubMed

Seo, Seung Hee; Kim, Sung-Eun; Kang, Yoon-Koo; Ryoo, Baek-Yeol; Ryu, Min-Hee; Jeong, Jae Ho; Kang, Shin Sook; Yang, Mihi; Lee, Jung Eun; Sung, Mi-Kyung

2016-11-18

Malnutrition in gastrectomized patients receiving chemotherapy is associated with the susceptibility to chemotherapy-related adverse events. This study evaluated pre-operative nutritional status-related indices associated with adverse events in post-operation gastric cancer patients receiving chemotherapy. Medical records of 234 gastrectomized patients under adjuvant tegafur/gimeracil/oteracil chemotherapy with extended lymph node dissection were analyzed. Nutritional status assessment included Patient-Generated Subjective Global Assessment (PG-SGA), body weight, body mass index, serum albumin concentration, and Nutrition Risk Index (NRI). Chemotherapy-originated adverse events were determined using Common Terminology Criteria for Adverse Events. PG-SGA indicated 59% of the patients were malnourished, and 27.8% of the patients revealed serious malnutrition with PG-SGA score of ≥9. Fifteen % of patients lost ≥10% of the initial body weight, 14.5% of the patients had hypoalbuminemia (<3.5 g/dL), and 66.2% had NRI score less than 97.5 indicating moderate to severe malnutrition. Hematological adverse events were present in 94% (≥grade 1) and 16.2% (≥grade 3). Non-hematological adverse events occurred in 95.7% (≥grade1) and 16.7% (≥grade 3) of the patients. PG-SGA and NRI score was not associated with treatment-induced adverse events. Multivariate analyses indicated that female, low body mass index, and hypoalbuminemia were independent risk factors for grade 3/4 hematological adverse events. Age was an independent risk factor for grade 3/4 non-hematological adverse events. Neutropenia was the most frequently occurring adverse event, and associated risk factors were female, total gastrectomy, and hypoalbuminemia. Hypoalbuminemia, not PG-SGA or NRI may predict chemotherapy-induced adverse events in gastrectomized cancer patients.

Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events

PubMed Central

2013-01-01

Background To address knowledge gaps regarding natural health product (NHP) usage in mental health populations, we examined their use in adults with mood disorders, and explored the potential for adverse events. Methods Food and NHP intake was obtained from 97 adults with mood disorders. NHP data was used to compare prevalence with population norms (British Columbia Nutrition Survey; BCNS). Bivariate and regression analyses examined factors associated with NHP use. Assessment of potential adverse effects of NHP use was based on comparing nutrient intakes from food plus supplements with the Dietary Reference Intakes and by reviewing databases for reported adverse health effects. Results Two-thirds (66%; 95% CI 56 to 75) were taking at least one NHP; 58% (95% CI 47 to 68) were taking NHPs in combination with psychiatric medications. The proportion of each type of NHP used was generally higher than the BCNS (range of p’s < 0.05 to 0.0001). When intakes from food and NHP sources were combined, a small proportion exceeded any Lowest-Observed-Adverse-Effect-Levels: only for niacin (n = 17) and magnesium (n = 6), two nutrients for which the potential for adverse effects is minimal. Conversely, about 38% (95% CI 28 to 49) of the sample were taking a non-nutrient based NHP for which previous adverse events had been documented. Conclusions The prevalent use of NHPs in this population suggests that health care providers need to be knowledgeable about their characteristics. The efficacy and safety of NHPs in relation to mental health warrants further investigation. PMID:23570306

[Adverse events management. Methods and results of a development project].

PubMed

Rabøl, Louise Isager; Jensen, Elisabeth Brøgger; Hellebek, Annemarie H; Pedersen, Beth Lilja

2006-11-27

This article describes the methods and results of a project in the Copenhagen Hospital Corporation (H:S) on preventing adverse events. The aim of the project was to raise awareness about patients' safety, test a reporting system for adverse events, develop and test methods of analysis of events and propagate ideas about how to prevent adverse events. H:S developed an action plan and a reporting system for adverse events, founded an organization and developed an educational program on theories and methods of learning from adverse events for both leaders and employees. During the three-year period from 1 January 2002 to 31 December 2004, the H:S staff reported 6011 adverse events. In the same period, the organization completed 92 root cause analyses. More than half of these dealt with events that had been optional to report, the other half events that had been mandatory to report. The number of reports and the front-line staff's attitude towards reporting shows that the H:S succeeded in founding a safety culture. Future work should be centred on developing and testing methods that will prevent adverse events from happening. The objective is to suggest and complete preventive initiatives which will help increase patient safety.

Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia.

PubMed

Regan, Annette K; Tracey, Lauren; Gibbs, Robyn

2015-11-17

In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p=0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p=0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Use of a trigger tool to detect adverse drug reactions in an emergency department.

PubMed

de Almeida, Silvana Maria; Romualdo, Aruana; de Abreu Ferraresi, Andressa; Zelezoglo, Giovana Roberta; Marra, Alexandre R; Edmond, Michael B

2017-11-15

Although there are systems for reporting adverse drug reactions (ADR), these safety events remain under reported. The low-cost, low-tech trigger tool method is based on the detection of events through clues, and it seems to increase the detection of adverse events compared to traditional methodologies. This study seeks to estimate the prevalence of adverse reactions to drugs in patients seeking care in the emergency department. Retrospective study from January to December, 2014, applying the Institute for Healthcare Improvement (IHI) trigger tool methodology for patients treated at the emergency room of a tertiary care hospital. The estimated prevalence of adverse reactions in patients presenting to the emergency department was 2.3% [CI 95 1.3% to 3.3%]; 28.6% of cases required hospitalization at an average cost of US$ 5698.44. The most common triggers were hydrocortisone (57% of the cases), diphenhydramine (14%) and fexofenadine (14%). Anti-infectives (19%), cardiovascular agents (14%), and musculoskeletal drugs (14%) were the most common causes of adverse reactions. According to the Naranjo Scale, 71% were classified as possible and 29% as probable. There was no association between adverse reactions and age and sex in the present study. The use of the trigger tool to identify adverse reactions in the emergency department was possible to identify a prevalence of 2.3%. It showed to be a viable method that can provide a better understanding of adverse drug reactions in this patient population.

Dietary Supplements: Knowledge and Adverse Event Reporting Among American Medical Society for Sports Medicine Physicians.

PubMed

Pascale, Blaise; Steele, Clay; Attipoe, Selasi; OʼConnor, Francis G; Deuster, Patricia A

2016-03-01

Certain dietary supplements (DSs) used by military populations pose a threat to overall readiness. This study assessed members of the American Medical Society for Sports Medicine (AMSSM) regarding their knowledge of DS use among their patients and reporting of suspected adverse events. A thirteen-question retrospective, cross-sectional, Web-based survey sought data on practices regarding DSs and adverse event reporting. Anonymous Web-based survey. Military and civilian sports medicine physicians. The primary finding of the study was how frequently practitioners report adverse events associated with DS use. A total of 311 physicians responded to the survey. Only 51% of respondents had a reliable source for information on DS safety and 58% routinely discussed DS use with their patients. Although a majority (71%) of respondents had encountered adverse events associated with DS use, few of those (10%) confirmed reporting such events. Reasons that physicians did not report adverse events were lack of knowledge regarding where to report (68%), how to report (61%), and availability of time (9%). Our results indicate that some AMSSM physicians are familiar with DSs and have encountered adverse events associated with their use. However, reporting of these adverse events to the appropriate agency is minimal at best. The significant gaps in physician knowledge regarding how and where to report such events indicate a need to educate physicians on this subject. The findings of this survey indicate the need for provider education on reporting adverse events associated with DS use. Although reporting of adverse events is essential for removing harmful DSs from the market, a majority of physicians have limited knowledge on this issue. Moreover, the survey provides insight into the barriers to physician reporting of adverse events.

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Conclusions Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors' Summary PMID:24311990

The Sensitivity of Adverse Event Cost Estimates to Diagnostic Coding Error

PubMed Central

Wardle, Gavin; Wodchis, Walter P; Laporte, Audrey; Anderson, Geoffrey M; Baker, Ross G

2012-01-01

Objective To examine the impact of diagnostic coding error on estimates of hospital costs attributable to adverse events. Data Sources Original and reabstracted medical records of 9,670 complex medical and surgical admissions at 11 hospital corporations in Ontario from 2002 to 2004. Patient specific costs, not including physician payments, were retrieved from the Ontario Case Costing Initiative database. Study Design Adverse events were identified among the original and reabstracted records using ICD10-CA (Canadian adaptation of ICD10) codes flagged as postadmission complications. Propensity score matching and multivariate regression analysis were used to estimate the cost of the adverse events and to determine the sensitivity of cost estimates to diagnostic coding error. Principal Findings Estimates of the cost of the adverse events ranged from $16,008 (metabolic derangement) to $30,176 (upper gastrointestinal bleeding). Coding errors caused the total cost attributable to the adverse events to be underestimated by 16 percent. The impact of coding error on adverse event cost estimates was highly variable at the organizational level. Conclusions Estimates of adverse event costs are highly sensitive to coding error. Adverse event costs may be significantly underestimated if the likelihood of error is ignored. PMID:22091908

Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive study.

PubMed

Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn; Lundh, Andreas; Gøtzsche, Peter C

2014-06-04

To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports. Systematic electronic search for adverse events of suicidality in tables, narratives, and listings of adverse events in individual patients within clinical study reports. Where possible, for each event we extracted the original term reported by the investigator, the term as coded by the medical coding dictionary, medical coding dictionary used, and the patient's trial identification number. Using the patient's trial identification number, we attempted to reconcile data on the same event between the different formats for presenting data on adverse events within the clinical study report. 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency for marketing approval. Clinical study reports obtained from the EMA in 2011. Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly identifiable in all formats of adverse event data in clinical study reports. Suicide attempts presented in tables included both definitive and provisional diagnoses. Suicidal ideation and preparatory behaviour were obscured in some tables owing to the lack of specificity of the medical coding dictionary, especially COSTART. Furthermore, we found one event of suicidal ideation described in narrative text that was absent from tables and adverse event listings of individual patients. The reason for this is unclear, but may be due to the coding conventions used. Data on adverse events in tables in clinical study reports may not accurately represent the underlying patient data because of the medical dictionaries and coding conventions used. In clinical study reports, the listings of adverse events for individual patients and narratives of adverse events can provide additional information, including original investigator reported adverse event terms, which can enable a more accurate estimate of harms. © Maund et al 2014.

Patients use an internet technology to report when things go wrong

PubMed Central

Wasson, John H; MacKenzie, Todd A; Hall, Michael

2007-01-01

Background As patients directly experience harm from adverse events, investigators have proposed patient‐report to complement professional reporting of adverse events. Objective To investigate how an automated health assessment system can be used to identify adverse events. Design and setting Internet survey responses from April 2003 to April 2005 involving communities and clinical practices across the USA. Patients 44 860 adults aged 19–69 years. Outcome Patient perceptions of adverse events experienced during the previous year. Independent legal review was also used to estimate how many patient‐reports were serious enough to be potentially compensable. Results Although patient reports of possible adverse events was low (1.4%), the percentage of adverse events was eight times higher for patients with the greatest burden of illness than for those with the least (3.4% vs 0.4%). Two expert malpractice attorneys agreed that 9% of the adverse events seemed to be serious. Conclusions Patients will use internet technology to report their perceptions of health‐related adverse events. Some of the patient‐reported events reported will be serious. PMID:17545349

[Validation of an adverse event reporting system in primary care].

PubMed

de Lourdes Rojas-Armadillo, María; Jiménez-Báez, María Valeria; Chávez-Hernández, María Margarita; González-Fondón, Araceli

2016-01-01

Patient safety is a priority issue in health systems, due to the damage costs, institutional weakening, lack of credibility, and frustration on those who committed an error that resulted in an adverse event. There is no standardized instrument for recording, reporting, and analyzing sentinel or adverse events (AE) in primary care. Our aim was to design and validate a surveillance system for recording sentinel events, adverse events and near miss incidents in primary care. We made a review of systems for recording and reporting adverse events in primary care. Then, we proposed an instrument to record these events, and register faults in the structure and process, in primary health care units in the Instituto Mexicano del Seguro Social. We showed VENCER-MF format to 35 subjects. Out of them, 100% identified a failure in care process, 90% recorded a sentinel event, 85% identified the cause of this event, 75% of them suggested some measures for avoiding the recurrence of adverse events. We used a Cronbach's alpha of 0.6, p=0.03. The instrument VENCER-MF has a good consistency for the identification of adverse events.

The Safety of Flavocoxid, a Medical Food, in the Dietary Management of Knee Osteoarthritis

PubMed Central

Baggott, Joseph E.; Moreland, Larry; Desmond, Renee; Kendrach, Angela C.

2009-01-01

Abstract This study was designed to determine the safety of a medical food, flavocoxid, a proprietary blend of free-B ring flavonoids and flavans from the root of Scutellaria baicalensis (Chinese skullcap) and the bark of Acacia catechu in the dietary management of knee osteoarthritis. The 12-week, randomized, double-blind, placebo-controlled trial in an academic medical center enrolled 59 patients with moderate osteoarthritis of at least one knee who were recruited who were classified as having “below average” to “a moderately above average cardiovascular risk” with a Framingham-based scoring tool. Subjects were randomized to flavocoxid 250 mg twice a day versus identical placebo. Safety measures, including recording of adverse events, incidence of serious adverse events, and results of routine laboratory values, were compared between the two groups. There were no major differences in the baseline demographic characteristics of the placebo and flavocoxid groups. With one exception no significant differences were found between the two groups with respect to adverse events by body system, blood pressure, or laboratory values. There was a significantly higher incidence of upper respiratory adverse events in the placebo group (35.4% vs. 5.8%, P = .0003). There were no intra- or inter-group differences in any of the laboratory parameters from study baseline to completion. Thus, flavocoxid is safe when used in a population with “below average” to “moderately above average cardiovascular risk” compared to placebo. PMID:19857081

Simultaneous vs sequential bilateral cataract surgery for infants with congenital cataracts: Visual outcomes, adverse events, and economic costs.

PubMed

Dave, Hreem; Phoenix, Vidya; Becker, Edmund R; Lambert, Scott R

2010-08-01

To compare the incidence of adverse events and visual outcomes and to compare the economic costs of sequential vs simultaneous bilateral cataract surgery for infants with congenital cataracts. Retrospective review of simultaneous vs sequential bilateral cataract surgery for infants with congenital cataracts who underwent cataract surgery when 6 months or younger at our institution. Records were available for 10 children who underwent sequential surgery at a mean age of 49 days for the first eye and 17 children who underwent simultaneous surgery at a mean age of 68 days (P = .25). We found a similar incidence of adverse events between the 2 treatment groups. Intraoperative or postoperative complications occurred in 14 eyes. The most common postoperative complication was glaucoma. No eyes developed endophthalmitis. The mean (SD) absolute interocular difference in logMAR visual acuities between the 2 treatment groups was 0.47 (0.76) for the sequential group and 0.44 (0.40) for the simultaneous group (P = .92). Payments for the hospital, drugs, supplies, and professional services were on average 21.9% lower per patient in the simultaneous group. Simultaneous bilateral cataract surgery for infants with congenital cataracts is associated with a 21.9% reduction in medical payments and no discernible difference in the incidence of adverse events or visual outcomes. However, our small sample size limits our ability to make meaningful comparisons of the relative risks and visual benefits of the 2 procedures.

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2013 CFR

2013-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2012 CFR

2012-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

Partial and no recovery from delirium after hospital discharge predict increased adverse events.

PubMed

Cole, Martin G; McCusker, Jane; Bailey, Robert; Bonnycastle, Michael; Fung, Shek; Ciampi, Antonio; Belzile, Eric

2017-01-08

The implications of partial and no recovery from delirium after hospital discharge are not clear. We sought to explore whether partial and no recovery from delirium among recently discharged patients predicted increased adverse events (emergency room visits, hospitalisations, death) during the subsequent 3 months. Prospective study of recovery from delirium in older hospital inpatients. The Confusion Assessment Method was used to diagnose delirium in hospital and determine recovery status after discharge (T0). Adverse events were determined during the 3 months T0. Survival analysis to the first adverse event and counting process modelling for one or more adverse events were used to examine associations between recovery status (ordinal variable, 0, 1 or 2 for full, partial or no recovery, respectively) and adverse events. Of 278 hospital inpatients with delirium, 172 were discharged before the assessment of recovery status (T0). Delirium recovery status at T0 was determined for 152: 25 had full recovery, 32 had partial recovery and 95 had no recovery. Forty-four patients had at least one adverse event during the subsequent 3 months. In multivariable analysis of one or more adverse events, poorer recovery status predicted increased adverse events; the hazard ratio (HR) (95% confidence interval, CI) was 1.72 (1.09, 2.71). The association of recovery status with adverse events was stronger among patients without dementia. Partial and no recovery from delirium after hospital discharge appear to predict increased adverse events during the subsequent 3 months These findings have potentially important implications for in-hospital and post-discharge management and policy.

Rate of contrast material extravasations and allergic-like reactions: effect of extrinsic warming of low-osmolality iodinated CT contrast material to 37 degrees C.

PubMed

Davenport, Matthew S; Wang, Carolyn L; Bashir, Mustafa R; Neville, Amy M; Paulson, Erik K

2012-02-01

To retrospectively determine whether extrinsic warming of the low-osmolality contrast material iopamidol to 37°C prior to intravenous administration at computed tomography (CT) affects extravasation and allergic-like reaction rates. The need to obtain informed patient consent was waived for this HIPAA-compliant and institutional review board-approved analysis. All adverse events related to the intravenous administration of iopamidol during CT examinations occurring 200 days before (period 1) and 200 days after (period 2) the cessation of extrinsic contrast material warming (37°C) for intravenous injections of less than 6 mL/sec at Duke University Medical Center (Durham, NC) were retrospectively reviewed. Adverse event rates were compared by using χ2 statistics. There were 12,682 injections during period 1 (10,831 injections of iopamidol 300 and 1851 injections of iopamidol 370) and 12,138 injections (10, 064 injections of iopamidol 300 and 2074 injections of iopamidol 370) during period 2. Adverse event rates for iopamidol 300 were not affected by extrinsic warming (extravasation rates: 0.30% [32 of 10,831] in period 1 vs 0.23% [23 of 10,064] in period 2, P=.64; allergic-like reaction rates: 0.39% [42 of 10,831] in period 1 vs 0.46% [46 of 10,064] in period 2, P=.74; overall adverse events: 0.68% [74 of 10,831] in period 1 vs 0.69% [69 of 10,064] in period 2, P=.99). Discontinuation of extrinsic warming was associated with significantly increased extravasation and overall adverse event rates for iopamidol 370 (extravasation rates: 0.27% [five of 1851] vs 0.87% [18 of 2074], P=.05; allergic-like reaction rates: 0.16% [three of 1851] vs 0.39% [eight of 2074], P=.42; overall adverse events: 0.43% [eight of 1851] vs 1.25% [26 of 2074], P=.02). Extrinsic warming (to 37°C) does not appear to affect adverse event rates for intravenous injections of iopamidol 300 of less than 6 mL/sec but is associated with a significant reduction in extravasation and overall adverse event rates for the more viscous iopamidol 370. © RSNA, 2011

Aquapheresis Versus Intravenous Diuretics and Hospitalizations for Heart Failure.

PubMed

Costanzo, Maria Rosa; Negoianu, Daniel; Jaski, Brian E; Bart, Bradley A; Heywood, James T; Anand, Inder S; Smelser, James M; Kaneshige, Alan M; Chomsky, Don B; Adler, Eric D; Haas, Garrie J; Watts, James A; Nabut, Jose L; Schollmeyer, Michael P; Fonarow, Gregg C

2016-02-01

The AVOID-HF (Aquapheresis versus Intravenous Diuretics and Hospitalization for Heart Failure) trial tested the hypothesis that patients hospitalized for HF treated with adjustable ultrafiltration (AUF) would have a longer time to first HF event within 90 days after hospital discharge than those receiving adjustable intravenous loop diuretics (ALD). Congestion in hospitalized heart failure (HF) patients portends unfavorable outcomes. The AVOID-HF trial, designed as a multicenter, 1-to-1 randomized study of 810 hospitalized HF patients, was terminated unilaterally and prematurely by the sponsor (Baxter Healthcare, Deerfield, Illinois) after enrollment of 224 patients (27.5%). Aquadex FlexFlow System (Baxter Healthcare) was used for AUF. A Clinical Events Committee, blinded to the randomized treatment, adjudicated whether 90-day events were due to HF. A total of 110 patients were randomized to AUF and 114 to ALD. Baseline characteristics were similar. Estimated days to first HF event for the AUF and ALD group were, respectively, 62 and 34 (p = 0.106). At 30 days, compared with the ALD group, the AUF group had fewer HF and cardiovascular events. Renal function changes were similar. More AUF patients experienced an adverse effect of special interest (p = 0.018) and a serious study product-related adverse event (p = 0.026). The 90-day mortality was similar. Compared with the ALD group, the AUF group trended toward a longer time to first HF event within 90 days and fewer HF and cardiovascular events. More patients in the AUF group experienced special interest or serious product-related adverse event. Due to the trial's untimely termination, additional AUF investigation is warranted. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Quantifying the utilization of medical devices necessary to detect postmarket safety differences: A case study of implantable cardioverter defibrillators.

PubMed

Bates, Jonathan; Parzynski, Craig S; Dhruva, Sanket S; Coppi, Andreas; Kuntz, Richard; Li, Shu-Xia; Marinac-Dabic, Danica; Masoudi, Frederick A; Shaw, Richard E; Warner, Frederick; Krumholz, Harlan M; Ross, Joseph S

2018-06-12

To estimate medical device utilization needed to detect safety differences among implantable cardioverter defibrillators (ICDs) generator models and compare these estimates to utilization in practice. We conducted repeated sample size estimates to calculate the medical device utilization needed, systematically varying device-specific safety event rate ratios and significance levels while maintaining 80% power, testing 3 average adverse event rates (3.9, 6.1, and 12.6 events per 100 person-years) estimated from the American College of Cardiology's 2006 to 2010 National Cardiovascular Data Registry of ICDs. We then compared with actual medical device utilization. At significance level 0.05 and 80% power, 34% or fewer ICD models accrued sufficient utilization in practice to detect safety differences for rate ratios <1.15 and an average event rate of 12.6 events per 100 person-years. For average event rates of 3.9 and 12.6 events per 100 person-years, 30% and 50% of ICD models, respectively, accrued sufficient utilization for a rate ratio of 1.25, whereas 52% and 67% for a rate ratio of 1.50. Because actual ICD utilization was not uniformly distributed across ICD models, the proportion of individuals receiving any ICD that accrued sufficient utilization in practice was 0% to 21%, 32% to 70%, and 67% to 84% for rate ratios of 1.05, 1.15, and 1.25, respectively, for the range of 3 average adverse event rates. Small safety differences among ICD generator models are unlikely to be detected through routine surveillance given current ICD utilization in practice, but large safety differences can be detected for most patients at anticipated average adverse event rates. Copyright © 2018 John Wiley & Sons, Ltd.

Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study.

PubMed

Tanaka, Yoshiya; Emoto, Kahaku; Cai, Zhihong; Aoki, Takehiro; Schlichting, Douglas; Rooney, Terence; Macias, William

2016-03-01

To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult-onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of ≥ 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses ≤ 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013).

Use of failure modes, effects, and criticality analysis to compare the vulnerabilities of laparoscopic versus open appendectomy.

PubMed

Guida, Edoardo; Rosati, Ubaldo; Pini Prato, Alessio; Avanzini, Stefano; Pio, Luca; Ghezzi, Michele; Jasonni, Vincenzo; Mattioli, Girolamo

2015-06-01

To measure the feasibility of using FMECA applied to the surgery and then compare the vulnerabilities of laparoscopic versus open appendectomy by using FMECA. The FMECA study was performed on each single selected phase of appendectomy and on complication-related data during the period January 1, 2009, to December 31, 2010. The risk analysis phase was completed by evaluation of the criticality index (CI) of each appendectomy-related failure mode (FM). The CI is calculated by multiplying the estimated frequency of occurrence (O) of the FM, by the expected severity of the injury to the patient (S), and the detectability (D) of the FM. In the first year of analysis (2009), 177 appendectomies were performed, 110 open and 67 laparoscopic. Eleven adverse events were related to the open appendectomy: 1 bleeding (CI: 8) and 10 postoperative infections (CI: 32). Three adverse events related to the laparoscopic approach were recorded: 1 postoperative infection (CI: 8) and 2 incorrect extractions of the appendix through the umbilical port (CI: 6). In the second year of analysis (2010), 158 appendectomies were performed, 69 open and 89 laparoscopic. Four adverse events were related to the open appendectomy: 1 incorrect management of the histological specimen (CI: 2), 1 dehiscence of the surgical wound (CI: 6), and 2 infections (CI: 6). No adverse events were recorded in laparoscopic approach. FMECA helped the staff compare the 2 approaches through an accurate step-by-step analysis, highlighting that laparoscopic appendectomy is feasible and safe, associated with a lower incidence of infection and other complications, reduced length of hospital stay, and an apparent lower procedure-related risk.

Comparison of closed-cell and hybrid-cell stent designs in carotid artery stenting: clinical and procedural outcomes

PubMed Central

Tatli, Ersan; Vatan, Mehmet Bulent; Agac, Mustafa Tarik; Gunduz, Huseyin; Akdemir, Ramazan; Kilic, Harun

2017-01-01

Introduction Carotid artery stenting (CAS) is a promising alternative to surgery in high-risk patients. However, the impact of stent cell design on outcomes in CAS is a matter of continued debate. Aim To compare the periprocedural and clinical outcomes of different stent designs for CAS with distal protection devices. Material and methods All CAS procedures with both closed- and hybrid-cell stents performed at our institution between February 2010 and December 2015 were analyzed retrospectively. Adverse events were defined as death, major stroke, minor stroke, transient ischemic attack and myocardial infarction. Periprocedural and 30-day adverse events and internal carotid artery (ICA) vasospasm rates were compared between the closed-cell and hybrid-cell stent groups. Results The study included 234 patients comprising 146 patients with a closed-cell stent (Xact stent, Abbott Vascular) (mean age: 68.5 ±8.6; 67.1% male) and 88 patients with a hybrid-cell stent (Cristallo Ideale, Medtronic) (mean age: 67.2 ±12.8; 68.2% male). There was no significant difference between the groups with respect to periprocedural or 30-day adverse event rates. While there was no difference in terms of tortuosity index between the groups, there was a higher procedural ICA vasospasm rate in the closed-cell stent group (35 patients, 23%) compared with the hybrid-cell stent group (10 patients, 11%) (p = 0.017). Conclusions The results of this study showed no significant difference in the clinical adverse event rates after CAS between the closed-cell stent group and the hybrid-cell stent group. However, procedural ICA vasospasm was more common in the closed-cell stent group. PMID:28798784

Impact of medication reconciliation and review and counselling, on adverse drug events and healthcare resource use.

PubMed

Al-Hashar, Amna; Al-Zakwani, Ibrahim; Eriksson, Tommy; Sarakbi, Alaa; Al-Zadjali, Badriya; Al Mubaihsi, Saif; Al Zaabi, Mohammed

2018-05-12

Background Adverse drug events from preventable medication errors can result in patient morbidity and mortality, and in cost to the healthcare system. Medication reconciliation can improve communication and reduce medication errors at transitions in care. Objective Evaluate the impact of medication reconciliation and counselling intervention delivered by a pharmacist for medical patients on clinical outcomes 30 days after discharge. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods A randomized controlled study comparing standard care with an intervention delivered by a pharmacist and comprising medication reconciliation on admission and discharge, a medication review, a bedside medication counselling, and a take-home medication list. Medication discrepancies during hospitalization were identified and reconciled. Clinical outcomes were evaluated by reviewing electronic health records and telephone interviews. Main outcome measures Rates of preventable adverse drug events as primary outcome and healthcare resource utilization as secondary outcome at 30 days post discharge. Results A total of 587 patients were recruited (56 ± 17 years, 57% female); 286 randomized to intervention; 301 in the standard care group. In intervention arm, 74 (26%) patients had at least one discrepancy on admission and 100 (35%) on discharge. Rates of preventable adverse drug events were significantly lower in intervention arm compared to standard care arm (9.1 vs. 16%, p = 0.009). No significant difference was found in healthcare resource use. Conclusion The implementation of an intervention comprising medication reconciliation and counselling by a pharmacist has significantly reduced the rate of preventable ADEs 30 days post discharge, compared to the standard care. The effect of the intervention on healthcare resource use was insignificant. Pharmacists should be included in decentralized, patient-centred roles. The findings should be interpreted in the context of the study's limitations.

Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS.

PubMed

Engel, Samuel S; Suryawanshi, Shailaja; Stevens, Susanna R; Josse, Robert G; Cornel, Jan H; Jakuboniene, Neli; Riefflin, Axel; Tankova, Tsvetalina; Wainstein, Julio; Peterson, Eric D; Holman, Rury R

2017-11-01

To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m 2 ) vs those without CKD. Within the CKD cohort, the same analyses were performed, comparing sitagliptin- and placebo-assigned participants. Baseline characteristics were summarized for all participants, and serious adverse events were analysed in those who received at least 1 dose of study medication. Adverse events of interest and diabetes complications were summarized for the intention-to-treat population. CKD was present in 3324 (23%) participants at entry into TECOS. The mean (SD) age for this CKD cohort was 68.8 (7.9) years, mean diabetes duration was 13.7 (9.0) years, and 62% were men. Incidences of serious adverse events, malignancy, bone fracture, severe hypoglycaemia and most categories of diabetes complications were higher in the CKD cohort compared with those without CKD. Over ~2.8 median years of follow-up, CKD participants assigned to sitagliptin had rates of diabetic eye disease, diabetic neuropathy, renal failure, malignancy, bone fracture, pancreatitis and severe hypoglycaemia similar to those of placebo-assigned participants. Participants in TECOS with CKD had higher incidences of serious adverse events and diabetes complications than those without CKD. Treatment with sitagliptin was generally well tolerated, with no meaningful differences in safety outcomes observed between those with CKD assigned to sitagliptin or placebo. © 2017 John Wiley & Sons Ltd.

Syncope paradox in the outcome of patients with pulmonary thromboembolism: short-term and midterm outcome.

PubMed

Seyyedi, Seyyed-reza; Jenab, Yaser; Tokaldany, Masoumeh Lotfi; Shirani, Shapoor; Sadeghian, Saeed; Jalali, Arash

2016-01-01

We compare the early and midterm outcomes of pulmonary thromboembolism (PTE) in patients with and without syncope in our single-center registry. Between December 2006 and May 2013, 351 consecutive patients (mean age = 60.21 ± 16.91 years, 55.3% male) with confirmed acute symptomatic PTE were divided in with and without syncope groups. Groups were compared in terms of the effect of syncope on 30-day mortality and adverse events, and mortality in a median follow-up time of 16.9 months. From 351 patients, 39 (11.1%) had syncope and 312 (88.9%) did not. Syncope group had less frequently chest pain (30.8% vs 51.4%; P value = 0.015). Also, the rates of 30-day adverse events and mortality were 12.8% and 5.1% for the group with syncope, and 14.4% and 10.3% for the group without syncope, respectively, with no significant difference. At follow up, 65 patients died and mortality was 18.5% for 351 patients (5.1% in the group with syncope and 20.2% for the other group). After adjustment for confounding factors, the effect of syncope on 30-day adverse events and mortality remained non-significant and on the midterm mortality was significant, showing that the presence of syncope was associated with lower midterm mortality (P value = 0.038). Among PTE patients in our registry, 11.1% presented with syncope. Relationship between syncope and 30-day adverse events and mortality remained non-significant after adjustments for other factors. However, in midterm follow up, patients with syncope were significantly at decreased risk of mortality compared to those without syncope. © 2014 John Wiley & Sons Ltd.

Use of the Spine Adverse Events Severity System (SAVES) in patients with traumatic spinal cord injury. A comparison with institutional ICD-10 coding for the identification of acute care adverse events.

PubMed

Street, J T; Thorogood, N P; Cheung, A; Noonan, V K; Chen, J; Fisher, C G; Dvorak, M F

2013-06-01

Observational cohort comparison. To compare the previously validated Spine Adverse Events Severity system (SAVES) with International Classification of Diseases, Tenth Revision codes (ICD-10) codes for identifying adverse events (AEs) in patients with traumatic spinal cord injury (TSCI). Quaternary Care Spine Program. Patients discharged between 2006 and 2010 were identified from our prospective registry. Two consecutive cohorts were created based on the system used to record acute care AEs; one used ICD-10 coding by hospital coders and the other used SAVES data prospectively collected by a multidisciplinary clinical team. The ICD-10 codes were appropriately mapped to the SAVES. There were 212 patients in the ICD-10 cohort and 173 patients in the SAVES cohort. Analyses were adjusted to account for the different sample sizes, and the two cohorts were comparable based on age, gender and motor score. The SAVES system identified twice as many AEs per person as ICD-10 coding. Fifteen unique AEs were more reliably identified using SAVES, including neuropathic pain (32 × more; P<0.001), urinary tract infections (1.4 × ; P<0.05), pressure sores (2.9 × ; P<0.001) and intra-operative AEs (2.3 × ; P<0.05). Eight of these 15 AEs more frequently identified by SAVES significantly impacted length of stay (P<0.05). Risk factors such as patient age and severity of paralysis were more reliably correlated to AEs collected through SAVES than ICD-10. Implementation of the SAVES system for patients with TSCI captured more individuals experiencing AEs and more AEs per person compared with ICD-10 codes. This study demonstrates the utility of prospectively collecting AE data using validated tools.

[Pre-hospital adverse events: a way to go].

PubMed

Alvarez-Ortiz, Nancy Jezzi; Aranaz Andrés, Jesús María; Gea Velázquez De Castro, María Teresa; Miralles Bueno, Juan José

2010-01-01

The occurrence of adverse events is a problem at all levels of care and creates a significant burden of morbidity and mortality. In Spain there have been significant investigations of adverse effects (AE) in hospitals and primary care, however, studies of pre-hospital care are not yet developed. The aim of this study was to determine the frequency, type, preventability, severity and impact of "pre-hospital" adverse events, which were detected in the hospitalization index and the comparing those that occurred in ambulatory and non-ambulatory care. Case Series Study, with analytical components, of a sample of subjects included in the "National study of adverse events related to hospitalization (ENEAS). Qualitative data are presented as proportions with confidence intervals. For comparative analysis of qualitative data, we used the chi-square test. Of a total of 5624 patients, 2.3% (N=131) ((95%)CI: 1.94-2.72) had an AE that occurred prior to hospitalization or "pre-hospital", and 40.5% of these (N=53) ((95%)CI: 32.05-48.86) were preventable. In 44 patients the AE had its origin in ambulatory care and 85 patients in non-ambulatory care. The characteristic of patients with ambulatory AE are men and older women (median 76 years) who consulted for medical problems (84.1%) and the AE were related to medication in 77.8%. The characteristic of patients with non-ambulatory AE, were men (median 73 years), consulting for medical and surgical problems (44,7-55,3%) and the EA is related to medications, infections and procedures. The characteristics of patients with AE and undesirable effects that occurred during pre-hospitalization period depended on whether they originated during ambulatory care or non-ambulatory care. Therefore prevention strategies should take these differences into account. Copyright 2009 SECA. Published by Elsevier Espana. All rights reserved.

Disclosure of adverse events and errors in surgical care: challenges and strategies for improvement.

PubMed

Lipira, Lauren E; Gallagher, Thomas H

2014-07-01

The disclosure of adverse events to patients, including those caused by medical errors, is a critical part of patient-centered healthcare and a fundamental component of patient safety and quality improvement. Disclosure benefits patients, providers, and healthcare institutions. However, the act of disclosure can be difficult for physicians. Surgeons struggle with disclosure in unique ways compared with other specialties, and disclosure in the surgical setting has specific challenges. The frequency of surgical adverse events along with a dysfunctional tort system, the team structure of surgical staff, and obstacles created inadvertently by existing surgical patient safety initiatives may contribute to an environment not conducive to disclosure. Fortunately, there are multiple strategies to address these barriers. Participation in communication and resolution programs, integration of Just Culture principles, surgical team disclosure planning, refinement of informed consent and morbidity and mortality processes, surgery-specific professional standards, and understanding the complexities of disclosing other clinicians' errors all have the potential to help surgeons provide patients with complete, satisfactory disclosures. Improvement in the regularity and quality of disclosures after surgical adverse events and errors will be key as the field of patient safety continues to advance.

Clinical experience of infective endocarditis complicated by acute cerebrovascular accidents.

PubMed

Hsu, Chan-Yang; Chi, Nai-Hsin; Wang, Shoei-Shen; Chen, Yih-Sharng; Yu, Hsi-Yu

2017-04-01

To evaluate the clinical results of patients with infective endocarditis (IE) complicated by acute cerebrovascular accidents (CVAs). A total of 44 patients with IE complicated by CVA at admission were retrospectively analyzed in a single medical institute from 2005 to 2011. At the time of admission, 18 patients were diagnosed with hemorrhagic stroke, and 26 patients were diagnosed with ischemic stroke. Fifteen patients received surgical intervention during hospitalization. The hospital mortality rate was 38.9% for the hemorrhagic stroke group and 42.3% for the ischemic stroke group (p = 0.821). The mortality rate was 33.3% for the surgical group and 44.8% for the nonsurgical group (p = 0.531). At 30 days of hospitalization, 45.8% of the patients experienced an adverse event (defined as death due to organ failure, restroke, cardiogenic shock, or septic shock during the treatment period), and the attrition rate was 1.5% per day. Surgery performed after the adverse events increased mortality (80.0%) compared with surgery performed on patients with no adverse events (10.0%; p = 0.017). A Cox regression analysis revealed that creatinine > 2 mg/dL, diabetes, and staphylococcal infection were the risk factors of the adverse events. Early surgical intervention for IE with ischemic stroke may prevent adverse events, particularly in patients with impaired renal function, diabetes, or staphylococcal infection. A delay in operation of > 30 days is recommended after hemorrhagic stroke. Copyright © 2017. Published by Elsevier Taiwan.

Adverse life events as risk factors for behavioural and emotional problems in a 7-year follow-up of a population-based child cohort.

PubMed

Rasmussen, Cathrine Skovmand; Nielsen, Louise Gramstrup; Petersen, Dorthe Janne; Christiansen, Erik; Bilenberg, Niels

2014-04-01

The aim of the study was to identify risk factors for significant changes in emotional and behavioural problem load in a community-based cohort of Danish children aged 9-16 years, the risk factors being seven parental and two child-related adverse life events. Data on emotional and behavioural problems was obtained from parents filling in the Child Behavior Checklist (CBCL) when the child was 8-9 and again when 15 years old. Data on risk factors was drawn from Danish registers. Analysis used was logistic regression for crude and adjusted change. Parental divorce significantly raised the odds ratio of an increase in emotional and behavioural problems; furthermore, the risk of deterioration in problem behaviour rose significantly with increasing number of adverse life events. By dividing the children into four groups based on the pathway in problem load (increasers, decreasers, high persisters and low persisters), we found that children with a consistently high level of behavioural problems also had the highest number of adverse life events compared with any other group. Family break-up was found to be a significant risk factor. This supports findings in previous studies. The fact that no other risk factor proved to be of significance might be due to lack of power in the study. Children experiencing high levels of adverse life events are at high risk of chronic problem behaviour. Thus these risk factors should be assessed in daily clinical practice.

Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection.

PubMed

Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

2016-01-18

Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe).In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence).In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence).In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials).Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole.

Standardization of immunotherapy adverse events in patient information leaflets and development of an interface terminology for outpatients' monitoring.

PubMed

Zini, E M; Lanzola, G; Quaglini, S; Cornet, R

2018-01-01

Immunotherapy is effective for treating cancer, but it is also associated with a wide spectrum of adverse events. In order to detect them early, the patients need to be monitored at home, between the therapy administrations, e.g., by asking them to report outcomes, usually including symptoms and quality of life measures. For the collected data to be reusable, the symptoms need to be in a standardized form. The aim of this study is to explore the standardization of the information contained in the patient information leaflets (PILs) of immunotherapy drugs, by creating an interface terminology of immunotherapy-related adverse events, which should support a consistent collection of symptoms from the patients. PILs contain a significant amount of information in free text, but they mix patient-reportable and clinically assessable events. We extracted a list of patient-reportable adverse events, mapped them to reference terminologies and compared the mapping results to choose the best-performing reference terminology. The PILs standardization led to the extraction of 151 symptoms and 424 terms, including both preferred terms and synonyms in English and Italian. Among the reference terminologies we considered, SNOMED CT allowed us to map all concepts and became, hence, the main reference terminology for the resulting interface terminology. A preliminary validation on the PIL of a new immunotherapy drug showed that our interface terminology already contained all the mentioned symptoms. PILs provide a valuable source for determining adverse events. The resulting interface terminology includes Italian and English terms for patient-reportable adverse events for five immunotherapy drugs representative of their category. Further work will be undertaken to evaluate the usability of the interface terminology and the patients' experience and satisfaction with the proposed terms, made available for example through an app, as well as its effectiveness on data quality and quality of care. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of High-Reliability Education on Adverse Event Reporting by Registered Nurses.

PubMed

McFarland, Diane M; Doucette, Jeffrey N

Adverse event reporting is one strategy to identify risks and improve patient safety, but, historically, adverse events are underreported by registered nurses (RNs) because of fear of retribution and blame. A program was provided on high reliability to examine whether education would impact RNs' willingness to report adverse events. Although the findings were not statistically significant, they demonstrated a positive impact on adverse event reporting and support the need to create a culture of high reliability.

Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults.

PubMed

Hristovska, Ana-Marija; Duch, Patricia; Allingstrup, Mikkel; Afshari, Arash

2017-08-14

Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources. The main objective of this review was to compare the efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade caused by non-depolarizing neuromuscular agents in adults. We searched the following databases on 2 May 2016: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (WebSPIRS Ovid SP), Embase (WebSPIRS Ovid SP), and the clinical trials registries www.controlled-trials.com, clinicaltrials.gov, and www.centerwatch.com. We re-ran the search on 10 May 2017. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We included adults, classified as American Society of Anesthesiologists (ASA) I to IV, who received non-depolarizing neuromuscular blocking agents for an elective in-patient or day-case surgical procedure. We included all trials comparing sugammadex versus neostigmine that reported recovery times or adverse events. We included any dose of sugammadex and neostigmine and any time point of study drug administration. Two review authors independently screened titles and abstracts to identify trials for eligibility, examined articles for eligibility, abstracted data, assessed the articles, and excluded obviously irrelevant reports. We resolved disagreements by discussion between review authors and further disagreements through consultation with the last review author. We assessed risk of bias in 10 methodological domains using the Cochrane risk of bias tool and examined risk of random error through trial sequential analysis. We used the principles of the GRADE approach to prepare an overall assessment of the quality of evidence. For our primary outcomes (recovery times to train-of-four ratio (TOFR) > 0.9), we presented data as mean differences (MDs) with 95 % confidence intervals (CIs), and for our secondary outcomes (risk of adverse events and risk of serious adverse events), we calculated risk ratios (RRs) with CIs. We included 41 studies (4206 participants) in this updated review, 38 of which were new studies. Twelve trials were eligible for meta-analysis of primary outcomes (n = 949), 28 trials were eligible for meta-analysis of secondary outcomes (n = 2298), and 10 trials (n = 1647) were ineligible for meta-analysis.We compared sugammadex 2 mg/kg and neostigmine 0.05 mg/kg for reversal of rocuronium-induced moderate neuromuscular blockade (NMB). Sugammadex 2 mg/kg was 10.22 minutes (6.6 times) faster then neostigmine 0.05 mg/kg (1.96 vs 12.87 minutes) in reversing NMB from the second twitch (T2) to TOFR > 0.9 (MD 10.22 minutes, 95% CI 8.48 to 11.96; I 2 = 84%; 10 studies, n = 835; GRADE: moderate quality).We compared sugammadex 4 mg/kg and neostigmine 0.07 mg/kg for reversal of rocuronium-induced deep NMB. Sugammadex 4 mg/kg was 45.78 minutes (16.8 times) faster then neostigmine 0.07 mg/kg (2.9 vs 48.8 minutes) in reversing NMB from post-tetanic count (PTC) 1 to 5 to TOFR > 0.9 (MD 45.78 minutes, 95% CI 39.41 to 52.15; I 2 = 0%; two studies, n = 114; GRADE: low quality).For our secondary outcomes, we compared sugammadex, any dose, and neostigmine, any dose, looking at risk of adverse and serious adverse events. We found significantly fewer composite adverse events in the sugammadex group compared with the neostigmine group (RR 0.60, 95% CI 0.49 to 0.74; I 2 = 40%; 28 studies, n = 2298; GRADE: moderate quality). Risk of adverse events was 28% in the neostigmine group and 16% in the sugammadex group, resulting in a number needed to treat for an additional beneficial outcome (NNTB) of 8. When looking at specific adverse events, we noted significantly less risk of bradycardia (RR 0.16, 95% CI 0.07 to 0.34; I 2 = 0%; 11 studies, n = 1218; NNTB 14; GRADE: moderate quality), postoperative nausea and vomiting (PONV) (RR 0.52, 95% CI 0.28 to 0.97; I 2 = 0%; six studies, n = 389; NNTB 16; GRADE: low quality) and overall signs of postoperative residual paralysis (RR 0.40, 95% CI 0.28 to 0.57; I 2 = 0%; 15 studies, n = 1474; NNTB 13; GRADE: moderate quality) in the sugammadex group when compared with the neostigmine group. Finally, we found no significant differences between sugammadex and neostigmine regarding risk of serious adverse events (RR 0.54, 95% CI 0.13 to 2.25; I 2 = 0%; 10 studies, n = 959; GRADE: low quality).Application of trial sequential analysis (TSA) indicates superiority of sugammadex for outcomes such as recovery time from T2 to TOFR > 0.9, adverse events, and overall signs of postoperative residual paralysis. Review results suggest that in comparison with neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular block regardless of the depth of the block. Sugammadex 2 mg/kg is 10.22 minutes (˜ 6.6 times) faster in reversing moderate neuromuscular blockade (T2) than neostigmine 0.05 mg/kg (GRADE: moderate quality), and sugammadex 4 mg/kg is 45.78 minutes (˜ 16.8 times) faster in reversing deep neuromuscular blockade (PTC 1 to 5) than neostigmine 0.07 mg/kg (GRADE: low quality). With an NNTB of 8 to avoid an adverse event, sugammadex appears to have a better safety profile than neostigmine. Patients receiving sugammadex had 40% fewer adverse events compared with those given neostigmine. Specifically, risks of bradycardia (RR 0.16, NNTB 14; GRADE: moderate quality), PONV (RR 0.52, NNTB 16; GRADE: low quality), and overall signs of postoperative residual paralysis (RR 0.40, NNTB 13; GRADE: moderate quality) were reduced. Both sugammadex and neostigmine were associated with serious adverse events in less than 1% of patients, and data showed no differences in risk of serious adverse events between groups (RR 0.54; GRADE: low quality).

Adverse Events With Ketamine Versus Ketofol for Procedural Sedation on Adults: A Double-blind, Randomized Controlled Trial.

PubMed

Lemoel, Fabien; Contenti, Julie; Giolito, Didier; Boiffier, Mathieu; Rapp, Jocelyn; Istria, Jacques; Fournier, Marc; Ageron, François-Xavier; Levraut, Jacques

2017-12-01

The goal of our study was to compare the frequency and severity of recovery reactions between ketamine and ketamine-propofol 1:1 admixture ("ketofol"). We performed a multicentric, randomized, double-blind trial in which adult patients received emergency procedural sedations with ketamine or ketofol. Our primary outcome was the proportion of unpleasant recovery reactions. Other outcomes were frequency of interventions required by these recovery reactions, rates of respiratory or hemodynamic events, emesis, and satisfaction of patients as well as providers. A total of 152 patients completed the study, 76 in each arm. Compared with ketamine, ketofol determined a 22% reduction in recovery reactions incidence (p < 0.01) and less clinical and pharmacologic interventions required by these reactions. There was no serious adverse event in both groups. Rates in hemodynamic or respiratory events as well as satisfaction scores were similar. Significantly fewer patients experienced emesis with ketofol, with a threefold reduction in incidence compared with ketamine. We found a significant reduction in recovery reactions and emesis frequencies among adult patients receiving emergency procedural sedations with ketofol, compared with ketamine. © 2017 by the Society for Academic Emergency Medicine.

Blood pressure targets for hypertension in older adults.

