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Sample records for adverse clinical consequences

  1. Unintended adverse consequences of a clinical decision support system: two cases.

    PubMed

    Stone, Erin G

    2018-05-01

    Many institutions have implemented clinical decision support systems (CDSSs). While CDSS research papers have focused on benefits of these systems, there is a smaller body of literature showing that CDSSs may also produce unintended adverse consequences (UACs). Detailed here are 2 cases of UACs resulting from a CDSS. Both of these cases were related to external systems that fed data into the CDSS. In the first case, lack of knowledge of data categorization in an external pharmacy system produced a UAC; in the second case, the change of a clinical laboratory instrument produced the UAC. CDSSs rely on data from many external systems. These systems are dynamic and may have changes in hardware, software, vendors, or processes. Such changes can affect the accuracy of CDSSs. These cases point to the need for the CDSS team to be familiar with these external systems. This team (manager and alert builders) should include members in specific clinical specialties with deep knowledge of these external systems.

  2. A Systematic Review of the Unintended Consequences of Clinical Interventions to Reduce Adverse Outcomes.

    PubMed

    Manojlovich, Milisa; Lee, Soohee; Lauseng, Deborah

    2016-12-01

    This is a systematic review of the literature on unintended consequences of clinical interventions to reduce falls, catheter-related urinary tract infection, and vascular catheter-related infections in hospitalized patients. A systematic search of the literature was conducted in CINAHL and PubMed. We developed a screening tool and a two-stage screening process to identify relevant articles. Nine articles met inclusion criteria, and of those, 8 reported on interventions to reduce patient falls. Four studies reported a positive, unexpected benefit; 3 studies reported a negative, unexpected detriment; and 4 reported a perverse effect (different from what was expected). Three studies reported both positive and perverse effects arising from the intervention. In 4 of the studies, despite fall prevention interventions, patients fell while trying to get to the bathroom, suggesting that interventions to reduce one adverse outcome (i.e., CAUTI) may be associated with another outcome (i.e., patient falls). In some cases, there were positive outcomes for those who implemented and/or evaluated interventions. We encourage colleagues to collect and report data on possible unintended consequences of their interventions to allow a fuller picture of the relationship between intervention and all outcomes to emerge.

  3. Adverse consequences of lysergic acid diethylamide.

    PubMed

    Abraham, H D; Aldridge, A M

    1993-10-01

    The continued endemic use of hallucinogenic drugs, and of LSD in particular, raises concern regarding their short and long term adverse consequences. The epidemiology of LSD abuse is reviewed suggesting an increase in LSD use among the young as the prevalence rates for other substances continues to fall. Evidence supports the association of LSD use with panic reactions, prolonged schizoaffective psychoses and post-hallucinogen perceptual disorder, the latter being present continually for as long as 5 years. Evidence does not support claims of genetic disorders arising from hallucinogens. In light of the foregoing, current data confirm earlier findings of long lasting psychopathology arising in vulnerable individuals from the use of LSD. A hypothetical long term molecular mechanism of adverse effects is proposed.

  4. Adverse consequences of neonatal antibiotic exposure.

    PubMed

    Cotten, Charles M

    2016-04-01

    Antibiotics have not only saved lives and improved outcomes, but they also influence the evolving microbiome. This review summarizes reports on neonatal infections and variation in antibiotic utilization, discusses the emergence of resistant organisms, and presents data from human neonates and animal models demonstrating the impact of antibiotics on the microbiome, and how microbiome alterations impact health. The importance of antibiotic stewardship is also discussed. Infections increase neonatal morbidity and mortality. Furthermore, the clinical presentation of infections can be subtle, prompting clinicians to empirically start antibiotics when infection is a possibility. Antibiotic-resistant infections are a growing problem. Cohort studies have identified extensive center variations in antibiotic usage and associations between antibiotic exposures and outcomes. Studies of antibiotic-induced microbiome alterations and downstream effects on the developing immune system have increased our understanding of the mechanisms underlying the associations between antibiotics and adverse outcomes. The emergence of resistant microorganisms and recent evidence linking antibiotic practice variations with health outcomes has led to the initiation of antibiotic stewardship programs. The review encourages practitioners to assess local antibiotic use with regard to local microbiology, and to adopt steps to reduce infections and use antibiotics wisely.

  5. Workplace Bullying: A Tale of Adverse Consequences

    PubMed Central

    Sansone, Lori A.