PubMed

Garrison, Scott R; Kolber, Michael R; Korownyk, Christina S; McCracken, Rita K; Heran, Balraj S; Allan, G Michael

2017-08-08

Eight out of 10 major antihypertensive trials in older adults attempted to achieve a target systolic blood pressure (BP) less than 160 mmHg. Collectively these trials demonstrated benefit for treatment, as compared to no treatment, for an older adult with BP greater than 160 mmHg. However an even lower BP target of less than 140 mmHg is commonly applied to all age groups. At the present time it is not known whether a lower or higher BP target is associated with better cardiovascular outcomes in older adults. To assess the effects of a higher (less than 150 to 160/95 to 105 mmHg) BP target compared to the lower BP target of less than 140/90 mmHg in hypertensive adults 65 years of age or older. The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We also contacted authors of relevant papers regarding further published and unpublished work. Randomised trials, of at least one year's duration, conducted on hypertensive adults aged 65 years or older, which report the effect on mortality and morbidity of a higher systolic or diastolic BP treatment target (whether ambulatory, home, or office measurements) in the range of systolic BP less than 150 to 160 mmHg or diastolic BP less than 95 to 105 mmHg as compared to a lower BP treatment target of less than 140/90 mmHg or lower. Two authors independently screened and selected trials for inclusion, assessed risk of bias, and extracted data. We combined data for dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI) and for continuous outcomes we used mean difference (MD). Primary outcomes were all-cause mortality, stroke, institutionalisation, and cardiovascular serious adverse events. Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved. We found and included three unblinded randomised trials in 8221 older adults (mean age 74.8 years), in which higher BP targets of less than 150/90 mmHg (two trials) and less than 160/90 mmHg (one trial) were compared to a lower target of less than 140/90 mmHg. Treatment to the two different BP targets over two to four years failed to produce a difference in any of our primary outcomes, including all-cause mortality (RR 1.24 95% CI 0.99 to 1.54), stroke (RR 1.25 95% CI 0.94 to 1.67) and total cardiovascular serious adverse events (RR 1.19 95% CI 0.98 to 1.45). However, the 95% confidence intervals of these outcomes suggest the lower BP target is probably not worse, and might offer a clinically important benefit. We judged all comparisons to be based on low-quality evidence. Data on adverse effects were not available from all trials and not different, including total serious adverse events, total minor adverse events, and withdrawals due to adverse effects. At the present time there is insufficient evidence to know whether a higher BP target (less than150 to 160/95 to 105 mmHg) or a lower BP target (less than 140/90 mmHg) is better for older adults with high BP. Additional good-quality trials assessing BP targets in this population are needed.

Efficacy and safety of TMC278 in antiretroviral-naive HIV-1 patients: week 96 results of a phase IIb randomized trial.

PubMed

Pozniak, Anton L; Morales-Ramirez, Javier; Katabira, Elly; Steyn, Dewald; Lupo, Sergio H; Santoscoy, Mario; Grinsztejn, Beatriz; Ruxrungtham, Kiat; Rimsky, Laurence T; Vanveggel, Simon; Boven, Katia

2010-01-02

TMC278 is a next-generation nonnucleoside reverse transcriptase inhibitor highly active against wild-type and nonnucleoside reverse transcriptase inhibitor-resistant HIV-1 in vitro. The week 96 analysis of TMC278-C204, a large dose-ranging study of TMC278 in treatment-naive HIV-1-infected patients, is presented. Phase IIb randomized trial. Three hundred sixty-eight patients were randomized and treated with three blinded once-daily TMC278 doses 25, 75 or 150 mg, or an open-label, active control, efavirenz 600 mg once daily, all with two nucleoside reverse transcriptase inhibitors. The primary analysis was at week 48. No TMC278 dose-response relationship for efficacy and safety was observed. TMC278 demonstrated potent antiviral efficacy comparable with efavirenz over 48 weeks that was sustained to week 96 (76.9-80.0% and 71.4-76.3% of TMC278-treated patients with confirmed viral load <50 copies/ml, respectively; time-to-loss of virological-response algorithm). Median increases from baseline in CD4 cell count with TMC278 at week 96 (138.0-149.0 cells/microl) were higher than at week 48 (108.0-123.0 cells/microl). All TMC278 doses were well tolerated. The incidences of the most commonly reported grade 2-4 adverse events at least possibly related to study medication, including nausea, dizziness, abnormal dreams/nightmare, dyspepsia, asthenia, rash, somnolence and vertigo, were low and lower with TMC278 than with efavirenz. Incidences of serious adverse events, grade 3 or 4 adverse events and discontinuations due to adverse events were similar among groups. All TMC278 doses demonstrated potent and sustained efficacy comparable with efavirenz in treatment-naive patients over 96 weeks. TMC278 was well tolerated with lower incidences of neurological and psychiatric adverse events, rash and lower lipid elevations than those with efavirenz. TMC278 25 mg once daily was selected for further clinical development.

Adverse events following pandemic influenza A (H1N1) 2009 monovalent and seasonal influenza vaccinations during the 2009-2010 season in the active component U.S. military and civilians aged 17-44years reported to the Vaccine Adverse Event Reporting System.

PubMed

Bardenheier, Barbara H; Duderstadt, Susan K; Engler, Renata J M; McNeil, Michael M

2016-08-17

No comparative review of Vaccine Adverse Event Reporting System (VAERS) submissions following pandemic influenza A (H1N1) 2009 and seasonal influenza vaccinations during the pandemic season among U.S. military personnel has been published. We compared military vs. civilian adverse event reporting rates. Adverse events (AEs) following vaccination were identified from VAERS for adults aged 17-44years after pandemic (monovalent influenza [MIV], and seasonal (trivalent inactivated influenza [IIV3], live attenuated influenza [LAIV3]) vaccines. Military vaccination coverage was provided by the Department of Defense's Defense Medical Surveillance System. Civilian vaccination coverage was estimated using data from the National 2009 H1N1 Flu Survey and the Behavioral Risk Factor Surveillance System survey. Vaccination coverage was more than four times higher for MIV and more than twenty times higher for LAIV3 in the military than in the civilian population. The reporting rate of serious AE reports following MIV in service personnel (1.19 per 100,000) was about half that reported by the civilian population (2.45 per 100,000). Conversely, the rate of serious AE reports following LAIV3 among service personnel (1.32 per 100,000) was more than twice that of the civilian population. Although fewer military AEs following MIV were reported overall, the rate of Guillain-Barré Syndrome (GBS) (4.01 per million) was four times greater than that in the civilian population. (1.04 per million). Despite higher vaccination coverage in service personnel, the rate of serious AEs following MIV was about half that in civilians. The rate of GBS reported following MIV was higher in the military. Published by Elsevier Ltd.

Effect of iron content on the tolerability of prenatal multivitamins in pregnancy.

PubMed

Nguyen, Patricia; Nava-Ocampo, Alejandro; Levy, Amalia; O'Connor, Deborah L; Einarson, Tom R; Taddio, Anna; Koren, Gideon

2008-05-15

Gastrointestinal irritability can deter pregnant women from starting or continuing prenatal multivitamin supplementation. In a previous study, suboptimal tolerability was observed among pregnant women taking a large tablet (18 mm x 8 mm x 8 mm) multivitamin with high elemental iron content (60 mg as ferrous fumarate). The objective of the present study was to compare rates of adherence and reported adverse events among pregnant women who were randomized to commence supplementation with a small-tablet prenatal multivitamin, containing either low or high iron content. Pregnant women who called the Motherisk Program (Hospital for Sick Children, Toronto) and had not started taking or had discontinued any multivitamin due to adverse events were included in this prospective, randomized, open-label, 2-arm study. Women were randomized to take a small-size (16 mm x 9 mm x 4 mm), low elemental iron content (35 mg as ferrous fumarate) multivitamin ('35 mg' group); or a small-size (5 mm radius, 5 mm thickness), high elemental iron content (60 mg as ferrous sulphate) multivitamin ('60 mg' group). Follow-up interviews documented pill intake and adverse events. Rates of adherence and adverse events were compared between groups using chi-squared tests and Kaplan-Meier survival curves. Of 167 randomized women, 92 in the '35 mg' group and 75 in the '60 mg' group were included in the analysis. Despite ideal conditions and regular follow-ups, mean adherence based on pill intake recall, in both groups was approximately 50%. No statistically significant difference was detected in proportions of women who actually started taking either multivitamin. Among those who started, no difference was detected in rates of adherence or reported adverse events. The present results suggest that iron content is not a major determinant of adherence to prenatal multivitamins. Combined with our previous study, tablet size may be the more definitive factor affecting adherence.

A Markov chain model to evaluate the effect of CYP3A5 and ABCB1 polymorphisms on adverse events associated with tacrolimus in pediatric renal transplantation.

PubMed

Sy, Sherwin K B; Heuberger, Jules; Shilbayeh, Sireen; Conrado, Daniela J; Derendorf, Hartmut

2013-10-01

The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.

Short-term open-label chamomile (Matricaria chamomilla L.) therapy of moderate to severe generalized anxiety disorder.

PubMed

Keefe, John R; Mao, Jun J; Soeller, Irene; Li, Qing S; Amsterdam, Jay D

2016-12-15

Conventional drug treatments for Generalized Anxiety Disorder (GAD) are often accompanied by substantial side effects, dependence, and/or withdrawal syndrome. A prior controlled study of oral chamomile (Matricaria chamomilla L.) extract showed significant efficacy versus placebo, and suggested that chamomile may have anxiolytic activity for individuals with GAD. We hypothesized that treatment with chamomile extract would result in a significant reduction in GAD severity ratings, and would be associated with a favorable adverse event and tolerability profile. We report on the open-label phase of a two-phase randomized controlled trial of chamomile versus placebo for relapse-prevention of recurrent GAD. Subjects with moderate to severe GAD received open-label treatment with pharmaceutical-grade chamomile extract 1500mg/day for up to 8 weeks. Primary outcomes were the frequency of clinical response and change in GAD-7 symptom scores by week 8. Secondary outcomes included the change over time on the Hamilton Rating Scale for Anxiety, the Beck Anxiety Inventory, and the Psychological General Well Being Index. Frequency of treatment-emergent adverse events and premature treatment discontinuation were also examined. Of 179 subjects, 58.1% (95% CI: 50.9% to 65.5%) met criteria for response, while 15.6% prematurely discontinued treatment. Significant improvement over time was also observed on the GAD-7 rating (β=-8.4 [95% CI=-9.1 to -7.7]). A similar proportion of subjects demonstrated statistically significant and clinically meaningful reductions in secondary outcome ratings of anxiety and well-being. Adverse events occurred in 11.7% of subjects, although no serious adverse events occurred. Chamomile extract produced a clinically meaningful reduction in GAD symptoms over 8 weeks, with a response rate comparable to those observed during conventional anxiolytic drug therapy and a favorable adverse event profile. Future comparative effectiveness trials between chamomile and conventional drugs may help determine the optimal risk/benefit of these therapies for patients suffering from GAD. Copyright © 2016 Elsevier GmbH. All rights reserved.

[Education Program of Kampo-medicine for Undergraduates in Preparation for Clinical Setting].

PubMed

Homma, Masato

2016-01-01

Kampo-medicine has become popular in Japanese medical practice combined with western medicine. For example, Daikenchu-To for intestinal obstruction after surgical operation, Shakuyakukanzo-To and Goshajinki-Gan for anti-cancer agents-induced neuropathy, and Yokkan-San for behavioral psychological symptoms of dementia are alternatively used in addition to conventional treatments in Japan. However, combined use of Kampo-medicine and western medicine may cause unexpected adverse events including undesirable drug-drug interactions because Kampo-medicine was not originally developed to be used with western medicine. Although adverse effects of Kampo-medicine are rare compared with those of western medicine, severe events such as liver dysfunction and interstitial pneumonia have been reported in increasing trends. Medical staff including pharmacists, therefore, should be aware of the onset of adverse events before the patients' symptoms become severe. Several adverse effects are caused by chemical constituents such as glycyrrhizin in licorice for pseudoaldosteronism and geniposide in Gardeniae fructus for mesenteric phlebosclerosis. To understand the adverse effects of Kampo-medicine, pharmacists should learn trends in current medication as well as pharmacology and toxicology of the chemical constituents in pharmacognosy. These issues should also be addressed in educational materials for students of clinical pharmacy and pharmacy practice.

Exploring unplanned ICU admissions: a systematic review.

PubMed

Vlayen, Annemie; Verelst, Sandra; Bekkering, Geertruida E; Schrooten, Ward; Hellings, Johan; Claes, Nerée

Adverse events are unintended patient injuries or complications that arise from healthcare management resulting in death, disability or prolonged hospital stay. Adverse events that require critical care are a considerable financial burden to the healthcare system. Medical record review seems to be a reliable method for detecting adverse events. To synthesize the best available evidence regarding the estimates of the incidence and preventability of adverse events that necessitate intensive care admission; to determine the type and consequences (patient harm, mortality, length of ICU stay and direct medical costs) of these adverse events. MEDLINE (from 1966 to present), EMBASE (from 1974 to present) and CENTRAL (version 1-2010) were searched for studies reporting on unplanned admissions to intensive care units (ICUs). Databases of reports, conference proceedings, grey literature, ongoing research, relevant patient safety organizations and two journals were searched for additional studies. Reference lists of retrieved papers were searched and authors were contacted in an attempt to find any further published or unpublished work. Only quantitative studies that used chart review for the detection of adverse events requiring intensive care admission were considered for eligibility. Studies that were published in the English, Dutch, German, French or Spanish language were included. Two reviewers independently extracted data and assessed the methodological quality of the included studies. 28 studies in the English language and one study in French were included. Of these, two were considered duplicate publications and therefore 27 studies were reviewed. Meta-analysis of the data was not appropriate due to statistical heterogeneity between studies; therefore, results are presented in a descriptive way. Studies were categorized according to the population and the providers of care. 1) The majority of the included studies investigated unplanned intensive care admissions after anesthetic procedures (UIA). 2) Only a few studies examined patients on general wards being at risk for clinical deterioration. The overall incidence of surgical and medical adverse events compared with ICU admissions ranged from 1.1% to 37.2%. 3) The third category of studies examined patients that were readmitted on ICUs. ICU readmission rates varied from 0% to 18.3%. Nine studies explicitly reported on the preventability of adverse outcomes. The preventability rates of the adverse events varied from 17% to 76.5%. Preventable adverse events are further synthesized by type of event and patterns of preventability are being formulated. Consequences of the adverse events included a mean length of ICU stay that ranged from 1.5 days to 10.4 days for the patient's first stay in ICU. Mortality rates varied between 0% and 58%. Adverse events are a persistent and an important reason for admission to the ICU. However, there is relatively weak evidence to estimate an overall incidence and preventability rate of these events. In addition, estimates on preventability are prone to subjective judgments. Variability in methodology and definitions, and poor reporting in studies may be the main reasons for study heterogeneity. Unplanned intensive care admission within 24 hours of a procedure with an anesthetist in attendance (UIA) is a recommended clinical indicator in surgical patients. Several authors recommend early detection of patients with clinical instability on general wards and the implementation of rapid response teams. Step-down or intermediate care units could be a useful strategy for patients that require monitoring to avoid ICU readmissions. There is a need for further studies on the detection of adverse events. The poor quality of current research evidence and the heterogeneity across studies requires that planning of future studies should aim to standardize measures of outcomes to allow for comparisons across studies. This area of research is important in order to identify and explain failure of healthcare systems leading to patient harm, with the ultimate aim to improve the quality and safety of care.

A Multi-center Comparison of the Safety of Oral versus Intravenous Acetylcysteine for Treatment of Acetaminophen Overdose

PubMed Central

2010-01-01

Oral and intravenous (IV) acetylcysteine are used for treatment of acetaminophen poisoning. The objective of this multi-center study was to compare the safety of these two routes of administration. METHODS We conducted a multi-center chart review of all patients treated with acetylcysteine for acetaminophen poisoning. The primary safety outcome was the percentage of patients with of acetylcysteine-related adverse events. RESULTS A total of 503 subjects were included in the safety analysis (306 IV only, 145 oral only and 52 both routes).There were no serious adverse events related to acetylcysteine for either route. Nausea and vomiting were the most common related adverse events and were more common with oral treatment (23% vs 9%). Anaphylactoid reactions were more common with IV administration (6% vs 2%). Conclusions Intravenous and oral acetylcysteine are both associated with minimal side effects and are safe for treatment of acetaminophen toxicity. PMID:20524832

Adverse events attributed to traditional Korean medical practices: 1999–2010

PubMed Central

Shin, Hyeun-Kyoo; Jeong, Soo-Jin; Ernst, Edzard

2013-01-01

Abstract Objective To investigate adverse events attributed to traditional medical treatments in the Republic of Korea. Methods Adverse events recorded in the Republic of Korea between 1999 and 2010 – by the Food and Drug Administration, the Consumer Agency or the Association of Traditional Korean Medicine – were reviewed. Records of adverse events attributed to the use of traditional medical practices, including reports of medicinal accidents and consumers’ complaints, were investigated. Findings Overall, 9624 records of adverse events attributed to traditional medical practices – including 522 linked to herbal treatments – were identified. Liver problems were the most frequently reported adverse events. Only eight of the adverse events were recorded by the pharmacovigilance system run by the Food and Drug Administration. Of the 9624 events, 1389 – mostly infections, cases of pneumothorax and burns – were linked to physical therapy (n = 285) or acupuncture/moxibustion (n = 1104). Conclusion In the Republic of Korea, traditional medical practices often appear to have adverse effects, yet almost all of the adverse events attributed to such practices between 1999 and 2010 were missed by the national pharmacovigilance system. The Consumer Agency and the Association of Traditional Korean Medicine should be included in the national pharmacovigilance system. PMID:23940404

Adverse events during rotary-wing transport of mechanically ventilated patients: a retrospective cohort study

PubMed Central

Seymour, Christopher W; Kahn, Jeremy M; Schwab, C William; Fuchs, Barry D

2008-01-01

Introduction Patients triaged to tertiary care centers frequently undergo rotary-wing transport and may be exposed to additional risk for adverse events. The incidence of physiologic adverse events and their predisposing factors in mechanically ventilated patients undergoing aeromedical transport are unknown. Methods We performed a retrospective review of flight records of all interfacility, rotary-wing transports to a tertiary care, university hospital during 2001 to 2003. All patients receiving mechanical ventilation via endotracheal tube or tracheostomy were included; trauma, scene flights, and fixed transports were excluded. Data were abstracted from patient flight and hospital records. Adverse events were classified as either major (death, arrest, pneumothorax, or seizure) or minor (physiologic decompensation, new arrhythmia, or requirement for new sedation/paralysis). Bivariate associations between hospital and flight characteristics and the presence of adverse events were examined. Results Six hundred eighty-two interfacility flights occurred during the period of review, with 191 patients receiving mechanical ventilation. Fifty-eight different hospitals transferred patients, with diagnoses that were primarily cardiopulmonary (45%) and neurologic (37%). Median flight distance and time were 42 (31 to 83) km and 13 (8 to 22) minutes, respectively. No major adverse events occurred during flight. Forty patients (22%) experienced a minor physiologic adverse event. Vasopressor requirement prior to flight and flight distance were associated with the presence of adverse events in-flight (P < 0.05). Patient demographics, time of day, season, transferring hospital characteristics, and ventilator settings before and during flight were not associated with adverse events. Conclusion Major adverse events are rare during interfacility, rotary-wing transfer of critically ill, mechanically ventilated patients. Patients transferred over a longer distance or transferred on vasopressors may be at greater risk for minor adverse events during flight. PMID:18498659

Evaluation of adverse events noted in children receiving continuous infusions of dexmedetomidine in the intensive care unit.

PubMed

Honey, Brooke L; Harrison, Donald L; Gormley, Andrew K; Johnson, Peter N

2010-01-01

Dexmedetomidine is an α(2)-adrenergic receptor agonist with sedative and analgesic effects in mechanically ventilated adults and children. Safety and efficacy data are limited in children. The purpose of this study is to retrospectively identify the incidence and types of adverse events noted in children receiving continuous infusions of dexmedetomidine and evaluate potential risk factors for adverse events. Between July 1, 2006, and July 31, 2007, data were collected on all children (< 18 years) who received continuous infusions of dexmedetomidine. Data collection included demographics, dexmedetomidine regimen, and type/number of adverse events. The primary endpoint was the total number of adverse events noted, including: transient hypertension, hypotension, neurological manifestations, apnea, and bradycardia. Secondary endpoints included categorization of each type of adverse event and an assessment of risk factors. A logistic regression model was used to assess the relationship of adverse events with independent variables including length of ICU stay, cumulative dose, peak infusion rate, duration of therapy, PRISM III score, and bolus dose. Thirty-six patients received dexmedetomidine representing 41 infusions. The median age was 16 months (range, 0.1-204 months) and median PRISM III score was 2 (range, 0-18). Eighteen (43.9%) patients received a bolus dose of dexmedetomidine. The median cumulative dose (mcg/kg) and peak dose (mcg/kg/hr) were 8.5 (range, 2.2-193.7) and 0.5 (range, 0.2-0.7), respectively. Dexmedetomidine was continued for a median of 20 (range, 3-263) hours. Six (14.6%) patients were slowly tapered off the continuous infusions. Twenty-one adverse events were noted in 17 patients, including 4 neurologic manifestations. Fourteen patients required interventions for adverse events. ICU length of stay was the only independent risk factor (p=0.036) for development of adverse events. Several potential adverse events were noted with dexmedetomidine continuous infusions including possible neurological manifestations. Further studies are needed looking at adverse events associated with dexmedetomidine use in the pediatric population.

Impact of Extended-Duration Shifts on Medical Errors, Adverse Events, and Attentional Failures

PubMed Central

Barger, Laura K; Ayas, Najib T; Cade, Brian E; Cronin, John W; Rosner, Bernard; Speizer, Frank E; Czeisler, Charles A

2006-01-01

Background A recent randomized controlled trial in critical-care units revealed that the elimination of extended-duration work shifts (≥24 h) reduces the rates of significant medical errors and polysomnographically recorded attentional failures. This raised the concern that the extended-duration shifts commonly worked by interns may contribute to the risk of medical errors being made, and perhaps to the risk of adverse events more generally. Our current study assessed whether extended-duration shifts worked by interns are associated with significant medical errors, adverse events, and attentional failures in a diverse population of interns across the United States. Methods and Findings We conducted a Web-based survey, across the United States, in which 2,737 residents in their first postgraduate year (interns) completed 17,003 monthly reports. The association between the number of extended-duration shifts worked in the month and the reporting of significant medical errors, preventable adverse events, and attentional failures was assessed using a case-crossover analysis in which each intern acted as his/her own control. Compared to months in which no extended-duration shifts were worked, during months in which between one and four extended-duration shifts and five or more extended-duration shifts were worked, the odds ratios of reporting at least one fatigue-related significant medical error were 3.5 (95% confidence interval [CI], 3.3–3.7) and 7.5 (95% CI, 7.2–7.8), respectively. The respective odds ratios for fatigue-related preventable adverse events, 8.7 (95% CI, 3.4–22) and 7.0 (95% CI, 4.3–11), were also increased. Interns working five or more extended-duration shifts per month reported more attentional failures during lectures, rounds, and clinical activities, including surgery and reported 300% more fatigue-related preventable adverse events resulting in a fatality. Conclusions In our survey, extended-duration work shifts were associated with an increased risk of significant medical errors, adverse events, and attentional failures in interns across the United States. These results have important public policy implications for postgraduate medical education. PMID:17194188

Life adversity in depressed and non-depressed older adults: A cross-sectional comparison of the brief LTE-Q questionnaire and life events and difficulties interview as part of the CASPER study.

PubMed

Donoghue, Hjördis M; Traviss-Turner, Gemma D; House, Allan O; Lewis, Helen; Gilbody, Simon

2016-03-15

There is a paucity of research on the nature of life adversity in depressed and non-depressed older adults. Early life events work used in-depth interviews; however, larger epidemiological trials investigate life adversity using brief questionnaires. This study investigates the type of life adversity experienced in later life and its association with depression and compares adversity captured using a brief (LTE-Q) and in-depth (LEDS) measure. 960 participants over 65 years were recruited in UK primary care to complete the PHQ-9 and LTE-Q. A sub-sample (n=19) completed the LEDS and a question exploring the subjective experience of the LTE-Q and LEDS. Important life adversity was reported on the LTE-Q in 48% of the sample. In the LTE-Q sample the prevalence of depression (PHQ-9≥10) was 12%. Exposure to recent adversity was associated with doubling of the odds of depression. The LTE-Q only captured a proportion of adversity measured by the LEDS (42% vs 84%). Both measures showed health, bereavement and relationship events were most common. The cross-sectional design limits the extent to which inferences can be drawn around the direction of causality between adversity and depression. Recall in older adults is questionable. UK older adults face adversity in areas of health, bereavement and relationships which are associated with depression. This has clinical relevance for psychological interventions for older adults to consider social context and social support. It helps identify the strengths and weaknesses of a brief adversity measure in large scale research. Further research is needed to explore the mechanisms of onset and direction of causality. Copyright © 2016 Elsevier B.V. All rights reserved.

Risks and Benefits Associated With Antibiotic Use for Acute Respiratory Infections: A Cohort Study

PubMed Central

Meropol, Sharon B.; Localio, A. Russell; Metlay, Joshua P.

2013-01-01

PURPOSE Antibiotics are frequently prescribed for acute nonspecific respiratory infections (ARIs), presumably to avoid small risks of progression to serious bacterial illness. However, even low risks of associated adverse drug events could result in many such events at the population level. Our objective was to assess the risks and benefits of antibiotic use in a cohort of patients with ARIs, comparing outcomes of patients who were prescribed antibiotics with outcomes of patients not receiving antibiotics. METHODS We used a June 1986 to August 2006 cohort of adult patients with ARI visits from a UK primary care database. Exposure was an antibiotic prescribed with the visit. Primary outcomes were hospitalization within 15 days for (1) severe adverse drug events (hypersensitivity, diarrhea, seizure, arrhythmia, hepatic or renal failure), and (2) community-acquired pneumonia. RESULTS The cohort included 1,531,019 visits with an ARI diagnosis; prescriptions for antibiotics were given in 65% of cases. The adjusted risk difference for treated vs untreated patients per 100,000 visits was 1.07 fewer adverse events (95% CI, −4.52 to 2.38; P = .54) and 8.16 fewer pneumonia hospitalizations (95% CI, −13.24 to −3.08; P = .002). The number needed to treat to prevent 1 hospitalization for pneumonia was 12,255. CONCLUSIONS Compared with patients with ARI who were not treated with antibiotics, patients who were treated with antibiotics were not at increased risk of severe adverse drug events and had a small decreased risk of pneumonia hospitalization. This small benefit from antibiotics for a common ambulatory diagnosis creates persistent tension; at the societal level, physicians are compelled to reduce antibiotic prescribing, thus minimizing future resistance, whereas at the encounter level, they are compelled to optimize the benefit-risk balance for that patient. PMID:23508604

Risks and benefits associated with antibiotic use for acute respiratory infections: a cohort study.

PubMed

Meropol, Sharon B; Localio, A Russell; Metlay, Joshua P

2013-01-01

Antibiotics are frequently prescribed for acute nonspecific respiratory infections (ARIs), presumably to avoid small risks of progression to serious bacterial illness. However, even low risks of associated adverse drug events could result in many such events at the population level. Our objective was to assess the risks and benefits of antibiotic use in a cohort of patients with ARIs, comparing outcomes of patients who were prescribed antibiotics with outcomes of patients not receiving antibiotics. We used a June 1986 to August 2006 cohort of adult patients with ARI visits from a UK primary care database. Exposure was an antibiotic prescribed with the visit. Primary outcomes were hospitalization within 15 days for (1) severe adverse drug events (hypersensitivity, diarrhea, seizure, arrhythmia, hepatic or renal failure), and (2) community-acquired pneumonia. The cohort included 1,531,019 visits with an ARI diagnosis; prescriptions for antibiotics were given in 65% of cases. The adjusted risk difference for treated vs untreated patients per 100,000 visits was 1.07 fewer adverse events (95% CI, -4.52 to 2.38; P = .54) and 8.16 fewer pneumonia hospitalizations (95% CI, -13.24 to -3.08; P = .002). The number needed to treat to prevent 1 hospitalization for pneumonia was 12,255. Compared with patients with ARI who were not treated with antibiotics, patients who were treated with antibiotics were not at increased risk of severe adverse drug events and had a small decreased risk of pneumonia hospitalization. This small benefit from antibiotics for a common ambulatory diagnosis creates persistent tension; at the societal level, physicians are compelled to reduce antibiotic prescribing, thus minimizing future resistance, whereas at the encounter level, they are compelled to optimize the benefit-risk balance for that patient.

Adverse Events to Food Supplements Containing Red Yeast Rice: Comparative Analysis of FAERS and CAERS Reporting Systems.

PubMed

Raschi, Emanuel; Girardi, Anna; Poluzzi, Elisabetta; Forcesi, Emanuele; Menniti-Ippolito, Francesca; Mazzanti, Gabriela; De Ponti, Fabrizio

2018-03-26

Food supplements containing red yeast rice (RYR) are proposed as an alternative in statin-intolerant patients, although they actually contain natural statin(s) and their safety in clinical practice is still incompletely characterized. We described and compared adverse events (AEs) associated with RYR products submitted to reporting systems maintained by the Food and Drug Administration (FDA), with a focus on liver and muscular events. We extracted RYR-related AEs from the FDA Adverse Event Reporting System (FAERS) [first quarter (Q1)-2004 to Q2-2016], a drug-based archive, and the Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS) (Q1-2004 to Q1-2017). Disproportionality via reporting odds ratio (ROR) with 95% confidence interval (CI) calculation and case-by-case inspection were performed, with a focus on muscular and hepatic AEs. One thousand three hundred AEs were extracted from FAERS (RYR mainly reported as a concomitant agent), whereas only 159 AEs were found in CAERS (RYR recorded mainly as a suspect agent). In FAERS, a large number of reports emerged for "general disorders and administration site conditions," whereas CAERS received also a high number of reports for "investigations" and "musculoskeletal and connective tissue disorders". Disproportionality analyses confirmed higher reporting of serious muscular and liver injuries: in FAERS, five cases of hepatic disorders (ROR = 13.71; 95% CI 5.44-34.57); in CAERS, 27 cases of rhabdomyolysis/myopathy (8.44; 5.44-13.10). Notwithstanding recognized limitations, these findings strengthen the importance of exploring multiple databases in safety assessment of RYR products, which should be monitored by clinicians for muscular and hepatic safety, and call for urgent review by policymakers to harmonize their regulatory status.

A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement

PubMed Central

Macchi, Zachary; Wang, Yunxia; Moore, Dan; Katz, Jonathan; Saperstein, David; Walk, David; Simpson, Ericka; Genge, Angela; Bertorini, Tulio; Fernandes, J Americo; Swenson, Andrea; Elman, Lauren; Dimachkie, Mazen; Herbelin, Laura; Miller, Joann; Lu, Jianghua; Wilkins, Heather; Swerdlow, Russell H; Statland, Jeffrey; Barohn, Richard

2015-01-01

OBJECTIVE Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. METHODS We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2mg oral rasagiline daily for 12 months. Outcomes included the slope of deterioration of the revised ALS Functional Rating Scale (ALSFRS-R), adverse event monitoring, time to treatment failure, and exploratory biomarkers. RESULTS Participants experienced no serious drug-related adverse events, and the most common adverse event was nausea (11.1%). Rasagiline did not improve the rate of decline in the ALSFRS-R; however, differences in symptom duration compared to historical placebo controls differentially affected ALSFRS-R slope estimates. Rasagiline changed biomarkers over 12 months, such that the mitochondrial membrane potential increased (JC-1 red/green fluorescent ratio 1.92, P=0.0001) and apoptosis markers decreased (Bcl-2/Bax ratio 0.24, P<0.0001). CONCLUSION Engagement of exploratory biomarkers and questions about comparability of baseline characteristics lead us to recommend a further placebo-controlled trial. PMID:25832828

The comparative effectiveness of fine-needle aspiration cytology sampling policies: a simulation study.

PubMed

Schmidt, Robert L; Howard, Kirsten; Hall, Brian J; Layfield, Lester J

2012-12-01

Sample adequacy is an important aspect of overall fine-needle aspiration cytology (FNAC) performance. FNAC effectiveness is augmented by an increasing number of needle passes, but increased needle passes are associated with higher costs and greater risk of adverse events. The objective of this study was to compare the impact of several different sampling policies on FNAC effectiveness and adverse event rates using discrete event simulation. We compared 8 different sampling policies in 12 different sampling environments. All sampling policies were effective when the per-pass accuracy is high (>80%). Rapid on-site evaluation (ROSE) improves FNAC effectiveness when the per-pass adequacy rate is low. ROSE is unlikely to be cost-effective in sampling environments in which the per-pass adequacy is high. Alternative ROSE assessors (eg, cytotechnologists) may be a cost-effective alternative to pathologists when the per-pass adequacy rate is moderate (60%-80%) or when the number of needle passes is limited.

Ultrasonographic evaluation of vincristine-induced gastric hypomotility and the prokinetic effect of mosapride in dogs.

PubMed

Tsukamoto, A; Ohno, K; Tsukagoshi, T; Maeda, S; Nakashima, K; Fukushima, K; Fujino, Y; Takeuchi, A; Tsujimoto, H

2011-01-01

Vincristine induces gastrointestinal motility disorders in humans. Adverse gastrointestinal events are commonly observed in dogs receiving vincristine. To evaluate gastric motility after vincristine administration in dogs and the prophylactic effect of a prokinetic agent, mosapride. Five healthy Beagle dogs. Five dogs received vincristine i.v. at a dosage of 0.75 mg/m(2). The motility index (MI) of the antral contraction was ultrasonographically evaluated 30 minutes postfeeding before administration of vincristine and for 6 days after vincristine treatment. After a 6-week washout period, the dogs received vincristine with mosapride (2 mg/kg p.o., q24h for 6 days), and the MI was re-evaluated. Adverse gastrointestinal events were evaluated according to the Veterinary Co-operative Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE). After vincristine administration, a significant decrease (P < .05) in MI was observed on days 3 (6.64 ± 0.30) and 4 (8.02 ± 0.94), compared with pretreatment levels (10.00 ± 0.62). Gastrointestinal adverse events were observed in 4 dogs (grade 2 decreased appetite: 3 dogs; grade 1 vomiting: 2 dogs; and grade 1 diarrhea and grade 2 hematochezia: 1 dog). When mosapride citrate was administered with vincristine and for the next 5 days, no decrease in MI was observed. Furthermore, adverse gastrointestinal events occurred less frequently (grade 1 vomiting and grade 2 hematochezia in 1 dog each). Vincristine (0.75 mg/m(2)) induces gastric hypomotility in dogs. Preventive administration of mosapride citrate (2.0 mg/kg p.o., q24h) improves hypomotility and may decrease the adverse gastrointestinal effects of vincristine. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive study

PubMed Central

Tendal, Britta; Hróbjartsson, Asbjørn; Lundh, Andreas; Gøtzsche, Peter C

2014-01-01

Objective To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports. Design Systematic electronic search for adverse events of suicidality in tables, narratives, and listings of adverse events in individual patients within clinical study reports. Where possible, for each event we extracted the original term reported by the investigator, the term as coded by the medical coding dictionary, medical coding dictionary used, and the patient’s trial identification number. Using the patient’s trial identification number, we attempted to reconcile data on the same event between the different formats for presenting data on adverse events within the clinical study report. Setting 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency for marketing approval. Data sources Clinical study reports obtained from the EMA in 2011. Results Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly identifiable in all formats of adverse event data in clinical study reports. Suicide attempts presented in tables included both definitive and provisional diagnoses. Suicidal ideation and preparatory behaviour were obscured in some tables owing to the lack of specificity of the medical coding dictionary, especially COSTART. Furthermore, we found one event of suicidal ideation described in narrative text that was absent from tables and adverse event listings of individual patients. The reason for this is unclear, but may be due to the coding conventions used. Conclusion Data on adverse events in tables in clinical study reports may not accurately represent the underlying patient data because of the medical dictionaries and coding conventions used. In clinical study reports, the listings of adverse events for individual patients and narratives of adverse events can provide additional information, including original investigator reported adverse event terms, which can enable a more accurate estimate of harms. PMID:24899651

Family perceptions of insulin pump adverse events in children and adolescents.

PubMed

Wheeler, Benjamin J; Donaghue, Kim C; Heels, Kristine; Ambler, Geoffrey R

2014-04-01

Insulin pumps (for continuous subcutaneous insulin infusion [CSII]) are used widely in type 1 diabetes mellitus. Although there has been considerable study of outcomes, there are few recent data on CSII-associated adverse events and no data on family perceptions of adverse events and their confidence in dealing with them. We approached all families of children and adolescents ≤ 19 years of age on CSII attending the diabetes clinic over a 16-week clinic cycle. Participants completed a retrospective questionnaire examining issues over the previous 12 months. Data on pump adverse events as well as answers to questions pertaining to education and confidence were collected. Our survey received a response rate of 99%, with 235 of the 238 families approached participating. In the preceding 12 months, 104 of 230 (45%) had reported at least one pump-related adverse event (either mechanical or set-related), with an associated 52 of 229 (23%) resulting in pump replacement. This equated to a minimum incidence density of 53 adverse events/100 person-years. Additionally, 18 of 230 (8%) reported a hospital admission or emergency department attendance as a consequence. Pump malfunction and infusion set/site failures were the most common events reported, with one or more events in 58 of 104 (56%) and 47 of 104 (45%), respectively. Adverse events, excluding set/site failures, were associated with older age (13.1 ± 3.4 years vs. 11.9 ± 4 years; P = 0.02). This is the first study to look at family perceptions of adverse events while using modern CSII. It highlights a high self-reported rate of CSII-related adverse events, pump replacement, and subsequent presentation to the hospital. Potential areas for additional targeted education are identified. Further prospective study examining pump adverse event characteristics and incidence is warranted.

Patients' Perceptions of Physician-Patient Discussions and Adverse Events with Cancer Therapy.

PubMed

Hershman, Dawn; Calhoun, Elizabeth; Zapert, Kinga; Wade, Shawn; Malin, Jennifer; Barron, Rich

2008-09-01

OBJECTIVES: Patients with cancer who are treated with chemotherapy report adverse events during their treatment, which can affect their quality of life and increase the likelihood that their treatment will not be completed. In this study, patients' perceptions of the physician-patient relationship and communication about cancer-related issues, particularly adverse events were examined. METHODS: We surveyed 508 patients with cancer concerning the occurrence of adverse events and their relationship and communication with their physicians regarding cancer, treatment, and adverse events. RESULTS: Most individuals surveyed (>90%) discussed diagnosis, treatment plan, goals, and schedule, and potential adverse events with their physicians before initiating chemotherapy; approximately 75% of these individuals understood these topics completely or very well. Physician-patient discussions of adverse events were common, with tiredness, nausea and vomiting, and loss of appetite discussed prior to chemotherapy in over 80% of communications. These events were also the most often experienced (ranging in 95% to 64% of the respondents) along with low white blood cell counts (WBCs), which were experienced in 67% of respondents. Approximately 75% of the individuals reported that their overall quality of life was affected by adverse events. CONCLUSIONS: These findings suggest that discussions alone do not provide patients with sufficient understanding of the events, nor do they appear to adequately equip patients to cope with them. Therefore, efforts to improve cancer care should focus on developing tools to improve patients' understanding of the toxicities of chemotherapy, as well as providing resources to reduce the effects of adverse events.

ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION IN THE DIAGNOSIS OF ADRENAL METASTASIS IN A HIGH-RISK POPULATION.

PubMed

Zhang, Catherine D; Erickson, Dana; Levy, Michael J; Gleeson, Ferga C; Salomao, Diva R; Delivanis, Danae A; Bancos, Irina

2017-12-01

While the left adrenal gland is readily accessible via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), data regarding the utility of EUS-FNA in the diagnosis of adrenal lesions remain limited. We aimed to ( 1) describe the clinical context, adverse event rate, and diagnostic performance of EUS-FNA, and ( 2) compare the safety profile and diagnostic accuracy of EUS-FNA with percutaneous adrenal biopsy. Single-center, retrospective cohort study. Medical records of patients who underwent adrenal EUS-FNA from 2005-2016 were reviewed. Biopsy outcomes were evaluated using a predefined reference standard. Results were compared to patients who underwent percutaneous biopsy (n = 419; 1994-2014) at the same institution. A total of 121 patients underwent EUS-FNA of 122 adrenal lesions (left [n = 121]; right [n = 1]; mean lesion size, 1.8 cm). Cytology was positive for malignancy in 35 (29%), suspicious for malignancy in 1 (1%), atypical in 1 (1%), negative for malignancy in 81 (66%), and nondiagnostic in 4 (3%). No adverse events were reported. EUS-FNA diagnosed metastasis with a sensitivity of 100%, specificity of 97.4%, positive predictive value of 91.7%, and negative predictive value of 100%. When compared to percutaneous biopsy, lesion size (1.8 cm vs. 3.7 cm; P<.001) and biopsy site (99% vs. 62% left adrenal; P<.001) were significantly different. EUS-FNA adverse event rate was lower than percutaneous biopsy (0% vs. 4%; P = .024), but nondiagnostic rates were similar (3.3% vs. 4.8%; P = .48). EUS-FNA is a sensitive technique to sample adrenal lesions in patients at high risk for adrenal metastasis with fewer adverse events compared to percutaneous biopsy. CI = confidence interval CT = computed tomography EUS-FNA = endoscopic ultrasound-guided fine-needle aspiration NPV = negative predictive value PPV = positive predictive value TUS = transabdominal ultra-sound.

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials

PubMed Central

Kahn, S. E.; Jones, N. P.; Noronha, D.; Beck-Nielsen, H.; Viberti, G.

2010-01-01

Aims/hypothesis Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone. Methods Neoplasm occurrences were collected as adverse events in these studies. We reviewed and re-analysed the individual participant data in both studies for serious adverse events, malignancies reported as adverse events and related neoplasms of special interest. Results In ADOPT, 50 participants (3.4%) on metformin and 55 (3.8%) on each of rosiglitazone and glibenclamide (known as glyburide in the USA and Canada) developed serious adverse event malignancies (excluding non-melanoma skin cancers). This corresponds to 1.03, 1.12 and 1.31 per 100 person-years, giving hazard ratios for metformin of 0.92 (95% CI 0.63–1.35) vs rosiglitazone and 0.78 (0.53–1.14) vs glibenclamide. In RECORD, on a background of sulfonylurea, 69 (6.1%) participants developed malignant neoplasms in the metformin group, compared with 56 (5.1%) in the rosiglitazone group (HR 1.22 [0.86–1.74]). On a background of metformin, 74 (6.7%) participants in the sulfonylurea group developed malignant neoplasms, compared with 57 (5.1%) in the rosiglitazone group (HR 1.33 [0.94–1.88]). Conclusions/interpretation The malignancy rates in these two randomised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone. However, they do not refute the possibility of a difference compared with sulfonylureas. PMID:20532476

Experience of malignancies with oral glucose-lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials.

PubMed

Home, P D; Kahn, S E; Jones, N P; Noronha, D; Beck-Nielsen, H; Viberti, G

2010-09-01

Observational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes. We extracted data for malignancies from the ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) randomised controlled clinical trials, in which the efficacy and/or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone. Neoplasm occurrences were collected as adverse events in these studies. We reviewed and re-analysed the individual participant data in both studies for serious adverse events, malignancies reported as adverse events and related neoplasms of special interest. In ADOPT, 50 participants (3.4%) on metformin and 55 (3.8%) on each of rosiglitazone and glibenclamide (known as glyburide in the USA and Canada) developed serious adverse event malignancies (excluding non-melanoma skin cancers). This corresponds to 1.03, 1.12 and 1.31 per 100 person-years, giving hazard ratios for metformin of 0.92 (95% CI 0.63-1.35) vs rosiglitazone and 0.78 (0.53-1.14) vs glibenclamide. In RECORD, on a background of sulfonylurea, 69 (6.1%) participants developed malignant neoplasms in the metformin group, compared with 56 (5.1%) in the rosiglitazone group (HR 1.22 [0.86-1.74]). On a background of metformin, 74 (6.7%) participants in the sulfonylurea group developed malignant neoplasms, compared with 57 (5.1%) in the rosiglitazone group (HR 1.33 [0.94-1.88]). The malignancy rates in these two randomised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone. However, they do not refute the possibility of a difference compared with sulfonylureas.

A Propensity Score Matched Comparison of Clinical Outcomes in Atrial Fibrillation Patients Taking Vitamin K Antagonists: Comparing the "Real-World" vs Clinical Trials.

PubMed

Rivera-Caravaca, José Miguel; Esteve-Pastor, María Asunción; Marín, Francisco; Valdés, Mariano; Vicente, Vicente; Roldán, Vanessa; Lip, Gregory Y H

2018-05-02

To investigate the incidence and risk of adverse clinical outcomes in a "real- world" cohort of patients with atrial fibrillation (AF) anticoagulated with vitamin K antagonists (VKAs) from the Murcia AF Project in comparison with the warfarin arm of the randomized clinical trial (RCT) AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation). We included 1361 patients with AF from the Murcia AF Project (recruitment from May 1, 2007, to December 1, 2007) and 2293 from the AMADEUS trial (started in September 2003 and primary completed in March 2006), all taking VKA treatment. After propensity score matching (PSM), we investigated differences in rates and risks of several events, including major bleeding, ischemic stroke, and all-cause mortality at 365 (interquartile range, 275-428) days of follow-up. After PSM there were 1324 patients for the comparative analysis, whereby annual event rates for most adverse events were significantly higher in the "real-world" population. Cox regression analyses demonstrated that the risk of primary outcomes was also increased in the "real-world" (vs RCT: hazard ratio [HR], 6.32; 95% CI, 2.84-14.03 for major bleeding; HR, 3.56, 95% CI, 1.22-10.42 for ischemic stroke; HR, 5.13, 95% CI, 3.02-8.69 for all-cause mortality). The risk of all other adverse events was higher in the real-world cohort, except for cardiovascular mortality. This study comparing the Murcia AF Project and the AMADEUS trial demonstrates that there is a great heterogeneity in both populations, which is translated into a higher risk of several adverse outcomes in the real-world cohort, including major bleeding, ischemic stroke, and mortality. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Can Natural Language Processing Improve the Efficiency of Vaccine Adverse Event Report Review?

PubMed

Baer, B; Nguyen, M; Woo, E J; Winiecki, S; Scott, J; Martin, D; Botsis, T; Ball, R

2016-01-01

Individual case review of spontaneous adverse event (AE) reports remains a cornerstone of medical product safety surveillance for industry and regulators. Previously we developed the Vaccine Adverse Event Text Miner (VaeTM) to offer automated information extraction and potentially accelerate the evaluation of large volumes of unstructured data and facilitate signal detection. To assess how the information extraction performed by VaeTM impacts the accuracy of a medical expert's review of the vaccine adverse event report. The "outcome of interest" (diagnosis, cause of death, second level diagnosis), "onset time," and "alternative explanations" (drug, medical and family history) for the adverse event were extracted from 1000 reports from the Vaccine Adverse Event Reporting System (VAERS) using the VaeTM system. We compared the human interpretation, by medical experts, of the VaeTM extracted data with their interpretation of the traditional full text reports for these three variables. Two experienced clinicians alternately reviewed text miner output and full text. A third clinician scored the match rate using a predefined algorithm; the proportion of matches and 95% confidence intervals (CI) were calculated. Review time per report was analyzed. Proportion of matches between the interpretation of the VaeTM extracted data, compared to the interpretation of the full text: 93% for outcome of interest (95% CI: 91-94%) and 78% for alternative explanation (95% CI: 75-81%). Extracted data on the time to onset was used in 14% of cases and was a match in 54% (95% CI: 46-63%) of those cases. When supported by structured time data from reports, the match for time to onset was 79% (95% CI: 76-81%). The extracted text averaged 136 (74%) fewer words, resulting in a mean reduction in review time of 50 (58%) seconds per report. Despite a 74% reduction in words, the clinical conclusion from VaeTM extracted data agreed with the full text in 93% and 78% of reports for the outcome of interest and alternative explanation, respectively. The limited amount of extracted time interval data indicates the need for further development of this feature. VaeTM may improve review efficiency, but further study is needed to determine if this level of agreement is sufficient for routine use.

Corneal transplantation: study of the data of a regional eye bank for the year 2013 and analysis of the evolution of the adverse events reported in France since 2010.

PubMed

Gauthier, Anne-Sophie; Castelbou, Marie; Garnier, Mélanie Bidaut; Pizzuto, Joëlle; Roux, Stephan; Gain, Philippe; Pouthier, Fabienne; Delbosc, Bernard

2017-03-01

To analyze the data of the adverse events collected in a single major eye bank (EFS Bourgogne Franche Comté, Besançon, France) for the year 2013 and to report the French data of biovigilance provided by the French National Agency for Medicines and Health Products Safety (ANSM) between 2010 and 2013. we have set up a study of adverse events in 2013, in collaboration with a single eye bank (EFS Bourgogne Franche Comté, Besançon, France). A survey was sent to the surgeon for each delivered corneal button by the eye bank in 2013. They were asked for each grafted patient performed in their center, the type of graft (penetrating keratoplasty, anterior keratoplasty or endothelial keratoplasty), the occurrence of adverse events (primary failure, infectious keratis, endophthalmitis, immune rejection, and other events) and the time interval between surgery and events (Less than 1 postoperative month, between 1 month and 1 year postoperatively, >1 year postoperatively). In 2013, 407 corneal buttons were delivered by the eye bank of Besançon in 21 medical centers which performed corneal grafts and we sent 407 surveys. We received 243 completed questionnaires (59.75%) from 11 centers (52.38%). The global reported rate of adverse events was 27.54% of the graft (n = 65/236 corneal grafts performed in 11 centers in 2013; 20% of Primary graft failure, 11% of infectious keratitis, 1% of endophthalmitis, 34% of rejection, 34% of other incidents). 30.16% of complications were noticed before the first month after surgery versus 52.38% of complications noticed between the first month and the first year after surgery and 17.46% of complications noticed after the post-operative first year The most common causes of adverse events after PK were Immune rejection (13.17%), surgical causes (5.98%) and infection (4.79%) and after EK were Primary graft failure (8.2%) and surgical causes (19.67%). In 2013, in France 0.83% of adverse events were notified in ANSM. For the 236 performed graft issued from a major eye bank (EFS Besançon) in 2013 the global reported rate of post-graft adverse events was 27.54% of the grafts (20% of Primary graft failure, 11% of infectious keratitis, 1% of endophthalmitis, 34% of rejection and 34% of other incidents). Compared to the ANSM data (0.83% of adverse events reported in 2013) this rate is high. This difference can be explained by the low rate of annual notification to the ANSM and shows that biovigilance in France must be more developed. Since biovigilance needs constant improvement for the safety of the graft system, training, information for practitioners, simplifications of procedures and international standardization of the definition are the main points that could be improved.

[Analysis of Kudiezi injection's security literature].

PubMed

Chang, Yan-Peng; Xie, Yan-Ming

2012-09-01

By retrieving the relevant database, aim was to achieve the security reported of Kudiezi injection (Yueanxin). To analysis the gender, age, underlying disease, medication dosage, solvent, adverse event/adverse reaction time of occurrence, clinical presentation of patients, It was found the adverse event/adverse reaction usually occur in older people, involving the organs and systems include skin and its appendages, digestive system, nervous system, circulatory system, respiratory system, systemic reaction, part of the adverse event/adverse reaction's cause were not according to the instructions. It was found on the adverse event/adverse reaction of the judgment on the lack of objective evidence, to produce certain effect for objective evaluation of security of Kudiezi injection (Yueanxin).

Treatment for Adolescents with Depression Study (TADS): Safety Results

ERIC Educational Resources Information Center

Emslie, Graham; Kratochvil, Christopher; Vitiello, Benedetto; Silva, Susan; Mayes, Taryn; McNulty, Steven; Weller, Elizabeth; Waslick, Bruce; Casat, Charles; Walkup, John; Pathak, Sanjeev; Rohde, Paul; Posner, Kelly; March, John

2006-01-01

Objective: To compare the rates of physical, psychiatric, and suicide-related events in adolescents with MDD treated with fluoxetine alone (FLX), cognitive-behavioral therapy (CBT), combination treatment (COMB), or placebo (PBO). Method: Safety assessments included adverse events (AEs) collected by spontaneous report, as well as systematic…

A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States.

PubMed

Spivey, Christina A; Griffith, Jenny; Kaplan, Cameron; Postlethwaite, Arnold; Ganguli, Arijit; Wang, Junling

2018-06-01

Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as < or ≥ 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5 and high as ≥ 7.5 mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P < 0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. AbbVie Inc.

Analysis of economic and social costs of adverse events associated with blood transfusions in Spain.

PubMed

Ribed-Sánchez, Borja; González-Gaya, Cristina; Varea-Díaz, Sara; Corbacho-Fabregat, Carlos; Bule-Farto, Isabel; Pérez de-Oteyza, Jaime

To calculate, for the first time, the direct and social costs of transfusion-related adverse events in order to include them in the National Healthcare System's budget, calculation and studies. In Spain more than 1,500 patients yearly are diagnosed with such adverse events. Blood transfusion-related adverse events recorded yearly in Spanish haemovigilance reports were studied retrospectively (2010-2015). The adverse events were coded according to the classification of Diagnosis-Related Groups. The direct healthcare costs were obtained from public information sources. The productivity loss (social cost) associated with adverse events was calculated using the human capital and hedonic salary methodologies. In 2015, 1,588 patients had adverse events that resulted in direct health care costs (4,568,914€) and social costs due to hospitalization (200,724€). Three adverse reactions resulted in patient death (at a social cost of 1,364,805€). In total, the cost of blood transfusion-related adverse events was 6,134,443€ in Spain. For the period 2010-2015: the trends show a reduction in the total amount of transfusions (2 vs. 1.91M€; -4.4%). The number of adverse events increased (822 vs. 1,588; +93%), as well as their related direct healthcare cost (3.22 vs. 4.57M€; +42%) and the social cost of hospitalization (110 vs 200M€; +83%). Mortality costs decreased (2.65 vs. 1.36M€; -48%). This is the first time that the costs of post-transfusion adverse events have been calculated in Spain. These new figures and trends should be taken into consideration in any cost-effectiveness study or trial of new surgical techniques or sanitary policies that influence blood transfusion activities. Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Drug formulary review process for sargramostim and filgrastim: focus on analysis of adverse drug reactions.

PubMed

Kellihan, M J

1993-01-01

Selection of a drug for formulary inclusion involves evaluation of safety, efficacy, and cost. The colony-stimulating factors (CSFs) sargramostim and filgrastim have a broad range of potential indications and represent a costly formulary addition when acquisition price alone is considered; their comparative safety is unclear. These factors suggest that the CSFs should be closely scrutinized prior to formulary addition. In the absence of direct comparative studies, an assessment of the safety of CSFs involves evaluation of information provided in the product circular, official drug compendia, adverse biologic reports submitted to the United States Food and Drug Administration, and data from key clinical trials. Data in the product circulars report on adverse events in small numbers of patients treated for chemotherapy-induced neutropenia (filgrastim) or neutropenia subsequent to bone marrow transplantation (sargramostim). The official compendia and clinical trials include experience with CSFs produced in a variety of expression systems; these data are not limited to sargramostim and filgrastim. Importantly, there was a similar incidence of adverse events in patients who received sargramostim or filgrastim and in those who took placebo reported in the product circulars and the pivotal trials, suggesting that the underlying disease may have an important role in determining the side-effect profile of these agents. Adverse biologic reports represent experience with sargramostim and filgrastim obtained under actual clinical conditions and suggest that the same types of adverse events are seen with sargramostim as with filgrastim. This analysis suggests that a decision to select filgrastim over sargramostim for formulary inclusion based on the safety profile is not appropriate because currently available data are equivocal and that such decisions would more appropriately be based on efficacy and cost.

Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

PubMed Central

Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

2016-01-01

Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

Does increasing the size of bi-weekly samples of records influence results when using the Global Trigger Tool? An observational study of retrospective record reviews of two different sample sizes.

PubMed

Mevik, Kjersti; Griffin, Frances A; Hansen, Tonje E; Deilkås, Ellen T; Vonen, Barthold

2016-04-25

To investigate the impact of increasing sample of records reviewed bi-weekly with the Global Trigger Tool method to identify adverse events in hospitalised patients. Retrospective observational study. A Norwegian 524-bed general hospital trust. 1920 medical records selected from 1 January to 31 December 2010. Rate, type and severity of adverse events identified in two different samples sizes of records selected as 10 and 70 records, bi-weekly. In the large sample, 1.45 (95% CI 1.07 to 1.97) times more adverse events per 1000 patient days (39.3 adverse events/1000 patient days) were identified than in the small sample (27.2 adverse events/1000 patient days). Hospital-acquired infections were the most common category of adverse events in both the samples, and the distributions of the other categories of adverse events did not differ significantly between the samples. The distribution of severity level of adverse events did not differ between the samples. The findings suggest that while the distribution of categories and severity are not dependent on the sample size, the rate of adverse events is. Further studies are needed to conclude if the optimal sample size may need to be adjusted based on the hospital size in order to detect a more accurate rate of adverse events. 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/

The impact of obesity on pediatric procedural sedation-related outcomes: results from the Pediatric Sedation Research Consortium.

PubMed

Scherrer, Patricia D; Mallory, Michael D; Cravero, Joseph P; Lowrie, Lia; Hertzog, James H; Berkenbosch, John W

2015-07-01

To evaluate the impact of obesity on adverse events and required interventions during pediatric procedural sedation. The Pediatric Sedation Research Consortium database of prospectively collected procedural sedation encounters was queried to identify patients for whom body mass index (BMI) could be calculated. Obesity was defined as BMI ≥95th percentile for age and gender. Sedation-related outcomes, adverse events, and therapeutic interventions were compared between obese and nonobese patients. For analysis, 28,792 records were eligible. A total of 5,153 patients (17.9%) were obese; they were predominantly male and older and had a higher median American Society of Anesthesiologists Physical Status classification (P < 0.001). Total adverse events were more common in obese patients (odds ratio [OR] 1.49, 95% confidence interval [1.31, 1.70]). Respiratory events (airway obstruction OR 1.94 [1.54, 2.44], oxygen desaturation OR 1.99 [1.50, 2.63], secretions OR 1.48 [1.01, 2.15], laryngospasm OR 2.30 [1.30, 4.05]), inability to complete the associated procedure (OR 1.96 [1.16, 3.30]), and prolonged recovery (OR 2.66 [1.26, 5.59]) were increased in obese patients. Obese patients more frequently required airway intervention including repositioning, suctioning, jaw thrust, airway adjuncts, and bag-valve-mask ventilation. Multivariate regression analysis demonstrated obesity to be independently associated with minor and moderate but not major adverse events. Obesity is an independent risk factor for adverse respiratory events during procedural sedation and is associated with an increased frequency of airway interventions, suggesting that additional vigilance and expertise are required when sedating these patients. © 2015 John Wiley & Sons Ltd.

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.

PubMed

Sparks, Jeffrey A; Barbhaiya, Medha; Karlson, Elizabeth W; Ritter, Susan Y; Raychaudhuri, Soumya; Corrigan, Cassandra C; Lu, Fengxin; Selhub, Jacob; Chasman, Daniel I; Paynter, Nina P; Ridker, Paul M; Solomon, Daniel H

2017-08-01

The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. CIRT will randomize up to 7000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose: 15-20mg/week) or placebo for an average follow-up period of 3-5 years; subjects in both treatment arms receive folic acid 1mg daily for 6 days each week. The primary endpoints of CIRT include recurrent cardio vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Gastrointestinal and hematologic adverse events after administration of vincristine, cyclophosphamide, and doxorubicin in dogs with lymphoma that underwent a combination multidrug chemotherapy protocol.

PubMed

Tomiyasu, Hirotaka; Takahashi, Masashi; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

2010-11-01

The present study aimed to objectively evaluate the adverse events after the administration of chemotherapeutic agents used in the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25) for canine lymphoma, using the Veterinary Co-operative Oncology Group common terminology criteria for adverse events (VCOG-CTCAE). The medical records of 40 dogs with multicentric high-grade lymphoma that underwent UW-25 were reviewed. Gastrointestinal adverse events of grade 2 and above and blood/bone marrow adverse events of all grades were evaluated. Gastrointestinal adverse events occurring at least once during the entire period of UW-25 were observed in 50% (20/40), 17.9% (7/39), and 8.1% (3/37) of the dogs after the administration of vincristine (VCR), cyclophosphamide (CPA), and doxorubicin (DXR), respectively. Blood/bone marrow adverse events occurring at least once during UW-25 were observed in 57.5% (23/40), 41% (16/39), and 8.1% (3/37) of the dogs after the administration of VCR, CPA, and DXR, respectively. The rate of patients that experienced gastrointestinal adverse events was higher after the first administration of VCR than after the first administration of DXR. Findings obtained in this study will be helpful in predicting the adverse events that could occur when dogs with lymphoma are treated with UW-25.

The incidence and cost of cardiac surgery adverse events in Australian (Victorian) hospitals 2003-2004.

PubMed

Ehsani, Jonathon Pouya; Duckett, Stephen J; Jackson, Terri

2007-12-01

The aim of this study was to estimate the incidence of adverse events in acute surgical admissions for cardiac disease in admitted episodes in the year 2003-2004 and to estimate the cost of these complications to the Victorian health system. Cardiac surgery adverse events are among the most frequent and significant contributors to the morbidity, mortality and cost associated with hospitalisation. Patient-level costing data set for major Victorian public hospitals in 2003-2004 was analysed for adverse events using C-prefixed markers, denoting complications that arose during the course of hospital treatment for cardiac surgery diagnosis related groups (DRGs). The cost of adverse events was estimated by linear regression modelling, adjusted for age and co-morbidity. A total of 16,766 multi-day cardiac disease cases were identified, of whom 6,181 (36.85%) had at least one adverse event. Patients with adverse events stayed approximately 7 days longer and had four times the case fatality rate than those without. After adjustment for age and co-morbidity, the presence of an adverse event adds AUS$5,751. The sum of the total cost of adverse events for each DRG was AUS$42.855 million, representing 21.6% of total expenditure on cardiac surgery and adding 27.5% in broad terms to the cardiac surgery budget.

Consumer perceptions of safety in hospitals.

PubMed

Evans, Sue M; Berry, Jesia G; Smith, Brian J; Esterman, Adrian J

2006-02-22

Studies investigating adverse events have traditionally been principally undertaken from a medical perspective. The impact that experience of an adverse event has on consumer confidence in health care is largely unknown. The objectives of the study were to seek public opinion on 1) the rate and severity of adverse events experienced in hospitals; and 2) the perception of safety in hospitals, so that predictors of lack of safety could be identified. A multistage, clustered survey of persons residing in South Australia (2001), using household interviews (weighted n = 2,884). A total of 67% of respondents aged over forty years reported having at least one member of their household hospitalised in the past five years; with the average being two hospital admissions in five years. Respondents stated that 7.0% (95%CI: 6.2% to 7.9%) of those hospital admissions were associated with an adverse event; 59.7% of respondents (95% CI: 51.4% to 67.5%) rated the adverse event as really serious and 48.5% (95% CI: 40.4% to 56.8%) stated prolonged hospitalisation was required as a consequence of the adverse event. Perception of safety in hospitals was largely affected by the experience of an adverse event; really serious events were the most significant predictor of lack of safety in those aged 40 years and over (RR 2.38; p<0.001). The experience of adverse events negatively impacted on public confidence in hospitals. The consumer-reported adverse event rate in hospitals (7.0%) is similar to that identified using medical record review. Based on estimates from other studies, self-reported claims of adverse events in hospital by consumers appear credible, and should be considered when developing appropriate treatment regimes.

Consumer perceptions of safety in hospitals

PubMed Central

Evans, Sue M; Berry, Jesia G; Smith, Brian J; Esterman, Adrian J

2006-01-01

Background Studies investigating adverse events have traditionally been principally undertaken from a medical perspective. The impact that experience of an adverse event has on consumer confidence in health care is largely unknown. The objectives of the study were to seek public opinion on 1) the rate and severity of adverse events experienced in hospitals; and 2) the perception of safety in hospitals, so that predictors of lack of safety could be identified. Methods A multistage, clustered survey of persons residing in South Australia (2001), using household interviews (weighted n = 2,884). Results A total of 67% of respondents aged over forty years reported having at least one member of their household hospitalised in the past five years; with the average being two hospital admissions in five years. Respondents stated that 7.0% (95%CI: 6.2% to 7.9%) of those hospital admissions were associated with an adverse event; 59.7% of respondents (95% CI: 51.4% to 67.5%) rated the adverse event as really serious and 48.5% (95% CI: 40.4% to 56.8%) stated prolonged hospitalisation was required as a consequence of the adverse event. Perception of safety in hospitals was largely affected by the experience of an adverse event; really serious events were the most significant predictor of lack of safety in those aged 40 years and over (RR 2.38; p<0.001). Conclusion The experience of adverse events negatively impacted on public confidence in hospitals. The consumer-reported adverse event rate in hospitals (7.0%) is similar to that identified using medical record review. Based on estimates from other studies, self-reported claims of adverse events in hospital by consumers appear credible, and should be considered when developing appropriate treatment regimes. PMID:16504067

Towards Standardized Stem Cell Therapy in Type 2 Diabetes Mellitus: A Systematic Review.

PubMed

Pawitan, Jeanne Adiwinata; Yang, Zheng; Wu, Ying Nan; Leed, Eng Hin

2018-05-02

To compile and analyze the published studies on cell therapy for type 2 diabetes mellitus (T2DM) to obtain a better insight into management of T2DM that involved stem cell therapy. We searched all published studies in Pubmed/Medline, and Cochrane library, using keywords: 'stem cell' AND 'therapy' AND 'diabetes type 2'. original articles on the use of stem cells in humans with T2DM. articles in the non-English literature, studies on T2DM complications that did not assess both adverse events and any of the common diabetes study outcomes. type of study, number of cases, and all data that were related to outcome and adverse events. Data were analyzed descriptively to conclude the possible cause of adverse reactions, and which protocols gave a satisfactory outcome. We collected 26 original articles, out of which 17 studies did not have controls and were classified as case reports, while there were 8 studies that were controlled clinical trials. Most studies used autologous bone marrow mononuclear cells (BM-MNCs) or autologous or allogeneic mesenchymal stem cells (MSCs) from various sources. Adverse events were mild and mostly intervention related. Efficacy of autologous BM-MNCs that were given via interventional route was comparable to Wharton jelly or umbilical cord MSCs that were given via intravenous (IV), Intra muscular (IM), or subcutaneous (SC) route. Further controlled studies that compare BM-MNCs to BM-MSCs or WJ-MSCs or UCSCs are recommended to prove their comparable efficacy. In addition, studies that compare various routes of administration (IV, IM or SC) versus the more invasive interventional routes are needed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Vaccine adverse event text mining system for extracting features from vaccine safety reports.

PubMed

Botsis, Taxiarchis; Buttolph, Thomas; Nguyen, Michael D; Winiecki, Scott; Woo, Emily Jane; Ball, Robert

2012-01-01

To develop and evaluate a text mining system for extracting key clinical features from vaccine adverse event reporting system (VAERS) narratives to aid in the automated review of adverse event reports. Based upon clinical significance to VAERS reviewing physicians, we defined the primary (diagnosis and cause of death) and secondary features (eg, symptoms) for extraction. We built a novel vaccine adverse event text mining (VaeTM) system based on a semantic text mining strategy. The performance of VaeTM was evaluated using a total of 300 VAERS reports in three sequential evaluations of 100 reports each. Moreover, we evaluated the VaeTM contribution to case classification; an information retrieval-based approach was used for the identification of anaphylaxis cases in a set of reports and was compared with two other methods: a dedicated text classifier and an online tool. The performance metrics of VaeTM were text mining metrics: recall, precision and F-measure. We also conducted a qualitative difference analysis and calculated sensitivity and specificity for classification of anaphylaxis cases based on the above three approaches. VaeTM performed best in extracting diagnosis, second level diagnosis, drug, vaccine, and lot number features (lenient F-measure in the third evaluation: 0.897, 0.817, 0.858, 0.874, and 0.914, respectively). In terms of case classification, high sensitivity was achieved (83.1%); this was equal and better compared to the text classifier (83.1%) and the online tool (40.7%), respectively. Our VaeTM implementation of a semantic text mining strategy shows promise in providing accurate and efficient extraction of key features from VAERS narratives.

OK432 versus doxycycline for treatment of macrocystic lymphatic malformations.

PubMed

Motz, Kevin M; Nickley, Katherine B; Bedwell, Joshua R; Yadav, Bhupender; Guzzetta, Philip C; Oh, Albert K; Bauman, Nancy M

2014-02-01

A variety of sclerotherapy agents are used to treat macrocystic lymphatic malformations (LMs). This retrospective study at a single institution was performed to compare the outcomes of pediatric macrocystic LMs of the head and neck that were treated with doxycycline or with OK432. The outcomes measured included early response to therapy, number of treatments required, operating room time, and adverse events. The rates of clinical success for OK432 and doxycycline were similar (83% and 82%, respectively; p > 0.05), although OK432-treated patients required more treatments than did doxycycline-treated patients (1.9 versus 1.0 injections; p = 0.01; 95% confidence interval, 1.57 to 0.27). The average operating room time for a single OK432 injection was significantly shorter than that for doxycycline (53.2 versus 98.1 minutes; p < 0.001); however, when the total number of treatments administered was considered, the overall times in the operating room were similar. Adverse events in the early postoperative period were more common in OK432-treated patients, who experienced marked postoperative swelling compared to doxycycline-treated patients. OK432 and doxycycline are both effective sclerosants for the treatment of predominantly macrocystic LMs. The administration time for OK432 is shorter than that for doxycycline, but OK432 required more treatments overall to achieve clinical success. Early adverse events were more common in OK432-treated patients, but longer follow-up is necessary to determine whether rates of recurrence and adverse events are similar, particularly in light of the risk of tooth discoloration in doxycycline-treated patients.

Recent life events and psychosis: The role of childhood adversities.

PubMed

Mansueto, Giovanni; Faravelli, Carlo

2017-10-01

Life events are commonly reported to be related to psychosis. However, less attention has been given to the role that recent events play on psychosis, in relation to exposure to childhood adversity. The current study aimed to evaluate the relationship between recent events and psychosis, taking into account the role of early adversities. 78 psychotic patients and 156 controls were enrolled. Childhood adversity was evaluated using a validated semi-structured interview and the Childhood Experience of Care and Abuse Questionnaire. Recent events were recorded using a semi-structured interview with a normative and contextual approach. The diagnosis of psychosis was made according to Jablenski's criteria. Chi-square, t-test, odds ratio, and binary logistic regression statistical analyses were performed. Psychotic patients reported an excess of recent events. The occurrence of more than one recent event increased the risk of psychosis; there was a cumulative effect between recent and childhood events on psychosis. Recent events were significantly related to psychosis, even in the absence of childhood adversity or when adjusted for it. Our findings suggested that the effect of recent events on psychosis may be amplified by previous exposure to early adversity. Recent events alone, could be also linked to psychosis independently of childhood adversity. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of Statin-Associated Myopathy Case Reports in Thailand Using the Health Product Vigilance Center Database.

PubMed

Boonmuang, Pornwalai; Nathisuwan, Surakit; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Pokhagul, Pattreya; Teerawattanapong, Nattawat; Supsongserm, Pairin

2013-09-01

HMG-CoA reductase inhibitors [statins], a widely prescribed cholesterol-lowering therapy, are associated with muscle-related adverse events. While characteristics of such events are well documented in Western countries, little data exists for the Thai population. The aim of this study was to determine the characteristics of patients, type and dosing of statin, and to identify patterns of drug use that may be associated with such adverse events using the national pharmacovigilance database known as Thai Vigibase. Muscle-related adverse events involving statins in the Thai Vigibase from 1996 to December 2009 were identified. For each report, the following information was extracted: patient demographics, co-morbidities, detailed information of adverse event, detailed information of suspected drug, treatment and outcome, as well as causality assessment and quality of reports. Descriptive statistics were performed for all study variables. A total of 198 cases of statin-associated muscle-related adverse events were identified. Mean age was 61.4 ± 12.4 years of age and 59.6% were female. Simvastatin, atorvastatin, rosuvastatin and cerivastatin were implicated as the suspected drug in 163 (82.3%), 24 (12.1%), 10 (5.1%) and 1 (0.5%) cases, respectively. Rhabdomyolysis accounted for 55.6% of all muscle-related adverse events. Drug interactions known to enhance such toxicity of statins were identified in 40.9% of the total set of reports. Similar to studies from Western countries, fibrates, HIV protease inhibitors, non-dihydropyridine calcium channel blockers, azole antifungals and macrolides were commonly found in such cases. Interestingly, colchicine has been identified as the second most common drug interaction in our database. Case fatality rates were 0.9, 1.6 and 16.7%, when there were 0, 1 and ≥2 interacting drugs, respectively. Characteristics of muscle-related adverse events with statins in the Thai population showed some similarities and differences compared with Western countries. Such similarities included advanced age, female sex, certain co-morbidities and drug interactions. While the majority of interacting drugs are well known, a big proportion of cases of statin-colchicine interaction attributed to long-term use of colchicine in Thailand was noted and should be further investigated. Based on these results, an attempt to avoid dangerous and well-known drug interactions among statin users should be implemented nationwide.

Confidential Clinician-reported Surveillance of Adverse Events Among Medical Inpatients

PubMed Central

Weingart, Saul N; Ship, Amy N; Aronson, Mark D

2000-01-01

BACKGROUND Although iatrogenic injury poses a significant risk to hospitalized patients, detection of adverse events (AEs) is costly and difficult. METHODS The authors developed a confidential reporting method for detecting AEs on a medicine unit of a teaching hospital. Adverse events were defined as patient injuries. Potential adverse events (PAEs) represented errors that could have, but did not result in harm. Investigators interviewed house officers during morning rounds and by e-mail, asking them to identify obstacles to high quality care and iatrogenic injuries. They compared house officer reports with hospital incident reports and patients' medical records. A multivariate regression model identified correlates of reporting. RESULTS One hundred ten events occurred, affecting 84 patients. Queries by e-mail (incidence rate ratio [IRR ]=0.16; 95% confidence interval [95% CI], 0.05 to 0.49) and on days when house officers rotated to a new service (IRR =0.12; 95% CI, 0.02 to 0.91) resulted in fewer reports. The most commonly reported process of care problems were inadequate evaluation of the patient (16.4%), failure to monitor or follow up (12.7%), and failure of the laboratory to perform a test (12.7%). Respondents identified 29 (26.4%) AEs, 52 (47.3%) PAEs, and 29 (26.4%) other house officer-identified quality problems. An AE occurred in 2.6% of admissions. The hospital incident reporting system detected only one house officer-reported event. Chart review corroborated 72.9% of events. CONCLUSIONS House officers detect many AEs among inpatients. Confidential peer interviews of front-line providers is a promising method for identifying medical errors and substandard quality. PMID:10940133

[Adverse events in patients from a pediatric hospital.

PubMed

Ornelas-Aguirre, José Manuel; Arriaga-Dávila, José de Jesús; Domínguez-Serrano, María Isabel; Guzmán-Bihouet, Beatriz Filomena; Navarrete-Navarro, Susana

2013-01-01

Background: detection of adverse events is part of the safety management in hospitalized patients. The objective of this study was to describe the incidence of adverse events that occurred in a pediatric hospital. Methods: cross-sectional study of the adverse events occurred in a pediatric hospital from 2007 to 2009. Factors associated with their developmental causes were identified. The statistical analysis was descriptive and bivariate, with contingency tables to estimate the relationship between those factors. A p value = 0.05 was considered significant. Results: a total of 177 adverse events were registered. When they began, human factor occurred in 23 cases (13 %, OR = 1.41, p = 0.001), organizational factor was present in 71 cases (40 %, OR = 1.91, p = 0.236) and technical factor in 46 cases (26 %, OR = 0.87, p = 0.01). Blows or bruises from falls as a result of adverse events occurred in 71 cases (40 %, 95 % CI = 64-78). Conclusions: we found 1.84 events per 100 hospital discharges during the study period. The fall of patients ranked first of the adverse events identified.

Endotracheal Intubation in Neonates: A Prospective Study of Adverse Safety Events in 162 Infants

PubMed Central

Hatch, L. Dupree; Grubb, Peter H.; Lea, Amanda S.; Walsh, William F.; Markham, Melinda H.; Whitney, Gina M.; Slaughter, James C.; Stark, Ann R.; Ely, E. Wesley

2015-01-01

Objective To determine the rate of adverse events associated with endotracheal intubation in newborns and modifiable factors contributing to these events. Study design We conducted a prospective, observational study in a 100-bed, academic, level IV Neonatal Intensive Care Unit (NICU) from September 2013 through June 2014. We collected data on intubations using standardized data collection instruments with validation by medical record review. Intubations in the delivery or operating rooms were excluded. The primary outcome was an intubation with any adverse event. Adverse events were defined and tracked prospectively as non-severe or severe. We measured clinical variables including number of attempts to successful intubation and intubation urgency (elective, urgent or emergent). We used logistic regression models to estimate the association of these variables with adverse events. Results During the study period, 304 intubations occurred in 178 infants. Data were available for 273 intubations (90%) in 162 patients. Adverse events occurred in 107 (39%) intubations with non-severe and severe events in 96 (35%) and 24 (8.8%) intubations, respectively. Increasing number of intubation attempts (odds ratio [OR] 2.1, 95% confidence intervals [CI], 1.6–2.6) and emergent intubations (OR 4.7, 95% CI, 1.7– 13) were predictors of adverse events. The primary cause of emergent intubations was unplanned extubation (62%). Conclusion Adverse events are common in the NICU, occurring in 4 of 10 intubations. The odds of an adverse event doubled with increasing number of attempts and quadrupled in the emergent setting. Quality improvement efforts to address these factors are needed to improve patient safety. PMID:26541424

Radiofrequency ablation of pulmonary tumors near the diaphragm.

PubMed

Iguchi, T; Hiraki, T; Gobara, H; Fujiwara, H; Sakurai, J; Matsui, Y; Mitsuhashi, T; Toyooka, S; Kanazawa, S

To retrospectively evaluate the feasibility, safety, and efficacy of radiofrequency ablation (RFA) of lung tumors located near the diaphragm. A total of 26 patients (15 men, 11 women; mean age, 61.5 years±13.0 [SD]) with a total of 29 lung tumors near the diaphragm (i.e., distance<10mm) were included. Mean tumor diameter was 11.0mm±5.3 (SD) (range, 2-23mm). Efficacy of RFA, number of adverse events and number of adverse events with a grade≥3, based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, were compared between patients with lung tumors near the diaphragm and a control group of patients with more distally located lung tumors (i.e., distance≥10mm). RFA was technically feasible for all tumors near the diaphragm. Four grade 3 adverse events (1 pneumothorax requiring pleurodesis and 3 phrenic nerve injuries) were observed. No grade≥4 adverse events were reported. The median follow-up period for tumors near the diaphragm was 18.3 months. Local progression was observed 3.3 months after RFA in 1 tumor. The technique efficacy rates were 96.2% at 1 year and 96.2% at 2 years and were not different, from those observed in control subjects (186 tumors; P=0.839). Shoulder pain (P<0.001) and grade 1 pleural effusion (P<0.001) were more frequently observed in patients with lung tumor near the diaphragm. The rates of grade≥3 adverse events did not significantly differ between tumors near the diaphragm (4/26 sessions) and the controls (7/133 sessions) (P=0.083). RFA is a feasible and effective therapeutic option for lung tumors located near the diaphragm. However, it conveys a higher rate of shoulder pain and asymptomatic pleural effusion by comparison with more distant lung tumors. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

PubMed

Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

2017-01-01

The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

Adverse events and treatment failure leading to discontinuation of recently approved antipsychotic drugs in schizophrenia: A network meta-analysis.

PubMed

Tonin, Fernanda S; Piazza, Thais; Wiens, Astrid; Fernandez-Llimos, Fernando; Pontarolo, Roberto

2015-12-01

Objective:We aimed to gather evidence of the discontinuation rates owing to adverse events or treatment failure for four recently approved antipsychotics (asenapine, blonanserin, iloperidone, and lurasidone).Methods: A systematic review followed by pairwise meta-analysis and mixed treatment comparison meta analysis(MTC) was performed, including randomized controlled trials (RCTs) that compared the use of the above-mentioned drugs versus placebo in patients with schizophrenia. An electronic search was conducted in PubMed, Scopus, Science Direct, Scielo, the Cochrane Library, and International Pharmaceutical Abstracts(January 2015). The included trials were at least single blinded. The main outcome measures extracted were discontinuation owing to adverse events and discontinuation owing to treatment failure.Results: Fifteen RCTs were identified (n = 5400 participants) and 13 of them were amenable for use in our meta-analyses. No significant differences were observed between any of the four drugs and placebo as regards discontinuation owing to adverse events, whether in pairwise meta-analysis or in MTC. All drugs presented a better profile than placebo on discontinuation owing to treatment failure, both in pairwise meta-analysis and MTC. Asenapine was found to be the best therapy in terms of tolerability owing to failure,while lurasidone was the worst treatment in terms of adverse events. The evidence around blonanserin is weak.Conclusion: MTCs allowed the creation of two different rank orders of these four antipsychotic drugs in two outcome measures. This evidence-generating method allows direct and indirect comparisons, supporting approval and pricing decisions when lacking sufficient, direct, head-to-head trials.

Pharmacologic therapies for severe steroid refractory hospitalized ulcerative colitis: A network meta-analysis.

PubMed

Komaki, Yuga; Komaki, Fukiko; Micic, Dejan; Yamada, Akihiro; Suzuki, Yasuo; Sakuraba, Atsushi

2017-06-01

A limited option of therapies is available for hospitalized patients with severe steroid refractory ulcerative colitis (UC). Furthermore, there exists a paucity of direct comparisons between them. To provide a comparative evaluation of the efficacy and safety of pharmacologic therapies, we conducted a network meta-analysis combined with a benefit-risk analysis of randomized controlled trials (RCTs) performed in hospitalized patients with severe steroid refractory UC. Electronic databases were searched through November 2015 for RCTs evaluating the efficacy of therapies for severe steroid refractory hospitalized UC. The outcomes were clinical response, colectomy free rate, and severe adverse events leading to discontinuation of therapy. The primary endpoints were the rank of therapies based on network meta-analysis combined with benefit-risk analysis between clinical response and severe adverse events as well as colectomy free rate and severe adverse events. Eight RCTs of 421 patients were identified. Cyclosporine, infliximab, and tacrolimus as well as placebo were included in our analysis. Network meta-analysis with benefit-risk analysis simultaneously assessing clinical response and severe adverse events demonstrated the rank order of efficacy as infliximab, cyclosporine, tacrolimus, and placebo. Similar analysis for colectomy-free rate and severe adverse events demonstrated the same rank order of efficacy. The differences among infliximab, cyclosporine, and tacrolimus were small in all analyses. The results of the present comprehensive benefit-risk assessment using network meta-analysis provide RCT-based evidence on efficacy and safety of infliximab, cyclosporine, and tacrolimus for hospitalized patients with severe steroid refractory UC. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Evaluating imbalances of adverse events during biosimilar development

PubMed Central

Vana, Alicia M.; Freyman, Amy W.; Reich, Steven D.; Yin, Donghua; Li, Ruifeng; Anderson, Scott; Jacobs, Ira A.; Zacharchuk, Charles M.; Ewesuedo, Reginald

2016-01-01

ABSTRACT Biosimilars are designed to be highly similar to approved or licensed (reference) biologics and are evaluated based on the totality of evidence from extensive analytical, nonclinical and clinical studies. As part of the stepwise approach recommended by regulatory agencies, the first step in the clinical evaluation of biosimilarity is to conduct a pharmacokinetics similarity study in which the potential biosimilar is compared with the reference product. In the context of biosimilar development, a pharmacokinetics similarity study is not necessarily designed for a comparative assessment of safety. Development of PF-05280014, a potential biosimilar to trastuzumab, illustrates how a numerical imbalance in an adverse event in a small pharmacokinetics study can raise questions on safety that may require additional clinical trials. PMID:27050730

Frequency and Acceptability of Adverse Events After Anterior Cervical Discectomy and Fusion: A Survey Study From the Cervical Spine Research Society.

PubMed

Wilson, Jefferson R; Radcliff, Kris; Schroeder, Gregory; Booth, Madison; Lucasti, Christopher; Fehlings, Michael; Ahmad, Nassr; Vaccaro, Alexander; Arnold, Paul; Sciubba, Daniel; Ching, Alex; Smith, Justin; Shaffrey, Christopher; Singh, Kern; Darden, Bruce; Daffner, Scott; Cheng, Ivan; Ghogawala, Zoher; Ludwig, Steven; Buchowski, Jacob; Brodke, Darrel; Wang, Jeffrey; Lehman, Ronald A; Hilibrand, Alan; Yoon, Tim; Grauer, Jonathan; Dailey, Andrew; Steinmetz, Michael; Harrop, James S

2018-06-01

Anterior cervical discectomy and fusion has a low but well-established profile of adverse events. The goal of this study was to gauge surgeon opinion regarding the frequency and acceptability of these events. A 2-page survey was distributed to attendees at the 2015 Cervical Spine Research Society (CSRS) meeting. Respondents were asked to categorize 18 anterior cervical discectomy and fusion-related adverse events as either: "common and acceptable," "uncommon and acceptable," "uncommon and sometimes acceptable," or "uncommon and unacceptable." Results were compiled to generate the relative frequency of these responses for each complication. Responses for each complication event were also compared between respondents based on practice location (US vs. non-US), primary specialty (orthopedics vs. neurosurgery) and years in practice. Of 150 surveys distributed, 115 responses were received (76.7% response rate), with the majority of respondents found to be US-based (71.3%) orthopedic surgeons (82.6%). Wrong level surgery, esophageal injury, retained drain, and spinal cord injury were considered by most to be unacceptable and uncommon complications. Dysphagia and adjacent segment disease occurred most often, but were deemed acceptable complications. Although surgeon experience and primary specialty had little impact on responses, practice location was found to significantly influence responses for 12 of 18 complications, with non-US surgeons found to categorize events more toward the uncommon and unacceptable end of the spectrum as compared with US surgeons. These results serve to aid communication and transparency within the field of spine surgery, and will help to inform future quality improvement and best practice initiatives.

Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events?

PubMed

Durfey, Nicole; Lehnhof, Brian; Bergeson, Andrew; Durfey, Shayla N M; Leytin, Victoria; McAteer, Kristina; Schwam, Eric; Valiquet, Justin

2017-08-01

The electrocardiogram (ECG) is often used to identify which hyperkalemic patients are at risk for adverse events. However, there is a paucity of evidence to support this practice. This study analyzes the association between specific hyperkalemic ECG abnormalities and the development of short-term adverse events in patients with severe hyperkalemia. We collected records of all adult patients with potassium (K+) ≥6.5 mEq/L in the hospital laboratory database from August 15, 2010, through January 30, 2015. A chart review identified patient demographics, concurrent laboratory values, ECG within one hour of K+ measurement, treatments and occurrence of adverse events within six hours of ECG. We defined adverse events as symptomatic bradycardia, ventricular tachycardia, ventricular fibrillation, cardiopulmonary resuscitation (CPR) and/or death. Two emergency physicians blinded to study objective independently examined each ECG for rate, rhythm, peaked T wave, PR interval duration and QRS complex duration. Relative risk was calculated to determine the association between specific hyperkalemic ECG abnormalities and short-term adverse events. We included a total of 188 patients with severe hyperkalemia in the final study group. Adverse events occurred within six hours in 28 patients (15%): symptomatic bradycardia (n=22), death (n=4), ventricular tachycardia (n=2) and CPR (n=2). All adverse events occurred prior to treatment with calcium and all but one occurred prior to K + -lowering intervention. All patients who had a short-term adverse event had a preceding ECG that demonstrated at least one hyperkalemic abnormality (100%, 95% confidence interval [CI] [85.7-100%]). An increased likelihood of short-term adverse event was found for hyperkalemic patients whose ECG demonstrated QRS prolongation (relative risk [RR] 4.74, 95% CI [2.01-11.15]), bradycardia (HR<50) (RR 12.29, 95%CI [6.69-22.57]), and/or junctional rhythm (RR 7.46, 95%CI 5.28-11.13). There was no statistically significant correlation between peaked T waves and short-term adverse events (RR 0.77, 95% CI [0.35-1.70]). Our findings support the use of the ECG to risk stratify patients with severe hyperkalemia for short-term adverse events.

Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events?

PubMed Central

Durfey, Nicole; Lehnhof, Brian; Bergeson, Andrew; Durfey, Shayla N.M.; Leytin, Victoria; McAteer, Kristina; Schwam, Eric; Valiquet, Justin

2017-01-01

Introduction The electrocardiogram (ECG) is often used to identify which hyperkalemic patients are at risk for adverse events. However, there is a paucity of evidence to support this practice. This study analyzes the association between specific hyperkalemic ECG abnormalities and the development of short-term adverse events in patients with severe hyperkalemia. Methods We collected records of all adult patients with potassium (K+) ≥6.5 mEq/L in the hospital laboratory database from August 15, 2010, through January 30, 2015. A chart review identified patient demographics, concurrent laboratory values, ECG within one hour of K+ measurement, treatments and occurrence of adverse events within six hours of ECG. We defined adverse events as symptomatic bradycardia, ventricular tachycardia, ventricular fibrillation, cardiopulmonary resuscitation (CPR) and/or death. Two emergency physicians blinded to study objective independently examined each ECG for rate, rhythm, peaked T wave, PR interval duration and QRS complex duration. Relative risk was calculated to determine the association between specific hyperkalemic ECG abnormalities and short-term adverse events. Results We included a total of 188 patients with severe hyperkalemia in the final study group. Adverse events occurred within six hours in 28 patients (15%): symptomatic bradycardia (n=22), death (n=4), ventricular tachycardia (n=2) and CPR (n=2). All adverse events occurred prior to treatment with calcium and all but one occurred prior to K+-lowering intervention. All patients who had a short-term adverse event had a preceding ECG that demonstrated at least one hyperkalemic abnormality (100%, 95% confidence interval [CI] [85.7–100%]). An increased likelihood of short-term adverse event was found for hyperkalemic patients whose ECG demonstrated QRS prolongation (relative risk [RR] 4.74, 95% CI [2.01–11.15]), bradycardia (HR<50) (RR 12.29, 95%CI [6.69–22.57]), and/or junctional rhythm (RR 7.46, 95%CI 5.28–11.13). There was no statistically significant correlation between peaked T waves and short-term adverse events (RR 0.77, 95% CI [0.35–1.70]). Conclusion Our findings support the use of the ECG to risk stratify patients with severe hyperkalemia for short-term adverse events. PMID:28874951

Assessing the detection, reporting and investigation of adverse events in clinical trial protocols implemented in Cameroon: a documentary review of clinical trial protocols.

PubMed

Ebile, Akoh Walter; Ateudjieu, Jerome; Yakum, Martin Ndinakie; Djuidje, Marceline Ngounoue; Watcho, Pierre

2015-09-29

International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee.

The role of media and the Internet on vaccine adverse event reporting: a case study of human papillomavirus vaccination.

PubMed

Eberth, Jan M; Kline, Kimberly N; Moskowitz, David A; Montealegre, Jane R; Scheurer, Michael E

2014-03-01

This study aimed to determine the temporal association of print media coverage and Internet search activity with adverse events reports associated with the human papillomavirus vaccine Gardasil (HPV4) and the meningitis vaccine Menactra (MNQ) among United States adolescents. We used moderated linear regression to test the relationships between print media reports in top circulating newspapers, Internet search activity, and reports to the Vaccine Adverse Event Reporting System (VAERS) for HPV4 and MNQ during the first 2.5 years after Food and Drug Administration approval. Compared with MNQ, HPV4 had more coverage in the print media and Internet search activity, which corresponded with the frequency of VAERS reports. In February 2007, we observed a spike in print media for HPV4. Although media coverage waned, Internet search activity remained stable and predicted the rise in HPV4-associated VAERS reports. We demonstrate that media coverage and Internet search activity, in particular, may promote increased adverse event reporting. Public health officials who have long recognized the importance of proactive engagement with news media must now consider strategies for meaningful participation in Internet discussions. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Toxicogenomics of nevirapine-associated cutaneous and hepatic adverse events among populations of African, Asian, and European descent

PubMed Central

Yuan, Jing; Guo, Sheng; Hall, David; Cammett, Anna M.; Jayadev, Supriya; Distel, Manuel; Storfer, Stephen; Huang, Zimei; Mootsikapun, Piroon; Ruxrungtham, Kiat; Podzamczer, Daniel; Haas, David W.

2012-01-01

Objective Nevirapine is widely prescribed for HIV-1 infection. We characterized relationships between nevirapine-associated cutaneous and hepatic adverse events and genetic variants among HIV-infected adults. Design We retrospectively identified cases and controls. Cases experienced symptomatic nevirapine-associated severe (grade III/IV) cutaneous and/or hepatic adverse events within 8 weeks of initiating nevirapine. Controls did not experience adverse events during more than 18 weeks of nevirapine therapy. Methods Cases and controls were matched 1 : 2 on baseline CD4 T-cell count, sex, and race. Individuals with 150 or less CD4 T cells/μl at baseline were excluded. We characterized 123 human leukocyte antigen (HLA) alleles and 2744 single-nucleotide polymorphisms in major histocompatibility complex (MHC) and drug metabolism and transport genes. Results We studied 276 evaluable cases (175 cutaneous adverse events, 101 hepatic adverse events) and 587 controls. Cutaneous adverse events were associated with CYP2B6 516G→T (OR 1.66, all), HLA-Cw*04 (OR 2.51, all), and HLA-B*35 (OR 3.47, Asians; 5.65, Thais). Risk for cutaneous adverse events was particularly high among Blacks with CYP2B6 516TT and HLA-Cw*04 (OR 18.90) and Asians with HLA-B*35 and HLA-Cw*04 (OR 18.34). Hepatic adverse events were associated with HLA-DRB*01 (OR 3.02, Whites), but not CYP2B6 genotypes. Associations differed by population, at least in part reflecting allele frequencies. Conclusion Among patients with at least 150 CD4 T cells/μl, polymorphisms in drug metabolism and immune response pathways were associated with greater likelihood of risk for nevirapine-related adverse events. Results suggest fundamentally different mechanisms of adverse events: cutaneous, most likely MHC class I-mediated, influenced by nevirapine CYP2B6 metabolism; hepatic, most likely MHC class II-mediated and unaffected by such metabolism. These risk variants are insensitive for routine clinical screening. PMID:21505298

Factors Associated with Complications in Older Adults with Isolated Blunt Chest Trauma

PubMed Central

Lotfipour, Shahram; Kaku, Shawn K.; Vaca, Federico E.; Patel, Chirag; Anderson, Craig L.; Ahmed, Suleman S.; Menchine, Michael D.

2009-01-01

Objective: To determine the prevalence of adverse events in elderly trauma patients with isolated blunt thoracic trauma, and to identify variables associated with these adverse events. Methods: We performed a chart review of 160 trauma patients age 65 and older with significant blunt thoracic trauma, drawn from an American College of Surgeons Level I Trauma Center registry. Patients with serious injury to other body areas were excluded to prevent confounding the cause of adverse events. Adverse events were defined as acute respiratory distress syndrome or pneumonia, unanticipated intubation, transfer to the intensive care unit for hypoxemia, or death. Data collected included history, physical examination, radiographic findings, length of hospital stay, and clinical outcomes. Results: Ninety-nine patients had isolated chest injury, while 61 others had other organ systems injured and were excluded. Sixteen patients developed adverse events [16.2% 95% confidence interval (CI) 9.5–24.9%], including two deaths. Adverse events were experienced by 19.2%, 6.1%, and 28.6% of those patients 65–74, 75–84, and ≥85 years old, respectively. The mean length of stay was 14.6 days in patients with an adverse event and 5.8 days in patients without. Post hoc analysis revealed that all 16 patients with an adverse event had one or more of the following: age ≥85, initial systolic blood pressure <90 mmHg, hemothorax, pneumothorax, three or more unilateral rib fractures, or pulmonary contusion (sensitivity 100%, CI 79.4–100%; specificity 38.6%, CI 28.1–49.9%). Conclusion: Adverse events from isolated thoracic trauma in elderly patients complicate 16% of our sample. These criteria were 100% sensitive and 38.5% specific for these adverse events. This study is a first step to identifying variables that might aid in identifying patients at high risk for serious adverse events. PMID:19561823

Comparative efficacy and safety of oxcarbazepine versus divalproex sodium in the treatment of acute mania: a pilot study.

PubMed

Kakkar, Ashish Kumar; Rehan, H S; Unni, K E S; Gupta, Neeraj Kumar; Chopra, Deepti; Kataria, Dinesh

2009-04-01

This study compared the efficacy and safety of oxcarbazepine and divalproex sodium in acute mania patients. In this 12 week, randomized, double-blind pilot study, 60 patients diagnosed with acute mania (DSM-IV) and a baseline Young Mania Rating Scale (YMRS) score of 20 or more received flexibly dosed oxcarbazepine (1,000-2,400 mg/day) or divalproex (750-2,000 mg/day). The mean decrease in the YMRS score from baseline was used as the main outcome measure of response to treatment. A priori protocol-defined threshold scores were or=15 for relapse. Number of patients showing adequate response and the time taken to achieve improvement was compared. Adverse events were systematically recorded throughout the study. Over 12 weeks, mean improvement in YMRS scores was comparable for both the groups including the mean total scores as well as percentage fall from baseline. There were no significant differences between treatments in the rates of symptomatic mania remission (90% in divalproex and 80% in oxcarbazepine group) and subsequent relapse. Median time taken to symptomatic remission was 56 days in divalproex group while it was 70 days in the oxcarbazepine group (p=0.123). A significantly greater number of patients in divalproex group experienced one or more adverse drug events as compared to patients in the oxcarbazepine group (66.7% versus 30%, p<0.01). Oxcarbazepine demonstrated comparable efficacy to divalproex sodium in the management of acute mania. Also the overall adverse event profile was found to be superior for oxcarbazepine.

Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

PubMed

Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

2017-08-15

Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital.