    2015-01-01

    Workplace bullying is defined as the repetitive and systematic engagement of interpersonally abusive behaviors that negatively affect both the targeted individual and the work organization. According to the findings of 12 studies, being bullied in the workplace affects approximately 11 percent of workers. Victims are frequently blue-collar and unskilled workers. However, there also appear to be gender and milieu/management factors. Emotional/psychological consequences of workplace bullying may include increased mental distress, sleep disturbances, fatigue in women and lack of vigor in men, depression and anxiety, adjustment disorders, and even work-related suicide. Medical consequences of workplace bullying may include an increase in health complaints such as neck pain, musculoskeletal complaints, acute pain, fibromyalgia, and cardiovascular symptoms. Finally, socioeconomic consequences of workplace bullying may include absenteeism due to sick days and unemployment. Clinicians in both mental health and primary care settings need to be alert to the associations between bullying in the workplace and these potential negative consequences, as patients may not disclose workplace maltreatment due to embarrassment or fears of retribution. PMID:25852978

  6. Workplace bullying: a tale of adverse consequences.

    PubMed

    Sansone, Randy A; Sansone, Lori A

    2015-01-01

    Workplace bullying is defined as the repetitive and systematic engagement of interpersonally abusive behaviors that negatively affect both the targeted individual and the work organization. According to the findings of 12 studies, being bullied in the workplace affects approximately 11 percent of workers. Victims are frequently blue-collar and unskilled workers. However, there also appear to be gender and milieu/management factors. Emotional/psychological consequences of workplace bullying may include increased mental distress, sleep disturbances, fatigue in women and lack of vigor in men, depression and anxiety, adjustment disorders, and even work-related suicide. Medical consequences of workplace bullying may include an increase in health complaints such as neck pain, musculoskeletal complaints, acute pain, fibromyalgia, and cardiovascular symptoms. Finally, socioeconomic consequences of workplace bullying may include absenteeism due to sick days and unemployment. Clinicians in both mental health and primary care settings need to be alert to the associations between bullying in the workplace and these potential negative consequences, as patients may not disclose workplace maltreatment due to embarrassment or fears of retribution.

  7. New Unintended Adverse Consequences of Electronic Health Records

    PubMed Central

    Wright, A.; Ash, J.; Singh, H.

    2016-01-01

    Summary Although the health information technology industry has made considerable progress in the design, development, implementation, and use of electronic health records (EHRs), the lofty expectations of the early pioneers have not been met. In 2006, the Provider Order Entry Team at Oregon Health & Science University described a set of unintended adverse consequences (UACs), or unpredictable, emergent problems associated with computer-based provider order entry implementation, use, and maintenance. Many of these originally identified UACs have not been completely addressed or alleviated, some have evolved over time, and some new ones have emerged as EHRs became more widely available. The rapid increase in the adoption of EHRs, coupled with the changes in the types and attitudes of clinical users, has led to several new UACs, specifically: complete clinical information unavailable at the point of care; lack of innovations to improve system usability leading to frustrating user experiences; inadvertent disclosure of large amounts of patient-specific information; increased focus on computer-based quality measurement negatively affecting clinical workflows and patient-provider interactions; information overload from marginally useful computer-generated data; and a decline in the development and use of internally-developed EHRs. While each of these new UACs poses significant challenges to EHR developers and users alike, they also offer many opportunities. The challenge for clinical informatics researchers is to continue to refine our current systems while exploring new methods of overcoming these challenges and developing innovations to improve EHR interoperability, usability, security, functionality, clinical quality measurement, and information summarization and display. PMID:27830226

  8. Health consequences of adverse childhood experiences: a systematic review.

    PubMed

    Kalmakis, Karen A; Chandler, Genevieve E

    2015-08-01

    Adverse childhood experiences (ACEs) have been associated with negative health outcomes, but the evidence has had limited application in primary care practice. The purpose of this study was to systematically review the research on associations between ACEs and adult health outcomes to inform nurse practitioners (NPs) in primary care practice. The databases PubMed, CINAHL, PsycINFO, and Social Abstracts were searched for articles published in English between 2008 and 2013 using the search term "adverse childhood experiences." Forty-two research articles were included in the synthesis. The evidence was synthesized and is reported following the preferred reporting items for systematic reviews and meta-analysis procedure (PRISMA). ACEs have been associated with health consequences including physical and psychological conditions, risk behaviors, developmental disruption, and increased healthcare utilization. Generalization of the results is limited by a majority of studies (41/42) measuring childhood adversity using self-report measures. NPs are encouraged to incorporate assessment of patients' childhood history in routine primary care and to consider the evidence that supports a relationship between ACEs and health. Although difficult, talking about patient's childhood experiences may positively influence health outcomes. ©2015 American Association of Nurse Practitioners.