Contemporary Toxicity Profile of Breast Brachytherapy Versus External Beam Radiation After Lumpectomy for Breast Cancer

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

Huo, Jinhai; Giordano, Sharon H.; Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas

Purpose: We compared toxicities after brachytherapy versus external beam radiation therapy (EBRT) in contemporary breast cancer patients. Methods and Materials: Using MarketScan healthcare claims, we identified 64,112 women treated from 2003 to 2012 with lumpectomy followed by radiation (brachytherapy vs EBRT). Brachytherapy was further classified by multichannel versus single-channel applicator approach. We identified the risks and predictors of 1-year infectious and noninfectious postoperative adverse events using logistic regression and temporal trends using Cochran-Armitage tests. We estimated the 5-year Kaplan-Meier cumulative incidence of radiation-associated adverse events. Results: A total of 4522 (7.1%) patients received brachytherapy (50.2% multichannel vs 48.7% single-channel applicator).more » The overall risk of infectious adverse events was higher after brachytherapy than after EBRT (odds ratio [OR] = 1.21; 95% confidence interval [CI] 1.09-1.34, P<.001). However, over time, the frequency of infectious adverse events after brachytherapy decreased, from 17.3% in 2003 to 11.6% in 2012, and was stable after EBRT at 9.7%. Beyond 2007, there were no longer excess infections with brachytherapy (P=.97). The overall risk of noninfectious adverse events was higher after brachytherapy than after EBRT (OR=2.27; 95% CI 2.09-2.47, P<.0001). Over time, the frequency of noninfectious adverse events detected increased: after multichannel brachytherapy, from 9.1% in 2004 to 18.9% in 2012 (Ptrend = .64); single-channel brachytherapy, from 12.8% to 29.8% (Ptrend<.001); and EBRT, from 6.1% to 10.3% (Ptrend<.0001). The risk was significantly higher with single-channel than with multichannel brachytherapy (hazard ratio = 1.32; 95% CI 1.03-1.69, P=.03). Of noninfectious adverse events, 70.9% were seroma. Seroma significantly increased breast pain risk (P<.0001). Patients with underlying diabetes, cardiovascular disease, and treatment with chemotherapy had increased infectious and noninfectious adverse events. The 5-year incidences of fat necrosis, breast pain, and rib fracture were slightly higher after brachytherapy than after EBRT (13.7% vs 8.1%, 19.4% vs 16.0%, and 1.6% vs 1.3%, respectively), but the risks were not significantly different for multichannel versus single-channel applicators. Conclusion: Toxicities after breast brachytherapy were distinct from those after EBRT. Temporal toxicity trends may reflect changing technology and evolving practitioner experience with brachytherapy.« less

Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

PubMed Central

Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

2016-01-01

Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole, there was little or no difference in parasitological cure (RR 1.07, 95% CI 0.96 to 1.20; 467 participants, three trials, low quality evidence). However, adverse events were less common with ivermectin (RR 0.31, 95% CI 0.20 to 0.50; 507 participants; three trials, moderate quality evidence). In trials comparing different dosages of ivermectin, taking a second dose of 200 μg/kg of ivermectin was not associated with higher cure in a small subgroup of participants (RR 1.02, 95% CI 0.94 to 1.11; 94 participants, two trials). Dizziness, nausea, and disorientation were commonly reported in all drug groups. There were no reports of serious adverse events or death. Authors' conclusions Ivermectin results in more people cured than albendazole, and is at least as well tolerated. In trials of ivermectin with thiabendazole, parasitological cure is similar but there are more adverse events with thiabendazole. Ivermectin versus benzimidazoles for treating Strongyloides stercoralis infection What is strongyloides infection and how might ivermectin work Strongyloides stercoralis is a parasite that lives in the gut of infected people. The infection is not serious for most people, but it can be fatal in people with immune deficiency. People become infected when they come in contact with soil or water contaminated with infectious worms. The chronic infection usually causes skin rash, vomiting, diarrhoea, and constipation, and respiratory problems, such as asthma-like illness. This disease may be treated with ivermectin or albendazole or thiabendazole. We wanted to know if ivermectin was better or worse than the other alternative therapies. What the research says We reviewed the evidence about the effect of ivermectin compared with albendazole and thiabendazole. After searching for relevant trials up to August 2015, we included seven randomized controlled trials, enrolling 1147 adults with chronic strongyloides infection, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America, and Europe). Four trials assessed the effectiveness of ivermectin compared with albendazole and three trials assessed the effectiveness of ivermectin compared with thiabendazole. Comparison ivermectin versus albendazole Treatment with ivermectin probably cures more people than albendazole (moderate quality evidence), and may be equally or better tolerated (low quality evidence). The included trials did not report serious adverse events or death. Comparison ivermectin versus thiabendazole Treatment with ivermectin and thiabendazole may cure similar numbers of people with strongyloides infection (low quality evidence), but ivermectin is probably better tolerated (moderate quality evidence). The included trials did not report serious adverse events or death. PMID:26778150

Childhood Adversities and Adult Cardiometabolic Health: Does the Quantity, Timing, and Type of Adversity Matter?

PubMed Central

Friedman, Esther M.; Montez, Jennifer Karas; Sheehan, Connor McDevitt; Guenewald, Tara L.; Seeman, Teresa E.

2015-01-01

Objective Adverse events in childhood can indelibly influence adult health. While evidence for this association has mounted, a fundamental set of questions about how to operationalize adverse events has been understudied. Method We used data from the National Survey of Midlife Development in the United States to examine how quantity, timing, and types of adverse events in childhood are associated with adult cardiometabolic health. Results The best-fitting specification of quantity of events was a linear measure reflecting a dose–response relationship. Timing of event mattered less than repeated exposure to events. Regarding the type of event, academic interruptions and sexual/physical abuse were most important. Adverse childhood events elevated the risk of diabetes and obesity similarly for men and women but had a greater impact on women’s risk of heart disease. Discussion Findings demonstrate the insights that can be gleaned about the early-life origins of adult health by examining operationalization of childhood exposures. PMID:25903978

Application of a temporal reasoning framework tool in analysis of medical device adverse events.

PubMed

Clark, Kimberly K; Sharma, Deepak K; Chute, Christopher G; Tao, Cui

2011-01-01

The Clinical Narrative Temporal Relation Ontology (CNTRO)1 project offers a semantic-web based reasoning framework, which represents temporal events and relationships within clinical narrative texts, and infer new knowledge over them. In this paper, the CNTRO reasoning framework is applied to temporal analysis of medical device adverse event files. One specific adverse event was used as a test case: late stent thrombosis. Adverse event narratives were obtained from the Food and Drug Administration's (FDA) Manufacturing and User Facility Device Experience (MAUDE) database2. 15 adverse event files in which late stent thrombosis was confirmed were randomly selected across multiple drug eluting stent devices. From these files, 81 events and 72 temporal relations were annotated. 73 temporal questions were generated, of which 65 were correctly answered by the CNTRO system. This results in an overall accuracy of 89%. This system should be pursued further to continue assessing its potential benefits in temporal analysis of medical device adverse events.

Data-mining for detecting signals of adverse drug reactions of fluoxetine using the Korea Adverse Event Reporting System (KAERS) database.

PubMed

Kim, Seonji; Park, Kyounghoon; Kim, Mi-Sook; Yang, Bo Ram; Choi, Hyun Jin; Park, Byung-Joo

2017-10-01

Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of a quality program with adverse events identification on airway management during overtube-assisted enteroscopy.

PubMed

Lara, Luis F; Ukleja, Andrew; Pimentel, Ronnie; Charles, Roger J

2014-11-01

Adverse events associated with overtube-assisted enteroscopy are similar to those with routine endoscopy. Our endoscopy quality program identified a number of respiratory adverse events resulting in emergency resuscitation efforts. The aim is to report all adverse events identified by quality monitoring and outcomes of adverse events associated with overtube-assisted enteroscopy. A retrospective study used data prospectively obtained from consecutive patients undergoing overtube-assisted enteroscopy between December 2008 and July 2012. Patient characteristics, medical history, procedure indication, and procedure outcomes, including diagnosis, endoscopic therapy, and complications, were obtained. In 432 overtube-assisted enteroscopies, 15 adverse events (most frequently hypoxemia, 9 /15, 60 %) occurred in 14 patients (3.2 % of total cohort; 12 were outpatients) mostly during antegrade enteroscopy. Four patients required endotracheal intubation and 4 /12 outpatients required intensive care. The procedure was aborted in 13 /14 patients, and only 1 of 10 patients scheduled for repeat antegrade enteroscopy returned. There was no mortality. Based on the frequency of adverse events, and in consultation with anesthesia providers, from August 2012 all antegrade overtube-assisted enteroscopies at our institution were done with general anesthesia. From then till September 2013, 145 antegrade and 52 retrograde overtube-assisted enteroscopies have been done, with no adverse events. Monitoring of endoscopy practice identified adverse events associated with overtube-assisted enteroscopy. The peer-review prompted a change in practice: all patients undergoing antegrade overtube-assisted enteroscopy at our institution now have endotracheal intubation which has dramatically decreased the rate of respiratory adverse events. The impact of endoscopic quality measurements on practices, procedures, and outcomes will be of further interest. © Georg Thieme Verlag KG Stuttgart · New York.

Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

PubMed

Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

2011-01-01

Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

Intraoperative adverse events can be compensated by technical performance in neonates and infants after cardiac surgery: a prospective study.

PubMed

Nathan, Meena; Karamichalis, John M; Liu, Hua; del Nido, Pedro; Pigula, Frank; Thiagarajan, Ravi; Bacha, Emile A

2011-11-01

Our objective was to define the relationship between surgical technical performance score, intraoperative adverse events, and major postoperative adverse events in complex pediatric cardiac repairs. Infants younger than 6 months were prospectively followed up until discharge from the hospital. Technical performance scores were graded as optimal, adequate, or inadequate based on discharge echocardiograms and need for reintervention after initial surgery. Case complexity was determined by Risk Adjustment in Congenital Heart Surgery (RACHS-1) category, and preoperative illness severity was assessed by Pediatric Risk of Mortality (PRISM) III score. Intraoperative adverse events were prospectively monitored. Outcomes were analyzed using nonparametric methods and a logistic regression model. A total of 166 patients (RACHS 4-6 [49%]), neonates [50%]) were observed. Sixty-one (37%) had at least 1 intraoperative adverse event, and 47 (28.3%) had at least 1 major postoperative adverse event. There was no correlation between intraoperative adverse events and RACHS, preoperative PRISM III, technical performance score, or postoperative adverse events on multivariate analysis. For the entire cohort, better technical performance score resulted in lower postoperative adverse events, lower postoperative PRISM, and lower length of stay and ventilation time (P < .001). Patients requiring intraoperative revisions fared as well as patients without, provided the technical score was at least adequate. In neonatal and infant open heart repairs, technical performance score is one of the main predictors of postoperative morbidity. Outcomes are not affected by intraoperative adverse events, including surgical revisions, provided technical performance score is at least adequate. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Lessons learnt from Dental Patient Safety Case Reports

PubMed Central

Obadan, Enihomo M.; Ramoni, Rachel B.; Kalenderian, Elsbeth

2015-01-01

Background Errors are commonplace in dentistry, it is therefore our imperative as dental professionals to intercept them before they lead to an adverse event, and/or mitigate their effects when an adverse event occurs. This requires a systematic approach at both the profession-level, encapsulated in the Agency for Healthcare Research and Quality’s Patient Safety Initiative structure, as well as at the practice-level, where Crew Resource Management is a tested paradigm. Supporting patient safety at both the dental practice and profession levels relies on understanding the types and causes of errors, an area in which little is known. Methods A retrospective review of dental adverse events reported in the literature was performed. Electronic bibliographic databases were searched and data were extracted on background characteristics, incident description, case characteristics, clinic setting where adverse event originated, phase of patient care that adverse event was detected, proximal cause, type of patient harm, degree of harm and recovery actions. Results 182 publications (containing 270 cases) were identified through our search. Delayed and unnecessary treatment/disease progression after misdiagnosis was the largest type of harm reported. 24.4% of reviewed cases were reported to have experienced permanent harm. One of every ten case reports reviewed (11.1%) reported that the adverse event resulted in the death of the affected patient. Conclusions Published case reports provide a window into understanding the nature and extent of dental adverse events, but for as much as the findings revealed about adverse events, they also identified the need for more broad-based contributions to our collective body of knowledge about adverse events in the dental office and their causes. Practical Implications Siloed and incomplete contributions to our understanding of adverse events in the dental office are threats to dental patients’ safety. PMID:25925524

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem.

PubMed

Kabiru, Caroline W; Elung'ata, Patricia; Mojola, Sanyu A; Beguy, Donatien

2014-01-01

Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? We used cross-sectional data from 3,064 males and females aged 12-19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries.

Meta-Analysis of Rare Binary Adverse Event Data

PubMed Central

Bhaumik, Dulal K.; Amatya, Anup; Normand, Sharon-Lise; Greenhouse, Joel; Kaizar, Eloise; Neelon, Brian; Gibbons, Robert D.

2013-01-01

We examine the use of fixed-effects and random-effects moment-based meta-analytic methods for analysis of binary adverse event data. Special attention is paid to the case of rare adverse events which are commonly encountered in routine practice. We study estimation of model parameters and between-study heterogeneity. In addition, we examine traditional approaches to hypothesis testing of the average treatment effect and detection of the heterogeneity of treatment effect across studies. We derive three new methods, simple (unweighted) average treatment effect estimator, a new heterogeneity estimator, and a parametric bootstrapping test for heterogeneity. We then study the statistical properties of both the traditional and new methods via simulation. We find that in general, moment-based estimators of combined treatment effects and heterogeneity are biased and the degree of bias is proportional to the rarity of the event under study. The new methods eliminate much, but not all of this bias. The various estimators and hypothesis testing methods are then compared and contrasted using an example dataset on treatment of stable coronary artery disease. PMID:23734068

Association between Concomitant Use of Acyclovir or Valacyclovir with NSAIDs and an Increased Risk of Acute Kidney Injury: Data Mining of FDA Adverse Event Reporting System.

PubMed

Yue, Zhihua; Shi, Jinhai; Li, Haona; Li, Huiyi

2018-02-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are likely to be used concomitantly with acyclovir or valacyclovir in clinical practice, but the study on the safety of such combinations was seldom reported. The objective of the study was to investigate reports of acute kidney injury (AKI) events associated with the concomitant use of oral acyclovir or valacyclovir with an NSAID by using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) database between January 2004 and June 2012. The frequency of AKI events in patients while simultaneously taking either acyclovir or valacyclovir and an NSAID was compared using the Chi-square test. The effect of concomitant use of acyclovir or valacyclovir and individual NSAIDs on AKI was analyzed by the reporting odds ratio (ROR). The results showed that AKI was reported as the adverse event in 8.6% of the 10923 patients taking valacyclovir compared with 8.7% of the 2556 patients taking acyclovir (p=NS). However, AKI was significantly more frequently reported in patients simultaneously taking valacyclovir and an NSAID (19.4%) than in patients simultaneously taking acyclovir and an NSAID (10.5%) (p<0.01). The results also suggested that increased risk of AKI was likely associated with the concomitant use of valacyclovir and some NSAIDs such as loxoprofen, diclofenac, etodolac, ketorolac, piroxicam or lornoxicam. The case series from the AERS indicated that compared with acyclovir, valacyclovir is more likely to be affected by NSAIDs, and the concomitant use of valacyclovir with some NSAIDs might be associated with increased risk of AKI. The drug interactions with this specific combination of medications are worth exploring further.

Teaching dental students about patient communication following an adverse event: a pilot educational module.

PubMed

Raja, Sheela; Rajagopalan, Chelsea F; Patel, Janki; Van Kanegan, Kevin

2014-05-01

Adverse events are an important but understudied area in dentistry. Most dentists will face the issue of an adverse event several times in their clinical careers. The authors implemented a six-hour pilot educational module at one dental school to improve fourth-year dental students' knowledge and confidence in communicating with patients about adverse events. Based on results from the twenty-nine students who completed both the pre- and posttests, the module significantly increased the students' knowledge of the key concepts involved in adverse events. However, the module did not improve the students' confidence that they would be able to implement these communication skills in clinical situations. Based on these results, this article discusses how future educational efforts can be modified to better prepare students for the communication challenges associated with adverse events.

Incidence of adverse events in ferrets vaccinated with distemper or rabies vaccine: 143 cases (1995-2001).

PubMed

Greenacre, Cheryl B

2003-09-01

To determine the incidence of adverse events in ferrets vaccinated with a modified-live avian cell culture canine distemper virus vaccine licensed for use in ferrets, an inactivated rabies vaccine licensed for use in ferrets, or both. Retrospective study. 143 ferrets. Medical records were reviewed to identify ferrets that had an adverse event after vaccination. Adverse events developed within 25 minutes after vaccination in 13 ferrets. One ferret developed an adverse event after receiving a distemper and a rabies vaccine simultaneously and developed a second adverse event the following year after receiving the rabies vaccine alone. Therefore, a total of 14 adverse events were identified. All adverse events were an anaphylactic reaction characterized by generalized hyperemia, hypersalivation, and vomiting. Ten of the 14 anaphylactic reactions occurred after ferrets received both vaccines, 3 occurred after ferrets received the distemper vaccine alone, and 1 occurred after a ferret received the rabies vaccine alone. Incidences of adverse events after administration of both vaccines, the distemper vaccine alone, and the rabies vaccine alone were 5.6, 5.9, and 5.6%, respectively. Ferrets that had an anaphylactic reaction were significantly older at the time of vaccination than were ferrets that did not. Results suggest that there may be a high incidence of anaphylactic reactions after vaccination of domestic ferrets. Ferrets should be observed for at least 25 minutes after vaccination, and veterinarians who vaccinate ferrets should be prepared to treat anaphylactic reactions.

Automatically Recognizing Medication and Adverse Event Information From Food and Drug Administration’s Adverse Event Reporting System Narratives

PubMed Central

Polepalli Ramesh, Balaji; Belknap, Steven M; Li, Zuofeng; Frid, Nadya; West, Dennis P

2014-01-01

Background The Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem. Objective The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives. Methods We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features. Results The annotated corpus had an agreement of over .9 Cohen’s kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities. Conclusions In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance. PMID:25600332

[Assessing the economic impact of adverse events in Spanish hospitals by using administrative data].

PubMed

Allué, Natalia; Chiarello, Pietro; Bernal Delgado, Enrique; Castells, Xavier; Giraldo, Priscila; Martínez, Natalia; Sarsanedas, Eugenia; Cots, Francesc

2014-01-01

To evaluate the incidence and costs of adverse events registered in an administrative dataset in Spanish hospitals from 2008 to 2010. A retrospective study was carried out that estimated the incremental cost per episode, depending on the presence of adverse events. Costs were obtained from the database of the Spanish Network of Hospital Costs. This database contains data from 12 hospitals that have costs per patient records based on activities and clinical records. Adverse events were identified through the Patient Safety Indicators (validated in the Spanish Health System) created by the Agency for Healthcare Research and Quality together with indicators of the EuroDRG European project. This study included 245,320 episodes with a total cost of 1,308,791,871€. Approximately 17,000 patients (6.8%) experienced an adverse event, representing 16.2% of the total cost. Adverse events, adjusted by diagnosis-related groups, added a mean incremental cost of between €5,260 and €11,905. Six of the 10 adverse events with the highest incremental cost were related to surgical interventions. The total incremental cost of adverse events was € 88,268,906, amounting to an additional 6.7% of total health expenditure. Assessment of the impact of adverse events revealed that these episodes represent significant costs that could be reduced by improving the quality and safety of the Spanish Health System. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Adverse event reporting in cancer clinical trial publications.

PubMed

Sivendran, Shanthi; Latif, Asma; McBride, Russell B; Stensland, Kristian D; Wisnivesky, Juan; Haines, Lindsay; Oh, William K; Galsky, Matthew D

2014-01-10

Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

Committee Opinion No. 681: Disclosure and Discussion of Adverse Events.

PubMed

2016-12-01

Adverse outcomes, preventable or otherwise, are a reality of medical care. Most importantly, adverse events affect patients, but they also affect health care practitioners. Disclosing information about adverse events has benefits for the patient and the physician and, ideally, strengthens the patient-physician relationship and promotes trust. Studies show that after an adverse outcome, patients expect and want timely and full disclosure of the event, an acknowledgment of responsibility, an understanding of what happened, expressions of sympathy, and a discussion of what is being done to prevent recurrence. Surveys have shown that patients are less likely to pursue litigation if they perceive that the event was honestly disclosed. Barriers to full disclosure are many and include fear of retribution for reporting an adverse event, lack of training, a culture of blame, and fear of lawsuits. To reduce these concerns, it is recommended that health care facilities establish a nonpunitive, blame-free culture that encourages staff to report adverse events and near misses (close calls) without fear of retaliation. Health care institutions should have written policies that address the management of adverse events. Having a responsive process to inform and aid the patient, loved ones, and practitioners is required. A commitment on the part of all health care practitioners and institutions to establish programs and develop the tools needed to help patients, families, health care practitioners, and staff members deal with adversity is essential.

Committee Opinion No. 681 Summary: Disclosure and Discussion of Adverse Events.

PubMed

2016-12-01

Adverse outcomes, preventable or otherwise, are a reality of medical care. Most importantly, adverse events affect patients, but they also affect health care practitioners. Disclosing information about adverse events has benefits for the patient and the physician and, ideally, strengthens the patient-physician relationship and promotes trust. Studies show that after an adverse outcome, patients expect and want timely and full disclosure of the event, an acknowledgment of responsibility, an understanding of what happened, expressions of sympathy, and a discussion of what is being done to prevent recurrence. Surveys have shown that patients are less likely to pursue litigation if they perceive that the event was honestly disclosed. Barriers to full disclosure are many and include fear of retribution for reporting an adverse event, lack of training, a culture of blame, and fear of lawsuits. To reduce these concerns, it is recommended that health care facilities establish a nonpunitive, blame-free culture that encourages staff to report adverse events and near misses (close calls) without fear of retaliation. Health care institutions should have written policies that address the management of adverse events. Having a responsive process to inform and aid the patient, loved ones, and practitioners is required. A commitment on the part of all health care practitioners and institutions to establish programs and develop the tools needed to help patients, families, health care practitioners, and staff members deal with adversity is essential.

Radiofrequency ablation of stage IA non-small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial.

PubMed

Dupuy, Damian E; Fernando, Hiran C; Hillman, Shauna; Ng, Thomas; Tan, Angelina D; Sharma, Amita; Rilling, William S; Hong, Kelvin; Putnam, Joe B

2015-10-01

This study evaluated the 2-year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non-small cell lung cancer (NSCLC) undergoing computed tomography (CT)-guided radiofrequency ablation (RFA) in a prospective, multicenter trial. Fifty-four patients (25 men and 29 women) with a median age of 76 years (range, 60-89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy-proven stage IA NSCLC and were deemed medically inoperable by a board-certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed. The overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence-free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors > 2 cm. In the 19 patients with local recurrence, 11 were re-treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years. RFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2-year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. © 2015 American Cancer Society.

Impact of patient communication problems on the risk of preventable adverse events in acute care settings

PubMed Central

Bartlett, Gillian; Blais, Régis; Tamblyn, Robyn; Clermont, Richard J.; MacGibbon, Brenda

2008-01-01

Background Up to 50% of adverse events that occur in hospitals are preventable. Language barriers and disabilities that affect communication have been shown to decrease quality of care. We sought to assess whether communication problems are associated with an increased risk of preventable adverse events. Methods We randomly selected 20 general hospitals in the province of Quebec with at least 1500 annual admissions. Of the 145 672 admissions to the selected hospitals in 2000/01, we randomly selected and reviewed 2355 charts of patients aged 18 years or older. Reviewers abstracted patient characteristics, including communication problems, and details of hospital admission, and assessed the cause and preventability of identified adverse events. The primary outcome was adverse events. Results Of 217 adverse events, 63 (29%) were judged to be preventable, for an overall population rate of 2.7% (95% confidence interval [CI] 2.1%–3.4%). We found that patients with preventable adverse events were significantly more likely than those without such events to have a communication problem (odds ratio [OR] 3.00; 95% CI 1.43–6.27) or a psychiatric disorder (OR 2.35; 95% CI 1.09–5.05). Patients who were admitted urgently were significantly more likely than patients whose admissions were elective to experience an event (OR 1.64, 95% CI 1.07–2.52). Preventable adverse events were mainly due to drug errors (40%) or poor clinical management (32%). We found that patients with communication problems were more likely than patients without these problems to experience multiple preventable adverse events (46% v. 20%; p = 0.05). Interpretation Patients with communication problems appeared to be at highest risk for preventable adverse events. Interventions to reduce the risk for these patients need to be developed and evaluated. PMID:18519903

Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients.

PubMed

Muralidharan, Niveditha; Gulati, Reena; Misra, Durga Prasanna; Negi, Vir S

2018-02-01

The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR-RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5' nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.

Using self-report and adverse event measures to track health's impact on productivity in known groups.

PubMed

Allen, Harris M; Bunn, William B

2003-09-01

The use of survey data to measure and monitor health and productivity differences between groups is an issue of increasing importance. This article examines the capacity of productivity self-reports (derived from surveys) and adverse event measures (derived from administrative sources) to differentiate groups with a priori known characteristics. A replication strategy is used to test the contributions that productivity self-reports make, alone as well as above and beyond measures of adverse events, to the discrimination of 5 pairs of groups classified by clinical, job type, and demographic criteria. These tests are conducted on representative samples of the active, largely blue-collar employee population at International Truck and Engine Corporation. The results show that both productivity self-reports and adverse event measures differentiate and track known groups. Even in the presence of highly significant effects from adverse event measures, self-reports improve the assessment of productivity. We conclude that: 1) although the joint use of self-reports and adverse event measures is the better approach, practitioners can use self-reports with the expectation that this method will track group differences in health and productivity when adverse event measures are not available; and 2) survey self-reports make unique and independent contributions when adverse events measures are used.

Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee

PubMed Central

Zeng, Chao; Wei, Jie; Li, Hui; Wang, Yi-lun; Xie, Dong-xing; Yang, Tuo; Gao, Shu-guang; Li, Yu-sheng; Luo, Wei; Lei, Guang-hua

2015-01-01

This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone, and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA. PMID:26576862

[Adverse events of anesthesia in pediatric surgery scheduled at Gabriel Toure hospital].

PubMed

Samaké, B; Keita, M; Magalie, I M C; Diallo, G; Diallo, A

2010-01-01

The occurrence of an event planned or unplanned during anesthesia is a concern for staff. This event may jeopardize the success of surgery gesture. Pediatric Surgery therefore has its own specific complications that it requires anesthesia. To evaluate the incidence of adverse events during anesthesia in pediatric surgery scheduled. Descriptive non-randomized study. Descriptive non-randomized study on adverse events related to anesthesia in children over a period of seven months. It took place in the anesthesia and intensive care unit and the pediatric surgery unit of Gabriel Toure hospital in Bamako. It focused on patients aged 0 to 12 years scheduled for surgery under general anesthesia during the study period. Sixty six percent of patients selected was male gender with a sex ratio of 3 in favor of males. The average age was 2 years with extremes of 16 days and 12 years and a standard deviation of 2.93. The old history of premature was found in 36% of patients and 2% of asthmatic. The number of patients experiencing an adverse event is 42 on a total of 107 patients collected either 39.25%. When the children were younger than one year adverse events occurred with 30, 76%. The occurrence of adverse events was more frequent when the child was not intubated with P < 0.05. All adverse events have received support except tachycardia, late revival but all developed positively. This study estimates the incidence of adverse events in anesthesia during pediatric surgery. The overall rate of patients experiencing an adverse event is relatively high. Children age less than or equal to one year are most vulnerable.

Adverse events reported to the Food and Drug Administration from 2004 to 2016 for cosmetics and personal care products marketed to newborns and infants.

PubMed

Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai

2018-03-01

Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.

Use of HIT for adverse event reporting in nursing homes: barriers and facilitators.

PubMed

Wagner, Laura M; Castle, Nicholas G; Handler, Steven M

2013-01-01

Approximately 8 million adverse events occur annually in nursing homes (NHs). The focus of this research is to determine barriers and health information technology (HIT)-related facilitators to adverse event reporting among U.S. NHs. Surveys were returned by 399 nursing home administrators using a mailed survey approach. Respondents were asked to report on their adverse event reporting processes focusing on barriers and role of HIT facilitators. About 15% of NHs had computerized entry by the nurse on the unit and almost 18% used no computer technology to track, monitor, or maintain adverse event data. One-third of nursing directors conducted data analysis "by-hand." NHs without HIT were more likely to not be accredited (p = 0.04) and not part of a chain/corporation (p = 0.03). Two of the top three barriers focused on fears of reporting as a barrier. This study found numerous barriers and few HIT-related facilitators to assist with adverse event reporting. Improvements in facilitating adverse event reporting through the use of HIT approaches may be warranted. Copyright © 2013 Mosby, Inc. All rights reserved.

Benefit and harm of intensive blood pressure treatment: Derivation and validation of risk models using data from the SPRINT and ACCORD trials

PubMed Central

Denton, Brian T.; Hayward, Rodney A.

2017-01-01

Background Intensive blood pressure (BP) treatment can avert cardiovascular disease (CVD) events but can cause some serious adverse events. We sought to develop and validate risk models for predicting absolute risk difference (increased risk or decreased risk) for CVD events and serious adverse events from intensive BP therapy. A secondary aim was to test if the statistical method of elastic net regularization would improve the estimation of risk models for predicting absolute risk difference, as compared to a traditional backwards variable selection approach. Methods and findings Cox models were derived from SPRINT trial data and validated on ACCORD-BP trial data to estimate risk of CVD events and serious adverse events; the models included terms for intensive BP treatment and heterogeneous response to intensive treatment. The Cox models were then used to estimate the absolute reduction in probability of CVD events (benefit) and absolute increase in probability of serious adverse events (harm) for each individual from intensive treatment. We compared the method of elastic net regularization, which uses repeated internal cross-validation to select variables and estimate coefficients in the presence of collinearity, to a traditional backwards variable selection approach. Data from 9,069 SPRINT participants with complete data on covariates were utilized for model development, and data from 4,498 ACCORD-BP participants with complete data were utilized for model validation. Participants were exposed to intensive (goal systolic pressure < 120 mm Hg) versus standard (<140 mm Hg) treatment. Two composite primary outcome measures were evaluated: (i) CVD events/deaths (myocardial infarction, acute coronary syndrome, stroke, congestive heart failure, or CVD death), and (ii) serious adverse events (hypotension, syncope, electrolyte abnormalities, bradycardia, or acute kidney injury/failure). The model for CVD chosen through elastic net regularization included interaction terms suggesting that older age, black race, higher diastolic BP, and higher lipids were associated with greater CVD risk reduction benefits from intensive treatment, while current smoking was associated with fewer benefits. The model for serious adverse events chosen through elastic net regularization suggested that male sex, current smoking, statin use, elevated creatinine, and higher lipids were associated with greater risk of serious adverse events from intensive treatment. SPRINT participants in the highest predicted benefit subgroup had a number needed to treat (NNT) of 24 to prevent 1 CVD event/death over 5 years (absolute risk reduction [ARR] = 0.042, 95% CI: 0.018, 0.066; P = 0.001), those in the middle predicted benefit subgroup had a NNT of 76 (ARR = 0.013, 95% CI: −0.0001, 0.026; P = 0.053), and those in the lowest subgroup had no significant risk reduction (ARR = 0.006, 95% CI: −0.007, 0.018; P = 0.71). Those in the highest predicted harm subgroup had a number needed to harm (NNH) of 27 to induce 1 serious adverse event (absolute risk increase [ARI] = 0.038, 95% CI: 0.014, 0.061; P = 0.002), those in the middle predicted harm subgroup had a NNH of 41 (ARI = 0.025, 95% CI: 0.012, 0.038; P < 0.001), and those in the lowest subgroup had no significant risk increase (ARI = −0.007, 95% CI: −0.043, 0.030; P = 0.72). In ACCORD-BP, participants in the highest subgroup of predicted benefit had significant absolute CVD risk reduction, but the overall ACCORD-BP participant sample was skewed towards participants with less predicted benefit and more predicted risk than in SPRINT. The models chosen through traditional backwards selection had similar ability to identify absolute risk difference for CVD as the elastic net models, but poorer ability to correctly identify absolute risk difference for serious adverse events. A key limitation of the analysis is the limited sample size of the ACCORD-BP trial, which expanded confidence intervals for ARI among persons with type 2 diabetes. Additionally, it is not possible to mechanistically explain the physiological relationships explaining the heterogeneous treatment effects captured by the models, since the study was an observational secondary data analysis. Conclusions We found that predictive models could help identify subgroups of participants in both SPRINT and ACCORD-BP who had lower versus higher ARRs in CVD events/deaths with intensive BP treatment, and participants who had lower versus higher ARIs in serious adverse events. PMID:29040268

How transformational leadership appears in action with adverse events? A study for Finnish nurse manager.

PubMed

Liukka, Mari; Hupli, Markku; Turunen, Hannele

2017-12-26

The aim of this study was to determine whether elements of transformational leadership are present in nursing managers' actions following adverse events. Transformational leadership exerts a positive influence on organisational culture and patient safety. Eleven nursing managers were interviewed individually using a semi-structured format. Data were analysed using inductive content analysis. Four themes emerged relating to nursing managers' actions following adverse events: patient-centredness as a principle for common action, courage to reform operational models to prevent future adverse events, nursing staff's encouragement of open and blame-free discussion, and challenge to recognize adverse events. Nursing managers must understand their responsibilities and the importance of making it clear to staff that patient-centredness should be evident in all health care actions. Nursing managers must also recognize the need to ensure that staff treat patients' interests as the top priority. If an adverse event occurs, the situation should be discussed with the nursing staff and any unique aspects of the event must be accounted for. Nursing managers must have the skill to motivate and empower staff to find new ways to work, to prevent adverse events and to promote patient safety. © 2017 John Wiley & Sons Ltd.

Medication errors: an analysis comparing PHICO's closed claims data and PHICO's Event Reporting Trending System (PERTS).

PubMed

Benjamin, David M; Pendrak, Robert F

2003-07-01

Clinical pharmacologists are all dedicated to improving the use of medications and decreasing medication errors and adverse drug reactions. However, quality improvement requires that some significant parameters of quality be categorized, measured, and tracked to provide benchmarks to which future data (performance) can be compared. One of the best ways to accumulate data on medication errors and adverse drug reactions is to look at medical malpractice data compiled by the insurance industry. Using data from PHICO insurance company, PHICO's Closed Claims Data, and PHICO's Event Reporting Trending System (PERTS), this article examines the significance and trends of the claims and events reported between 1996 and 1998. Those who misread history are doomed to repeat the mistakes of the past. From a quality improvement perspective, the categorization of the claims and events is useful for reengineering integrated medication delivery, particularly in a hospital setting, and for redesigning drug administration protocols on low therapeutic index medications and "high-risk" drugs. Demonstrable evidence of quality improvement is being required by state laws and by accreditation agencies. The state of Florida requires that quality improvement data be posted quarterly on the Web sites of the health care facilities. Other states have followed suit. The insurance industry is concerned with costs, and medication errors cost money. Even excluding costs of litigation, an adverse drug reaction may cost up to $2500 in hospital resources, and a preventable medication error may cost almost $4700. To monitor costs and assess risk, insurance companies want to know what errors are made and where the system has broken down, permitting the error to occur. Recording and evaluating reliable data on adverse drug events is the first step in improving the quality of pharmacotherapy and increasing patient safety. Cost savings and quality improvement evolve on parallel paths. The PHICO data provide an excellent opportunity to review information that typically would not be in the public domain. The events captured by PHICO are similar to the errors and "high-risk" drugs described in the literature, the U.S. Pharmacopeia's MedMARx Reporting System, and the Sentinel Event reporting system maintained by the Joint Commission for the Accreditation of Healthcare Organizations. The information in this report serves to alert clinicians to the possibility of adverse events when treating patients with the reported drugs, thus allowing for greater care in their use and closer monitoring. Moreover, when using high-risk drugs, patients should be well informed of known risks, dosage should be titrated slowly, and therapeutic drug monitoring and laboratory monitoring should be employed to optimize therapy and minimize adverse effects.

Outcomes of Propofol Sedation During Emergency Endoscopy Performed for Upper Gastrointestinal Bleeding.

PubMed

Park, Chan Hyuk; Han, Dong Soo; Jeong, Jae Yoon; Eun, Chang Soo; Yoo, Kyo-Sang; Jeon, Yong Cheol; Sohn, Joo Hyun

2016-03-01

Although propofol-based sedation can be used during emergency endoscopy for upper gastrointestinal bleeding (UGIB), there is a potential risk of sedation-related adverse events, especially in patients with variceal bleeding. We compared adverse events related to propofol-based sedation during emergency endoscopy between patients with non-variceal and variceal bleeding. Clinical records of patients who underwent emergency endoscopy for UGIB under sedation were reviewed. Adverse events, including shock, hypoxia, and paradoxical reaction, were compared between the non-variceal and variceal bleeding groups. Of 703 endoscopies, 539 and 164 were performed for non-variceal and variceal bleeding, respectively. Shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding (12.2 vs. 3.5%, P < 0.001). All patients except one recovered from shock after normal saline hydration, and emergency endoscopy could be finished without interruption in most cases. The incidence of hypoxia and paradoxical reaction did not differ based on the source of bleeding (non-variceal bleeding vs. variceal bleeding: hypoxia, 3.5 vs. 1.8%, P = 0.275; paradoxical reaction interfering with the procedure, 4.1 vs. 5.5%, P = 0.442). Although shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding, most cases could be controlled without procedure interruption. Paradoxical reaction, rather than shock or hypoxia, was the most common cause of procedure interruption in patients with variceal bleeding, but the rate did not differ between patients with non-variceal and variceal bleeding.

Benzodiazepine use in seizure emergencies: A systematic review.

PubMed

Haut, Sheryl R; Seinfeld, Syndi; Pellock, John

2016-10-01

The aim of this review was to systematically examine safety and efficacy outcomes, as well as patient/caregiver satisfaction, from clinical studies in pediatric and adult patients treated with benzodiazepines (BZDs) through various administration routes in response to seizure emergencies. A literature search was conducted to identify articles describing the use of various routes of administration (RoAs) of BZDs for the treatment of seizure emergencies through April 21, 2015, using Embase™ and PubMed®. Eligible studies included (a) randomized controlled trials or (b) controlled nonrandomized clinical trials, either retrospective or prospective. Outcome assessments reviewed were 1) time to administration, 2) time to seizure termination, 3) rate of treatment failure, 4) prevention of seizure recurrence, 5) patient and caregiver treatment satisfaction, 6) adverse events related to BDZ treatment or RoA, and 7) respiratory adverse events. Seventy-five studies evaluated safety and efficacy using individual or comparator BDZs of various RoAs for treating seizure emergencies in all-aged patients with epilepsy. Buccal, intranasal (IN), or intramuscular (IM) BZDs were often more rapidly administered compared with rectal and intravenous (IV) formulations. Time to seizure termination, seizure recurrence rates, and adverse events were generally similar among RoAs, whereas nonrectal RoAs resulted in greater patient and caregiver satisfaction compared with rectal RoA. Results of this systematic literature review suggest that nonrectal and non-IV BZD formulations provide equal or improved efficacy and safety outcomes compared with rectal and IV formulations for the treatment of seizure emergencies. Copyright © 2016. Published by Elsevier Inc.

An analysis of leukapheresis and central venous catheter use in the randomized, placebo controlled, phase 3 IMPACT trial of Sipuleucel-T for metastatic castrate resistant prostate cancer.

PubMed

Flanigan, Robert C; Polcari, Anthony J; Shore, Neil D; Price, Thomas H; Sims, Robert B; Maher, Johnathan C; Whitmore, James B; Corman, John M

2013-02-01

Sipuleucel-T is an autologous cellular immunotherapy. We review the safety of the leukapheresis procedure required for sipuleucel-T preparation and complications related to venous catheter use in the randomized, placebo controlled phase 3 IMPACT (IMmunotherapy for ProstAte Cancer Trial) study (NCT 00065442). A total of 512 patients with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer were enrolled in the study. All patients were scheduled to undergo 3 standard 1.5 to 2.0 blood volume leukapheresis procedures at 2-week intervals. Leukapheresis related adverse events and those related to venous catheter use were reviewed. Immune cell counts were examined throughout the treatment course. Of 512 enrolled patients 506 underwent 1 or more leukapheresis procedures and were included in this analysis. Adverse events were comparable between the sipuleucel-T and control arms. Leukapheresis related adverse events were primarily associated with transient hypocalcemia (39.3%). Most leukapheresis related adverse events (97%) were of mild/moderate intensity. Median white blood cell count and absolute monocyte and lymphocyte counts were stable and within normal ranges throughout the treatment course. Of all patients 23.3% had a central venous catheter placed primarily for leukapheresis. Patients with vs without a central venous catheter had a higher risk of infection potentially related to catheter use (11.9% vs 1.3%, p <0.0001) and a trend toward a higher incidence of venous vascular events potentially related to catheter use, excluding the central nervous system (5.9% vs 2.1%, p = 0.06). Adverse events related to leukapheresis are manageable and quickly reversible. The majority of patients can undergo leukapheresis without a central venous catheter. Central venous catheters are associated with an increased risk of infections and venous vascular events. Peripheral intravenous access should be used when feasible. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Improving patient safety by optimizing the use of nursing human resources.

PubMed

Rochefort, Christian M; Buckeridge, David L; Abrahamowicz, Michal

2015-06-14

Recent ecological studies have suggested that inadequate nurse staffing may contribute to the incidence of adverse events in acute care hospitals. However, longitudinal studies are needed to further examine these associations and to identify the staffing patterns that are of greatest risk. The aims of this study are to determine if (a) nurse staffing levels are associated with an increased risk of adverse events, (b) the risk of adverse events in relationship to nurse staffing levels is modified by the complexity of patient requirements, and (c) optimal nurse staffing levels can be established. A dynamic cohort of all adult medical, surgical, and intensive care unit patients admitted between 2010 and 2015 to a Canadian academic health center will be followed during the inpatient and 7-day post-discharge period to assess the occurrence and frequency of adverse events in relationship to antecedent nurse staffing levels. Four potentially preventable adverse events will be measured: (a) hospital-acquired pneumonia, (b) ventilator-associated pneumonia, (c) venous thromboembolism, and (d) in-hospital fall. These events were selected for their high incidence, morbidity and mortality rates, and because they are hypothesized to be related to nurse staffing levels. Adverse events will be ascertained from electronic health record data using validated automated detection algorithms. Patient exposure to nurse staffing will be measured on every shift of the hospitalization using electronic payroll records. To examine the association between nurse staffing levels and the risk of adverse events, four Cox proportional hazards regression models will be used (one for each adverse event), while adjusting for patient characteristics and risk factors of adverse event occurrence. To determine if the association between nurse staffing levels and the occurrence of adverse events is modified by the complexity of patient requirements, interaction terms will be included in the regression models, and their significance assessed. To assess for the presence of optimal nurse staffing levels, flexible nonlinear spline functions will be fitted. This study will likely generate evidence-based information that will assist managers in making the most effective use of scarce nursing resources and in identifying staffing patterns that minimize the risk of adverse events.

Can the frequency and risks of fatal adverse drug events be determined?

PubMed

Kelly, W N

2001-05-01

Death is the ultimate adverse drug event. Despite its importance, the frequency of fatal adverse drug events is unknown. Estimates in the United States are as high as 140,000/year, although this number is heavily disputed. Potential reasons and risks for fatal adverse drug events, as well as epidemiologic designs for studying this important public health issue, are discussed and issues are raised to promote further thought.

Orthopaedic Snafus: When Adverse Events Happen in Orthopaedics.

PubMed

Smith, Mary Atkinson; Walsh, Colleen; Levin, Barbara; Eaten, Kathyrn; Yager, Melissa

The potential for adverse events exists when treating and managing orthopaedic patients in the intraoperative or postoperative environments, especially when it comes to falls, surgical site infections, venous thromboembolism, and injuries to nerves and blood vessels. Orthopaedic nurses play a vital role in the promotion and use of evidence-based interventions to decrease the incidence of these adverse events, improve quality of care, and minimize the financial burden related to these adverse events.

Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial.

PubMed

Han, Yaling; Guo, Jincheng; Zheng, Yang; Zang, Hongyun; Su, Xi; Wang, Yu; Chen, Shaoliang; Jiang, Tiemin; Yang, Ping; Chen, Jiyan; Jiang, Dongju; Jing, Quanmin; Liang, Zhenyang; Liu, Haiwei; Zhao, Xin; Li, Jing; Li, Yi; Xu, Bo; Stone, Gregg W

2015-04-07

The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain. To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI. Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013. Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes). The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year. Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, -11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar. Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis. clinicaltrials.gov Identifier: NCT01696110.

Can Disproportionality Analysis of Post-marketing Case Reports be Used for Comparison of Drug Safety Profiles?

PubMed

Michel, Christiane; Scosyrev, Emil; Petrin, Michael; Schmouder, Robert

2017-05-01

Clinical trials usually do not have the power to detect rare adverse drug reactions. Spontaneous adverse reaction reports as for example available in post-marketing safety databases such as the FDA Adverse Event Reporting System (FAERS) are therefore a valuable source of information to detect new safety signals early. To screen such large data-volumes for safety signals, data-mining algorithms based on the concept of disproportionality have been developed. Because disproportionality analysis is based on spontaneous reports submitted for a large number of drugs and adverse event types, one might consider using these data to compare safety profiles across drugs. In fact, recent publications have promoted this practice, claiming to provide guidance on treatment decisions to healthcare decision makers. In this article we investigate the validity of this approach. We argue that disproportionality cannot be used for comparative drug safety analysis beyond basic hypothesis generation because measures of disproportionality are: (1) missing the incidence denominators, (2) subject to severe reporting bias, and (3) not adjusted for confounding. Hypotheses generated by disproportionality analyses must be investigated by more robust methods before they can be allowed to influence clinical decisions.

Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013.

PubMed

Tohme, Rania A; François, Jeannot; Wannemuehler, Kathleen; Iyengar, Preetha; Dismer, Amber; Adrien, Paul; Hyde, Terri B; Marston, Barbara J; Date, Kashmira; Mintz, Eric; Katz, Mark A

2015-06-01

In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours.

Double whammy: Adverse childhood events and pain reflect symptomology and quality of life in women in substance abuse treatment.

PubMed

Zlotnick, Cheryl; Lawental, Maayan; Pud, Dorit

2017-03-01

This study examined the profiles of symptoms and health-related quality of life (QOL) of women in substance abuse treatment, comparing those with higher versus lower histories of adverse childhood events (ACE), and those with versus without current pain. Adult women in outpatient substance abuse treatment (n = 30) completed questionnaires (cross-sectional study) on topics including drug use, adverse childhood events (ACE), QOL, functional ability, current pain, and depression. Women with pain indicated significant differences in emotional (p < 0.05), and functional ability (p < 0.01); but no significant differences were found between women with high versus low levels of ACE. Yet, radar plots of women with both current pain and high levels of ACE, versus those without, portrayed a distinctive profile indicating high levels of anxiety and depression. Rather than a checklist, visual composites of symptoms experienced by women in substance abuse treatment illustrates areas of concern in the overall status of women in substance abuse treatment.

Biodegradable stent or balloon dilatation for benign oesophageal stricture: pilot randomised controlled trial.

PubMed

Dhar, Anjan; Close, Helen; Viswanath, Yirupaiahgari K; Rees, Colin J; Hancock, Helen C; Dwarakanath, A Deepak; Maier, Rebecca H; Wilson, Douglas; Mason, James M

2014-12-28

To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in patients with strictures. This British multi-site study recruited seventeen symptomatic adult patients with refractory strictures. Patients were randomised using a multicentre, blinded assessor design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The primary endpoint was the average dysphagia score during the first 6 mo. Secondary endpoints included repeat endoscopic procedures, quality of life, and adverse events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses explored alternative estimation methods for dysphagia and multiple imputation of missing values. Nonparametric tests were used. Although both groups improved, the average dysphagia scores for patients receiving stents were higher after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under different estimation methods. Use of additional endoscopic procedures and quality of life (QALY) estimates were similar for BS and ED patients at 6 and 12 mo. Concomitant use of gastrointestinal prescribed medication was greater in the stent group (BS 5.1, ED 2.0 prescriptions; P < 0.001), as were related adverse events (BS 1.4, ED 0.0 events; P = 0.024). Groups were comparable at baseline and findings were statistically significant but numbers were small due to under-recruitment. The oesophageal tract has somatic sensitivity and the process of the stent dissolving, possibly unevenly, might promote discomfort or reflux. Stenting was associated with greater dysphagia, co-medication and adverse events. Rigorously conducted and adequately powered trials are needed before widespread adoption of this technology.

Biodegradable stent or balloon dilatation for benign oesophageal stricture: Pilot randomised controlled trial

PubMed Central

Dhar, Anjan; Close, Helen; Viswanath, Yirupaiahgari K; Rees, Colin J; Hancock, Helen C; Dwarakanath, A Deepak; Maier, Rebecca H; Wilson, Douglas; Mason, James M

2014-01-01

AIM: To undertake a randomised pilot study comparing biodegradable stents and endoscopic dilatation in patients with strictures. METHODS: This British multi-site study recruited seventeen symptomatic adult patients with refractory strictures. Patients were randomised using a multicentre, blinded assessor design, comparing a biodegradable stent (BS) with endoscopic dilatation (ED). The primary endpoint was the average dysphagia score during the first 6 mo. Secondary endpoints included repeat endoscopic procedures, quality of life, and adverse events. Secondary analysis included follow-up to 12 mo. Sensitivity analyses explored alternative estimation methods for dysphagia and multiple imputation of missing values. Nonparametric tests were used. RESULTS: Although both groups improved, the average dysphagia scores for patients receiving stents were higher after 6 mo: BS-ED 1.17 (95%CI: 0.63-1.78) P = 0.029. The finding was robust under different estimation methods. Use of additional endoscopic procedures and quality of life (QALY) estimates were similar for BS and ED patients at 6 and 12 mo. Concomitant use of gastrointestinal prescribed medication was greater in the stent group (BS 5.1, ED 2.0 prescriptions; P < 0.001), as were related adverse events (BS 1.4, ED 0.0 events; P = 0.024). Groups were comparable at baseline and findings were statistically significant but numbers were small due to under-recruitment. The oesophageal tract has somatic sensitivity and the process of the stent dissolving, possibly unevenly, might promote discomfort or reflux. CONCLUSION: Stenting was associated with greater dysphagia, co-medication and adverse events. Rigorously conducted and adequately powered trials are needed before widespread adoption of this technology. PMID:25561787

Reverse translation of adverse event reports paves the way for de-risking preclinical off-targets.

PubMed

Maciejewski, Mateusz; Lounkine, Eugen; Whitebread, Steven; Farmer, Pierre; DuMouchel, William; Shoichet, Brian K; Urban, Laszlo

2017-08-08

The Food and Drug Administration Adverse Event Reporting System (FAERS) remains the primary source for post-marketing pharmacovigilance. The system is largely un-curated, unstandardized, and lacks a method for linking drugs to the chemical structures of their active ingredients, increasing noise and artefactual trends. To address these problems, we mapped drugs to their ingredients and used natural language processing to classify and correlate drug events. Our analysis exposed key idiosyncrasies in FAERS, for example reports of thalidomide causing a deadly ADR when used against myeloma, a likely result of the disease itself; multiplications of the same report, unjustifiably increasing its importance; correlation of reported ADRs with public events, regulatory announcements, and with publications. Comparing the pharmacological, pharmacokinetic, and clinical ADR profiles of methylphenidate, aripiprazole, and risperidone, and of kinase drugs targeting the VEGF receptor, demonstrates how underlying molecular mechanisms can emerge from ADR co-analysis. The precautions and methods we describe may enable investigators to avoid confounding chemistry-based associations and reporting biases in FAERS, and illustrate how comparative analysis of ADRs can reveal underlying mechanisms.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction.

PubMed

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-05-15

Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs.

Partially Covered Metal Stents May Not Prolong Stent Patency Compared to Uncovered Stents in Unresectable Malignant Distal Biliary Obstruction

PubMed Central

Kim, Jae Yun; Ko, Gyu Bong; Lee, Tae Hoon; Park, Sang-Heum; Lee, Yun Nah; Cho, Young Sin; Jung, Yunho; Chung, Il-Kwun; Choi, Hyun Jong; Cha, Sang-Woo; Moon, Jong Ho; Cho, Young Deok; Kim, Sun-Joo

2017-01-01

Background/Aims Controversy still exists regarding the benefits of covered self-expandable metal stents (SEMSs) compared to uncovered SEMSs. We aimed to compare the patency and stent-related adverse events of partially covered SEMSs (PC-SEMSs) and uncovered SEMSs in unresectable malignant distal biliary obstruction. Methods A total of 134 patients who received a PC-SEMS or uncovered SEMS for palliation of unresectable malignant distal biliary obstruction were reviewed retrospectively. The main outcome measures were stent patency, stent-related adverse events, and overall survival. Results The median stent patency was 118 days (range, 3 to 802 days) with PC-SEMSs and 105 days (range, 2 to 485 days) with uncovered SEMSs (p=0.718). The overall endoscopic revision rate due to stent dysfunction was 36.6% (26/71) with PC-SEMSs and 36.5% (23/63) with uncovered SEMSs (p=0.589). Tumor ingrowth was more frequent with uncovered SEMSs (4.2% vs 19.1%, p=0.013), but migration was more frequent with PC-SEMSs (11.2% vs 1.5%, p=0.04). The incidence of stent-related adverse events was 2.8% (2/71) with PC-SEMSs and 9.5% (6/63) with uncovered SEMSs (p=0.224). The median overall survival was 166 days with PC-SEMSs and 168 days with uncovered SEMSs (p=0.189). Conclusions Compared to uncovered SEMSs, PC-SEMSs did not prolong stent patency in unresectable malignant distal biliary obstruction. Stent migration was more frequent with PC-SEMSs. However, tumor ingrowth was less frequent with PC-SEMSs compared to uncovered SEMSs. PMID:28208003

Association of Preprocedural Fasting With Outcomes of Emergency Department Sedation in Children.

PubMed

Bhatt, Maala; Johnson, David W; Taljaard, Monica; Chan, Jason; Barrowman, Nick; Farion, Ken J; Ali, Samina; Beno, Suzanne; Dixon, Andrew; McTimoney, C Michelle; Dubrovsky, Alexander Sasha; Roback, Mark G

2018-05-07

It is not clear whether adherence to preprocedural fasting guidelines prevent pulmonary aspiration and associated adverse outcomes during emergency department (ED) sedation of children. To examine the association between preprocedural fasting duration and the incidence of sedation-related adverse outcomes in a large sample of children. We conducted a planned secondary analysis of a multicenter prospective cohort study of children aged 0 to 18 years who received procedural sedation for a painful procedure in 6 Canadian pediatric EDs from July 2010 to February 2015. The primary risk factor was preprocedural fasting duration. Secondary risk factors were age, sex, American Society of Anesthesiologists classification, preprocedural and sedation medications, and procedure type. Four outcomes were examined: (1) pulmonary aspiration, (2) the occurrence of any adverse event, (3) serious adverse events, and (4) vomiting. A total of 6183 children with a median age of 8.0 years (interquartile range, 4.0-12.0 years), of whom 6166 (99.7%) had healthy or mild systemic disease (American Society of Anesthesiologists levels I or II), were included in the analysis. Of these, 2974 (48.1%) and 310 (5.0%) children did not meet American Society of Anesthesiologists fasting guidelines for solids and liquids, respectively. There were no cases of pulmonary aspiration. There were 717 adverse events (11.6%; 95% CI, 10.8%-12.4%), of which 68 (1.1%; 95% CI, 0.9%-1.3%) were serious adverse events and 315 (5.1%; 95% CI, 4.6%-5.7%) were vomiting. The odds ratio (OR) of occurrence of any adverse event, serious adverse events, and vomiting did not change significantly with each additional hour of fasting duration for both solids (any adverse event: OR, 1.00; 95% CI, 0.98 to 1.02; serious adverse events, OR, 1.01; 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.97-1.03) and liquids (any adverse event: OR, 1.00; 95% CI, 0.98-1.02; serious adverse events: 1.01, 95% CI, 0.95-1.07; vomiting: OR, 1.00; 95% CI, 0.96-1.03). In this study, there was no association between fasting duration and any type of adverse event. These findings do not support delaying sedation to meet established fasting guidelines.

Dietary Supplement Adverse Event Report Data From the FDA Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS), 2004-2013.

PubMed

Timbo, Babgaleh B; Chirtel, Stuart J; Ihrie, John; Oladipo, Taiye; Velez-Suarez, Loy; Brewer, Vickery; Mozersky, Robert

2018-05-01

The Food and Drug Administration (FDA)'s Center for Food Safety and Applied Nutrition (CFSAN) oversees the safety of the nation's foods, dietary supplements, and cosmetic products. To present a descriptive analysis of the 2004-2013 dietary supplement adverse event report (AER) data from CAERS and evaluate the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act as pertaining to dietary supplements adverse events reporting. We queried CAERS for data from the 2004-2013 AERs specifying at least 1 suspected dietary supplement product. We extracted the product name(s), the symptom(s) reported, age, sex, and serious adverse event outcomes. We examined time trends for mandatory and voluntary reporting and performed analysis using SAS v9.4 and R v3.3.0 software. Of the total AERs (n = 15 430) received from January 1, 2004, through December 31, 2013, indicating at least 1 suspected dietary supplement product, 66.9% were mandatory, 32.2% were voluntary, and 0.9% were both mandatory and voluntary. Reported serious outcomes included death, life-threatening conditions, hospitalizations, congenital anomalies/birth defects and events requiring interventions to prevent permanent impairments (5.1%). The dietary supplement adverse event reporting rate in the United States was estimated at ~2% based on CAERS data. This study characterizes CAERS dietary supplement adverse event data for the 2004-2013 period and estimates a reporting rate of 2% for dietary supplement adverse events based on CAERS data. The findings show that the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act had a substantial impact on the reporting of adverse events.

MedWatch, the FDA Safety Information and Adverse Event Reporting Program

MedlinePlus

... Information and Adverse Event Reporting Program MedWatch: The FDA Safety Information and Adverse Event Reporting Program Share ... use. [Posted 06/01/2018] More What's New FDA Approved Safety Information DailyMed (National Library of Medicine) ...

Fascia iliaca compartment nerve block versus systemic pain control for acute femur fractures in the pediatric emergency department.

PubMed

Neubrand, Tara L; Roswell, Kelley; Deakyne, Sara; Kocher, Kendra; Wathen, Joseph

2014-07-01

To compare management of acute femur fractures in children who received a fascia iliaca compartment nerve block (FICNB) to those who received systemic intravenously administered analgesics in the pediatric emergency department. The comparison evaluated frequency of use, effectiveness, and associated adverse event profiles. Study population was derived from a retrospective chart review of pediatric patients sustaining acute femur fractures between 2005 and 2009. Cases (received FICNB) were compared with controls (only systemic analgesia) in terms of effectiveness and adverse event. Outcomes included total doses of systemic medications received and comparison of preintervention and postintervention pain scores. Two hundred fifty-nine charts were reviewed: 158 who received FICNB versus 101 who did not. The median dose of systemic medications was 1 dose lower in the FICNB group compared with the systemic medications group. This remained significant after controlling for age and preintervention pain scores (P = 0.02). Median postintervention pain scores in the FICNB group were 1.5 points lower than those in the systemic medications group. This remained significant while controlling for preintervention pain scores and age (P < 0.01). There was no difference in the total adverse events between the FICNB and the control group in either the unadjusted or adjusted analyses (P = 0.08). The FICNB group had 2 seizure episodes, one of which had associated subarachnoid hemorrhage. No patient in either group experienced bradycardia, arrhythmia, visual disturbance, abnormal hearing, mouth numbness, motor tremors, pain or bleeding at injection site, or prolonged nerve block. We report on the largest number of FICNBs administered in a pediatric emergency department for acute femur fractures. Effectiveness, as measured by pain scores and total doses of systemic analgesia, was improved in the FICNB group versus the control. There was no difference in adverse events between the groups.

Peroral endoscopic myotomy for the treatment of esophageal achalasia: systematic review and pooled analysis.

PubMed

Patel, K; Abbassi-Ghadi, N; Markar, S; Kumar, S; Jethwa, P; Zaninotto, G

2016-10-01

Peroral endoscopic myotomy (POEM) is a novel approach to performing esophageal myotomy for the treatment of achalasia. This review aims to assess subjective and objective metrics of achalasia treatment efficacy, perioperative adverse events and the incidence of postoperative gastroesophageal reflux disease in patients treated with POEM. Secondary aims include a pooled analysis comparison of the clinical outcomes and procedural safety of POEM versus laparoscopic Heller's myotomy (LHM). A systematic review of the literature, up to and including January 15, 2015, was conducted for studies reporting POEM outcomes. Studies comparing POEM to LHM were also included for the purpose of pooled analysis. Outcomes from 1122 POEM patients, from 22 studies, are reported in this systematic review. Minor operative adverse events included capno/pneumo-peritoneum (30.6%), capno/pneumo-thorax (11.0%) and subcutaneous emphysema (31.6%). Major operative adverse events included mediastinal leak (0.3%), postoperative bleeding (1.1%) and a single mortality (0.09%). There was an improvement in lower esophageal sphincter pressure and timed barium esophagram column height of 66% and 80% post-POEM, respectively. Symptom improvement was demonstrated with a pre- and post-POEM Eckardt score ± standard deviation of 6.8 ± 1.0 and 1.2 ± 0.6, respectively. Pre- and post-POEM endoscopy showed esophagitis in 0% and 19% of patients, respectively. The median (interquartile range) points scored for study quality was 15 (14-16) out of total of 32. Pooled analysis of three comparative studies between LHM and POEM showed similar results for adverse events, perforation rate, operative time and a nonsignificant trend toward a reduced length of hospital stay in the POEM group. In conclusion, POEM is a safe and effective treatment for achalasia, showing significant improvements in objective metrics and achalasia-related symptoms. Randomized comparative studies of LHM and POEM are required to determine the most effective treatment modality for achalasia. © 2015 International Society for Diseases of the Esophagus.

Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

PubMed

Chen, Alice P; Setser, Ann; Anadkat, Milan J; Cotliar, Jonathan; Olsen, Elise A; Garden, Benjamin C; Lacouture, Mario E

2012-11-01

Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

PubMed

Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

2009-08-01

Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.

Subjective Numeracy and the Influence of Order and Amount of Audible Information on Perceived Medication Value

PubMed Central

Fraenkel, Liana; Stolar, Marilyn; Swift, Sarah; Street, Richard L.; Chowdhary, Harjinder; Peters, Ellen

2016-01-01

Background Order and amount of information influence patients’ risk perceptions, but most studies have evaluated patients’ reactions to written materials. The objective of this study was to examine the effect of four communication strategies, varying in their order and/or amount of information, on judgments related to an audible description of a new medication and among patients who varied in subjective numeracy. Methods We created five versions of a hypothetical scenario describing a new medication. The versions were composed to elucidate whether order and/or amount of the information describing benefits and adverse events influenced how subjects valued a new medication. After listening to a randomly assigned version, perceived medication value was measured by asking subjects to choose one of the following statements: the risks outweigh the benefits, the risks and benefits are equally balanced, or the benefits outweigh the risks. Results Of the 432 patients contacted, 389 participated in the study. Listening to a brief description of benefits followed by an extended description of adverse events resulted in a greater likelihood of perceiving that the medication’s benefits outweighed the risks compared to: 1) presenting the extended adverse events description before the benefits, 2) giving a greater amount of information related to benefits, and 3) sandwiching the adverse events between benefits. These associations were only observed among subjects with average or higher subjective numeracy. Conclusion If confirmed in future studies, our results suggest that, for patients with average or better subjective numeracy, perceived medication value is highest when a brief presentation of benefits is followed by an extended description of adverse events. PMID:27216580

Investigation of adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents in the iliac vein: insights into developing a better iliac vein stent.

PubMed

Shida, Takuya; Umezu, Mitsuo; Iwasaki, Kiyotaka

2018-06-01

We analyzed the adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents for the treatment of iliac venous thromboembolism and investigated their relationships with the anatomical features of the iliac vein, to gain insights into the development of a better iliac vein stent. Reports of adverse events following the use of stents in the iliac vein were retrieved from the Manufacturer and User Facility Device Experience (MAUDE) database that contain suspected device-associated complications reported to the Food and Drug Administration. Data from 2006 to 2016 were investigated. The literature analysis was also conducted using PubMed, Cochrane Library, EMBASE, and Web of Science focusing on English articles published up to 4 October 2016. The analysis of 88 adverse events from the MAUDE database and 182 articles from the literature revealed that a higher number of adverse events had been reported following the use of arterial stents in the iliac vein compared to CE-marked iliac vein stents. While stent migration and shortening were reported only for the arterial stents, stent fracture and compression occurred regardless of the stent type, even though a vein does not pulsate. A study of the anatomical features of the iliac vein implies that bending, compression, and kink loads are applied to the iliac vein stents in vivo. For designing, developing, and pre-clinical testing of stents intended for use in the iliac vein, the above mechanical load environments induced by the anatomical features should be considered.

Economic and clinical aspects of intravenous versus oral busulfan in adult patients for conditioning prior to HSCT.

PubMed

Berger, Karin; Schopohl, Dorothee; Rieger, Christina; Ostermann, Helmut

2015-12-01

Busulfan (BU) used as cytoreductive conditioning prior to hematopoietic stem cell transplantation (HSCT) is available as intravenous (IV) and oral (O) preparation. IV-BU has clinical advantages associated with relevant incremental costs. The aim was to determine the economic impact of IV-BU versus O-BU in adult HSCT recipients from a German health care providers' perspective. A budget-impact model (BIM) including costs and risks for oral mucositis (OM), infection with OM, and hepatic sinusoidal obstruction syndrome (SOS) was developed. Model inputs are literature data comparing clinical effects of IV-BU versus O-BU and German cost data (conditioning therapy, treatment of OM, infections, SOS without/with multiorgan failure) from literature and tariff lists. Base case calculations resulted the following: total costs of adverse events were €86,434 with O-BU and €44,376 with IV-BU for ten patients each. Considering costs of adverse events and drugs, about €5840 for ten patients receiving IV-BU are saved. Sensitivity analyses were conducted in several ways. Cost savings range between €4910 and €12,640 per ten patients for all adverse events and €2070 or €1140 per ten patients considering SOS only. Drug treatment of SOS and treatment of multiorgan failure during severe SOS are major cost drivers. Worst case scenario calculations (assuming -25% risk of all adverse events for O-BU and +25% for IV-BU) yield up to €27,570 per ten patients with IV-BU. Considering costs of adverse events and drugs, IV-BU is the dominant alternative from a German providers' perspective. For more comprehensive economic evaluations, additional epidemiological data, evidence on clinical outcomes, patient-reported outcomes, and treatment patterns are needed.

THE EFFECT OF INTERACTION BETWEEN CLOPIDOGREL AND PROTON PUMP INHIBITORS ON ADVERSE CARDIOVASCULAR EVENTS IN PATIENTS WITH ACUTE CORONARY SYNDROME

PubMed Central

Bhurke, Sharvari M.; Martin, Bradley C.; Li, Chenghui; Franks, Amy M.; Bursac, Zoran; Said, Qayyim

2012-01-01

Study Objective This study examined the effect of clopidogrel and proton pump inhibitors (PPIs) interaction on subsequent acute coronary syndrome (ACS)-related inpatient and emergency room (ER) visits. Design Population based, retrospective cohort study. Data Source IMS LifeLink Health Plan administrative claims database containing a large nationally dispersed group of commercially insured subjects between 2001 and 2008. Patients Subjects age ≥18 years with a diagnosis of ACS and at least one clopidogrel prescription within 90 days after the diagnosis were included. Exposed group was defined as having overlapping clopidogrel-PPI prescriptions. Subjects were followed from their first clopidogrel prescription until they experienced an adverse cardiovascular event (re-hospitalization or errors visit due to ACS), were disenrolled or reached the end of study period. Measurements and Main Results The clopidogrel plus PPIs group was matched 1:1 with the clopidogrel alone group using the propensity scoring method. Exposure to overlapping clopidogrel-PPI prescriptions was modeled as a time dependent covariate. Cox hazards regression was used to estimate the risk of an adverse cardiovascular event for those having overlapping clopidogrel-PPI prescriptions versus those having clopidogrel alone. Propensity score matching resulted in 2,674 patient pairs. The mean age was 61.30 years with a mean follow-up of 268 days and 70.04% were male. Clopidogrel use co-medicated with PPIs was associated with a significantly increased risk of cardiovascular adverse events (HR=1.438; 95% CI, 1.237-1.671), as compared to clopidogrel use not co-medicated with PPIs. Conclusion Concurrent use of clopidogrel plus PPIs was associated with a significant increase in risk of adverse cardiovascular events for ACS patients. PMID:22744772

Safety and tolerability of atomoxetine in treatment of attention deficit hyperactivity disorder in adult patients: an integrated analysis of 15 clinical trials.

PubMed

Camporeale, Angelo; Porsdal, Vibeke; De Bruyckere, Katrien; Tanaka, Yoko; Upadhyaya, Himanshu; Deix, Claudia; Deberdt, Walter

2015-01-01

The safety profile of atomoxetine in the treatment of attention deficit hyperactivity disorder has been studied in many clinical trials. We performed an integrated safety analysis of 15 clinical trials in adults with attention deficit hyperactivity disorder. The analysis pooled patient data into three groups: acute placebo-controlled trials; long-term placebo-controlled trials; all trials. In total, 4829 adults (18-77 years, median: 36 years) were exposed to atomoxetine. Statistically significantly more atomoxetine-treated than placebo-treated patients experienced treatment-emergent adverse events (81.3% vs. 68.3% acute; 90.6% vs. 76.8% long term) and discontinued due to adverse events (8.9% vs. 4.0% acute; 17.9% vs. 6.3% long term). No statistically significant differences were observed in the proportion of patients experiencing serious adverse events. No previously unknown adverse events were identified. The most common adverse events included nausea, dry mouth, decreased appetite, insomnia and erectile dysfunction. Mean increases in heart rate (+5.2 beats per min) and blood pressure (systolic +2 mmHg, diastolic +1.9 mmHg) were modest. The proportion of patients experiencing clinically significant increases in blood pressure and heart rate at any time was statistically significantly higher with atomoxetine (systolic blood pressure 13-17%, diastolic blood pressure 37-40%, heart rate 42-43%) compared to placebo (systolic blood pressure 8-13%, diastolic blood pressure 29-34%, heart rate 21-26%). There was no increased risk of suicidal ideation or behaviour. Our findings confirm atomoxetine's known safety profile. From a safety perspective, atomoxetine is a useful treatment option for adults with attention deficit hyperactivity disorder. © The Author(s) 2014.

Type D personality predicts death or myocardial infarction after bare metal stent or sirolimus-eluting stent implantation: a Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry substudy.

PubMed

Pedersen, Susanne S; Lemos, Pedro A; van Vooren, Priya R; Liu, Tommy K K; Daemen, Joost; Erdman, Ruud A M; Smits, Pieter C; Serruys, Patrick W J C; van Domburg, Ron T

2004-09-01

We investigated the effect of Type D personality on the occurrence of adverse events at nine months in patients with ischemic heart disease (IHD) after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SESs) or bare stents. Type D patients experience increased negative emotions and tend not to express these emotions in social interactions. The SES is a new advent in interventional cardiology that reduces the restenosis rate and the risk of a major adverse cardiac event, but the SES has not been shown to confer any benefits on death or myocardial infarction (MI). Consecutive patients with IHD (n = 875) enrolled in the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry completed the Type D Personality Scale (DS14) six months after PCI. The end point was a composite of death and MI. Events occurring before administration of the DS14 were excluded from analyses. At nine months' follow-up, there were 20 events. Type D patients were at a cumulative increased risk of adverse outcome compared with non-Type D patients: 5.6% versus 1.3% (p < 0.002). Type D personality (odds ratio [OR] 5.31; 95% confidence interval [CI] 2.06 to 13.66) remained an independent predictor of adverse outcome adjusting for all other variables, including SES versus bare-stent implantation. Type D personality was an independent predictor of adverse events in patients optimally treated with the latest advent in interventional cardiology. The DS14 could be used as a screening instrument in routine clinical practice to optimize risk stratification in IHD patients.

Concomitant use of low-dose methotrexate and NSAIDs and the risk of serious adverse events among patients with rheumatoid arthritis.

PubMed

Svanström, Henrik; Lund, Marie; Melbye, Mads; Pasternak, Björn

2018-05-24

Case reports and pharmacokinetic studies have suggested that concomitant use of low-dose methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with increased risk of methotrexate toxicity. This study aimed to investigate the risk of serious adverse events associated with concomitant use of low-dose methotrexate and NSAIDs, compared with use of methotrexate alone, among patients with rheumatoid arthritis. The study was conducted as a register-based cohort study in Denmark, 2004 to 2015, including episodes of concomitant use of methotrexate and NSAIDs (n = 21 536) and control episodes of use of methotrexate alone (n = 21 725). The primary outcome was the composite end point any serious adverse event, including liver toxicity, acute renal failure, and cytopenia. Secondary outcomes were the individual outcome components. Analyses were conducted using proportional-hazards regression, with adjustment using inverse-probability-of-treatment weighting based on propensity scores. During follow-up, 110 cases of the primary outcome occurred during concomitant use of methotrexate and NSAIDs (unadjusted incidence rate 12.1 per 1000 person-years) and 129 during control episodes (11.0 per 1000 person-years). Concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of any serious adverse event (weighted hazard ratio 1.40; 95% CI, 1.07-1.82). In secondary analyses, concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of acute renal failure and cytopenia. Concomitant use of low-dose methotrexate and NSAIDs was associated with a significantly increased risk of serious adverse events, expanding on the evidence base for current regulatory recommendations that advocate caution when low-dose methotrexate and NSAID are coprescribed. Copyright © 2018 John Wiley & Sons, Ltd.

Factors influencing adverse events reporting within the health care system: the case of artemisinin-based combination treatments in northern Ghana.

PubMed

Chatio, Samuel; Aborigo, Raymond; Adongo, Philip Baba; Anyorigiya, Thomas; Dalinjong, Philip Ayizem; Akweongo, Patricia; Oduro, Abraham

2016-02-27

The use of artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria was a policy recommended by World Health Organization. In 2004, Ghana changed her first-line anti-malarial drug policy to use ACT. This study examined factors affecting adverse events reporting in northern Ghana after the introduction of ACT. This was a qualitative study based on sixty in-depth interviews with health workers, chemical shop owners and patients with malaria who were given ACT at the health facilities. Purposive sampling method was used to select study participants. The interviews were transcribed, coded into themes using Nvivo 9 software. The thematic analysis framework was used to analyse the data. Study respondents reported body weakness and dizziness as the most frequent side effects they had experienced from the used of ACT. Other side effects they reported were swollen testes, abdominal pain and shivering. These side effects were mostly associated with the use of artesunate-amodiaquine compared to other artemisinin-based combinations. Patients were not provided information about the side effects of the drugs and so did not report when they experienced them. Also long queues at health facilities and unfriendly health worker attitude were the main factors affecting adverse events reporting. Other factors such as wrong use of ACT at home, farming and commercial activities also affected effective adverse events reporting in the study area. Patients' lack of knowledge and health sector drawbacks affected side effect reporting on ACT. Intensive health education on likely side effects of ACT should be provided to patients by health workers. Also, improving health worker attitude toward clients will encourage patients to visit the health facilities when they react negatively to ACT and, subsequently, will improve on adverse events reporting.

[Risk Management: concepts and chances for public health].

PubMed

Palm, Stefan; Cardeneo, Margareta; Halber, Marco; Schrappe, Matthias

2002-01-15

Errors are a common problem in medicine and occur as a result of a complex process involving many contributing factors. Medical errors significantly reduce the safety margin for the patient and contribute additional costs in health care delivery. In most cases adverse events cannot be attributed to a single underlying cause. Therefore an effective risk management strategy must follow a system approach, which is based on counting and analysis of near misses. The development of defenses against the undesired effects of errors should be the main focus rather than asking the question "Who blundered?". Analysis of near misses (which in this context can be compared to indicators) offers several methodological advantages as compared to the analysis of errors and adverse events. Risk management is an integral element of quality management.

Impact of stent length on clinical outcomes of first-generation and new-generation drug-eluting stents.

PubMed

Konishi, Hirokazu; Miyauchi, Katsumi; Dohi, Tomotaka; Tsuboi, Shuta; Ogita, Manabu; Naito, Ryo; Kasai, Takatoshi; Tamura, Hiroshi; Okazaki, Shinya; Isoda, Kikuo; Daida, Hiroyuki

2016-04-01

The aim of this study is to compare first- and new-generation drug-eluting stents (DESs) which are implanted in long lesion. Stent length is known to be a predictor of adverse events after percutaneous coronary intervention (PCI), even with the first-generation DESs. The introduction of new-generation DESs has reduced the rates of adverse clinical events. However, the impact of stent length on long-term clinical outcomes is not well known. A total of 1181 consecutive patients who underwent PCI using either a first-generation DES (n = 885) or a new-generation DES (n = 296) between 2004 and 2011 were investigated. In each of the stent groups, the patients were divided into two groups by stent length (>32 and ≤32 mm) and compared. During the follow-up period, the incidence of major adverse cardiac events (MACEs) was significantly higher for patients with long stents implanted than with short stents (P < 0.01; log-rank test) in the first-generation DES group. However, there was no difference in the incidence of MACEs between the long- and short-stent groups in the new-generation DES group (P = 0.24; log-rank test). On multivariate Cox regression analysis, stent length was not associated with adverse events in the new-generation DES groups [hazard ratio (HR) 0.87; 95 % confidence interval (95 % CI) 0.71-1.04; P = 0.14]. Implanted stent length was significantly associated with a higher risk of MACEs in patients who received first-generation DESs, but not in patients who received the new-generation DESs.

Pseudomonas aeruginosa keratitis: outcomes and response to corticosteroid treatment.

PubMed

Sy, Aileen; Srinivasan, Muthiah; Mascarenhas, Jeena; Lalitha, Prajna; Rajaraman, Revathi; Ravindran, Meenakshi; Oldenburg, Catherine E; Ray, Kathryn J; Glidden, David; Zegans, Michael E; McLeod, Stephen D; Lietman, Thomas M; Acharya, Nisha R

2012-01-25

To compare the clinical course and effect of adjunctive corticosteroid therapy in Pseudomonas aeruginosa with those of all other strains of bacterial keratitis. Subanalyses were performed on data collected in the Steroids for Corneal Ulcers Trial (SCUT), a large randomized controlled trial in which patients were treated with moxifloxacin and were randomly assigned to 1 of 2 adjunctive treatment arms: corticosteroid or placebo (4 times a day with subsequent reduction). Multivariate analysis was used to determine the effect of predictors, organism, and treatment on outcomes, 3-month best-spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size. The incidence of adverse events over a 3-month follow-up period was compared using Fisher's exact test. SCUT enrolled 500 patients. One hundred ten patients had P. aeruginosa ulcers; 99 of 110 (90%) enrolled patients returned for follow-up at 3 months. Patients with P. aeruginosa ulcers had significantly worse visual acuities than patients with other bacterial ulcers (P = 0.001) but showed significantly more improvement in 3-month BSCVA than those with other bacterial ulcers, adjusting for baseline characteristics (-0.14 logMAR; 95% confidence interval, -0.23 to -0.04; P = 0.004). There was no significant difference in adverse events between P. aeruginosa and other bacterial ulcers. There were no significant differences in BSCVA (P = 0.69), infiltrate/scar size (P = 0.17), and incidence of adverse events between patients with P. aeruginosa ulcers treated with adjunctive corticosteroids and patients given placebo. Although P. aeruginosa corneal ulcers have a more severe presentation, they appear to respond better to treatment than other bacterial ulcers. The authors did not find a significant benefit with corticosteroid treatment, but they also did not find any increase in adverse events. (ClinicalTrials.gov number, NCT00324168.).

Pseudomonas aeruginosa Keratitis: Outcomes and Response to Corticosteroid Treatment

PubMed Central

Sy, Aileen; Srinivasan, Muthiah; Mascarenhas, Jeena; Lalitha, Prajna; Rajaraman, Revathi; Ravindran, Meenakshi; Oldenburg, Catherine E.; Ray, Kathryn J.; Glidden, David; Zegans, Michael E.; McLeod, Stephen D.; Lietman, Thomas M.

2012-01-01

Purpose. To compare the clinical course and effect of adjunctive corticosteroid therapy in Pseudomonas aeruginosa with those of all other strains of bacterial keratitis. Methods. Subanalyses were performed on data collected in the Steroids for Corneal Ulcers Trial (SCUT), a large randomized controlled trial in which patients were treated with moxifloxacin and were randomly assigned to 1 of 2 adjunctive treatment arms: corticosteroid or placebo (4 times a day with subsequent reduction). Multivariate analysis was used to determine the effect of predictors, organism, and treatment on outcomes, 3-month best-spectacle-corrected visual acuity (BSCVA), and infiltrate/scar size. The incidence of adverse events over a 3-month follow-up period was compared using Fisher's exact test. Results. SCUT enrolled 500 patients. One hundred ten patients had P. aeruginosa ulcers; 99 of 110 (90%) enrolled patients returned for follow-up at 3 months. Patients with P. aeruginosa ulcers had significantly worse visual acuities than patients with other bacterial ulcers (P = 0.001) but showed significantly more improvement in 3-month BSCVA than those with other bacterial ulcers, adjusting for baseline characteristics (−0.14 logMAR; 95% confidence interval, −0.23 to −0.04; P = 0.004). There was no significant difference in adverse events between P. aeruginosa and other bacterial ulcers. There were no significant differences in BSCVA (P = 0.69), infiltrate/scar size (P = 0.17), and incidence of adverse events between patients with P. aeruginosa ulcers treated with adjunctive corticosteroids and patients given placebo. Conclusions. Although P. aeruginosa corneal ulcers have a more severe presentation, they appear to respond better to treatment than other bacterial ulcers. The authors did not find a significant benefit with corticosteroid treatment, but they also did not find any increase in adverse events. (ClinicalTrials.gov number, NCT00324168.) PMID:22159005

Patient care transitions from the emergency department to the medicine ward: evaluation of a standardized electronic signout tool.

PubMed

Gonzalo, Jed D; Yang, Julius J; Stuckey, Heather L; Fischer, Christopher M; Sanchez, Leon D; Herzig, Shoshana J

2014-08-01

To evaluate the impact of a new electronic handoff tool for emergency department to medicine ward patient transfers over a 1-year period. Prospective mixed-methods analysis of data submitted by medicine residents following admitting shifts before and after eSignout implementation. University-based, tertiary-care hospital. Internal medicine resident physicians admitting patients from the emergency department. An electronic handoff tool (eSignout) utilizing automated paging communication and responsibility acceptance without mandatory verbal communication between emergency department and medicine ward providers. (i) Incidence of reported near misses/adverse events, (ii) communication of key clinical information and quality of verbal communication and (iii) characterization of near misses/adverse events. Seventy-eight of 80 surveys (98%) and 1058 of 1388 surveys (76%) were completed before and after eSignout implementation. Compared with pre-intervention, residents in the post-intervention period reported similar number of shifts with a near miss/adverse event (10.3 vs. 7.8%; P = 0.27), similar communication of key clinical information, and improved verbal signout quality, when it occurred. Compared with the former process requiring mandatory verbal communication, 93% believed the eSignout was more efficient and 61% preferred the eSignout. Patient safety issues related to perceived sufficiency/accuracy of diagnosis, treatment or disposition, and information quality. The eSignout was perceived as more efficient and preferred over the mandatory verbal signout process. Rates of reported adverse events were similar before and after the intervention. Our experience suggests electronic platforms with optional verbal communication can be used to standardize and improve the perceived efficiency of patient handoffs. © The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

Efficacy and safety of meditative movement therapies in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Langhorst, Jost; Klose, Petra; Dobos, Gustav J; Bernardy, Kathrin; Häuser, Winfried

2013-01-01

A systematic review with meta-analysis of the efficacy and safety of meditative movement therapies (Qigong, Tai Chi and Yoga) in fibromyalgia syndrome (FMS) was carried out. We screened Clinicaltrials.Gov, Cochrane Library, PsycINFO, PubMed and Scopus (through December 2010) and the reference sections of original studies for meditative movement therapies (MMT) in FMS. Randomized controlled trials (RCT) comparing MMT to controls were analysed. Outcomes of efficacy were pain, sleep, fatigue, depression and health-related quality of life (HRQOL). Effects were summarized using standardized mean differences (SMD [95% confidence interval]). Outcomes of safety were drop out because of adverse events and serious adverse events. A total of 7 out of 117 studies with 362 subjects and a median of 12 sessions (range 8-24) were included. MMT reduced sleep disturbances (-0.61 [-0.95, -0.27]; 0.0004), fatigue (-0.66 [-0.99, -0.34]; <0.0001), depression (-0.49 [-0.76, -0.22]; 0.0004) and limitations of HRQOL (-0.59 [-0.93, -0.24]; 0.0009), but not pain (-0.35 [-0.80, 0.11]; 0.14) compared to controls at final treatment. The significant effects on sleep disturbances (-0.52 [-0.97, -0.07]; 0.02) and HRQOL (-0.66 [-1.31, -0.01]; 0.05) could be maintained after a median of 4.5 (range 3-6) months. In subgroup analyses, only Yoga yielded significant effects on pain, fatigue, depression and HRQOL at final treatment. Drop out rate because of adverse events was 3.1%. No serious adverse events were reported. MMT are safe. Yoga had short-term beneficial effects on some key domains of FMS. There is a need for high-quality studies with larger sample sizes to confirm the results.

Randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection.

PubMed

Colvin, Richard A; Tanwandee, Tawesak; Piratvisuth, Teerha; Thongsawat, Satawat; Hui, Aric Josun; Zhang, Hongfei; Ren, Hong; Chen, Pei-Jer; Chuang, Wan-Long; Sobhonslidsuk, Abhasnee; Li, Ruobing; Qi, Yin; Praestgaard, Jens; Han, Yi; Xu, Junfang; Stein, Daniel S

2015-01-01

Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections. This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e-antigen (HBeAg) positive. One hundred and forty-one patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV-DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events. The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV-DNA from baseline. Reductions in HBV-DNA were not significantly different, except the 1200 μg every 4 weeks albinterferon dose which was inferior compared with pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups. Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665). © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Percutaneous Coronary Intervention Is More Beneficial Than Optimal Medical Therapy in Elderly Patients with Angina Pectoris.

PubMed

Won, Hoyoun; Her, Ae Young; Kim, Byeong Keuk; Kim, Yong Hoon; Shin, Dong Ho; Kim, Jung Sun; Ko, Young Guk; Choi, Donghoon; Kwon, Hyuck Moon; Jang, Yangsoo; Hong, Myeong Ki

2016-03-01

Data comparing the clinical benefits of medical treatment with those of percutaneous coronary intervention (PCI) in an elderly population with angina pectoris are limited. Therefore, we evaluated the efficacy of elective PCI versus optimal medical treatment (OMT) in elderly patients (between 75 and 84 years old) with angina pectoris. One hundred seventy-seven patients with significant coronary artery stenosis were randomly assigned to either the PCI group (n=90) or the OMT group (n=87). The primary outcome was a composite of major adverse events in the 1-year follow-up period that included cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and stroke. Major adverse events occurred in 5 patients (5.6%) of the PCI group and in 17 patents (19.5%) of the OMT group (p=0.015). There were no significant differences between the PCI group and the OMT group in cardiac death [hazard ratio (HR) for the PCI group 0.454; 95% confidence interval (CI) 0.041-5.019, p=0.520], myocardial infarction (HR 0.399; 95% CI 0.039-4.050, p=0.437), or stroke (HR 0.919; 95% CI 0.057-14.709, p=0.952). However, the PCI group showed a significant preventive effect of the composite of major adverse events (HR 0.288; 95% CI 0.106-0.785, p=0.015) and against the need for coronary revascularization (HR 0.157; 95% CI 0.035-0.703, p=0.016). Elective PCI reduced major adverse events and was found to be an effective treatment modality in elderly patients with angina pectoris and significant coronary artery stenosis, compared to OMT.

Adverse events after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine administered to adults 65 years of age and older reported to the Vaccine Adverse Event Reporting System (VAERS), 2005-2010.

PubMed

Moro, Pedro L; Yue, Xin; Lewis, Paige; Haber, Penina; Broder, Karen

2011-11-21

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was not licensed for use in adults aged ≥65 years due to lack of sufficient efficacy and safety data. To characterize reports to the Vaccine Adverse Event Reporting System (VAERS) among adults aged ≥65 years who received Tdap vaccine 'off-label' to assess for potential vaccine safety concerns. We searched VAERS for US reports of adverse events (AEs) in subjects aged ≥65 years who received Tdap vaccine from 9/1/2005 to 9/08/2010. Medical records were requested for all reports coded as serious (death, hospitalization, prolonged hospitalization, permanent disability, life-threatening-illness). Proportional reporting ratio (PRR) was used to assess for higher proportionate reporting for AEs after Tdap compared with Td reports in subjects aged ≥65 years. VAERS received 243 reports following Tdap administered to persons aged ≥65 years. Eleven (4.5%) reports were serious, including two deaths. Most common AEs were local reactions in 100 (41.2%) reports. Seventy-eight (32.1%) reports contained coding terms that denoted inappropriate administration of vaccine. 'Cough' was the only term associated with disproportionately higher reporting after Tdap compared with Td. Six of seven Tdap reports containing the term 'Cough' were non-serious. Clinical review of serious reports identified no unusual patterns of AEs. Our VAERS review of the 'off-label' use of Tdap vaccine in adults ≥65 years did not find any safety concerns that warrant further study. These data will provide useful baseline information to assist CDC and FDA with monitoring efforts as permissive recommendations for Tdap in older persons are adopted. Published by Elsevier Ltd.

Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naïve to anti-TNF therapy: an indirect treatment comparison meta-analysis.

PubMed

Thorlund, Kristian; Druyts, Eric; Mills, Edward J; Fedorak, Richard N; Marshall, John K

2014-07-01

To compare the efficacy of adalimumab and infliximab for the treatment of moderate to severe ulcerative colitis using indirect treatment comparison meta-analysis. A systematic review and Bayesian indirect treatment comparison meta-analyses were performed for seven patient-important clinical outcomes at 8 weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible intervals (CrIs) were produced. Five eligible RCTs informed clinical remission, response, mucosal healing, quality of life, colectomy, serious adverse events, and discontinuation due to adverse events at 8 weeks and 52 weeks. At 8 weeks of induction therapy, clinical remission (OR=0.42, 95% CrI 0.17-0.97), clinical response (OR=0.45, 95% CrI 0.23-0.89) and mucosal healing (OR=0.46, 95% CrI 0.25-0.86) statistically favored infliximab. However, after 52 weeks of maintenance therapy OR estimates showed no significant difference between infliximab and adalimumab. For serious adverse events and discontinuations due to adverse events, adalimumab and infliximab were similar to placebo. Further, the indirect treatment comparison of adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible intervals. The findings of this indirect treatment comparison meta-analysis suggest that both infliximab and adalimumab are superior to placebo in the treatment of moderate to moderately severe ulcerative colitis. While infliximab is statistically more effective than adalimumab in the induction of remission, response and mucosal healing at 8 weeks, infliximab and adalimumab are comparable in efficacy at 52 weeks of maintenance treatment. Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study).

PubMed

Didden, Paul; Reijm, Agnes N; Erler, Nicole S; Wolters, Leonieke M M; Tang, Thjon J; Ter Borg, Pieter C J; Leeuwenburgh, Ivonne; Bruno, Marco J; Spaander, Manon C W

2018-06-12

 Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis.  In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first.  Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs ( P  = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively ( P  = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events.  Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia. © Georg Thieme Verlag KG Stuttgart · New York.

Bleeding and Blood Disorders in Clients of Voluntary Medical Male Circumcision for HIV Prevention - Eastern and Southern Africa, 2015-2016.

PubMed

Hinkle, Lawrence E; Toledo, Carlos; Grund, Jonathan M; Byams, Vanessa R; Bock, Naomi; Ridzon, Renee; Cooney, Caroline; Njeuhmeli, Emmanuel; Thomas, Anne G; Odhiambo, Jacob; Odoyo-June, Elijah; Talam, Norah; Matchere, Faustin; Msungama, Wezi; Nyirenda, Rose; Odek, James; Come, Jotamo; Canda, Marcos; Wei, Stanley; Bere, Alfred; Bonnecwe, Collen; Choge, Isaac Ang'Ang'A; Martin, Enilda; Loykissoonlal, Dayanund; Lija, Gissenge J I; Mlanga, Erick; Simbeye, Daimon; Alamo, Stella; Kabuye, Geoffrey; Lubwama, Joseph; Wamai, Nafuna; Chituwo, Omega; Sinyangwe, George; Zulu, James Exnobert; Ajayi, Charles A; Balachandra, Shirish; Mandisarisa, John; Xaba, Sinokuthemba; Davis, Stephanie M

2018-03-23

Male circumcision reduces the risk for female-to-male human immunodeficiency virus (HIV) transmission by approximately 60% (1) and has become a key component of global HIV prevention programs in countries in Eastern and Southern Africa where HIV prevalence is high and circumcision coverage is low. Through September 2017, the President's Emergency Plan for AIDS Relief (PEPFAR) had supported 15.2 million voluntary medical male circumcisions (VMMCs) in 14 priority countries in Eastern and Southern Africa (2). Like any surgical intervention, VMMC carries a risk for complications or adverse events. Adverse events during circumcision of males aged ≥10 years occur in 0.5% to 8% of procedures, though the majority of adverse events are mild (3,4). To monitor safety and service quality, PEPFAR tracks and reports qualifying notifiable adverse events. Data reported from eight country VMMC programs during 2015-2016 revealed that bleeding resulting in hospitalization for ≥3 days was the most commonly reported qualifying adverse event. In several cases, the bleeding adverse event revealed a previously undiagnosed or undisclosed bleeding disorder. Bleeding adverse events in men with potential bleeding disorders are serious and can be fatal. Strategies to improve precircumcision screening and performance of circumcisions on clients at risk in settings where blood products are available are recommended to reduce the occurrence of these adverse events or mitigate their effects (5).

Adverse events associated with pediatric exposures to dextromethorphan.

PubMed

Paul, Ian M; Reynolds, Kate M; Kauffman, Ralph E; Banner, William; Bond, G Randall; Palmer, Robert B; Burnham, Randy I; Green, Jody L

2017-01-01

Dextromethorphan is the most common over-the-counter (OTC) antitussive medication. We sought to characterize adverse events associated with dextromethorphan in children <12 years old from a surveillance program of OTC cough/cold medication exposures. This is a retrospective case series of oral exposures to dextromethorphan with ≥1 adverse event from multiple U.S. sources (National Poison Data System, FDA Adverse Event Reporting System, manufacturer safety reports, news/media, medical literature) reported between 2008 and 2014. An expert panel determined the relationship between exposure and adverse events, estimated dose ingested, intent of exposure, and identified contributing factors to exposure. 1716 cases contained ≥1 adverse event deemed at least potentially related to dextromethorphan; 1417 were single product exposures. 773/1417 (55%) involved only one single-ingredient dextromethorphan product (dextromethorphan-only). Among dextromethorphan-only cases, 3% followed ingestion of a therapeutic dose; 78% followed an overdose. 69% involved unsupervised self-administration and 60% occurred in children <4 years old. No deaths or pathologic dysrhythmias occurred. Central nervous system [e.g., ataxia (N = 420)] and autonomic symptoms [e.g., tachycardia (N = 224)] were the most common adverse events. Flushing and/or urticarial rash occurred in 18.1% of patients. Dystonia occurred in 5.4%. No fatalities were identified in this multifaceted surveillance program following a dextromethorphan-only ingestion. Adverse events were predominantly associated with overdose, most commonly affecting the central nervous and autonomic systems.

Ultrasonography versus computed tomography for suspected nephrolithiasis.

PubMed

Smith-Bindman, Rebecca; Aubin, Chandra; Bailitz, John; Bengiamin, Rimon N; Camargo, Carlos A; Corbo, Jill; Dean, Anthony J; Goldstein, Ruth B; Griffey, Richard T; Jay, Gregory D; Kang, Tarina L; Kriesel, Dana R; Ma, O John; Mallin, Michael; Manson, William; Melnikow, Joy; Miglioretti, Diana L; Miller, Sara K; Mills, Lisa D; Miner, James R; Moghadassi, Michelle; Noble, Vicki E; Press, Gregory M; Stoller, Marshall L; Valencia, Victoria E; Wang, Jessica; Wang, Ralph C; Cummings, Steven R

2014-09-18

There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography. In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy. A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic accuracy did not differ significantly among the groups. Initial ultrasonography was associated with lower cumulative radiation exposure than initial CT, without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department visits, or hospitalizations. (Funded by the Agency for Healthcare Research and Quality.).

Reporting rates of yellow fever vaccine 17D or 17DD-associated serious adverse events in pharmacovigilance data bases: systematic review.

PubMed

Thomas, Roger E; Lorenzetti, Diane L; Spragins, Wendy; Jackson, Dave; Williamson, Tyler

2011-07-01

To assess the reporting rates of serious adverse events attributable to yellow fever vaccination with 17D and 17DD strains as reported in pharmacovigilance databases, and assess reasons for differences in reporting rates. We searched 9 electronic databases for peer reviewed and grey literature (government reports, conferences), in all languages. Reference lists of key studies were also reviewed to identify additional studies. We identified 2,415 abstracts, of which 472 were selected for full text review. We identified 15 pharmacovigilance databases which reported adverse events attributed to yellow fever vaccination, of which 10 contributed data to this review with about 107,600,000 patients (allowing for overlapping time periods for the studies of the US VAERS database), and the data are very heavily weighted (94%) by the Brazilian database. The estimates of serious adverse events form three groups. The estimates for Australia were low at 0/210,656 for "severe neurological disease" and 1/210,656 for YEL-AVD, and also low for Brazil with 9 hypersensitivity events, 0.23 anaphylactic shock events, 0.84 neurologic syndrome events and 0.19 viscerotropic events cases/million doses. The five analyses of partly overlapping periods for the US VAERS database provide an estimate of 3.6/cases per million YEL-AND in one analysis and 7.8 in another, and 3.1 YEL-AVD in one analysis and 3.9 in another. The estimates for the UK used only the inclusive term of "serious adverse events" not further classified into YEL-And or YEL-AND and reported 34 "serious adverse events." The Swiss database used the term "serious adverse events" and reported 7 such events (including 4 "neurologic reactions") for a reporting rate of 25 "serious adverse events"/million doses. Reporting rates for serious adverse events following yellow fever vaccination are low. Differences in reporting rates may be due to differences in definitions, surveillance system organisation, methods of reporting cases, administration of YFV with other vaccines, incomplete information about denominators, time intervals for reporting events, the degree of passive reporting, access to diagnostic resources, and differences in time periods of reporting.