  9. Long Term Physical Health Consequences of Adverse Childhood Experiences

    PubMed Central

    Monnat, Shannon M.; Chandler, Raeven Faye

    2015-01-01

    This study examined associations between adverse childhood family experiences and adult physical health using data from 52,250 US adults aged 18–64 from the 2009–2012 Behavioral Risk Factor Surveillance System (BRFSS). We found that experiencing childhood physical, verbal, or sexual abuse, witnessing parental domestic violence, experiencing parental divorce, and living with someone who was depressed, abused drugs or alcohol, or who had been incarcerated were associated with one or more of the following health outcomes: self-rated health, functional limitations, diabetes, and heart attack. Adult socioeconomic status and poor mental health and health behaviors significantly mediated several of these associations. The results of this study highlight the importance of family-based adverse childhood experiences on adult health outcomes and suggest that adult SES and stress-related coping behaviors may be crucial links between trauma in the childhood home and adult health. PMID:26500379

  10. Mindfulness as a mediator of the association between adverse childhood experiences and alcohol use and consequences.

    PubMed

    Brett, Emma I; Espeleta, Hannah C; Lopez, Susanna V; Leavens, Eleanor L S; Leffingwell, Thad R

    2018-09-01

    One-third of college students report past-year heavy episodic drinking, making college student alcohol use an important area for continued research. Research has consistently linked early experiences of adversity to problematic substance use in adolescence and adulthood. Given the negative health consequences associated with heavy episodic drinking, it is imperative to identify mechanisms that contribute to this relation. Low levels of mindfulness have been linked to early adversity as well as impulsivity and alcohol use, therefore, the current study aims to examine the mediating role of mindfulness in the relation between early adversity and current alcohol use and consequences. Undergraduate students (N = 385) at a Midwestern university completed an online questionnaire assessing experiences of childhood adversity, trait mindfulness, and current alcohol use and related consequences. Results indicated that increased adverse experiences and lower levels of mindfulness predicted both increased alcohol consumption and consequences (ps < 0.025), with mindfulness mediating the relationships. Mindfulness is a predictor of alcohol outcomes and appears to mediate the relation between early adversity and alcohol use and consequences. Findings suggest that students with a history of adversity are more likely to exhibit lower levels of mindfulness, which may lead to an increase in alcohol consumption and consequences in early adulthood. Targeted alcohol intervention efforts that incorporate mindfulness skills may be particularly beneficial for those who have experienced early adversity. Copyright © 2018. Published by Elsevier Ltd.

  11. 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.

  12. 20 CFR 1002.194 - Can the application of the escalator principle result in adverse consequences when the employee...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... principle result in adverse consequences when the employee is reemployed? 1002.194 Section 1002.194... principle result in adverse consequences when the employee is reemployed? Yes. The Act does not prohibit lawful adverse job consequences that result from the employee's restoration on the seniority ladder...

  13. Contact lens deposits, adverse responses, and clinical ocular surface parameters.

    PubMed

    Zhao, Zhenjun; Naduvilath, Thomas; Flanagan, Judith L; Carnt, Nicole A; Wei, Xiaojia; Diec, Jennie; Evans, Vicki; Willcox, Mark D P

    2010-09-01

    To correlate clinical responses during contact lens wear with the amount of protein or cholesterol extracted from lenses after wear. Clinical parameters, including adverse response rates and corneal staining, and symptomatology rating during lens wear were collected from a series of clinical tests comprising four different silicone hydrogel lenses with four different multipurpose solutions. To test for correlates, the amount of total protein or cholesterol extracted from lenses after daily wear were compared statistically to clinical parameters. The amount of protein (p = 0.008) or cholesterol (p = 0.01) extracted from lenses was higher for those subjects who showed solution-induced corneal staining. Amount of protein extracted was correlated (p < 0.01) with conjunctival staining (R = -0.23), lens front surface wetting (r = 0.14), and lens fit tightness (R = -0.20). These clinical parameters accounted for 48% of lens protein deposition. The amount of cholesterol extracted from lenses was much more weakly associated with clinical variables. Amount of protein or cholesterol extracted from lenses was not associated with the production of any corneal infiltrative or mechanical adverse event during wear and was only very weakly correlated with insertion comfort of lenses. These results suggest that there may be no physiologically relevant consequence of cholesterol depositing on silicone hydrogel lenses. The amount of protein that deposits onto silicone hydrogel lenses during wear may have more affect on lens performance on-eye. However, the correlations were generally small and may still not indicate any causative relevant physiological response. Further work is required to determine whether there is any direct causative effect to support these correlative findings.

  14. Obesity and pregnancy: mechanisms of short term and long term adverse consequences for mother and child.

    PubMed

    Catalano, Patrick M; Shankar, Kartik

    2017-02-08

    Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  15. Different drinking motives, different adverse consequences? Evidence among adolescents from 10 European countries.