Life adversities and suicidal behavior in young individuals: a systematic review.

PubMed

Serafini, Gianluca; Muzio, Caterina; Piccinini, Giulia; Flouri, Eirini; Ferrigno, Gabriella; Pompili, Maurizio; Girardi, Paolo; Amore, Mario

2015-12-01

Suicidal behavior in young people is a significant public health problem. However, it is not yet clear whether adversities (adverse life events) may be related to suicidality in adolescence and early adulthood. This paper aimed to investigate systematically the association between the type/number of adverse life events and experiences and suicidal behavior in young people. We developed a detailed strategy to search relevant articles in Pubmed, Scopus, PsycInfo, and Science Direct (January 1980-January 2015) about adverse life events and suicidal behavior. Adverse life events and experiences included maltreatment and violence, loss events, intra-familial problems, school and interpersonal problems. Studies were restricted to suicidal behavior in young people aged 10-25 years. The search yielded 245 articles, of which 28 met our inclusion criteria. Most studies reported a strong association between adversities and suicidality (both suicidal ideation and attempts). Based on the main results, the number of adversities or negative life events experienced seemed to have a positive dose-response relationship with youth suicidal behavior. However, the type of event experienced also appeared to matter: one of the most consistent findings was the association between suicidal behavior and experience of sexual abuse. More prospective studies are needed to elucidate the relative importance of risk accumulation and risk specificity for youth suicide.

Paravertebral block can be an alternative to unilateral spinal anaesthesia for inguinal hernia repair.

PubMed

Mandal, M C; Das, S; Gupta, Sunil; Ghosh, T R; Basu, S R

2011-11-01

Inguinal hernia repair can be performed under satisfactory anaesthetic conditions using general, regional and peripheral nerve block anaesthesia. Unilateral spinal anaesthesia provides optimal anaesthesia, with stable haemodynamics and minimal adverse events. The paravertebral block, being segmental in nature, can be expected to produce some advantages regarding haemodynamic stability and early ambulation and may be a viable alternative. Fifty-four consenting male patients posted for inguinal hernia repair were randomized into two groups, to receive either the two-segment paravertebral block (group-P, n=26) at T10 and L1 or unilateral spinal anaesthesia (group-S, n=28), respectively. The time to ambulation (primary outcome), time to the first analgesic, total rescue analgesic consumption in the first 24-hour period and adverse events were noted. Block performance time and time to reach surgical anaesthesia were significantly higher in the patients of group-P (P<0.001). Time to ambulation was significantly shorter in group-P compared to group-S (P<0.001), while postoperative sensory block was prolonged in patients of group-S; P<0.001. A significantly higher number of patients could bypass the recovery room in group-P compared to group-S, (45% versus 0%, respectively, P<0.001). No statistically significant difference in adverse outcomes was recorded. Both the paravertebral block and unilateral spinal anaesthesia are effective anaesthetic techniques for uncomplicated inguinal hernia repair. However, the paravertebral block can be an attractive alternative as it provides early ambulation and prolonged postoperative analgesia with minimal adverse events.

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

PubMed Central

Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

2016-01-01

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.

PubMed

Puterman, Eli; Gemmill, Alison; Karasek, Deborah; Weir, David; Adler, Nancy E; Prather, Aric A; Epel, Elissa S

2016-10-18

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem

PubMed Central

2014-01-01

Background Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? Methods We used cross-sectional data from 3,064 males and females aged 12–19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Results Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Conclusions Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries. PMID:25210535

Effect of Daily Contact Lens Cleaning on Ocular Adverse Events during Extended Wear.

PubMed

Ozkan, Jerome; Rathi, Varsha M; de la Jara, Percy Lazon; Naduvilath, Thomas; Holden, Brien A; Willcox, Mark D P

2015-02-01

The purpose of the study was to assess what effect daily cleaning of contact lenses with a multipurpose disinfection solution (MPDS), during 30 nights extended wear, would have on contact lens-related adverse events. This was a prospective, open-label, randomized, controlled, parallel-group, 3-month clinical study in which 193 participants were dispensed with lotrafilcon A silicone hydrogel lenses for a 30-day extended-wear schedule and with lenses replaced monthly. Participants were randomized to a control or test group. Test subjects were required to remove lenses daily after waking, clean them with the MPDS, and reinsert the lenses. Control subjects wore lenses without removal for 30 days extended wear. Handling-related lens contamination was assessed at the baseline visit. There was no significant difference between the test and control groups for the incidence of significant corneal infiltrative events (1.3 vs. 4.9%, p = 0.368), total corneal infiltrative events (2.6 vs. 4.9%, p = 0.682), or mechanical events (1.3 vs. 2.5%, p = 1.00). The test group had greater corneal staining (p < 0.047) and fewer mucin balls (p = 0.033). Handling-related lens contamination (unworn lenses) resulted in isolation of Gram-positive bacteria from 92.5% of test lenses compared with 87.5% of control lenses (p = 0.712). Gram-negative bacteria were isolated from 5% of test subjects compared with 2.5% of control subjects (p = 1.00). Fungus was isolated from 2.5% of subjects in both the test and control groups (p = 1.00). The intervention of daily morning cleaning of the lens surface with an MPDS during extended wear did not significantly influence the incidence of adverse events.

Monitoring Haloperidol Plasma Concentration and Associated Adverse Events in Critically Ill Children With Delirium: First Results of a Clinical Protocol Aimed to Monitor Efficacy and Safety.

PubMed

Slooff, Valerie D; van den Dungen, Desley K; van Beusekom, Babette S; Jessurun, Naomi; Ista, Erwin; Tibboel, Dick; de Wildt, Saskia N

2018-02-01

As delirium in critically ill children is increasingly recognized, more children are treated with the antipsychotic drug haloperidol, while current dosing guidelines are lacking solid evidence and appear to be associated with a high risk of adverse events. We aim to report on the safety and efficacy of a recently implemented clinical dose-titration protocol with active monitoring of adverse events. From July 2014 until June 2015, when a potential delirium was identified by regular delirium scores and confirmed by a child psychiatrist, haloperidol was prescribed according to the Dutch Pediatric Formulary. Daily, adverse events were systematically assessed, haloperidol plasma concentrations were measured, and delirium symptoms followed. Dependent on the clinical response, plasma concentration, and adverse event, the dose was adjusted. A 28-bed tertiary PICU in the Netherlands. All patients admitted to the PICU diagnosed with delirium. Treatment with haloperidol according to a dose-titration protocol MEASUREMENTS AND MAIN RESULTS:: Thirteen children (median age [range] 8.3 yr [0.4-13.8 yr]) received haloperidol, predominantly IV (median dose [range] 0.027 mg/kg/d [0.005-0.085 mg/kg/d]). In all patients, pediatric delirium resolved, but five of 13 patients developed possible adverse event. These were reversed after biperiden (n = 2), discontinuing (n = 3), and/or lowering the dose (n = 3). Plasma concentrations were all below the presumed therapeutic threshold of 3-12 µg/L. Prospective systematic monitoring of adverse event in critically ill children receiving haloperidol revealed a significant proportion of possible adverse events. Adverse event developed despite low plasma concentrations and recommended dose administration in the majority of the patients. Our data suggest that haloperidol can potentially improve pediatric delirium, but it might also put patients at risk for developing adverse events.

Standardizing the classification of abortion incidents: the Procedural Abortion Incident Reporting and Surveillance (PAIRS) Framework.

PubMed

Taylor, Diana; Upadhyay, Ushma D; Fjerstad, Mary; Battistelli, Molly F; Weitz, Tracy A; Paul, Maureen E

2017-07-01

To develop and validate standardized criteria for assessing abortion-related incidents (adverse events, morbidities, near misses) for first-trimester aspiration abortion procedures and to demonstrate the utility of a standardized framework [the Procedural Abortion Incident Reporting & Surveillance (PAIRS) Framework] for estimating serious abortion-related adverse events. As part of a California-based study of early aspiration abortion provision conducted between 2007 and 2013, we developed and validated a standardized framework for defining and monitoring first-trimester (≤14weeks) aspiration abortion morbidity and adverse events using multiple methods: a literature review, framework criteria testing with empirical data, repeated expert reviews and data-based revisions to the framework. The final framework distinguishes incidents resulting from procedural abortion care (adverse events) from morbidity related to pregnancy, the abortion process and other nonabortion related conditions. It further classifies incidents by diagnosis (confirmatory data, etiology, risk factors), management (treatment type and location), timing (immediate or delayed), seriousness (minor or major) and outcome. Empirical validation of the framework using data from 19,673 women receiving aspiration abortions revealed almost an equal proportion of total adverse events (n=205, 1.04%) and total abortion- or pregnancy-related morbidity (n=194, 0.99%). The majority of adverse events were due to retained products of conception (0.37%), failed attempted abortion (0.15%) and postabortion infection (0.17%). Serious or major adverse events were rare (n=11, 0.06%). Distinguishing morbidity diagnoses from adverse events using a standardized, empirically tested framework confirms the very low frequency of serious adverse events related to clinic-based abortion care. The PAIRS Framework provides a useful set of tools to systematically classify and monitor abortion-related incidents for first-trimester aspiration abortion procedures. Standardization will assist healthcare providers, researchers and policymakers to anticipate morbidity and prevent abortion adverse events, improve care metrics and enhance abortion quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Surveillance of adverse effects following vaccination and safety of immunization programs.

PubMed

Waldman, Eliseu Alves; Luhm, Karin Regina; Monteiro, Sandra Aparecida Moreira Gomes; Freitas, Fabiana Ramos Martin de

2011-02-01

The aim of the review was to analyze conceptual and operational aspects of systems for surveillance of adverse events following immunization. Articles available in electronic format were included, published between 1985 and 2009, selected from the PubMed/Medline databases using the key words "adverse events following vaccine surveillance", "post-marketing surveillance", "safety vaccine" and "Phase IV clinical trials". Articles focusing on specific adverse events were excluded. The major aspects underlying the Public Health importance of adverse events following vaccination, the instruments aimed at ensuring vaccine safety, and the purpose, attributes, types, data interpretation issues, limitations, and further challenges in adverse events following immunization were describe, as well as strategies to improve sensitivity. The review was concluded by discussing the challenges to be faced in coming years with respect to ensuring the safety and reliability of vaccination programs.

Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

PubMed

Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

2008-02-01

Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

Why Clinicians Don't Report Adverse Drug Events: Qualitative Study.

PubMed

Hohl, Corinne M; Small, Serena S; Peddie, David; Badke, Katherin; Bailey, Chantelle; Balka, Ellen

2018-02-27

Adverse drug events are unintended and harmful events related to medications. Adverse drug events are important for patient care, quality improvement, drug safety research, and postmarketing surveillance, but they are vastly underreported. Our objectives were to identify barriers to adverse drug event documentation and factors contributing to underreporting. This qualitative study was conducted in 1 ambulatory center, and the emergency departments and inpatient wards of 3 acute care hospitals in British Columbia between March 2014 and December 2016. We completed workplace observations and focus groups with general practitioners, hospitalists, emergency physicians, and hospital and community pharmacists. We analyzed field notes by coding and iteratively analyzing our data to identify emerging concepts, generate thematic and event summaries, and create workflow diagrams. Clinicians validated emerging concepts by applying them to cases from their clinical practice. We completed 238 hours of observations during which clinicians investigated 65 suspect adverse drug events. The observed events were often complex and diagnosed over time, requiring the input of multiple providers. Providers documented adverse drug events in charts to support continuity of care but never reported them to external agencies. Providers faced time constraints, and reporting would have required duplication of documentation. Existing reporting systems are not suited to capture the complex nature of adverse drug events or adapted to workflow and are simply not used by frontline clinicians. Systems that are integrated into electronic medical records, make use of existing data to avoid duplication of documentation, and generate alerts to improve safety may address the shortcomings of existing systems and generate robust adverse drug event data as a by-product of safer care. ©Corinne M Hohl, Serena S Small, David Peddie, Katherin Badke, Chantelle Bailey, Ellen Balka. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 27.02.2018.

The effects of power, leadership and psychological safety on resident event reporting.

PubMed

Appelbaum, Nital P; Dow, Alan; Mazmanian, Paul E; Jundt, Dustin K; Appelbaum, Eric N

2016-03-01

Although the reporting of adverse events is a necessary first step in identifying and addressing lapses in patient safety, such events are under-reported, especially by frontline providers such as resident physicians. This study describes and tests relationships between power distance and leader inclusiveness on psychological safety and the willingness of residents to report adverse events. A total of 106 resident physicians from the departments of neurosurgery, orthopaedic surgery, emergency medicine, otolaryngology, neurology, obstetrics and gynaecology, paediatrics and general surgery in a mid-Atlantic teaching hospital were asked to complete a survey on psychological safety, perceived power distance, leader inclusiveness and intention to report adverse events. Perceived power distance (β = -0.26, standard error [SE] 0.06, 95% confidence interval [CI] -0.37 to 0.15; p < 0.001) and leader inclusiveness (β = 0.51; SE 0.07, 95% CI 0.38-0.65; p < 0.001) both significantly predicted psychological safety, which, in turn, significantly predicted intention to report adverse events (β = 0.34; SE 0.08, 95% CI 0.18-0.49; p < 0.001). Psychological safety significantly mediated the direct relationship between power distance and intention to report adverse events (indirect effect: -0.09; SE 0.02, 95% CI -0.13 to 0.04; p < 0.001). Psychological safety also significantly mediated the direct relationship between leader inclusiveness and intention to report adverse events (indirect effect: 0.17; SE 0.02, 95% CI 0.08-0.27; p = 0.001). Psychological safety was found to be a predictor of intention to report adverse events. Perceived power distance and leader inclusiveness both influenced the reporting of adverse events through the concept of psychological safety. Because adverse event reporting is shaped by relationships and culture external to the individual, it should be viewed as an organisational as much as a personal function. Supervisors and other leaders in health care should ensure that policies, procedures and leadership practices build psychological safety and minimise power distance between low- and high-status members in order to support greater reporting of adverse events. © 2016 John Wiley & Sons Ltd.

A novel approach to increase residents' involvement in reporting adverse events.

PubMed

Scott, David R; Weimer, Melissa; English, Clea; Shaker, Lynn; Ward, William; Choi, Dongseok; Cedfeldt, Andrea; Girard, Donald

2011-06-01

In the wake of the Patient Safety and Quality Improvement Act of 2005, national attention has increasingly focused on adverse-event reporting as a means of identifying systems changes to improve patient safety. However, physicians and residents have demonstrated meager involvement in this effort. In 2008-2009, the authors measured participation in adverse-event reporting by 680 residents at Oregon Health & Science University before and after implementing a quality improvement initiative, which consisted of a financial incentive and multifaceted educational campaign. The primary measure of success was an increase in the average monthly adverse-event reports submitted by residents to greater than 5% of the institution's overall report submissions. The average number of adverse events reported by residents increased from 1.6% to 9.0% of the institution's overall event reports, representing a 5.6-fold increase during the initiative (P < .001). The relative percentage of resident-submitted reports defined as "near-misses" increased from 6% to 27% during the initiative (P < .001). The novel approach of integrating a retirement benefit and educational campaign to increase residents' involvement in adverse-event reporting was successful. In addition to increasing residents' contributions to adverse-event reporting to levels higher than any documented in the current literature, there was also a remarkable increase in the relative frequency of near-miss reporting by residents.

Adverse events associated with deep brain stimulation for movement disorders: analysis of 510 consecutive cases.

PubMed

Patel, Daxa M; Walker, Harrison C; Brooks, Rebekah; Omar, Nidal; Ditty, Benjamin; Guthrie, Barton L

2015-03-01

Although numerous studies have focused on the efficacy of deep brain stimulation (DBS) for movement disorders, less is known about surgical adverse events, especially over longer time intervals. Here, we analyze adverse events in 510 consecutive cases from a tertiary movement disorders center at up to 10 years postoperatively. We conducted a retrospective review of adverse events from craniotomies between January 2003 and March 2013. The adverse events were categorized into 2 broad categories--immediate perioperative and time-dependent postoperative events. Across all targets, perioperative mental status change occurred in 18 (3.5%) cases, and symptomatic intracranial hemorrhage occurred in 4 (0.78%) cases. The most common hardware-related event was skin erosion in 13 (2.5%) cases. The most frequent stimulation-related event was speech disturbance in 16 (3.1%) cases. There were no significant differences among surgical targets with respect to the incidence of these events. Time-dependent postoperative events leading to the revision of a given DBS electrode for any reason occurred in 4.7% ± 1.0%, 9.3% ± 1.4%, and 12.4% ± 1.5% of electrodes at 1, 4, and 7 years postoperatively, respectively. Staged bilateral DBS was associated with approximately twice the risk of repeat surgery for electrode replacement vs unilateral surgery (P = .020). These data provide low incidences for adverse events in a large series of DBS surgeries for movement disorders at up to 10 years follow-up. Accurate estimates of adverse events will better inform patients and caregivers about the potential risks and benefits of surgery and provide normative data for process improvement.

An evaluation of computer-aided disproportionality analysis for post-marketing signal detection.

PubMed

Lehman, H P; Chen, J; Gould, A L; Kassekert, R; Beninger, P R; Carney, R; Goldberg, M; Goss, M A; Kidos, K; Sharrar, R G; Shields, K; Sweet, A; Wiholm, B E; Honig, P K

2007-08-01

To understand the value of computer-aided disproportionality analysis (DA) in relation to current pharmacovigilance signal detection methods, four products were retrospectively evaluated by applying an empirical Bayes method to Merck's post-marketing safety database. Findings were compared with the prior detection of labeled post-marketing adverse events. Disproportionality ratios (empirical Bayes geometric mean lower 95% bounds for the posterior distribution (EBGM05)) were generated for product-event pairs. Overall (1993-2004 data, EBGM05> or =2, individual terms) results of signal detection using DA compared to standard methods were sensitivity, 31.1%; specificity, 95.3%; and positive predictive value, 19.9%. Using groupings of synonymous labeled terms, sensitivity improved (40.9%). More of the adverse events detected by both methods were detected earlier using DA and grouped (versus individual) terms. With 1939-2004 data, diagnostic properties were similar to those from 1993 to 2004. DA methods using Merck's safety database demonstrate sufficient sensitivity and specificity to be considered for use as an adjunct to conventional signal detection methods.

[Analysis on the adverse events of cupping therapy in the application].

PubMed

Zhou, Xin; Ruan, Jing-wen; Xing, Bing-feng

2014-10-01

The deep analysis has been done on the cases of adverse events and common injury of cupping therapy encountered in recent years in terms of manipulation and patient's constitution. The adverse events of cupping therapy are commonly caused by improper manipulation of medical practitioners, ignoring contraindication and patient's constitution. Clinical practitioners should use cupping therapy cautiously, follow strictly the rules of standard manipulation and medical core system, pay attention to the contraindication and take strict precautions against the occurrence of adverse events.

Continuous event monitoring via a Bayesian predictive approach.

PubMed

Di, Jianing; Wang, Daniel; Brashear, H Robert; Dragalin, Vladimir; Krams, Michael

2016-01-01

In clinical trials, continuous monitoring of event incidence rate plays a critical role in making timely decisions affecting trial outcome. For example, continuous monitoring of adverse events protects the safety of trial participants, while continuous monitoring of efficacy events helps identify early signals of efficacy or futility. Because the endpoint of interest is often the event incidence associated with a given length of treatment duration (e.g., incidence proportion of an adverse event with 2 years of dosing), assessing the event proportion before reaching the intended treatment duration becomes challenging, especially when the event onset profile evolves over time with accumulated exposure. In particular, in the earlier part of the study, ignoring censored subjects may result in significant bias in estimating the cumulative event incidence rate. Such a problem is addressed using a predictive approach in the Bayesian framework. In the proposed approach, experts' prior knowledge about both the frequency and timing of the event occurrence is combined with observed data. More specifically, during any interim look, each event-free subject will be counted with a probability that is derived using prior knowledge. The proposed approach is particularly useful in early stage studies for signal detection based on limited information. But it can also be used as a tool for safety monitoring (e.g., data monitoring committee) during later stage trials. Application of the approach is illustrated using a case study where the incidence rate of an adverse event is continuously monitored during an Alzheimer's disease clinical trial. The performance of the proposed approach is also assessed and compared with other Bayesian and frequentist methods via simulation. Copyright © 2015 John Wiley & Sons, Ltd.

Patient survival and safety with biologic therapy. Results of the Mexican National Registry Biobadamex 1.0.

PubMed

Ventura-Ríos, Lucio; Bañuelos-Ramírez, David; Hernández-Quiroz, María del Carmen; Robles-San Román, Manuel; Irazoque-Palazuelos, Fedra; Goycochea-Robles, María Victoria

2012-01-01

This work reports patient treatment survival and adverse events related to Biologic Therapy (BT), identified by a multicenter ambispective registry of 2047 rheumatic patients undergoing BT and including a control group of Rheumatoid Arthritis (RA) patients not using BT. The most common diagnoses were: RA 79.09%, Ankylosing Spondilytis 7.96%, Psoriatic Arthritis 4.40%, Systemic Lupus Erythematosus 3.37%, Juvenile Idiopathic Arthritis 1.17%. A secondary analysis included 1514 cases from the total sample and was performed calculating an incidence rate of any adverse events of 178 × 1000/BT patients per year vs 1009 × 1000/control group patients per year with a 1.6 RR (95% CI 1.4-1.9). For serious adverse events the RR was: 15.4 (95% CI 3.7-63.0, P<.0001). Global BT survival was 80% at 12 months, 61% at 24 months, 52% at 36 months and 45% at 48 months and SMR: 0.23 (95% CI 0.0-49.0) for BT vs 0.00 (95% CI 0.0-0.2) for the control group. In conclusion, BT was associated to a higher infection risk and adverse events, compared to other patients. Mortality using BT was not higher than expected for general population with same gender and age. Copyright © 2011 Elsevier España, S.L. All rights reserved.

[Post-licensure passive safety surveillance of rotavirus vaccines: reporting sensitivity for intussusception].

PubMed

Pérez-Vilar, S; Díez-Domingo, J; Gomar-Fayos, J; Pastor-Villalba, E; Sastre-Cantón, M; Puig-Barberà, J

2014-08-01

The aims of this study were to describe the reports of suspected adverse events due to rotavirus vaccines, and assess the reporting sensitivity for intussusception. Descriptive study performed using the reports of suspected adverse events following rotavirus vaccination in infants aged less than 10 months, as registered in the Pharmacovigilance Centre of the Valencian Community during 2007-2011. The reporting rate for intussusception was compared to the intussusception rate in vaccinated infants obtained using the hospital discharge database (CMBD), and the regional vaccine registry. The adverse event reporting rate was 20 per 100,000 administered doses, with the majority (74%) of the reports being classified as non-serious. Fever, vomiting, and diarrhea were the adverse events reported more frequently. Two intussusception cases, which occurred within the first seven days post-vaccination, were reported as temporarily associated to vaccination. The reporting sensitivity for intussusception at the Pharmacovigilance Centre in the 1-7 day interval following rotavirus vaccination was 50%. Our results suggest that rotavirus vaccines have, in general, a good safety profile. Intussusception reporting to the Pharmacovigilance Centre shows sensitivity similar to other passive surveillance systems. The intussusception risk should be further investigated using well-designed epidemiological studies, and evaluated in comparison with the well-known benefits provided by these vaccines. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Simultaneous versus Sequential Bilateral Cataract Surgery for Infants with Congenital Cataracts: Visual Outcomes and Economic Costs

PubMed Central

Dave, Hreem; Phoenix, Vidya; Becker, Edmund R.; Lambert, Scott R.

2015-01-01

OBJECTIVES To compare the incidence of adverse events, visual outcomes and economic costs of sequential versus simultaneous bilateral cataract surgery for infants with congenital cataracts. METHODS We retrospectively reviewed the incidence of adverse events, visual outcomes and medical payments associated with simultaneous versus sequential bilateral cataract surgery for infants with congenital cataracts who underwent cataract surgery when 6 months of age or younger at our institution. RESULTS Records were available for 10 children who underwent sequential surgery at a mean age of 49 days for the first eye and 17 children who underwent simultaneous surgery at a mean age of 68 days (p=.25). We found a similar incidence of adverse events between the two treatment groups. Intraoperative or postoperative complications occurred in 14 eyes. The most common postoperative complication was glaucoma. No eyes developed endophthalmitis. The mean absolute interocular difference in logMAR visual acuities between the two treatment groups was 0.47±0.76 for the sequential group and 0.44±0.40 for the simultaneous group (p=.92). Hospital, drugs, supplies and professional payments were on average 21.9% lower per patient in the simultaneous group. CONCLUSIONS Simultaneous bilateral cataract surgery for infants with congenital cataracts was associated with a 21.9% reduction in medical payments and no discernible difference in the incidence of adverse events or visual outcome. PMID:20697007

Safety and tolerability of denosumab for the treatment of postmenopausal osteoporosis

PubMed Central

Lewiecki, E Michael

2011-01-01

Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL), a cytokine member of the tumor necrosis factor family that is the principal regulator of osteoclastic bone resorption. Postmenopausal osteoporosis (PMO) is a systemic skeletal disease associated with high levels of RANKL, resulting in a high rate of bone remodeling and an imbalance of bone resorption over bone formation. By inhibiting RANKL in women with PMO, denosumab reduces the rate of bone remodeling, thereby increasing bone mineral density, improving bone strength, and reducing the risk of fractures. In clinical trials of women with osteoporosis and low bone mineral density, denosumab has been well tolerated, with overall rates of adverse events and serious adverse events in women treated with denosumab similar to those receiving placebo. In the largest clinical trial of denosumab for the treatment of women with PMO, there was a significantly greater incidence of cellulitis reported as a serious adverse event, with no difference in the overall incidence of cellulitis, and a significantly lower incidence of the serious adverse event of concussions with denosumab compared with placebo. The evidence supports a favorable balance of benefits versus risks of denosumab for the treatment of PMO. Assessments of the long-term safety of denosumab are ongoing. Denosumab 60 mg subcutaneously every 6 months is an approved treatment for women with PMO who are at high risk for fracture. PMID:22279412

ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials.

PubMed

Schwartz, Lisa M; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A

2016-09-20

Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. To validate results posted on ClinicalTrials.gov against publicly available U.S. Food and Drug Administration (FDA) reviews on Drugs@FDA. ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical and statistical reviews). 100 parallel-group, randomized trials for new drug approvals (January 2013 to July 2014) with results posted on ClinicalTrials.gov (15 March 2015). 2 assessors extracted, and another verified, the trial design, primary and secondary outcomes, adverse events, and deaths. Most trials were phase 3 (90%), double-blind (92%), and placebo-controlled (73%) and involved 32 drugs from 24 companies. Of 137 primary outcomes identified from ClinicalTrials.gov, 134 (98%) had corresponding data at Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results. Most differences were nominal (that is, relative difference <10%). Primary outcome results in 14 trials could not be validated. Of 1927 secondary outcomes from ClinicalTrials.gov, Drugs@FDA mentioned 1061 (55%) and included results data for 367 (19%). Of 96 trials with 1 or more serious adverse events in either source, 14 could be compared and 7 had discordant numbers of persons experiencing the adverse events. Of 62 trials with 1 or more deaths in either source, 25 could be compared and 17 were discordant. Unknown generalizability to uncontrolled or crossover trial results. Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half the secondary outcomes, as well as serious events and deaths, could not be validated because Drugs@FDA includes only "key outcomes" for regulatory decision making and frequently includes only adverse event results aggregated across multiple trials. National Library of Medicine.

Effects of coding dictionary on signal generation: a consideration of use of MedDRA compared with WHO-ART.

PubMed

Brown, Elliot G

2002-01-01

To support signal generation a terminology should facilitate recognition of medical conditions by using terms which represent unique concepts, providing appropriate, homogeneous grouping of related terms. It should allow intuitive or mathematical identification of adverse events reaching a threshold frequency or with disproportionate incidence, permit identification of important events which are commonly drug-related, and support recognition of new syndromes. It is probable that the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms (PTs) or high level terms (HLTs) will be used to represent adverse events for the purposes of signal generation. A comparison with 315 WHO Adverse Reaction Terminology (WHO-ART) PTs showed that for about 72% of WHO-ART PTs, there were one or two corresponding MedDRA PTs. However, there were instances where there were many MedDRA PTs corresponding to single WHO-ART PTs. In many cases, MedDRA HLTs grouped large numbers of PTs and sometimes there could be problems when a single HLT comprises PTs which represent very different medical concepts, or conditions which differ greatly in their clinical importance. Further studies are needed to compare the way in which identical data sets coded with MedDRA and with other terminologies actually function in generating and exploring signals using the same methods of detection and evaluation.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib.

PubMed

Lipsky, Andrew H; Farooqui, Mohammed Z H; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U; Herman, Sarah E M; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M; Lozier, Jay N; Wiestner, Adrian

2015-12-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤ 2 in severity, and infrequently with grade ≥ 3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤ 2 bleeding-related adverse events in 55% of 85 patients. No grade ≥ 3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤ 2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733. Copyright© Ferrata Storti Foundation.

Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib

PubMed Central

Lipsky, Andrew H.; Farooqui, Mohammed Z.H.; Tian, Xin; Martyr, Sabrina; Cullinane, Ann M.; Nghiem, Khanh; Sun, Clare; Valdez, Janet; Niemann, Carsten U.; Herman, Sarah E. M.; Saba, Nakhle; Soto, Susan; Marti, Gerald; Uzel, Gulbu; Holland, Steve M.; Lozier, Jay N.; Wiestner, Adrian

2015-01-01

Ibrutinib is associated with bleeding-related adverse events of grade ≤2 in severity, and infrequently with grade ≥3 events. To investigate the mechanisms of bleeding and identify patients at risk, we prospectively assessed platelet function and coagulation factors in our investigator-initiated trial of single-agent ibrutinib for chronic lymphocytic leukemia. At a median follow-up of 24 months we recorded grade ≤2 bleeding-related adverse events in 55% of 85 patients. No grade ≥3 events occurred. Median time to event was 49 days. The cumulative incidence of an event plateaued by 6 months, suggesting that the risk of bleeding decreases with continued therapy. At baseline, von Willebrand factor and factor VIII levels were often high and normalized on treatment. Platelet function measured via the platelet function analyzer (PFA-100™) was impaired in 22 patients at baseline and in an additional 19 patients on ibrutinib (often transiently). Collagen and adenosine diphosphate induced platelet aggregation was tested using whole blood aggregometry. Compared to normal controls, response to both agonists was decreased in all patients with chronic lymphocytic leukemia, whether on ibrutinib or not. Compared to untreated chronic lymphocytic leukemia patients, response to collagen showed a mild further decrement on ibrutinib, while response to adenosine diphosphate improved. All parameters associated with a significantly increased risk of bleeding-related events were present at baseline, including prolonged epinephrine closure time (HR 2.74, P=0.012), lower levels of von Willebrand factor activity (HR 2.73, P=0.009) and factor VIII (HR 3.73, P=0.0004). In conclusion, both disease and treatment-related factors influence the risk of bleeding. Patients at greater risk for bleeding of grade ≤2 can be identified by clinical laboratory tests and counseled to avoid aspirin, non-steroidal anti-inflammatory drugs and fish oils. ClinicalTrials.gov identifier NCT01500733 PMID:26430171

Topical NSAIDs for acute pain in adults

PubMed Central

Massey, Thomas; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

2014-01-01

Background Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world, but not in others. Their main attraction is their potential to provide pain relief without associated systemic adverse events. Objectives To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain. Search methods We searched MEDLINE, EMBASE, The Cochrane Library, and our own in-house database to December 2009. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers web sites. Selection criteria We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adult patients with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Data collection and analysis Two review authors independently assessed trial quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Forty-seven studies were included; most compared topical NSAIDs in the form of a gel, spray, or cream with a similar placebo, with 3455 participants in the overall analysis of efficacy. For all topical NSAIDs combined, compared with placebo, the number needed to treat to benefit (NNT) for clinical success, equivalent to 50% pain relief, was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were of similar efficacy, but indomethacin and benzydamine were not significantly better than placebo. Local skin reactions were generally mild and transient, and did not differ from placebo. There were very few systemic adverse events or withdrawals due to adverse events. There were insufficient data to reliably compare individual topical NSAIDs with each other or the same oral NSAID. Authors’ conclusions Topical NSAIDs can provide good levels of pain relief, without the systemic adverse events associated with oral NSAIDs, when used to treat acute musculoskeletal conditions. PMID:20556778

Hylan G-F 20 Versus Low Molecular Weight Hyaluronic Acids for Knee Osteoarthritis: A Meta-Analysis.

PubMed

Zhao, Hongmou; Liu, Hongliang; Liang, Xiaojun; Li, Yi; Wang, Junhu; Liu, Cheng

2016-10-01

Hyaluronic acid injection has been reported to decrease pain compared with baseline levels in knee joint osteoarthritis. Hylan G-F 20 is distinguished from the other products by its chemical structure and relatively higher molecular weight. Many trials have compared hylan G-F 20 and low molecular weight hyaluronic acids (LMWHAs); however, their relative efficacy and safety are still debated. The aim was to compare the effectiveness and safety of intra-articular injection of hylan G-F 20 and LMWHA in the treatment of knee joint osteoarthritis. A comprehensive search of the literature up to February 2016 was performed; multiple databases were searched with 'Synvisc' or 'hylan' or 'hyaluronan' as free word terms. The pain-related outcomes and treatment-related adverse events from intent-to-treat analyzed studies were pooled for meta-analysis; other functional outcomes were included in the qualitative analysis. Twenty trials with a total of 3034 patients and 3153 knees were included, with a pooled dropout rate of 7.2 %. The pooled pain-related outcomes at 2 to 3 months reached a statistically significant difference in favor of hylan G-F 20 (I 2  = 88 %; random effects; P = 0.02), and the significance still existed with exclusion (in order to eliminate heterogeneity) of the three studies that most favored hylan G-F 20 (I 2  = 51 %; fixed effect; P = 0.03). No significant difference was reached for other group and subgroup analyses. No significant difference was reached in comparing the patients with treatment-related adverse events (seven trials; 2025 patients; P = 0.13) or the treatment-related adverse events (six trials; 1633 patients; P = 0.14). According to the current results, limited evidence showed a superior effect favoring hylan G-F 20 over LMWHA in the period from 2 to 3 months post-injection for pain-related outcomes. There was no evidence of increased risk of treatment-related adverse events for hylan G-F 20 injections.

Heterogeneous but “Standard” Coding Systems for Adverse Events: Issues in Achieving Interoperability between Apples and Oranges

PubMed Central

Richesson, Rachel L.; Fung, Kin Wah; Krischer, Jeffrey P.

2008-01-01

Monitoring adverse events (AEs) is an important part of clinical research and a crucial target for data standards. The representation of adverse events themselves requires the use of controlled vocabularies with thousands of needed clinical concepts. Several data standards for adverse events currently exist, each with a strong user base. The structure and features of these current adverse event data standards (including terminologies and classifications) are different, so comparisons and evaluations are not straightforward, nor are strategies for their harmonization. Three different data standards - the Medical Dictionary for Regulatory Activities (MedDRA) and the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) terminologies, and Common Terminology Criteria for Adverse Events (CTCAE) classification - are explored as candidate representations for AEs. This paper describes the structural features of each coding system, their content and relationship to the Unified Medical Language System (UMLS), and unsettled issues for future interoperability of these standards. PMID:18406213

The rate of adverse events during IV conscious sedation.

PubMed

Schwamburger, Nathan T; Hancock, Raymond H; Chong, Chol H; Hartup, Grant R; Vandewalle, Kraig S

2012-01-01

Conscious sedation has become an integral part of dentistry; it is often used to reduce anxiety or fear in some patients during oral surgery, periodontal surgery, implant placement, and general dentistry procedures. The purpose of this study was to evaluate the frequency of adverse events during IV conscious sedation provided by credentialed general dentists and periodontists in the United States Air Force (USAF). Sedation clinical records (Air Force Form 1417) from calendar year 2009 were requested from all USAF bases. A total of 1,468 records were reviewed and 19 adverse events were noted in 17 patients. IV complication (infiltration) was the most common adverse event. The overall adverse event rate was 1.3 per 100 patients treated. The results of this study show that moderate sedation provided by general dentists and periodontists in the USAF has a low incidence of adverse events, and conscious sedation remains a viable option for providers for the reduction of anxiety in select patients.

Hospital staff should use more than one method to detect adverse events and potential adverse events: incident reporting, pharmacist surveillance and local real‐time record review may all have a place

PubMed Central

Olsen, Sisse; Neale, Graham; Schwab, Kat; Psaila, Beth; Patel, Tejal; Chapman, E Jane; Vincent, Charles

2007-01-01

Background Over the past five years, in most hospitals in England and Wales, incident reporting has become well established but it remains unclear how well reports match clinical adverse events. International epidemiological studies of adverse events are based on retrospective, multi‐hospital case record review. In this paper the authors describe the use of incident reporting, pharmacist surveillance and local real‐time record review for the recognition of clinical risks associated with hospital inpatient care. Methodology Data on adverse events were collected prospectively on 288 patients discharged from adult acute medical and surgical units in an NHS district general hospital using incident reports, active surveillance of prescription charts by pharmacists and record review at time of discharge. Results Record review detected 26 adverse events (AEs) and 40 potential adverse events (PAEs) occurring during the index admission. In contrast, in the same patient group, incident reporting detected 11 PAEs and no AEs. Pharmacy surveillance found 10 medication errors all of which were PAEs. There was little overlap in the nature of events detected by the three methods. Conclusion The findings suggest that incident reporting does not provide an adequate assessment of clinical adverse events and that this method needs to be supplemented with other more systematic forms of data collection. Structured record review, carried out by clinicians, provides an important component of an integrated approach to identifying risk in the context of developing a safety and quality improvement programme. PMID:17301203

Mu-opioid antagonists for opioid-induced bowel dysfunction in people with cancer and people receiving palliative care.

PubMed

Candy, Bridget; Jones, Louise; Vickerstaff, Victoria; Larkin, Philip J; Stone, Patrick

2018-06-05

Opioid-induced bowel dysfunction (OIBD) is characterised by constipation, incomplete evacuation, bloating, and gastric reflux. It is one of the major adverse events of treatment for pain in cancer and in palliative care, resulting in increased morbidity and reduced quality of life.This is an update of two Cochrane reviews. One was published in 2011, Issue 1 on laxatives and methylnaltrexone for the management of constipation in people receiving palliative care; this was updated in 2015 and excluded methylnaltrexone. The other was published in 2008, Issue 4 on mu-opioid antagonists (MOA) for OIBD. In this updated review, we only included trials on MOA (including methylnaltrexone) for OIBD in people with cancer and people receiving palliative care. To assess the effectiveness and safety of MOA for OIBD in people with cancer and people receiving palliative care. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, and Web of Science to August 2017. We also searched clinical trial registries and regulatory websites. We contacted manufacturers of MOA to identify further data. We included randomised controlled trials (RCTs) that assessed the effectiveness and safety of MOA for OIBD in people with cancer and people at a palliative stage irrespective of the type of terminal disease they experienced. Two review authors assessed risk of bias and extracted data. The appropriateness of combining data from the trials depended upon sufficient homogeneity across the trials. Our primary outcomes were laxation, impact on pain relief, and adverse events. Impact on pain relief was a primary outcome because a possible adverse effect of MOAs is a reduction in pain relief from opioids. We assessed the evidence on these outcomes using GRADE. We identified four new trials for this update, bringing the total number included in this review to eight. In total, 1022 men and women with cancer irrespective of stage or at a palliative care stage of any disease were randomised across the trials. The MOAs evaluated were oral naldemedine and naloxone (alone or in combination with oxycodone), and subcutaneous methylnaltrexone. The trials compared with MOA with a placebo or with the active intervention administered at different doses or in combination with other drugs. The trial of naldemedine and the two of naloxone in combination with oxycodone were in people with cancer irrespective of disease stage. The trial on naloxone alone was in people with advanced cancer. The four trials on methylnaltrexone were undertaken in palliative care where most participants had cancer. All trials were vulnerable to biases; four were at a high risk as they involved a sample of fewer than 50 participants per arm.In the trial of naldemedine compared to placebo in 225 participants, there were more spontaneous laxations over the two-week treatment for the intervention group (risk ratio (RR) 1.93, 95% confidence intervals (CI) 1.36 to 2.74; moderate-quality evidence). In comparison with higher doses, lower doses resulted in fewer spontaneous laxations (0.1 mg versus 0.2 mg: RR 0.73, 95% CI 0.55 to 0.95; 0.1 mg versus 0.4 mg: RR 0.69, 95% CI 0.53 to 0.89; moderate-quality evidence). There was moderate-quality evidence that naldemedine had no effect on opiate withdrawal. There were five serious adverse events. All were in people taking naldemedine (low-quality evidence). There was an increase in the occurrence of other (non-serious) adverse events in the naldemedine groups (RR 1.36, 95% CI 1.04 to 1.79, moderate-quality evidence). The most common adverse event was diarrhoea.The trials on naloxone taken either on its own, or in combination with oxycodone (an opioid) compared to oxycodone only did not evaluate laxation response over the first two weeks of administration. There was very low-quality evidence that naloxone alone, and moderate-quality evidence that oxycodone/naloxone, had no effect on analgesia. There was low-quality evidence that oxycodone/naloxone did not increase the risk of serious adverse events and moderate-quality evidence that it did not increase risk of adverse events.In combined analysis of two trials of 287 participants, we found methylnaltrexone compared to placebo induced more laxations within 24 hours (RR 2.77, 95% CI 1.91 to 4.04. I² = 0%; moderate-quality evidence). In combined analysis, we found methylnaltrexone induced more laxation responses over two weeks (RR 9.98, 95% CI 4.96 to 20.09. I² = 0%; moderate-quality evidence). The proportion of participants who had a rescue-free laxation response within 24 hours of the first dose was 59.1% in the methylnaltrexone arms and 19.1% in the placebo arm. There was moderate-quality evidence that the rate of opioid withdrawal was not affected. Methylnaltrexone did not increase the likelihood of a serious adverse event; there were fewer in the intervention arm (RR 0.59, 95% CI 0.38 to 0.93; I² = 0%; moderate-quality evidence). There was no difference in the proportion of participants experiencing an adverse event (RR 1.17, 95% CI 0.94 to 1.45; I² = 74%; low-quality evidence). Methylnaltrexone increased the likelihood of abdominal pain and flatulence.Two trials compared differing methylnaltrexone schedules of higher doses with lower doses. For early laxation, there was low-quality evidence of no clear difference between doses on analgesia and adverse events. Both trials measured laxation response within 24 hours of first dose (trial one: RR 0.82, 95% CI 0.41 to 1.66; trial two: RR 1.07, 95% CI 0.81 to 1.42). In this update, the conclusions for naldemedine are new. There is moderate-quality evidence to suggest that, taken orally, naldemedine improves bowel function over two weeks in people with cancer and OIBD but increases the risk of adverse events. The conclusions on naloxone and methylnaltrexone have not changed. The trials on naloxone did not assess laxation at 24 hours or over two weeks. There is moderate-quality evidence that methylnaltrexone improves bowel function in people receiving palliative care in the short term and over two weeks, and low-quality evidence that it does not increase adverse events. There is a need for more trials including more evaluation of adverse events. None of the current trials evaluated effects in children.

Complications in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS): analysis of 7-year physician-reported adverse events

PubMed Central

Niv, Yaron; Gershtansky, Yael; Kenett, Ron S; Tal, Yossi; Birkenfeld, Shlomo

2011-01-01

Introduction: The number of malpractice claims against physicians and health institutes is increasing continuously in Israel as in the rest of the Western world, and has become a serious financial burden. Aim: In this study we analyzed the reports of gastroenterologists on endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) adverse events to the risk management authority between January 1, 2000 and December 31, 2006. Methods: All the reported adverse events associated with ERCP and EUS of health institutes and covered by Madanes Insurance Agency were summarized and analyzed. Clinical and epidemiological details about the patients, procedures, and adverse events were coded into an Excel worksheet, discussed, and evaluated. Results: Forty-two cases of ERCP and EUS adverse events were reported. There were nine cases of men (21.4%) and the average age was 69.3 ± 14.3 years. During this period, 10,647 procedures were performed by the institutes concerned and the number of adverse events was 20.2 to 67.8 per year for 10,000 procedures. Perforation occurred in one out of 367 procedures, bleeding in one out of 5323 procedures, teeth trauma in one out of 5323 procedures, and respiratory complications in one out of 10,647 procedures. Conclusion: This is the first study in Israel about physicians’ reports of ERCP and EUS adverse events. Physicians reported only about severe adverse events with high rate of mortality and morbidity. PMID:21753900

Admission factors can predict the need for ICU monitoring in gallstone pancreatitis.

PubMed

Arnell, T D; de Virgilio, C; Chang, L; Bongard, F; Stabile, B E

1996-10-01

The purpose was 1) to prospectively determine the prevalence of adverse events necessitating intensive care unit (ICU) monitoring in gallstone pancreatitis (GP) and 2) To identify admission prognostic indicators that predict the need for ICU unit monitoring. Prospective laboratory data, physiologic parameters, and APACHE II scores were gathered on 102 patients with GP over 14 months. Adverse events were defined as cardiac, respiratory, or renal failure, gastrointestinal bleeding, stroke, sepsis, and necrotizing pancreatitis. Patients were divided into Group 1 (no adverse events, n=95) and Group 2 (adverse events, n=7). There were no deaths and 7 (7%) adverse events, including necrotizing pancreatitis (3), cholangitis (2), and cardiac (2). APACHE 11 > or = 5 (P < 0.005), blood urea nitrogen (BUN) > or = 12 mmol/L (P < 0.005), white blood cell count (WBC) > or = 14.5 x 10(9)/L, (P < 0.001), heart rate > or = 100 bpm (P < 0.001), and glucose > or = 150 mg/dL (P < 0.005) were each independent predictors of adverse events. The sensitivity and specificity of these criteria for predicting severe complications requiring ICU care varied from 71 to 86 per cent and 78 to 87 per cent, respectively. The prevalence of adverse events necessitating ICU care in GP patients is low. Glucose, BUN, WBC, heart rate, and APACHE II scores are independent predictors of adverse events necessitating ICU care. Single criteria predicting the need for ICU care on admission are readily available on admission.

Arrhythmia Associated with Buprenorphine and Methadone Reported to the Food and Drug Administration

PubMed Central

Kao, David P; Haigney, Mark CP; Mehler, Philip S; Krantz, Mori J

2015-01-01

Aim To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, QTc prolongation, or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Design Retrospective pharmacoepidemiologic study Setting Adverse drug events spontaneously reported to the FDA between 1969-June 2011 originating in 196 countries (71% events from the US). Cases Adverse event cases mentioning methadone (n=14,915) or buprenorphine (n=7,283) were evaluated against all other adverse event cases (n= 4,796,141). Measurements The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR>2, χ2 error>4, with ≥3 cases. Findings There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.1 95% confidence interval (CI) 0.9–1.3, χ2=1.2) or QTc prolongation/torsade de pointes (1.0 95% CI 0.7–1.9, χ2=0.0006), but were for methadone (7.2 95% CI 6.9–7.5, χ2=9160; 10.6 95% CI 9.7–11.8, χ2=3305, respectively). Conclusion In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed and disproportionality analysis cannot quantify absolute risk per treatment episode. Population-based studies to definitively quantify differential incidence rates are warranted. PMID:26075588

Safety and utility of magnetic resonance imaging in patients with cardiac implantable electronic devices.

PubMed

Strom, Jordan B; Whelan, Jill B; Shen, Changyu; Zheng, Shuang Qi; Mortele, Koenraad J; Kramer, Daniel B

2017-08-01

Off-label magnetic resonance imaging (MRI) for patients with cardiac implantable electrical devices has been limited owing to concerns about safety and unclear diagnostic and prognostic utility. The purpose of this study was to define major and minor adverse events with off-label MRI scans. We prospectively evaluated patients with non-MRI-conditional cardiac implantable electrical devices referred for MRI scans under a strict clinical protocol. The primary safety outcome was incidence of major adverse events (loss of pacing, inappropriate shock or antitachycardia pacing, need for system revision, or death) or minor adverse events (inappropriate pacing, arrhythmias, power-on-reset events, heating at the generator site, or changes in device parameters at baseline or at 6 months). A total of 189 MRI scans were performed in 123 patients (63.1% [78] men; median age 70 ± 18.5 years; 56.9% [70] patients with implantable cardioverter-defibrillators; 33.3% [41] pacemaker-dependent patients) predominantly for brain or spinal conditions. A minority of scans (22.7% [43]) were performed for urgent or emergent indications. Major adverse events were rare: 1 patient with loss of pacing, no deaths, or system revisions (overall rate 0.5%; 95% confidence interval 0.01-2.91). Minor adverse events were similarly rare (overall rate 1.6%; 95% confidence interval 0.3-4.6). Nearly all studies (98.4% [186]) were interpretable, while 75.1% [142] were determined to change management according to the prespecified criteria. No clinically significant changes were observed in device parameters acutely after MRI or at 6 months as compared with baseline across all patient and device categories. Off-label MRI scans performed under a strict protocol demonstrated excellent short- and medium-term safety while providing interpretable imaging that frequently influenced clinical care. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Safety and utility of magnetic resonance imaging in patients with cardiac implantable electronic devices

PubMed Central

Strom, Jordan B.; Whelan, Jill B.; Shen, Changyu; Zheng, Shuang Qi; Mortele, Koenraad J.; Kramer, Daniel B.

2017-01-01

BACKGROUND Off-label magnetic resonance imaging (MRI) for patients with cardiac implantable electrical devices has been limited owing to concerns about safety and unclear diagnostic and prognostic utility. OBJECTIVE The purpose of this study was to define major and minor adverse events with off-label MRI scans. METHODS We prospectively evaluated patients with non–MRI-conditional cardiac implantable electrical devices referred for MRI scans under a strict clinical protocol. The primary safety outcome was incidence of major adverse events (loss of pacing, inappropriate shock or antitachycardia pacing, need for system revision, or death) or minor adverse events (inappropriate pacing, arrhythmias, power-on-reset events, heating at the generator site, or changes in device parameters at baseline or at 6 months). RESULTS A total of 189 MRI scans were performed in 123 patients (63.1% [78] men; median age 70 ± 18.5 years; 37.0% [70] patients with implantable cardioverter-defibrillators; 21.8% [41] pacemaker-dependent patients) predominantly for brain or spinal conditions. A minority of scans (22.7% [43]) were performed for urgent or emergent indications. Major adverse events were rare: 1 patient with loss of pacing, no deaths, or system revisions (overall rate 0.5%; 95% confidence interval 0.01–2.91). Minor adverse events were similarly rare (overall rate 1.6%; 95% confidence interval 0.3–4.6). Nearly all studies (98.4% [186]) were interpretable, while 74.9% [142] were determined to change management according to the prespecified criteria. No clinically significant changes were observed in device parameters acutely after MRI or at 6 months as compared with baseline across all patient and device categories. CONCLUSION Off-label MRI scans performed under a strict protocol demonstrated excellent short- and medium-term safety while providing interpretable imaging that frequently influenced clinical care. PMID:28385671

Application of a framework for extrapolating chemical effects ...

EPA Pesticide Factsheets

Cross-species extrapolation of toxicity data from limited surrogate test organisms to all wildlife with potential of chemical exposure remains a key challenge in ecological risk assessment. A number of factors affect extrapolation, including the chemical exposure, pharmacokinetics, life-stage, and pathway similarities/differences. Here we propose a framework using a tiered approach for species extrapolation that enables a transparent weight-of-evidence driven evaluation of pathway conservation (or lack thereof) in the context of adverse outcome pathways. Adverse outcome pathways describe the linkages from a molecular initiating event, defined as the chemical-biomolecule interaction, through subsequent key events leading to an adverse outcome of regulatory concern (e.g., mortality, reproductive dysfunction). Tier 1 of the extrapolation framework employs in silico evaluations of sequence and structural conservation of molecules (e.g., receptors, enzymes) associated with molecular initiating events or upstream key events. Such evaluations make use of available empirical and sequence data to assess taxonomic relevance. Tier 2 uses in vitro bioassays, such as enzyme inhibition/activation, competitive receptor binding, and transcriptional activation assays to explore functional conservation of pathways across taxa. Finally, Tier 3 provides a comparative analysis of in vivo responses between species utilizing well-established model organisms to assess departure from

Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews.

PubMed

Oaklander, Anne Louise; Lunn, Michael Pt; Hughes, Richard Ac; van Schaik, Ivo N; Frost, Chris; Chalk, Colin H

2017-01-13

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective. To summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments. We considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.On 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus. Five CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed. CorticosteroidsIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the evidence was very low (1 trial, 28 participants). According to moderate-quality evidence (1 trial, 41 participants), six months' treatment with high-dose monthly oral dexamethasone did not improve disability more than daily oral prednisolone. Observational studies tell us that prolonged use of corticosteroids sometimes causes serious side-effects. Plasma exchangeAccording to moderate-quality evidence (2 trials, 59 participants), twice-weekly plasma exchange produced more short-term improvement in disability than sham exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications. Intravenous immunoglobulinAccording to high-quality evidence (5 trials, 269 participants), intravenous immunoglobulin (IVIg) produced more short-term improvement than placebo. Adverse events were more common with IVIg than placebo (high-quality evidence), but serious adverse events were not (moderate-quality evidence, 3 trials, 315 participants). One trial with 19 participants provided moderate-quality evidence of little or no difference in short-term improvement of impairment with plasma exchange in comparison to IVIg. There was little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone (moderate-quality evidence; 1 trial, 29 participants) or intravenous methylprednisolone (high-quality evidence; 1 trial, 45 participants). One unpublished randomised open trial with 35 participants found little or no difference in disability after three months of IVIg compared to oral prednisone; this trial has not yet been included in a CSR. We know from observational studies that serious adverse events related to IVIg do occur. Other immunomodulatory treatmentsIt is uncertain whether the addition of azathioprine (2 mg/kg) to prednisone improved impairment in comparison to prednisone alone, as the quality of the evidence is very low (1 trial, 27 participants). Observational studies show that adverse effects truncate treatment in 10% of people.According to low-quality evidence (1 trial, 60 participants), compared to placebo, methotrexate 15 mg/kg did not allow more participants to reduce corticosteroid or IVIg doses by 20%. Serious adverse events were no more common with methotrexate than with placebo, but observational studies show that methotrexate can cause teratogenicity, abnormal liver function, and pulmonary fibrosis.According to moderate-quality evidence (2 trials, 77 participants), interferon beta-1a (IFN beta-1a) in comparison to placebo, did not allow more people to withdraw from IVIg. According to moderate-quality evidence, serious adverse events were no more common with IFN beta-1a than with placebo.We know of no other completed trials of immunosuppressant or immunomodulatory agents for CIDP. Other treatmentsWe identified no trials of treatments for fatigue or pain in CIDP. Adverse effectsNot all trials routinely collected adverse event data; when they did, the quality of evidence was variable. Adverse effects in the short, medium, and long term occur with all interventions. We are not able to make reliable comparisons of adverse events between the interventions included in CSRs. We cannot be certain based on available evidence whether daily oral prednisone improves impairment compared to no treatment. However, corticosteroids are commonly used, based on widespread availability, low cost, very low-quality evidence from observational studies, and clinical experience. The weakness of the evidence does not necessarily mean that corticosteroids are ineffective. High-dose monthly oral dexamethasone for six months is probably no more or less effective than daily oral prednisolone. Plasma exchange produces short-term improvement in impairment as determined by neurological examination, and probably produces short-term improvement in disability. IVIg produces more short-term improvement in disability than placebo and more adverse events, although serious side effects are probably no more common than with placebo. There is no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or plasma exchange. According to observational studies, adverse events related to difficult venous access, use of citrate, and haemodynamic changes occur in 3% to17% of plasma exchange procedures.It is uncertain whether azathioprine is of benefit as the quality of evidence is very low. Methotrexate may not be of benefit and IFN beta-1a is probably not of benefit.We need further research to identify predictors of response to different treatments and to compare their long-term benefits, safety and cost-effectiveness. There is a need for more randomised trials of immunosuppressive and immunomodulatory agents, routes of administration, and treatments for symptoms of CIDP.

Identifying Adverse Events Using International Classification of Diseases, Tenth Revision Y Codes in Korea: A Cross-sectional Study.

PubMed

Ock, Minsu; Kim, Hwa Jung; Jeon, Bomin; Kim, Ye-Jee; Ryu, Hyun Mi; Lee, Moo-Song

2018-01-01

The use of administrative data is an affordable alternative to conducting a difficult large-scale medical-record review to estimate the scale of adverse events. We identified adverse events from 2002 to 2013 on the national level in Korea, using International Classification of Diseases, tenth revision (ICD-10) Y codes. We used data from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). We relied on medical treatment databases to extract information on ICD-10 Y codes from each participant in the NHIS-NSC. We classified adverse events in the ICD-10 Y codes into 6 types: those related to drugs, transfusions, and fluids; those related to vaccines and immunoglobulin; those related to surgery and procedures; those related to infections; those related to devices; and others. Over 12 years, a total of 20 817 adverse events were identified using ICD-10 Y codes, and the estimated total adverse event rate was 0.20%. Between 2002 and 2013, the total number of such events increased by 131.3%, from 1366 in 2002 to 3159 in 2013. The total rate increased by 103.9%, from 0.17% in 2002 to 0.35% in 2013. Events related to drugs, transfusions, and fluids were the most common (19 446, 93.4%), followed by those related to surgery and procedures (1209, 5.8%) and those related to vaccines and immunoglobulin (72, 0.3%). Based on a comparison with the results of other studies, the total adverse event rate in this study was significantly underestimated. Improving coding practices for ICD-10 Y codes is necessary to precisely monitor the scale of adverse events in Korea.

Predictive modeling of structured electronic health records for adverse drug event detection.

PubMed

Zhao, Jing; Henriksson, Aron; Asker, Lars; Boström, Henrik

2015-01-01

The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and combined. We have demonstrated how machine learning can be applied to electronic health records for the purpose of detecting adverse drug events and proposed solutions to some of the challenges this presents, including how to represent the various data types. Overall, clinical codes are more useful than measurements and, in specific cases, it is beneficial to combine the two.

Endoscopic papillary large balloon dilation for the removal of bile duct stones.

PubMed

Kim, Jin Hong; Yang, Min Jae; Hwang, Jae Chul; Yoo, Byung Moo

2013-12-14

Endoscopic papillary large balloon dilation (EPLBD) with endoscopic sphincterotomy (EST) has been widely used as the alternative to EST along with endoscopic mechanical lithotripsy (EML) for the removal of large or difficult bile duct stones. Furthermore, EPLBD without EST was recently introduced as its simplified alternative technique. Thus, we systematically searched PubMed, Medline, the Cochrane Library and EMBASE, and analyzed all gathered data of EPLBD with and without EST, respectively, by using a single standardized definition, reviewing relevant literatures, published between 2003 and June 2013, where it was performed with large-diameter balloons (12-20 mm). The outcomes, including the initial success rate, the rate of needs for EML, and the overall success rate, and adverse events were assessed in each and compared between both of two procedures: "EPLBD with EST" and "EPLBD without EST". A total of 2511 procedures from 30 published articles were included in EPLBD with EST, while a total of 413 procedures from 3 published articles were included in EPLBD without EST. In the results of outcomes, the overall success rate was 96.5% in EPLBD with EST and 97.2% in EPLBD without EST, showing no significant difference between both of them. The initial success rate (84.0% vs 76.2%, P < 0.001) and the success rate of EPLBD without EML (83.2% vs 76.7%, P = 0.001) was significantly higher, while the rate of use of EML was significantly lower (14.1% vs 21.6%, P < 0.001), in EPLBD with EST. The rate of overall adverse events, pancreatitis, bleeding, perforation, other adverse events, surgery for adverse events, and fatal adverse events were 8.3%, 2.4%, 3.6%, 0.6%, 1.7%, 0.2% and 0.2% in EPLBD with EST and 7.0%, 3.9%, 1.9%, 0.5%, 0.7%, 0% and 0% in EPLBD without EST, respectively, showing no significant difference between both of them. In conclusion, recent accumulated results of EPLBD with or even without EST suggest that it is a safe and effective procedure for the removal of large or difficult bile duct stones without any additional risk of severe adverse events, when performed under appropriate guidelines.

Predictive modeling of structured electronic health records for adverse drug event detection

PubMed Central

2015-01-01

Background The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Methods Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Results Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and combined. Conclusions We have demonstrated how machine learning can be applied to electronic health records for the purpose of detecting adverse drug events and proposed solutions to some of the challenges this presents, including how to represent the various data types. Overall, clinical codes are more useful than measurements and, in specific cases, it is beneficial to combine the two. PMID:26606038

Cannabis for the Management of Pain: Assessment of Safety Study (COMPASS).

PubMed

Ware, Mark A; Wang, Tongtong; Shapiro, Stan; Collet, Jean-Paul

2015-12-01

Cannabis is widely used as a self-management strategy by patients with a wide range of symptoms and diseases including chronic non-cancer pain. The safety of cannabis use for medical purposes has not been systematically evaluated. We conducted a prospective cohort study to describe safety issues among individuals with chronic non-cancer pain. A standardized herbal cannabis product (12.5% tetrahydrocannabinol) was dispensed to eligible individuals for a 1-year period; controls were individuals with chronic pain from the same clinics who were not cannabis users. The primary outcome consisted of serious adverse events and non-serious adverse events. Secondary safety outcomes included pulmonary and neurocognitive function and standard hematology, biochemistry, renal, liver, and endocrine function. Secondary efficacy parameters included pain and other symptoms, mood, and quality of life. Two hundred and fifteen individuals with chronic pain were recruited to the cannabis group (141 current users and 58 ex-users) and 216 controls (chronic pain but no current cannabis use) from 7 clinics across Canada. The median daily cannabis dose was 2.5 g/d. There was no difference in risk of serious adverse events (adjusted incidence rate ratio = 1.08, 95% confidence interval = .57-2.04) between groups. Medical cannabis users were at increased risk of non-serious adverse events (adjusted incidence rate ratio = 1.73, 95% confidence interval = 1.41-2.13); most were mild to moderate. There were no differences in secondary safety assessments. Quality-controlled herbal cannabis, when used by patients with experience of cannabis use as part of a monitored treatment program over 1 year, appears to have a reasonable safety profile. Longer-term monitoring for functional outcomes is needed. The study was registered with www.controlled-trials.com (ISRCTN19449752). This study evaluated the safety of cannabis use by patients with chronic pain over 1 year. The study found that there was a higher rate of adverse events among cannabis users compared with controls but not for serious adverse events at an average dose of 2.5 g herbal cannabis per day. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The reliability of manual reporting of clinical events in an anesthesia information management system (AIMS).

PubMed

Simpao, Allan F; Pruitt, Eric Y; Cook-Sather, Scott D; Gurnaney, Harshad G; Rehman, Mohamed A

2012-12-01

Manual incident reports significantly under-report adverse clinical events when compared with automated recordings of intraoperative data. Our goal was to determine the reliability of AIMS and CQI reports of adverse clinical events that had been witnessed and recorded by research assistants. The AIMS and CQI records of 995 patients aged 2-12 years were analyzed to determine if anesthesia providers had properly documented the emesis events that were observed and recorded by research assistants who were present in the operating room at the time of induction. Research assistants recorded eight cases of emesis during induction that were confirmed with the attending anesthesiologist at the time of induction. AIMS yielded a sensitivity of 38 % (95 % confidence interval [CI] 8.5-75.5 %), while the sensitivity of CQI reporting was 13 % (95 % CI 0.3-52.7 %). The low sensitivities of the AIMS and CQI reports suggest that user-reported AIMS and CQI data do not reliably include significant clinical events.

75 FR 23271 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-03

... proposed information collection project: ``National Hospital Adverse Event Reporting System: Questionnaire...: Proposed Project National Hospital Adverse Event Reporting System: Questionnaire Redesign and Testing As... the impact of the PSOs and the Patient Safety Act on the use of adverse event reporting systems and...

75 FR 38102 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... proposed information collection project: ``National Hospital Adverse Event Reporting System: Questionnaire...: Proposed Project National Hospital Adverse Event Reporting System: Questionnaire Redesign and Testing As... the impact of the PSOs and the Patient Safety Act on the use of adverse event reporting systems and...

Incidence and preventability of adverse events requiring intensive care admission: a systematic review.

PubMed

Vlayen, Annemie; Verelst, Sandra; Bekkering, Geertruida E; Schrooten, Ward; Hellings, Johan; Claes, Neree

2012-04-01

Adverse events are unintended patient injuries or complications that arise from health care management resulting in death, disability or prolonged hospital stay. Adverse events that require critical care are a considerable financial burden to the health care system, but also their global impact on patients and society is probably underestimated. The objectives of this systematic review were to synthesize the best available evidence regarding the estimates of the incidence and preventability of adverse events that necessitate intensive care admission, to determine the type and consequences [mortality, length of intensive care unit (ICU) stay and costs] of these adverse events. MEDLINE (from 1966 to present), EMBASE (from 1974 to present) and CENTRAL (version 1-2010) were searched for studies reporting on unplanned admissions on ICUs. Several other sources were searched for additional studies. Only quantitative studies that used chart review for the detection of adverse events requiring intensive care admission were considered for eligibility. For the purposes of this systematic review, ICUs were defined as specialized hospital facilities which provide continuous monitoring and intensive care for acutely ill patients. Studies that were published in the English, Dutch, German, French or Spanish language were eligible for inclusion. Two reviewers independently extracted data and assessed the methodological quality of the included studies. A total of 27 studies were reviewed. Meta-analysis of the data was not appropriate because of methodological and statistical heterogeneity between studies; therefore, results are presented in a descriptive way. The percentage of surgical and medical adverse events that required ICU admission ranged from 1.1% to 37.2%. ICU readmissions varied from 0% to 18.3%. Preventability of the adverse events varied from 17% to 76.5%. Preventable adverse events are further synthesized by type of event. Consequences of the adverse events included a mean length of ICU stay that ranged from 1.5 days to 10.4 days for the patient's first stay in ICU and mortality percentages between 0% and 58%. Adverse events are an important reason for (re)admission to the ICU and a considerable proportion of these are preventable. It was not possible to estimate an overall incidence and preventability rate of these events as we found considerable heterogeneity. To decrease adverse events that necessitate ICU admission, several systems are recommended such as early detection of patients with clinical instability on general wards and the implementation of rapid response teams. Step-down or intermediate care units could be a useful strategy for patients who require monitoring to avoid ICU readmissions. However, the effectiveness of such systems needs to be investigated. © 2011 Blackwell Publishing Ltd.

Modeling Major Adverse Outcomes of Pediatric and Adult Patients With Congenital Heart Disease Undergoing Cardiac Catheterization: Observations From the NCDR IMPACT Registry (National Cardiovascular Data Registry Improving Pediatric and Adult Congenital Treatment).

PubMed

Jayaram, Natalie; Spertus, John A; Kennedy, Kevin F; Vincent, Robert; Martin, Gerard R; Curtis, Jeptha P; Nykanen, David; Moore, Phillip M; Bergersen, Lisa

2017-11-21

Risk standardization for adverse events after congenital cardiac catheterization is needed to equitably compare patient outcomes among different hospitals as a foundation for quality improvement. The goal of this project was to develop a risk-standardization methodology to adjust for patient characteristics when comparing major adverse outcomes in the NCDR's (National Cardiovascular Data Registry) IMPACT Registry (Improving Pediatric and Adult Congenital Treatment). Between January 2011 and March 2014, 39 725 consecutive patients within IMPACT undergoing cardiac catheterization were identified. Given the heterogeneity of interventional procedures for congenital heart disease, new procedure-type risk categories were derived with empirical data and expert opinion, as were markers of hemodynamic vulnerability. A multivariable hierarchical logistic regression model to identify patient and procedural characteristics predictive of a major adverse event or death after cardiac catheterization was derived in 70% of the cohort and validated in the remaining 30%. The rate of major adverse event or death was 7.1% and 7.2% in the derivation and validation cohorts, respectively. Six procedure-type risk categories and 6 independent indicators of hemodynamic vulnerability were identified. The final risk adjustment model included procedure-type risk category, number of hemodynamic vulnerability indicators, renal insufficiency, single-ventricle physiology, and coagulation disorder. The model had good discrimination, with a C-statistic of 0.76 and 0.75 in the derivation and validation cohorts, respectively. Model calibration in the validation cohort was excellent, with a slope of 0.97 (standard error, 0.04; P value [for difference from 1] =0.53) and an intercept of 0.007 (standard error, 0.12; P value [for difference from 0] =0.95). The creation of a validated risk-standardization model for adverse outcomes after congenital cardiac catheterization can support reporting of risk-adjusted outcomes in the IMPACT Registry as a foundation for quality improvement. © 2017 American Heart Association, Inc.

[Costs of serious adverse events in a community teaching hospital, in Mexico].

PubMed

Gutiérrez-Mendoza, Luis Meave; Torres-Montes, Abraham; Soria-Orozco, Manuel; Padrón-Salas, Aldanely; Ramírez-Hernández, María Elizabeth

2015-01-01

Serious adverse events during hospital care are a worldwide reality and threaten the safety of the hospitalised patient. To identify serious adverse events related to healthcare and direct hospital costs in a Teaching Hospital in México. A study was conducted in a 250-bed Teaching Hospital in San Luis Potosi, Mexico. Data were obtained from the Quality and Patient Safety Department based on 2012 incidents report. Every event was reviewed and analysed by an expert team using the "fish bone" tool. The costs were calculated since the event took place until discharge or death of the patient. A total of 34 serious adverse events were identified. The average cost was $117,440.89 Mexican pesos (approx. €7,000). The great majority (82.35%) were largely preventable and related to the process of care. Undergraduate medical staff were involved in 58.82%, and 14.7% of patients had suffered adverse events in other hospitals. Serious adverse events in a Teaching Hospital setting need to be analysed to learn and deploy interventions to prevent and improve patient safety. The direct costs of these events are similar to those reported in developed countries. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Adverse effects of caffeinated energy drinks among youth and young adults in Canada: a Web-based survey

PubMed Central

Hammond, David; Reid, Jessica L.; Zukowski, Sara

2018-01-01

Background: Energy drink consumption has increased dramatically among young Canadians, with anecdotal evidence of adverse health effects. There is a lack of population-based studies to examine the prevalence of adverse events from energy drinks, particularly among young people. The current study sought to assess adverse events from energy drinks among a population-based sample of youth and young adults in Canada. Methods: An online survey was conducted in 2015 with a national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr) recruited from a consumer panel. Respondents reported prior consumption of energy drinks as well as adverse outcomes, concurrent activities associated with the outcomes and whether medical attention was sought or considered. Adverse events from coffee were also assessed for comparison. Weighted analyses are reported. Results: Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted). Overall, 55.4% of respondents who had ever consumed an energy drink reported that they had experienced at least 1 adverse event, including fast heartbeat (24.7%), difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%), chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking medical help for an adverse event. The prevalence of reported adverse events was significantly greater among energy drink consumers than among coffee consumers (36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was the proportion who reported seeking or considering seeking medical help for adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). Interpretation: More than half of youth and young adults who had consumed energy drinks reported adverse outcomes, some serious enough to warrant seeking medical help. The adverse outcomes were consistent with the physiologic effects of caffeine but were significantly more prevalent than with other sources of caffeine such as coffee, consistent with data from national adverse event databases. PMID:29335277

Adverse effects of caffeinated energy drinks among youth and young adults in Canada: a Web-based survey.

PubMed

Hammond, David; Reid, Jessica L; Zukowski, Sara

2018-01-09

Energy drink consumption has increased dramatically among young Canadians, with anecdotal evidence of adverse health effects. There is a lack of population-based studies to examine the prevalence of adverse events from energy drinks, particularly among young people. The current study sought to assess adverse events from energy drinks among a population-based sample of youth and young adults in Canada. An online survey was conducted in 2015 with a national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr) recruited from a consumer panel. Respondents reported prior consumption of energy drinks as well as adverse outcomes, concurrent activities associated with the outcomes and whether medical attention was sought or considered. Adverse events from coffee were also assessed for comparison. Weighted analyses are reported. Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted). Overall, 55.4% of respondents who had ever consumed an energy drink reported that they had experienced at least 1 adverse event, including fast heartbeat (24.7%), difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%), chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking medical help for an adverse event. The prevalence of reported adverse events was significantly greater among energy drink consumers than among coffee consumers (36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was the proportion who reported seeking or considering seeking medical help for adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). More than half of youth and young adults who had consumed energy drinks reported adverse outcomes, some serious enough to warrant seeking medical help. The adverse outcomes were consistent with the physiologic effects of caffeine but were significantly more prevalent than with other sources of caffeine such as coffee, consistent with data from national adverse event databases. Copyright 2018, Joule Inc. or its licensors.

The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis.

PubMed

Cohen, Jonah; Grunwald, Douglas; Grossberg, Laurie B; Sawhney, Mandeep S

2017-10-01

Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.

Therapeutic effects of atorvastatin and ezetimibe compared with double-dose atorvastatin in very elderly patients with acute coronary syndrome.

PubMed

Liu, Zhi; Hao, Hengjian; Yin, Chunlin; Chu, Yanyan; Li, Jing; Xu, Dong

2017-06-20

Objective Compared the effect of atorvastatin 10 mg combined ezetimibe 10 mg therapy with atorvastatin 20 mg on the long-term outcomes in very elderly patients with acute coronary syndrome.Methods A total of 230 octogenarian patients with acute coronary syndrome underwent coronary angiography were randomized to combined therapy group (atorvastatin 10 mg/d and ezetimibe 10 mg/d, n=114) or double-dose atorvastatin group (atorvastatin 20mg/d, n=116). The primary end point was one-year incidence of major adverse cardiovascular events (including cardiac death, spontaneous myocardial infarction, unplanned revascularization).Result At the end of one year, the percentage of patients with low-density lipoprotein cholesterol level decreased more than 30% or 50% were comparable between the two groups (93.5% vs. 90.1%, p= 0.36; 54.6% vs. 49.6%, p= 0.45). The rate of major adverse cardiovascular events in combined therapy group was similar with double-dose atorvastatin group (23.2% vs. 19.8%, p=0.55). In COX regression model, the risk of major adverse cardiovascular events in combined group isn't significantly higher than double-dose atorvastatin group (HR [95% CI] 1.12 [0.51 to 2.55], p = 0.74). The patients whose alanine aminotransferase increasing more than upper normal limit in combined group was lower than double-dose atorvastatin group (2.8% vs. 9.0%, p = 0.05).Conclusions For very elderly patients with acute coronary syndrome, atorvastatin combining ezetimibe induced similar long-term outcomes compared with double-dose atorvastatin but with less liver dysfunction.

Fluoroquinolone-related neuropsychiatric and mitochondrial toxicity: a collaborative investigation by scientists and members of a social network.

PubMed

Kaur, Kamaljeet; Fayad, Raja; Saxena, Arpit; Frizzell, Norma; Chanda, Anindya; Das, Suvarthi; Chatterjee, Saurabh; Hegde, Shweta; Baliga, Manjeshwar Shrinath; Ponemone, Venkatesh; Rorro, Matthew; Greene, Jennifer; Elraheb, Yasmine; Redd, Alan J; Bian, John; Restaino, John; Norris, LeAnn B; Qureshi, Zaina P; Love, Bryan L; Brookstaver, Brandon; Georgantopoulos, Peter; Sartor, Oliver; Raisch, Dennis W; Rao, Gowtham; Lu, Kevin; Ray, Paul; Hrusheshky, William; Schulz, Richard; Ablin, Richard; Noxon, Virginia; Bennett, Charles L

2016-02-01

The 3 fluoroquinolone (FQ) antibiotics - ciprofoxacin, levofoxacin, and moxifoxacin - are commonly administered to oncology patients. Although these oral antibiotics are approved by the US Food and Drug Administration (FDA) for treatment of urinary tract infections, acute bacterial sinusitis, or bacterial infection in patients with chronic obstructive pulmonary disease, they are commonly prescribed off-label to neutropenic cancer patients for the prevention and treatment of infections associated with febrile neutropenia. New serious FQ-associated safety concerns have been identified through novel collaborations between FQ-treated persons who have developed long-term neuropsychiatric (NP) toxicity, pharmacovigilance experts, and basic scientists. To conduct basic science and clinical investigations of a newly identified adverse drug reaction, termed FQ-associated disability. 5 groups of C57BL/6 mice receiving the antibiotic ciprofoxacin in 10-mg increments (10 mg/kg-50 mg/kg) and 1 group of control mice were evaluated. The Southern Network on Adverse Reactions (SONAR) and a social network of FQ-treated persons with long-term NP toxicity (the Floxed Network) conducted a web-based survey. The clinical toxicity manifestations reported by 94 respondents to the web-based survey of persons who had received 1 or more doses of an FQ prescribed for any indication (generally at FDA-approved dosages) and who subsequently experienced possible adverse drug reactions were compared with adverse event information included on the product label for levofoxacin and with FQ-associated adverse events reported to the FDA's MedWatch program. Mice treated with ciprofoxacin had lower grip strengths, reduced balance, and depressive behavior compared with the controls. For the survey, 93 of 94 respondents reported FQ-associated events including anxiety, depression, insomnia, panic attacks, clouded thinking, depersonalization, suicidal thoughts, psychosis, nightmares, and impaired memory beginning within days of FQ initiation or days to months of FQ discontinuation. The FDA Adverse Event Reporting System (FAERS) included 210,705 adverse events and 2,991 fatalities for FQs. Levofoxacin and ciprofoxacin toxicities were neurologic (30% and 26%, respectively), tendon damage (8% and 6%), and psychiatric (10% and 2%). In 2013, an FDA safety review reported that FQs affect mammalian topoisomerase II, especially in mitochondria. In 2013 and 2014, SONAR fled citizen petitions requesting black box revisions identifying neuropsychiatric toxicities and mitochrondrial toxicity as serious levofoxacin-associated adverse drug reactions. In 2015, FDA advisors recommended that FQ product labels be revised to include information about this newly identified disability syndrome termed "FQ-associated disability" (FQAD). Basic science studies evaluated NP toxicity for only 1 FQ, ciprofoxacin. Pharmacovigilance investigators, a social network, and basic scientists can collaborate on pharmacovigilance investigations. Revised product labels describing a new serious adverse drug reaction, levofoxacin-associated long-term disability, as recommended by an FDA advisory committee, are advised. ©2016 Frontline Medical Communications.

Application of the Beers Criteria to Alternate Level of Care Patients in Hospital Inpatient Units

PubMed Central

Slaney, Heather; MacAulay, Stacey; Irvine-Meek, Janice; Murray, Joshua

2015-01-01

Background: The Beers criteria were developed to help in identifying potentially inappropriate medications (PIMs) for elderly patients. These medications are often associated with adverse events and limited effectiveness in older adults. Patients awaiting an alternate level of care (ALC patients) are those who no longer require acute care hospital services and are waiting for placement elsewhere. They are often elderly, have complex medication regimens, and are at high risk of adverse events. At the time of this study no studies had applied the Beers criteria to ALC patients in Canadian hospitals. Objectives: To determine the proportion of ALC patients receiving PIMs and the proportion experiencing selected PIM-related adverse events. Methods: A retrospective chart review of ALC patients 65 years of age or older was performed to identify PIMs and the occurrence of selected adverse events (specifically central nervous system [CNS] events, falls, bradycardia, hypoglycemia, seizures, insomnia, gastrointestinal bleeding, and urinary tract infections). A logistic regression model with a random intercept for each patient was constructed to estimate odds ratios and probabilities of adverse events. Results: Fifty-two ALC patients were included in the study. Of these, 48 (92%) were taking a PIM. Of the 922 adverse events evaluated, 407 (44.1%) were associated with a regularly scheduled PIM. Among patients who were taking regularly scheduled PIMs, there was a significantly increased probability of an adverse CNS event and of a fall (p < 0.001 for both). The most common PIM medication classes were first-generation antihistamines (24 [46%] of the 52 patients), antipsychotics (21 patients [40%]), short-acting benzodiazepines (15 patients [29%]), and nonbenzodiazepine hypnotics (14 patients [27%]). Conclusions: A high proportion of ALC patients were taking PIMs and experienced an adverse event that may have been related to these drugs. These findings suggest that the ALC population might benefit from regular medication review and monitoring to prevent or detect adverse events. PMID:26157183

Within-Hospital Variation in 30-Day Adverse Events: Implications for Measuring Quality.

PubMed

Burke, Robert E; Glorioso, Thomas; Barón, Anna K; Kaboli, Peter J; Ho, P Michael

Novel measures of hospital quality are needed. Because quality improvement efforts seek to reduce variability in processes and outcomes, hospitals with higher variability in adverse events may be delivering poorer quality care. We sought to evaluate whether within-hospital variability in adverse events after a procedure might function as a quality metric that is correlated with facility-level mortality rates. We analyzed all percutaneous coronary interventions (PCIs) performed in the Veterans Health Administration (VHA) system from 2007 to 2013 to evaluate the correlation between within-hospital variability in 30-day postdischarge adverse events (readmission, emergency department visit, and repeat revascularization), and facility-level mortality rates, after adjustment for patient demographics, comorbidities, PCI indication, and PCI urgency. The study cohort included 47,567 patients at 48 VHA hospitals. The overall 30-day adverse event rate was 22.0% and 1-year mortality rate was 4.9%. The most variable sites had relative changes of 20% in 30-day rates of adverse events period-to-period. However, within-hospital variability in 30-day events was not correlated with 1-year mortality rates (correlation coefficient = .06; p = .66). Thus, measuring within-hospital variability in postdischarge adverse events may not improve identification of low-performing hospitals. Evaluation in other conditions, populations, and in relationship with other quality metrics may reveal stronger correlations with care quality.

77 FR 11134 - Guidance for Industry on Postmarketing Adverse Event Reporting for Medical Products and Dietary...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

...] Guidance for Industry on Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements... entitled ``Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During an... reporting requirements for drugs, biologics, medical devices, and dietary supplements during an influenza...

Analysis of adverse events as a contribution to safety culture in the context of practice development

PubMed

Hoffmann, Susanne; Frei, Irena Anna

2017-01-01

Background: Analysing adverse events is an effective patient safety measure. Aim: We show, how clinical nurse specialists have been enabled to analyse adverse events with the „Learning from Defects-Tool“ (LFD-Tool). Method: Our multi-component implementation strategy addressed both, the safety knowledge of clinical nurse specialists and their attitude towards patient safety. The culture of practice development was taken into account. Results: Clinical nurse specialists relate competency building on patient safety due to the application of the LFD-tool. Applying the tool, fosters the reflection of adverse events in care teams. Conclusion: Applying the „Learning from Defects-Tool“ promotes work-based learning. Analysing adverse events with the „Learning from Defects-Tool“ contributes to the safety culture in a hospital.

[Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

PubMed

Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

2011-01-01

Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

Ventilator-Related Adverse Events: A Taxonomy and Findings From 3 Incident Reporting Systems.

PubMed

Pham, Julius Cuong; Williams, Tamara L; Sparnon, Erin M; Cillie, Tam K; Scharen, Hilda F; Marella, William M

2016-05-01

In 2009, researchers from Johns Hopkins University's Armstrong Institute for Patient Safety and Quality; public agencies, including the FDA; and private partners, including the Emergency Care Research Institute and the University HealthSystem Consortium (UHC) Safety Intelligence Patient Safety Organization, sought to form a public-private partnership for the promotion of patient safety (P5S) to advance patient safety through voluntary partnerships. The study objective was to test the concept of the P5S to advance our understanding of safety issues related to ventilator events, to develop a common classification system for categorizing adverse events related to mechanical ventilators, and to perform a comparison of adverse events across different adverse event reporting systems. We performed a cross-sectional analysis of ventilator-related adverse events reported in 2012 from the following incident reporting systems: the Pennsylvania Patient Safety Authority's Patient Safety Reporting System, UHC's Safety Intelligence Patient Safety Organization database, and the FDA's Manufacturer and User Facility Device Experience database. Once each organization had its dataset of ventilator-related adverse events, reviewers read the narrative descriptions of each event and classified it according to the developed common taxonomy. A Pennsylvania Patient Safety Authority, FDA, and UHC search provided 252, 274, and 700 relevant reports, respectively. The 3 event types most commonly reported to the UHC and the Pennsylvania Patient Safety Authority's Patient Safety Reporting System databases were airway/breathing circuit issue, human factor issues, and ventilator malfunction events. The top 3 event types reported to the FDA were ventilator malfunction, power source issue, and alarm failure. Overall, we found that (1) through the development of a common taxonomy, adverse events from 3 reporting systems can be evaluated, (2) the types of events reported in each database were related to the purpose of the database and the source of the reports, resulting in significant differences in reported event categories across the 3 systems, and (3) a public-private collaboration for investigating ventilator-related adverse events under the P5S model is feasible. Copyright © 2016 by Daedalus Enterprises.

The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines.

PubMed

Marcos, Erica; Zhao, Bin; He, Yongqun

2013-11-26

Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term 'human vaccinee population' is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. The ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents enables the identification of adverse events from vaccination in relation to predefined parts of the population (age groups) and certain groups of vaccines. The resulting ontology-based VAE knowledge base classifies vaccine-specific VAEs and supports better VAE understanding and future rational AE prevention and treatment.

Adverse Drug Events and Medication Errors in African Hospitals: A Systematic Review.

PubMed

Mekonnen, Alemayehu B; Alhawassi, Tariq M; McLachlan, Andrew J; Brien, Jo-Anne E

2018-03-01

Medication errors and adverse drug events are universal problems contributing to patient harm but the magnitude of these problems in Africa remains unclear. The objective of this study was to systematically investigate the literature on the extent of medication errors and adverse drug events, and the factors contributing to medication errors in African hospitals. We searched PubMed, MEDLINE, EMBASE, Web of Science and Global Health databases from inception to 31 August, 2017 and hand searched the reference lists of included studies. Original research studies of any design published in English that investigated adverse drug events and/or medication errors in any patient population in the hospital setting in Africa were included. Descriptive statistics including median and interquartile range were presented. Fifty-one studies were included; of these, 33 focused on medication errors, 15 on adverse drug events, and three studies focused on medication errors and adverse drug events. These studies were conducted in nine (of the 54) African countries. In any patient population, the median (interquartile range) percentage of patients reported to have experienced any suspected adverse drug event at hospital admission was 8.4% (4.5-20.1%), while adverse drug events causing admission were reported in 2.8% (0.7-6.4%) of patients but it was reported that a median of 43.5% (20.0-47.0%) of the adverse drug events were deemed preventable. Similarly, the median mortality rate attributed to adverse drug events was reported to be 0.1% (interquartile range 0.0-0.3%). The most commonly reported types of medication errors were prescribing errors, occurring in a median of 57.4% (interquartile range 22.8-72.8%) of all prescriptions and a median of 15.5% (interquartile range 7.5-50.6%) of the prescriptions evaluated had dosing problems. Major contributing factors for medication errors reported in these studies were individual practitioner factors (e.g. fatigue and inadequate knowledge/training) and environmental factors, such as workplace distraction and high workload. Medication errors in the African healthcare setting are relatively common, and the impact of adverse drug events is substantial but many are preventable. This review supports the design and implementation of preventative strategies targeting the most likely contributing factors.

Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007.

PubMed

Niu, Manette T; Ball, Robert; Woo, Emily Jane; Burwen, Dale R; Knippen, Maureen; Braun, M Miles

2009-01-07

During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted.

Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison.

PubMed

Adams, David H; Zhang, Lu; Millen, Brian A; Kinon, Bruce J; Gomez, Juan-Carlos

2014-01-01

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n = 516) or aripiprazole (n = 162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (-2.8 ± 0.4 versus 0.4 ± 0.6; P < 0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (-15.58 ± 1.58 versus -12.03 ± 0.99; P = 0.045). The incidences of SAEs (8.2% versus 3.1%; P = 0.032) and discontinuation due to AEs (16.2% versus 8.7%; P = 0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.gov NCT01328093.

The HVTN503/Phambili HIV vaccine trial: a comparison of younger and older participants

PubMed Central

Volk, Jonathan E.; Hessol, Nancy A.; Gray, Glenda E.; Kublin, James G.; Churchyard, Gavin J.; Mlisana, Koleka; Nchabeleng, Maphoshane; Buchbinder, Susan P.; Bekker, Linda-Gail

2014-01-01

By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January-September, 2007. Motivations for trial enrollment, social harms, adverse events, and loss to follow-up were compared between younger (18-20 years old) and older participants (21-35 years old). Both younger (n=238) and older participants (n=563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p=0.005), while younger males were more likely to enroll because the vaccine may provide protection from HIV-acquisition (p<0.001). There were no significant differences in the number of social harms reported. Compared to males over 20 years-old, 18-20-year-old females were less likely to experience adverse events (OR=0.1, CI 0.01-0.80) and no more likely to be lost to follow up (OR=0.7, CI 0.39-1.25), while 18-20-year-old males were no more likely to experience adverse events (OR=1.3, CI 0.58-2.83) or loss to follow-up (OR=0.8, CI 0.51-1.41). Our data support the inclusion of younger participants who are at risk for HIV in future HIV vaccine efficacy trials. PMID:24104693

The safety and effectiveness of a long-acting transdermal fentanyl solution compared with oxymorphone for the control of postoperative pain in dogs: a randomized, multicentered clinical study

PubMed Central

Martinez, S A; Wilson, M G; Linton, D D; Newbound, G C; Freise, K J; Lin, T-L; Clark, T P

2014-01-01

A prospective, double-blinded, positive-controlled, multicenter, noninferiority study was conducted to evaluate the safety and effectiveness of transdermal fentanyl solution (TFS) compared with oxymorphone for the control of postoperative pain in dogs. Five hundred and two (502) client-owned dogs were assigned to a single dose of TFS (2.7 mg/kg) applied 2–4 h prior to surgery or oxymorphone hydrochloride (0.22 mg/kg) administered subcutaneously 2–4 h prior to surgery and q6h through 90 h. Pain was evaluated over 4 days by blinded observers using a modified Glasgow composite pain scale, and the a priori criteria for treatment failure was a pain score ≥8 or adverse event necessitating withdrawal. Four TFS- and eight oxymorphone-treated dogs were withdrawn due to lack of pain control. Eighteen oxymorphone-treated, but no TFS-treated dogs were withdrawn due to severe adverse events. The one-sided upper 95% confidence interval of the difference between TFS and oxymorphone treatment failure rates was −5.3%. Adverse events associated with oxymorphone were greater in number and severity compared with TFS. It was concluded that a single administration of TFS was safe and noninferior to repeated injections of oxymorphone for the control of postoperative pain over 4 days at the dose rates of both formulations used in this study. PMID:24344787

Chlorhexidine with or without alcohol against biofilm formation: efficacy, adverse events and taste preference.

PubMed

Santos, Gabriela Otero Dos; Milanesi, Fernanda Carpes; Greggianin, Bruna Frizon; Fernandes, Marilene Issa; Oppermann, Rui Vicente; Weidlich, Patricia

2017-05-04

In recent years, different chlorhexidine formulations have been tested, including an alcohol-free alternative, but the effect of this solution on early biofilm formation is not clear. A crossover, randomized, double-blind clinical trial was conducted to evaluate the effect of two chlorhexidine solutions against supra- and subgingival biofilm formation (NCT#02656251). Thirty-five participants were randomized and asked to rinse twice daily with 15 ml of an alcohol-containing 0.12% chlorhexidine solution, an alcohol-free 0.12% chlorhexidine solution, or placebo. The study was conducted in three experimental periods of 4 days each, with a 10-day washout between the periods. All the experimental periods followed the same protocol, except that the solutions were switched. Biofilm distribution was evaluated every 24 hours by the Plaque-Free Zone Index, during 96 hours. Adverse events were self-reported and sensory evaluation was performed using a hedonic scale. Compared to the placebo, the chlorhexidine solutions resulted in a significantly higher number of surfaces free of plaque over 96 hours (p < 0.01), and were able to prevent subgingival biofilm formation (p < 0.01). The alcohol-free chlorhexidine solution was associated with a lower incidence of adverse events, compared with alcohol-containing chlorhexidine (p < 0.05); it also received better sensory evaluation and acceptance by trial participants, compared with the alcohol-containing chlorhexidine (p = 0.007), and had a similar inhibitory effect on the formation of supra- and subgingival biofilms.

Rotigotine transdermal patch in Parkinson's disease: a systematic review and meta-analysis.

PubMed

Zhou, Chang-Qing; Li, Shan-Shan; Chen, Zhong-Mei; Li, Feng-Qun; Lei, Peng; Peng, Guo-Guang

2013-01-01

The efficacy and safety of rotigotine transdermal patch in Parkinson's disease (PD) were studied in some clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the efficacy, tolerability, and safety of rotigotine transdermal patch versus placebo in PD. Six randomized controlled trials (1789 patients) were included in this meta-analysis. As compared with placebo, the use of rotigotine resulted in greater improvements in Unified Parkinson's Disease Rating Scale activities of daily living score (weighted mean difference [WMD] -1.69, 95% confidence interval [CI] -2.18 to -1.19), motor score (WMD -3.86, 95% CI -4.86 to -2.86), and the activities of daily living and motor subtotal score (WMD -4.52, 95% CI -5.86 to -3.17). Rotigotine was associated with a significantly higher rate of withdrawals due to adverse events (relative risk [RR] 1.82, 95% CI 1.29-2.59), and higher rates of application site reactions (RR 2.92, 95% CI 2.29-3.72), vomiting (RR 5.18, 95% CI 2.25-11.93), and dyskinesia (RR 2.52, 95% CI 1.47-4.32) compared with placebo. No differences were found in the relative risks of headache, constipation, back pain, diarrhea, or serious adverse events. Our meta-analysis showed that the use of rotigotine can reduce the symptoms of PD. However, rotigotine was also associated with a higher incidence of adverse events, especially application site reactions, compared with placebo.

Brand vs generic adverse event reporting patterns: An authorized generic-controlled evaluation of cardiovascular medications.

PubMed

Alatawi, Y; Rahman, Md M; Cheng, N; Qian, J; Peissig, P L; Berg, R L; Page, C D; Hansen, R A

2018-06-01

Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P < .01). Inconsistent reporting patterns were observed more between brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported. © 2017 John Wiley & Sons Ltd.

Clinical review: insulin pump-associated adverse events in adults and children.

PubMed

Ross, P L; Milburn, J; Reith, D M; Wiltshire, E; Wheeler, B J

2015-12-01

Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

Adverse life events and health: a population study in Hong Kong.

PubMed

Karatzias, Thanos; Yan, Elsie; Jowett, Sally

2015-02-01

Although the effects of adverse life events on mental health have been well documented in the literature, there has never been a population based study that investigated systematically the association between history of adverse life events and physical health (objective and subjective) in adults. Cross-sectional, face-to-face household population based survey of adults (18+) in Hong Kong (N=1147). Participants were asked if they had a diagnosis of six health conditions including hypertension, heart disease, arthritis, diabetes, eyesight degeneration, and hearing loss. They were also asked if they had experienced five adverse life events including death of a partner or spouse, abuse, natural disaster, life threatening illness or injury, and family disruption. Interviews also included the Short-Form 12 Health Survey (SFHS-12) and the short version of the Centre for Epidemiologic Studies Depression Scale (CES-D). Overall, results indicate that specific adverse life events may be associated with specific health conditions. However, all tested life events were associated with subjective physical and mental health. Death of partner or parent and life threatening illness or injury were found to have the strongest association with physical health problems. A dose-response relationship between adverse life events and physical health in general was evident but more so for heart disease and eyesight degeneration. Considering the high prevalence of traumatic events and how common the conditions associated with such events are in the general population, screening for adverse life events as part of comprehensive assessment will allow a deeper understanding of patients' needs. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.

PubMed

Kose, Eiji; Uno, Kana; Hayashi, Hiroyuki

2017-01-01

 Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.

[Try to achieve quickly the blood pressure target in newly diagnosed hypertensive patients is safe and effective].

PubMed

Kichou, B; Henine, N; Kichou, L; Boubchir, M A; Ait Said, M A; Zatout, M; Hammouche, A; Mazeghrane, A; Madiou, A; Benbouabdellah, M

2018-06-01

To compare a so-called an "accelerated" antihypertensive strategy to a "standard" strategy, in terms of blood pressure control rates and adverse events. Prospective open-label randomized controlled trial, which included consecutive hypertensive patients, newly diagnosed, 40 to 70 years old, with no prior antihypertensive treatment. Hypertension was diagnosed if office blood pressure was≥140/90mmHg, confirmed by an increase of Home or a daytime ambulatory blood pressure. The patients were randomly assigned according to 1:1 ratio to an "accelerated" strategy or to a "standard" strategy. The primary end-point was the rate of blood pressure control at 12weeks. The secondary end-point was the rate of adverse events (a safety end-point). We recruited 268 patients (132 in the "accelerated" strategy group), with a mean age of 55 years and 62% of men. The mean office blood pressure at baseline was 168/95mmHg. The clinical characteristics were on average similar between the 2 treatment groups. At 12 weeks, the rates of blood pressure control were 63.6% in the "accelerated" strategy and 38.2% in the "standard" strategy (P<0.001). There was no significantly difference between the rates of adverse events in the 2 strategies (6.06% versus 5.14%; P=0.8). The "accelerated" antihypertensive strategy was more effective than a standard one, in terms of blood pressure control, without an increase in adverse events rate. This could translate into a future cardiovascular events reduction. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Drug safety data mining with a tree-based scan statistic.

PubMed

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

Blood pressure lowering efficacy of renin inhibitors for primary hypertension.

PubMed

Musini, Vijaya M; Lawrence, Kendra Ak; Fortin, Patricia M; Bassett, Ken; Wright, James M

2017-04-05

Hypertension is a chronic condition associated with an increased risk of mortality and morbidity. Renin is the enzyme responsible for converting angiotensinogen to angiotensin I, which is then converted to angiotensin II. Renin inhibitors are a new class of drugs that decrease blood pressure (BP) by preventing the formation of both angiotensin I and angiotensin II. To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension.To determine the change in BP variability, pulse pressure, and heart rate and to evaluate adverse events (mortality, non-fatal serious adverse events, total adverse events, withdrawal due to adverse effects and specific adverse events such as dry cough, diarrhoea and angioedema). The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to February 2017: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2017, Issue 2), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. There was no restriction by language or publication status. We also searched the European Medicines Agency (EMA) for clinical study reports, the Novartis Clinical Study Results Database, bibliographic citations from retrieved references, and contacted authors of relevant papers regarding further published and unpublished work. We included randomized, double-blinded, placebo-controlled studies evaluating BP lowering efficacy of fixed-dose monotherapy with renin inhibitor compared with placebo for a minimum duration of three to 12 weeks in adult patients with primary hypertension. This systematic review is a comprehensive update which includes four additional studies and extensive detail from nine clinical study reports (CSRs) of previously included studies obtained from EMA. The remaining three CSRs are not available.Two review authors independently assessed study eligibility and extracted data. In all cases where there was a difference between the CSR and the published report, data from the CSR was used. Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence intervals (CIs) and continuous outcomes as mean difference (MD) with 95% CIs. 12 studies (mean duration of eight weeks) in 7439 mostly Caucasian patients (mean age 54 years) with mild-to-moderate uncomplicated hypertension were eligible for inclusion in the review. Aliskiren was the only renin inhibitor evaluated. All included studies were assessed to have high likelihood of attrition, reporting and funding bias.Aliskiren has a dose-related systolic/diastolic blood pressure (SBP/DBP) lowering effect as compared with placebo MD with 95% CI: aliskiren 75 mg (MD -2.97, 95% CI -4.76 to -1.18)/(MD -2.05, 95% CI -3.13 to -0.96) mm Hg (moderate-quality evidence), aliskiren 150 mg (MD -5.95, 95% CI -6.85 to -5.06)/ (MD -3.16, 95% CI -3.74 to -2.58) mm Hg (moderate-quality evidence), aliskiren 300 mg (MD -7.88, 95% CI -8.94 to -6.82)/ (MD -4.49, 95% CI -5.17 to -3.82) mm Hg (moderate-quality evidence), aliskiren 600 mg (MD -11.35, 95% CI -14.43 to -8.27)/ (MD -5.86, 95% CI -7.73 to -3.99) mm Hg (low-quality evidence). There was a dose-dependent decrease in blood pressure for aliskiren 75 mg, 150 mg and 300 mg. The blood pressure lowering effect of aliskiren 600 mg was not different from 300 mg (MD -0.61, 95% CI -2.78 to 1.56)/(MD -0.68, 95% CI -2.03 to 0.67). Aliskiren had no effect on blood pressure variability. Due to very limited information available regarding change in heart rate and pulse pressure, it was not possible to meta-analyze these outcomes.Mortality and non-fatal serious adverse events were not increased. This review found that in studies of eight week duration aliskiren may not increase withdrawal due to adverse events (low-quality evidence). Diarrhoea was increased in a dose-dependent manner (RR 7.00, 95% CI 2.48 to 19.72) with aliskiren 600 mg (low-quality evidence). The most frequent adverse events reported were headache, nasopharyngitis, diarrhoea, dizziness and fatigue. Compared to placebo, aliskiren lowered BP and this effect is dose-dependent. This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). There is no difference in mortality, nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy. Diarrhoea was considerably increased with aliskiren 600 mg.

A cross-country comparison of rivaroxaban spontaneous adverse event reports and concomitant medicine use with the potential to increase the risk of harm.

PubMed

McDonald, Cameron J; Kalisch Ellett, Lisa M; Barratt, John D; Caughey, Gillian E

2014-12-01

Concerns with the safety profiles of the newer anticoagulants have been raised because of differences in treatment populations between pre-marketing studies (randomized controlled trials) and clinical practice. Little is known about the potential safety issues and the reporting in spontaneous adverse event databases associated with rivaroxaban. To analyse spontaneous adverse event reports associated with the oral anticoagulant rivaroxaban from Australia, Canada and the USA; and to examine concomitant medicine use that may increase the risk of adverse events. Spontaneous adverse event report databases from Australia, Canada and the USA were examined for all reports of adverse events associated with rivaroxaban and concomitant medicines from 1 August 2005 to 31 March 2013. Disproportionality analysis (the proportional reporting ratio [PRR] and reporting odds ratio [ROR]) was conducted for quantitative detection of signals, using the US database. There were 244 spontaneous adverse event reports associated with rivaroxaban from Australia, 536 from Canada and 1,638 from the USA. Reporting of haemorrhage (any type) was common, ranging from 30.7% for Australia to 37.5% for Canada. Gastrointestinal haemorrhage was the most commonly reported haemorrhage, accounting for 13.9% of Australian, 16.4% of Canadian and 11.1% of US adverse event reports. Positive signals were confirmed in the US data (haemorrhage [any type] PRR 11.93, χ (2) 4,414.78 and ROR 13.41, 95% confidence interval [CI] 12.13-14.81; gastrointestinal haemorrhage PRR 12.52, χ (2) 2,018.48 and ROR 13.15, 95% CI 11.36-15.21). Reporting of concomitant use of medicines with the potential to increase bleeding risk ranged from 63.7% in Australia to 89.2% in Canada. A large proportion of adverse event reports for rivaroxaban were associated with use of concomitant medicines, which may have increased the risk of adverse events-in particular, haemorrhage. Increased awareness of a patient's comorbidity and associated medicine use is needed when rivaroxaban is used in clinical practice.

Serenoa repens (saw palmetto): a systematic review of adverse events.

PubMed

Agbabiaka, Taofikat B; Pittler, Max H; Wider, Barbara; Ernst, Edzard

2009-01-01

Serenoa repens (W. Bartram) Small, also known as saw palmetto, is one of the most widely used herbal preparations for the treatment of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Although a number of randomized controlled trials (RCTs) and systematic reviews of the efficacy of S. repens for the treatment of LUTS and BPH have been published, no systematic review on its drug interactions or adverse events currently exists. This review assesses all available human safety data of S. repens monopreparations. Systematic literature searches were conducted from date of inception to February 2008 in five electronic databases; reference lists and our departmental files were checked for further relevant publications. Information was requested from spontaneous reporting schemes of the WHO and national safety bodies. Twenty-four manufacturers/distributors of S. repens preparations and four herbalist organizations were contacted for additional information. No language restrictions were imposed. Only reports of adverse events in humans from monopreparations of S. repens were included. Data from all articles, regardless of study design, reporting adverse events or interactions were independently extracted by the first author and validated by the second. Forty articles (26 randomized controlled trials, 4 non-randomized controlled trials, 6 uncontrolled trials and 4 case reports/series) were included. They suggest that adverse events associated with the use of S. repens are mild and similar to those with placebo. The most frequently reported adverse events are abdominal pain, diarrhoea, nausea, fatigue, headache, decreased libido and rhinitis. More serious adverse events such as death and cerebral haemorrhage are reported in isolated case reports and data from spontaneous reporting schemes, but causality is questionable. No drug interactions were reported. Currently available data suggest that S. repens is well tolerated by most users and is not associated with serious adverse events. The majority of adverse events are mild, infrequent and reversible, and include abdominal pain, diarrhoea, nausea and fatigue, headache, decreased libido and rhinitis. We found no evidence for drug interactions with S. repens. However, higher quality reporting of adverse events is essential if safety assessments are to be improved in future.

Probiotics for the prevention of pediatric antibiotic-associated diarrhea.

PubMed

Goldenberg, Joshua Z; Lytvyn, Lyubov; Steurich, Justin; Parkin, Patricia; Mahant, Sanjay; Johnston, Bradley C

2015-12-22

Antibiotics are frequently prescribed in children. They alter the microbial balance within the gastrointestinal tract, commonly resulting in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via restoration of the gut microflora. The primary objectives were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. MEDLINE, EMBASE, CENTRAL, CINAHL, AMED, and the Web of Science (inception to November 2014) were searched along with specialized registers including the Cochrane IBD/FBD review group, CISCOM (Centralized Information Service for Complementary Medicine), NHS Evidence, the International Bibliographic Information on Dietary Supplements as well as trial registries. Letters were sent to authors of included trials, nutraceutical and pharmaceutical companies, and experts in the field requesting additional information on ongoing or unpublished trials. Conference proceedings, dissertation abstracts, and reference lists from included and relevant articles were also searched. Randomized, parallel, controlled trials in children (0 to 18 years) receiving antibiotics, that compare probiotics to placebo, active alternative prophylaxis, or no treatment and measure the incidence of diarrhea secondary to antibiotic use were considered for inclusion. Study selection, data extraction as well as methodological quality assessment using the risk of bias instrument was conducted independently and in duplicate by two authors. Dichotomous data (incidence of diarrhea, adverse events) were combined using a pooled risk ratio (RR) or risk difference (RD), and continuous data (mean duration of diarrhea, mean daily stool frequency) as mean difference (MD), along with their corresponding 95% confidence interval (95% CI). For overall pooled results on the incidence of diarrhea, sensitivity analyses included available case versus extreme-plausible analyses and random- versus fixed-effect models. To explore possible explanations for heterogeneity, a priori subgroup analysis were conducted on probiotic strain, dose, definition of antibiotic-associated diarrhea, as well as risk of bias. We also conducted post hoc subgroup analyses by patient diagnosis, single versus multi-strain, industry sponsorship, and inpatient status. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. Twenty-three studies (3938 participants) met the inclusion criteria. Trials included treatment with either Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., orStreptococcus spp., alone or in combination. Eleven studies used a single strain probiotic, four combined two probiotic strains, three combined three probiotic strains, one combined four probiotic strains, two combined seven probiotic strains, one included ten probiotic strains, and one study included two probiotic arms that used three and two strains respectively. The risk of bias was determined to be high or unclear in 13 studies and low in 10 studies. Available case (patients who did not complete the studies were not included in the analysis) results from 22/23 trials reporting on the incidence of diarrhea show a precise benefit from probiotics compared to active, placebo or no treatment control. The incidence of AAD in the probiotic group was 8% (163/1992) compared to 19% (364/1906) in the control group (RR 0.46, 95% CI 0.35 to 0.61; I(2) = 55%, 3898 participants). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate. This benefit remained statistically significant in an extreme plausible (60% of children loss to follow-up in probiotic group and 20% loss to follow-up in the control group had diarrhea) sensitivity analysis, where the incidence of AAD in the probiotic group was 14% (330/2294) compared to 19% (426/2235) in the control group (RR 0.69; 95% CI 0.54 to 0.89; I(2) = 63%, 4529 participants). None of the 16 trials (n = 2455) that reported on adverse events documented any serious adverse events attributable to probiotics. Meta-analysis excluded all but an extremely small non-significant difference in adverse events between treatment and control (RD 0.00; 95% CI -0.01 to 0.01). The majority of adverse events were in placebo, standard care or no treatment group. Adverse events reported in the studies include rash, nausea, gas, flatulence, abdominal bloating, abdominal pain, vomiting, increased phlegm, chest pain, constipation, taste disturbance, and low appetite. Moderate quality evidence suggests a protective effect of probiotics in preventing AAD. Our pooled estimate suggests a precise (RR 0.46; 95% CI 0.35 to 0.61) probiotic effect with a NNT of 10. Among the various probiotics evaluated, Lactobacillus rhamnosus or Saccharomyces boulardii at 5 to 40 billion colony forming units/day may be appropriate given the modest NNT and the likelihood that adverse events are very rare. It is premature to draw conclusions about the efficacy and safety of other probiotic agents for pediatric AAD. Although no serious adverse events were observed among otherwise healthy children, serious adverse events have been observed in severely debilitated or immuno-compromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation. Until further research has been conducted, probiotic use should be avoided in pediatric populations at risk for adverse events. Future trials would benefit from a standard and valid outcomes to measure AAD.

A long-term, phase 2, multicenter, randomized, open-label, comparative safety study of pomaglumetad methionil (LY2140023 monohydrate) versus atypical antipsychotic standard of care in patients with schizophrenia

PubMed Central

2013-01-01

Background We compared the time to discontinuation due to lack of tolerability over 24 weeks in patients suffering from schizophrenia treated with pomaglumetad methionil (LY2140023 monohydrate, the prodrug of metabotropic glutamate 2/3 receptor agonist, LY404039) or standard of care (SOC: olanzapine, risperidone, or aripiprazole). Methods Study HBBR was a multicenter, randomized, open-label study comparing the long-term safety and tolerability of LY2140023 with SOC for schizophrenia. Patients had moderate symptomatology with prominent negative symptoms and evidence of functional impairment. Those who met entry criteria were randomized to open-label treatment with either LY2140023 (target dose: 40 mg twice daily [BID]; n = 130) or SOC (n = 131). Results There was no statistically significant difference between LY2140023 and SOC for time to discontinuation due to lack of tolerability (primary objective; P = .184). The Kaplan-Meier estimates revealed comparable time to event profiles. Only 27% of LY2140023 and 45% of SOC patients completed the 24-week open-label, active treatment phase. Twenty-seven patients (20.8%) in the LY2140023 group and 15 patients (11.5%) in the SOC group discontinued due to lack of efficacy (P = .044). Twenty-three patients (17.7%) in the LY2140023 group and 19 patients (14.5%) in the SOC group discontinued due to adverse events (physician and subject decision combined, P = .505). The incidence of serious adverse events was comparable between groups. LY2140023-treated patients reported significantly more treatment-emergent adverse events of vomiting, agitation, and dyspepsia, while SOC-treated patients reported significantly more akathisia and weight gain. The incidence of treatment-emergent parkinsonism (P = .011) and akathisia (P = .029) was significantly greater in SOC group. Improvement in PANSS total score over the initial 6 to 8 weeks of treatment was similar between groups, but improvement was significantly greater in the SOC group at 24-week endpoint (P = .004). LY2140023 and SOC groups had comparable negative symptom improvement at 24-week endpoint (P = .444). Conclusion These data provide further evidence that the potential antipsychotic LY2140023 monohydrate, with a glutamatergic mechanism of action, may have a unique tolerability profile characterized by a low association with some adverse events such as extrapyramidal symptoms and weight gain that may characterize currently available dopaminergic antipsychotics. Trials registration A Long-term, Phase 2, Multicenter, Randomized, Open-label, Comparative Safety Study of LY2140023 Versus Atypical Antipsychotic Standard of Care in Patients with DSM-IV-TR Schizophrenia ClinicalTrials.gov identifier: NCT00845026. PMID:23694720

A Quantative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population Dynamics

EPA Science Inventory

A Quantitative Adverse Outcome Pathway Linking Aromatase Inhibition in Fathead Minnows with Population DynamicsAn adverse outcome pathway (AOP) is a qualitative description linking a molecular initiating event (MIE) with measureable key events leading to an adverse outcome (AO). ...

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia

PubMed Central

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

Background While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012–2013. Methods The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Findings Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Conclusions Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control. PMID:28339462

Safety of a topical insect repellent (picaridin) during community mass use for malaria control in rural Cambodia.

PubMed

Heng, Somony; Sluydts, Vincent; Durnez, Lies; Mean, Vanna; Polo, Koh; Tho, Sochantha; Coosemans, Marc; van Griensven, Johan

2017-01-01

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

Adverse events among Ontario home care clients associated with emergency room visit or hospitalization: a retrospective cohort study

PubMed Central

2013-01-01

Background Home care (HC) is a critical component of the ongoing restructuring of healthcare in Canada. It impacts three dimensions of healthcare delivery: primary healthcare, chronic disease management, and aging at home strategies. The purpose of our study is to investigate a significant safety dimension of HC, the occurrence of adverse events and their related outcomes. The study reports on the incidence of HC adverse events, the magnitude of the events, the types of events that occur, and the consequences experienced by HC clients in the province of Ontario. Methods A retrospective cohort design was used, utilizing comprehensive secondary databases available for Ontario HC clients from the years 2008 and 2009. The data were derived from the Canadian Home Care Reporting System, the Hospital Discharge Abstract Database, the National Ambulatory Care Reporting System, the Ontario Mental Health Reporting System, and the Continuing Care Reporting System. Descriptive analysis was used to identify the type and frequency of the adverse events recorded and the consequences of the events. Logistic regression analysis was used to examine the association between the events and their consequences. Results The study found that the incident rate for adverse events for the HC clients included in the cohort was 13%. The most frequent adverse events identified in the databases were injurious falls, injuries from other than a fall, and medication-related incidents. With respect to outcomes, we determined that an injurious fall was associated with a significant increase in the odds of a client requiring long-term-care facility admission and of client death. We further determined that three types of events, delirium, sepsis, and medication-related incidents were associated directly with an increase in the odds of client death. Conclusions Our study concludes that 13% of clients in homecare experience an adverse event annually. We also determined that an injurious fall was the most frequent of the adverse events and was associated with increased admission to long-term care or death. We recommend the use of tools that are presently available in Canada, such as the Resident Assessment Instrument and its Clinical Assessment Protocols, for assessing and mitigating the risk of an adverse event occurring. PMID:23800280

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

PubMed Central

Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011.

PubMed

Nordanger, Dag Ø; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents' proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care.

Safety of saxagliptin: events of special interest in 9156 patients with type 2 diabetes mellitus.

PubMed

Hirshberg, Boaz; Parker, Artist; Edelberg, Helen; Donovan, Mark; Iqbal, Nayyar

2014-10-01

A post hoc pooled analysis was undertaken to evaluate the safety of saxagliptin in patients with type 2 diabetes mellitus, with attention to events of special interest for dipeptidyl peptidase-4 inhibitors. Pooled analyses were performed for 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy, and a subset of 11 saxagliptin + metformin studies. Adverse events and events of special interest (gastrointestinal adverse events, infections, hypersensitivity, pancreatitis, skin lesions, lymphopenia, thrombocytopenia, hypoglycaemia, bone fracture, severe cutaneous adverse reactions, opportunistic infection, angioedema, malignancy, worsening renal function, and specific laboratory events) were assessed; incidence rates (events/100 person-years) and incidence rates ratios (saxagliptin/control) were calculated (Mantel-Haenszel method). In both pooled datasets, the incidence rates for deaths, serious adverse events, discontinuations due to adverse events, pancreatitis, malignancy, and most other events of special interest, excepting bone fractures and hypersensitivity, were similar between treatments, with 95% confidence intervals (CIs) for incidence rates ratios including 1. In the 20-study pool, the incidence rates per 100 person-years was higher with saxagliptin versus control for bone fractures [1.1 vs 0.6; incidence rates ratio (95% CI), 1.81 (1.04-3.28)] and hypersensitivity adverse events [1.3 vs 0.8; 1.67 (1.01-2.87)]. Pooled data from 20 studies confirm that saxagliptin has a favourable safety and benefit-risk profile. Copyright © 2013 John Wiley & Sons, Ltd.

Palivizumab for prophylaxis against respiratory syncytial virus infection in children with cystic fibrosis.

PubMed

Robinson, Karen A; Odelola, Olaide A; Saldanha, Ian J; McKoy, Naomi A

2012-02-15

Respiratory syncytial virus infection causes acute lung infection in infants and young children worldwide, resulting in considerable morbidity and mortality. Children with cystic fibrosis are prone to recurrent lung inflammation, bacterial colonisation and subsequent chronic airway disease, putting them at risk for severe respiratory syncytial virus infections requiring intensive care and respiratory support. No treatment currently exists, hence prevention is important. Palivizumab is effective in reducing respiratory syncytial virus hospitalisation rates and is recommended for prophylaxis in high-risk children with other conditions. It is unclear if palivizumab can prevent respiratory syncytial virus hospitalisations and intensive care unit admissions in children with cystic fibrosis. To determine the efficacy and safety of palivizumab (Synagis(®)) compared with placebo, no prophylaxis or other prophylaxis, in preventing hospitalisation and mortality from respiratory syncytial virus infection in children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the eligible study and related reviews.Date of last search: 25 October 2011. Randomised and quasi-randomised studies. The authors independently extracted data and assessed risk of bias. One study (186 infants up to two years old) comparing five monthly doses of palivizumab (N = 92) to placebo (N = 94) over one respiratory syncytial virus season was identified and met our inclusion criteria. At six months follow-up, one participant in each group was hospitalised due to respiratory syncytial virus; there were no deaths in either group. In the palivizumab and placebo groups, 86 and 90 children experienced any adverse event, while 5 and 4 children had related adverse events respectively. Nineteeen children receiving palivizumab and 16 receiving placebo suffered serious adverse events; one participant receiving palivizumab discontinued due to this. At 12 months follow-up, there were no significant differences between groups in number of Pseudomonas bacterial colonisations or change in weight-to-height ratio. We identified one randomised controlled trial comparing five monthly doses of palivizumab to placebo in infants up to two years old with cystic fibrosis. While the overall incidence of adverse events was similar in both groups, it is not possible to draw conclusions on the safety and tolerability of respiratory syncytial virus prophylaxis with palivizumab in infants with cystic fibrosis because the trial did not specify how adverse events were classified. Six months after treatment, the authors reported no clinically meaningful differences in outcomes; however no data were provided. Additional randomised studies are needed to establish the safety and efficacy of palivizumab in children with cystic fibrosis.

The Barnum Effect and Chaos Theory: Exploring College Student ACOA Traits

ERIC Educational Resources Information Center

Fineran, Kerrie; Laux, John M.; Seymour, Jennifer; Thomas, Tequilla

2010-01-01

The literature both supports and challenges the notion that adult children of alcoholics are a distinct and homogenous group. College students (n = 200) were placed into one of four categories: Adult Children of Alcoholics, Adverse Childhood Event Group, Alcohol and Adverse Childhood Event Group, and the No Adverse Event Group. Participating…

75 FR 29479 - Medicare and Medicaid Programs: Proposed Changes Affecting Hospital and Critical Access Hospital...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... have to include all adverse events that may result from telemedicine services provided by the distant... adverse events that result from the telemedicine services provided by the distant-site physician or... include all adverse events that result from the telemedicine services provided by the distant-site...

5 CFR 1305.4 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Procedure in the event of an adverse ruling. 1305.4 Section 1305.4 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE....4 Procedure in the event of an adverse ruling. If the court or other authority declines to stay the...

5 CFR 1216.210 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Procedure in the event of an adverse ruling. 1216.210 Section 1216.210 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION... Procedure in the event of an adverse ruling. If the court or other competent authority fails to stay a...

5 CFR 1216.210 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Procedure in the event of an adverse ruling. 1216.210 Section 1216.210 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION... Procedure in the event of an adverse ruling. If the court or other competent authority fails to stay a...

5 CFR 1631.33 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Procedure in the event of an adverse ruling. 1631.33 Section 1631.33 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD... Procedure in the event of an adverse ruling. If the court or other authority declines to stay the effect of...

5 CFR 2502.33 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Procedure in the event of an adverse ruling. 2502.33 Section 2502.33 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF... Other Authorities § 2502.33 Procedure in the event of an adverse ruling. If the court or other authority...

5 CFR 2502.33 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Procedure in the event of an adverse ruling. 2502.33 Section 2502.33 Administrative Personnel OFFICE OF ADMINISTRATION, EXECUTIVE OFFICE OF... Other Authorities § 2502.33 Procedure in the event of an adverse ruling. If the court or other authority...

5 CFR 1631.33 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 3 2011-01-01 2011-01-01 false Procedure in the event of an adverse ruling. 1631.33 Section 1631.33 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD... Procedure in the event of an adverse ruling. If the court or other authority declines to stay the effect of...

5 CFR 1216.210 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Procedure in the event of an adverse ruling. 1216.210 Section 1216.210 Administrative Personnel MERIT SYSTEMS PROTECTION BOARD ORGANIZATION... Procedure in the event of an adverse ruling. If the court or other competent authority fails to stay a...

5 CFR 1631.33 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Procedure in the event of an adverse ruling. 1631.33 Section 1631.33 Administrative Personnel FEDERAL RETIREMENT THRIFT INVESTMENT BOARD... Procedure in the event of an adverse ruling. If the court or other authority declines to stay the effect of...

5 CFR 1305.4 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 3 2012-01-01 2012-01-01 false Procedure in the event of an adverse ruling. 1305.4 Section 1305.4 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE....4 Procedure in the event of an adverse ruling. If the court or other authority declines to stay the...

5 CFR 1305.4 - Procedure in the event of an adverse ruling.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 3 2013-01-01 2013-01-01 false Procedure in the event of an adverse ruling. 1305.4 Section 1305.4 Administrative Personnel OFFICE OF MANAGEMENT AND BUDGET ADMINISTRATIVE....4 Procedure in the event of an adverse ruling. If the court or other authority declines to stay the...

Adverse drug events and the Freedom of Information Act: an apple in Eden.

PubMed

Stang, P E; Fox, J L

1992-02-01

To review some of the abuses and proper uses of the Food and Drug Administration's (FDA's) spontaneous adverse-reaction reporting system, as a way of educating the reader to its strengths and limitations. Published literature and reports based on information obtained from the FDA's database of spontaneous adverse drug-event reports. The Freedom of Information Act has increased public access to the FDA's database of spontaneous adverse drug reaction reports. As these reports are voluntarily received and reported to the FDA, their use for comparisons of drug safety is severely limited. Despite these limitations and the FDA's caveats for use of these data, consumer advocacy groups, researchers, and various pharmaceutical marketing groups have used this source to project the incidence of adverse drug reactions. The FDA's spontaneous adverse-event reporting system is designed to generate signals of unexpected adverse drug events. Use of the data gathered by this system to make drug safety comparisons is beyond their credible scope because many factors influence the reporting of adverse events. Researchers and peer reviewers should place these data in the proper perspective and support sound research into questions of drug safety.

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling.

PubMed

Wang, Yefeng; Gunashekar, Divya R; Adam, Terrence J; Zhang, Rui

2017-01-01

The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Data-base (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements.

[Epidemiology of the hospital adverse events in Catalonia, Spain: a first step for the patient safety improvement].

PubMed

Bañeres, Joaquim; Orrego, Carola; Navarro, Laura; Casas, Lidia; Banqué, Marta; Suñol, Rosa

2014-07-01

It has been published that hospital adverse events are an important source of morbidity and mortality in different countries and settings. The aim of this study was to evaluate the frequency, magnitude, distribution and degree of preventability of adverse events in the Autonomous Community of Catalonia (Spain). We conducted a retrospective cohort study of 4,790 hospital discharges that were selected by simple random sampling after stratified multistage sampling in 15 hospitals in Catalonia. 38.25% of patients had positive risk criteria (screening phase). We identified 356 cases of adverse events, which represent a 7.4% (95%CI: 6.7% to 8.1%). Of these, 43.5% (155 cases) were considered preventable. This study confirms that adverse events in hospitals in Catalonia are frequent, and generate a significant impact on morbidity and mortality. As in other studies, corroborated that a high proportion of these adverse events are considered preventable. It was possible to identify priority areas to focus improvement efforts. Copyright © 2014. Published by Elsevier Espana.

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling

PubMed Central

Wang, Yefeng; Gunashekar, Divya R.; Adam, Terrence J.; Zhang, Rui

2018-01-01

The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Database (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements. PMID:29295169

Exploration of a Preflight Acuity Scale for Fixed Wing Air Ambulance Transport.

PubMed

Phipps, Marcy; Conley, Virginia; Constantine, William H

Despite the prevalence of fixed wing medical flights for specialized care and repatriation, few acuity rating scales exist aimed at the prediction of adverse in-flight medical events. An acuity scoring system can provide information to flight crews, allowing for staffing enhancements, protocol modifications, and flight planning, with the aim of improving patient care, outcomes, and preventing losses to providers because of costly diversions. Our medical crew developed an acuity scale, which was applied retrospectively to 296 patients transported between January 2016 and March 2017. Patients received scores based on conditions identified during the preflight medical report, the initial patient assessment, demographics, and flight factors. Five patients were identified as high-risk transports based on our scale. Three patients suffered adverse events according to our defined criteria, 2 of which occurred before transport and 1 during transport. The 3 patients suffering adverse events did not receive a score that indicated adverse events in flight. Our scale was not predictive of adverse events in flight. However, it did illuminate factors worthy of consideration. Consideration of these factors may have prevented adverse events. Published by Elsevier Inc.

Towards Large-scale Twitter Mining for Drug-related Adverse Events.

PubMed

Bian, Jiang; Topaloglu, Umit; Yu, Fan

2012-10-29

Drug-related adverse events pose substantial risks to patients who consume post-market or Drug-related adverse events pose substantial risks to patients who consume post-market or investigational drugs. Early detection of adverse events benefits not only the drug regulators, but also the manufacturers for pharmacovigilance. Existing methods rely on patients' "spontaneous" self-reports that attest problems. The increasing popularity of social media platforms like the Twitter presents us a new information source for finding potential adverse events. Given the high frequency of user updates, mining Twitter messages can lead us to real-time pharmacovigilance. In this paper, we describe an approach to find drug users and potential adverse events by analyzing the content of twitter messages utilizing Natural Language Processing (NLP) and to build Support Vector Machine (SVM) classifiers. Due to the size nature of the dataset (i.e., 2 billion Tweets), the experiments were conducted on a High Performance Computing (HPC) platform using MapReduce, which exhibits the trend of big data analytics. The results suggest that daily-life social networking data could help early detection of important patient safety issues.

Reverse translation of adverse event reports paves the way for de-risking preclinical off-targets

PubMed Central

Maciejewski, Mateusz; Lounkine, Eugen; Whitebread, Steven; Farmer, Pierre; DuMouchel, William; Shoichet, Brian K; Urban, Laszlo

2017-01-01

The Food and Drug Administration Adverse Event Reporting System (FAERS) remains the primary source for post-marketing pharmacovigilance. The system is largely un-curated, unstandardized, and lacks a method for linking drugs to the chemical structures of their active ingredients, increasing noise and artefactual trends. To address these problems, we mapped drugs to their ingredients and used natural language processing to classify and correlate drug events. Our analysis exposed key idiosyncrasies in FAERS, for example reports of thalidomide causing a deadly ADR when used against myeloma, a likely result of the disease itself; multiplications of the same report, unjustifiably increasing its importance; correlation of reported ADRs with public events, regulatory announcements, and with publications. Comparing the pharmacological, pharmacokinetic, and clinical ADR profiles of methylphenidate, aripiprazole, and risperidone, and of kinase drugs targeting the VEGF receptor, demonstrates how underlying molecular mechanisms can emerge from ADR co-analysis. The precautions and methods we describe may enable investigators to avoid confounding chemistry-based associations and reporting biases in FAERS, and illustrate how comparative analysis of ADRs can reveal underlying mechanisms. DOI: http://dx.doi.org/10.7554/eLife.25818.001 PMID:28786378

Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.

PubMed

Derry, Sheena; Moore, R Andrew; McQuay, Henry J

2010-11-10

Migraine is a common, disabling condition and a burden for the individual, health services and society. Many sufferers choose not to, or are unable to, seek professional help and rely on over-the-counter analgesics. Co-therapy with an antiemetic should help to reduce nausea and vomiting commonly associated with migraine. To determine the efficacy and tolerability of paracetamol (acetaminophen), alone or in combination with an antiemetic, compared to placebo and other active interventions in the treatment of acute migraine in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies through 4 October 2010. We included randomised, double-blind, placebo- or active-controlled studies using self-administered paracetamol to treat a migraine headache episode, with at least 10 participants per treatment arm. Two review authors independently assessed trial quality and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Ten studies (2769 participants, 4062 attacks) compared paracetamol 1000 mg, alone or in combination with an antiemetic, with placebo or other active comparators, mainly sumatriptan 100 mg. For all efficacy outcomes paracetamol was superior to placebo, with NNTs of 12, 5.2 and 5.0 for 2-hour pain-free and 1- and 2-hour headache relief, respectively, when medication was taken for moderate to severe pain. Nausea, photophobia and phonophobia were reduced more with paracetamol than with placebo at 2 hours (NNTs of 7 to 11); more individuals were free of any functional disability at 2 hours with paracetamol (NNT 10); and fewer participants needed rescue medication over 6 hours (NNT 6).Paracetamol 1000 mg plus metoclopramide 10 mg was not significantly different from oral sumatriptan 100 mg for 2-hour headache relief; there were no 2-hour pain-free data. There was no significant difference between the paracetamol plus metoclopramide combination and sumatriptan for relief of "light/noise sensitivity" at 2 hours, but slightly more individuals needed rescue medication over 24 hours with the combination therapy (NNT 17).Adverse event rates were similar between paracetamol and placebo, and between paracetamol plus metoclopramide and sumatriptan. No serious adverse events occurred with paracetamol alone, but more "major" adverse events occurred with sumatriptan than with the combination therapy (NNH 32). Paracetamol 1000 mg alone is an effective treatment for acute migraine headaches, and the addition of 10 mg metoclopramide gives short-term efficacy equivalent to oral sumatriptan 100 mg. Adverse events with paracetamol did not differ from placebo; "major" adverse events were slightly more common with sumatriptan than with paracetamol plus metoclopramide.

[Serious systemic adverse events associated with allergen-specific immunotherapy in children with asthma].

PubMed

Dai, Li; Huang, Ying; Wang, Ying; Han, Huan-Li; Li, Qu-Bei; Jiang, Yong-Hui

2014-01-01

To retrospectively assess serious systemic adverse effects of standardized dust-mite vaccine in children with asthma. Medical records of 704 children (5-17 years in age) with asthma between January, 2005 and December, 2011 were reviewed. Serious systemic adverse events following treatment with a standardized dust-mite vaccine in these children were analyzed. A total of 336 systemic adverse reactions were observed in 17.0% (120/704) of the patients analyzed of these adverse reactions, 18 (5.4%) were serious (level 3), 318 (94.6%) were not serious (below level 3), and no single case of anaphylactic shock (level 4) was recorded. Systemic adverse events occurred most frequently in the 5 to 11-year age group and in the summer season (from June to August). In the 18 severe cases, the peak expiratory flow (PEF) dropped by 20% immediately after the vaccine injection, and other major clinical symptoms included cough, wheezing and urticaria. All children with serious systemic adverse effects were given inhaled hormone and atomized short-acting beta agonists, oral antihistamines, intravenous dexamethasone and/or intramuscular adrenaline. After these treatments, the clinical symptoms were significantly relieved. The rate of serious systemic adverse events following allergen-specific immunotherapy is relatively low in children with allergic asthma. Conventional medications are effective in managing these immunotherapy-associated adverse events.

Odor investigation of a Portland cement plant

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

Pleus, R.C.

1998-12-31

The main concern expressed by Smithville residents is whether the odors they were smelling during odor events were due to chemicals that could cause adverse health effects. Odors were allegedly emanating from the town`s Portland cement plant. The purpose of the study was to measure the ambient air for 20 reduced sulfur, 50 volatile organic compounds, and air samples for olfactometric analysis. Carbonyl sulfide was found to be at a concentration that could create a sense of odor and irritation. This sense of irritation may be due to a physiological response by the central nervous system, and is not associatedmore » with any known adverse effects. This physiological response could account for some or all of the irritation experienced by residents during odor events. Comparing chemical concentrations that were detected in air samples to standard and recognized guidelines for acceptable exposure, all measured concentrations were found to be well below the acceptable criteria. From these data the authors conclude that no acute or chronic adverse health effects are expected at the concentrations of the chemicals detected downwind of the cement plant, either routinely or during odor events.« less

Clinical review: Serious adverse events associated with the use of rituximab - a critical care perspective

PubMed Central

2012-01-01

The advent of biologic agents has provided a more specific and targeted approach to the treatment of various hematological malignancies and other autoimmune disorders. Such biologic agents have been relatively well tolerated with fewer adverse events reported as compared with many other chemotherapeutic agents. Rituximab is a monoclonal antibody to the B-cell marker CD20 and is a common biologic agent widely used for the treatment of B-cell lymphoma, lymphoproliferative disorders, and inflammatory conditions that are refractory to conventional treatment, including rheumatoid arthritis and some vasculitides. However, through randomized controlled trials and post-marketing surveillance, an increasing number of serious adverse events are being associated with the use of rituximab, often leading to or complicating an intensive care unit admission. The purpose of this review is to focus on the severe complications that are associated with the use of rituximab and that require critical care. Management and prevention strategies for the most common complications along with some examples of its uses within the critical care setting are also discussed. PMID:22967460

Options for treating postherpetic neuralgia in the medically complicated patient

PubMed Central

Bruckenthal, Patricia; Barkin, Robert L

2013-01-01

Patients with postherpetic neuralgia (PHN) are often of advanced age or immunocompromised and likely to have ≥1 comorbid medical condition for which they receive ≥1 medication (polypharmacy). Comorbidities affecting renal or hepatic function can alter pharmacokinetics, thereby impacting the efficacy or tolerability of PHN analgesic therapies. Cardiovascular, cerebrovascular, or psychiatric comorbidities may increase patient vulnerability to potential adverse events associated with some PHN analgesic therapies. Because PHN is a localized condition, localized therapy with a topical analgesic (lidocaine patch 5% and capsaicin 8% patch or cream) may provide adequate efficacy while mitigating the risk of systemic adverse events compared with oral analgesics (eg, tricyclic antidepressants, anticonvulsants, opioids). However, combined therapy with a topical and an oral analgesic or with >1 oral analgesic may be needed for optimal pain management in some patients. This review summarizes how comorbidities and concomitant medications should be taken into account when selecting among available pharmacotherapies for PHN and provides recommendations for the selection of therapies that will provide analgesia while minimizing the risk of adverse events. PMID:23990726

The effects of heat and massage application on autonomic nervous system.

PubMed

Lee, Young-Hee; Park, Bit Na Ri; Kim, Sung Hoon

2011-11-01

The objective of this study is to evaluate the effects of heat and massage application on autonomic nervous system. One hundred thirty-nine subjects volunteered and completed this study. Heat and massage was daily applied for 40 minutes, 5 days a week for 2 weeks. Primary-dependent measures included heart rate variability, sympathetic skin response, and serum cortisol and norepinephrine levels. Serum cortisol levels were significantly decreased at 2 weeks compared to baseline (p=0.003). Plasma norepinephrine levels at 4 weeks were significantly decreased compared to baseline (p=0.010). Heart rate, using the power spectra, increased significantly after 2 weeks compared to baseline. Of autonomic nerve conduction measures, latency was significantly increased at 2 and 4 weeks compared to baseline (p=0.023, 0.012), and amplitude was significantly decreased at 4 weeks compared to baseline (p=0.008). There were no serious adverse events such as burns or other major complications. The results of this study suggest that heat and massage applications provide relaxation to the autonomic nervous system without serious adverse events.

Signal detection on spontaneous reports of adverse events following immunisation: a comparison of the performance of a disproportionality-based algorithm and a time-to-onset-based algorithm

PubMed Central

van Holle, Lionel; Bauchau, Vincent

2014-01-01

Purpose Disproportionality methods measure how unexpected the observed number of adverse events is. Time-to-onset (TTO) methods measure how unexpected the TTO distribution of a vaccine-event pair is compared with what is expected from other vaccines and events. Our purpose is to compare the performance associated with each method. Methods For the disproportionality algorithms, we defined 336 combinations of stratification factors (sex, age, region and year) and threshold values of the multi-item gamma Poisson shrinker (MGPS). For the TTO algorithms, we defined 18 combinations of significance level and time windows. We used spontaneous reports of adverse events recorded for eight vaccines. The vaccine product labels were used as proxies for true safety signals. Algorithms were ranked according to their positive predictive value (PPV) for each vaccine separately; amedian rank was attributed to each algorithm across vaccines. Results The algorithm with the highest median rank was based on TTO with a significance level of 0.01 and a time window of 60 days after immunisation. It had an overall PPV 2.5 times higher than for the highest-ranked MGPS algorithm, 16th rank overall, which was fully stratified and had a threshold value of 0.8. A TTO algorithm with roughly the same sensitivity as the highest-ranked MGPS had better specificity but longer time-to-detection. Conclusions Within the scope of this study, the majority of the TTO algorithms presented a higher PPV than for any MGPS algorithm. Considering the complementarity of TTO and disproportionality methods, a signal detection strategy combining them merits further investigation. PMID:24038719

Safety of herbal products in Thailand: an analysis of reports in the thai health product vigilance center database from 2000 to 2008.

PubMed

Saokaew, Surasak; Suwankesawong, Wimon; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn

2011-04-01

The use of herbal products continues to expand rapidly across the world and concerns regarding the safety of these products have been raised. In Thailand, Thai Vigibase, developed by the Health Product Vigilance Center (HPVC) under the Thai Food and Drug Administration, is the national database that collates reports from health product surveillance systems and programmes. Thai Vigibase can be used to identify signals of adverse events in patients receiving herbal products. The purpose of the study was to describe the characteristics of reported adverse events in patients receiving herbal products in Thailand. Thai Vigibase data from February 2000 to December 2008 involving adverse events reported in association with herbal products were used. This database includes case reports submitted through the spontaneous reporting system and intensive monitoring programmes. Under the spontaneous reporting system, adverse event reports are collected nationwide via a national network of 22 regional centres covering more than 800 public and private hospitals, and health service centres. An intensive monitoring programme was also conducted to monitor the five single herbal products listed in the Thai National List of Essential Medicines (NLEM), while another intensive monitoring programme was developed to monitor the four single herbal products that were under consideration for inclusion in the NLEM. The database contained patient demographics, adverse events associated with herbal products, and details on seriousness, causality and quality of reports. Descriptive statistics were used for data analyses. A total of 593 reports with 1868 adverse events involving 24 different products were made during the study period. The age range of individuals was 1-86 years (mean 47 years). Most case reports were obtained from the intensive monitoring programme. Of the reports, 72% involved females. The herbal products for which adverse events were frequently reported were products containing turmeric (44%), followed by andrographis (10%), veld grape (10%), pennywort (7%), plai (6%), jewel vine (6%), bitter melon (5%) and snake plant (5%). Gastrointestinal problems were the most common adverse effect reported. Serious adverse events included Stevens-Johnson syndrome, anaphylactic shock and exfoliative dermatitis. Adverse event reports on herbals products were diverse, with most of them being reported through intensive monitoring programmes. Thai Vigibase is a potentially effective data source for signal detection of adverse events associated with herbal products.

Surveillance of adverse effects during a vaccination campaign against meningitis C.

PubMed

Laribière, Anne; Miremont-Salamé, Ghada; Reyre, Hadrien; Abouelfath, Abdelilah; Liège, Ludovic; Moore, Nicholas; Haramburu, Françoise

2005-12-01

To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Patterns in spontaneous adverse event reporting among branded and generic antiepileptic drugs.

PubMed

Bohn, J; Kortepeter, C; Muñoz, M; Simms, K; Montenegro, S; Dal Pan, G

2015-05-01

Spontaneous adverse event reports constitute an important source of information on previously unknown adverse reactions to marketed medicines. However, the dynamics of such reporting following generic introduction are poorly understood. Using adverse event reports on five antiepileptic drugs from the US Food and Drug Administration's Adverse Event Reporting System, we describe temporal trends in adverse event reporting before and after generic introduction, and survey the quality of product-identifying information contained therein. The majority of reports were sent by innovator drug manufacturers while few were sent by generic manufacturers, even when generics accounted for >90% of dispensed prescriptions. We manually reviewed narratives from 2,500 reports and found that the suspect product type (brand or generic) could not be determined in 84% of reports, while generic products (16%) were identified more often than brand-name products (<1%). These results suggest that pharmacovigilance stakeholders should act to promote more detailed reporting practices. © 2015 American Society for Clinical Pharmacology and Therapeutics.

Childhood adverse life events and parental psychopathology as risk factors for bipolar disorder.

PubMed

Bergink, V; Larsen, J T; Hillegers, M H J; Dahl, S K; Stevens, H; Mortensen, P B; Petersen, L; Munk-Olsen, T

2016-10-25

Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.

Ketamine as an adjuvant to opioids for cancer pain.

PubMed

Bell, Rae F; Eccleston, Christopher; Kalso, Eija A

2017-06-28

This is an update of a review first published in 2003 and updated in 2012.Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of refractory cancer pain, when opioids alone or in combination with appropriate adjuvant analgesics prove to be ineffective. Ketamine is known to have psychomimetic (including hallucinogenic), urological, and hepatic adverse effects. To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids for refractory cancer pain in adults. For this update, we searched MEDLINE (OVID) to December 2016. We searched CENTRAL (CRSO), Embase (OVID) and two clinical trial registries to January 2017. The intervention considered by this review was the addition of ketamine, given by any route of administration, in any dose, to pre-existing opioid treatment given by any route and in any dose, compared with placebo or active control. We included studies with a group size of at least 10 participants who completed the trial. Two review authors independently assessed the search results and performed 'Risk of bias' assessments. We aimed to extract data on patient-reported pain intensity, total opioid consumption over the study period; use of rescue medication; adverse events; measures of patient satisfaction/preference; function; and distress. We also assessed participant withdrawal (dropout) from trial. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation). One new study (185 participants) was identified by the updated search and included in the review. We included a total of three studies in this update.Two small studies, both with cross-over design, with 20 and 10 participants respectively, were eligible for inclusion in the original review. One study with 20 participants examined the addition of intrathecal ketamine to intrathecal morphine, compared with intrathecal morphine alone. The second study with 10 participants examined the addition of intravenous ketamine bolus in two different doses to ongoing morphine therapy, compared with placebo. Both of these studies reported reduction in pain intensity and reduction in morphine requirements when ketamine was added to opioid for refractory cancer pain. The new study identified by the updated search had a parallel group design and 185 participants. This placebo-controlled study examined rapid titration of subcutaneous ketamine to high dose (500 mg) in participants who were using different opioids. There were no differences between groups for patient-reported pain intensity.Pooling of the data from the three included trials was not appropriate because of clinical heterogeneity.The study examining intrathecal drug administration reported no adverse events related to ketamine. In the study using intravenous bolus administration, ketamine caused hallucinations in four of 10 participants. In the rapid dose escalation/high-dose subcutaneous ketamine study, there was almost twice the incidence of adverse events in the ketamine group, compared to the placebo group, with the most common adverse events being needle site irritation and cognitive disturbance. Two serious adverse events (bradyarrhythmia and cardiac arrest) thought to be related to ketamine were also reported in this trial.For all three studies there was an unclear risk of bias overall. Using GRADE, we judged the quality of the evidence to be very low due to study limitations and imprecision due to the small number of participants in all comparisons. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of refractory cancer pain. The evidence was of very low quality, meaning that it does not provide a reliable indication of the likely effect, and the likelihood that the effect will be substantially different is high. Rapid dose escalation of ketamine to high dose (500 mg) does not appear to have clinical benefit and may be associated with serious adverse events. More randomised controlled trials (RCTs) examining specific low-dose ketamine clinical regimens in current use are needed.

Cinnamon: A systematic review of adverse events.

PubMed

Hajimonfarednejad, Mahdie; Ostovar, Mohadeseh; Raee, Mohammad Javad; Hashempur, Mohammad Hashem; Mayer, Johannes Gottfried; Heydari, Mojtaba

2018-04-05

Cinnamon, from the genus Cinnamomum and Lauraceae family, has been used as a popular spice for thousands of years around the world. Many studies have shown therapeutic effects of cinnamon including its antimicrobial, antiviral, antifungal, antioxidant, antitumor, antihypertensive, antilipemic, antidiabetic, gastroprotective, and immunomodulatory effects. Due to popular use of cinnamon and several human reports on adverse events associated with short or long term use of cinnamon, we aimed to systematically review its human reports of adverse event. Databases including Medline, Scopus, Science Direct, Embase, PubMed Central and Google scholar were searched using the key words "cinnamon" or "cinnamomum" for clinical trials, case reports and case series. Also spontaneous reports about adverse effects of cinnamon were collected from five national and international spontaneous reporting schemes. Thirty eight clinical trials were found, five of them reported adverse events. Twenty case reports and seven case series, as well as, spontaneous reports including 160 adverse events were also included. The most frequent adverse events were gastrointestinal disorders and allergic reactions which were self-limiting in the majority of cases. The available data suggests that despite the safety of cinnamon use as a spice and/or flavoring agent, its use may be associated with significant adverse effects in medicinal uses with larger doses or longer duration of use and should be clinically monitored. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Short term safety assessment of cilazapril.

PubMed

Coulter, D M

1993-11-24

To undertake an event monitoring study of cilazapril in general practice during the early marketing period, to provide some comparisons with other angiotensin converting enzyme inhibitors and to assess the monitoring method. The monitoring was undertaken in the Intensive Medicines Monitoring Programme. Cilazapril was prescribed for mild to moderate hypertension in 996 patients at a recommended dose of 2.5-5.0 mg daily. The monitoring period was six months and practitioners were asked to report all adverse events. A reaction profile was prepared and compared with profiles for lisinopril, enalapril and captopril. The chi-square test was applied to differences in proportions. There were 84 (8.4%) reports describing 133 adverse events; 124 (93%) were assessed as reactions. Withdrawals totalled 53 (5.3%). The most common reactions were cough (2.9%), nausea and vomiting (1.3%) and lethargy (1.1%). Cilazapril had a higher proportion of neurological reactions (p < 0.001) (mainly headache) but a lower proportion of skin reactions (p = 0.001) than the other ACE inhibitors. It also had relatively less diarrhoea and there were differences in the patterns of psychiatric reactions. Cilazapril has a similar reaction profile to other ACE inhibitors but this paper shows differences, some not previously reported, that may assist selection when prescribing. Although there was a high rate of reporting of known adverse reactions, other events were reported at a very low rate and spontaneous reporting is thus confirmed as an unreliable method of monitoring for unexpected adverse reactions.