    PubMed

    Wicki, Matthias; Kuntsche, Emmanuel; Eichenberger, Yvonne; Aasvee, Katrin; Bendtsen, Pernille; Dankulincová Veselská, Zuzana; Demetrovics, Zsolt; Dzielska, Anna; Farkas, Judit; de Matos, Margarida Gaspar; Roberts, Chris; Tynjälä, Jorma; Välimaa, Raili; Vieno, Alessio

    2017-11-01

    This study, which builds on previous research demonstrating that drinking motives are associated with adverse consequences, investigates the associations between drinking motives and non-alcohol-attributed adverse consequences and disentangles alcohol-related and direct effects. On the basis of a sample of 22 841 alcohol-using 13- to 16-year-olds (50.6% female) from Belgium, Denmark, Estonia, Finland, Ireland, Portugal, Scotland, Slovakia, Switzerland and Wales, structural equation models were used to estimate direct and indirect effects. Additionally, differences across countries were tested in a multigroup analysis. The indirect effect (via alcohol use) was greater for injuries and academic problems than for more general outcomes such as life dissatisfaction and negative body image. For social, enhancement and coping motives, we found positive indirect effects (via alcohol use) on injuries and academic problems; the association was negative for conformity motives. The direct effect, that is, the effect above and beyond alcohol use, indicated more negative consequences among those who tended to drink more frequently for coping motives. More negative consequences, such as injuries and negative body image, were also found among those who drink for conformity motives. The pattern of association was largely comparable across countries. While the actual mean level of drinking motives, alcohol use and adverse consequence varied across countries, the consistency of association patterns implies that drinking motive-inspired health promotion efforts are likely to be beneficial across Europe. This is particularly important for coping drinkers because they are especially prone to adverse consequences over and above their alcohol use. [Wicki M, Kuntsche E, Eichenberger Y, Aasvee K, Bendtsen P, Dankulincová Veselská Z, Demetrovics Z, Dzielska A, Farkas J, de Matos MG, Roberts C, Tynjälä J, Välimaa R, Vieno A. Different drinking motives, different adverse consequences

  16. Obesity and pregnancy: Mechanisms of short term and long term adverse consequences for mother and child

    USDA-ARS?s Scientific Manuscript database

    Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomal...

  17. Clinical consequences of toxic envenomations by Hymenoptera.

    PubMed

    Schmidt, Justin O

    2018-05-19

    Many familiar Hymenoptera are brightly colored and can sting painfully-thus, their threat and clinical importance may be exaggerated. Most stinging insects only sting to defend themselves or their colonies from predators. The clinical nature of Hymenoptera envenomations contrasts that of other venomous animals, including other arthropods, primarily because allergic reaction, not direct intoxication, is the usual main concern. This review focuses mainly on the clinical features of direct toxicity to Hymenoptera envenomations, which can induce a high incidence of acute renal failure, liver failure, multiple organ failures, and death. Toxic mass envenomations by honeybees usually entail many hundreds or more stings per victim. In contrast to honeybee toxic envenomations, hornet sting envenomations can be clinically threatening with only 20-200 stings needed to cause kidney and other organ failures. Many lethal envenomations by honeybees occur in rural areas in the New World and Africa and are not recorded or documented. In contrast, deaths by hornets occur mainly to Asia. The most frequent and important envenomating taxa are honeybees, hornets, yellowjacket wasps, paper wasps, fire ants, and jack jumper ants. Occasional envenomating taxa include bumblebees, bullet ants, harvester ants, solitary wasps, solitary bees, and various ants of lesser clinical importance. Envenomations by Hymenoptera usually can be avoided if one considers that bees, wasps and ants "view" us as potential threats or predators, and that with information about the biology of stinging Hymenoptera, humans can minimize adverse incidents. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Adverse consequences of student drinking: the role of sex, social anxiety, drinking motives.

    PubMed

    Norberg, Melissa M; Olivier, Jake; Alperstein, Dion M; Zvolensky, Michael J; Norton, Alice R

    2011-08-01

    This study examined whether biological sex, social anxiety, and drinking motives relate differently to distinct types of alcohol-related consequences using Poisson regression. One hundred eighteen college students completed self-report measures assessing drinking motives and social anxiety and an interview assessing alcohol consumption and consequences. Highly socially anxious women were particularly apt to experience adverse role functioning consequences, while men were particularly apt to experience physical consequences. Although highly socially anxious women reported more personal consequences than did women with low to moderate social anxiety, men with low to moderate social anxiety reported experiencing more social and personal consequences than did women with low to moderate social anxiety. When taking into consideration the above associations, coping motives were statistically associated with social consequences and marginally related to personal consequences, while enhancement motives were significantly associated with physical consequences. Targeting these factors may lead to effective interventions for individuals with co-occurring social anxiety and drinking problems. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. "Partier" self-concept mediates the relationship between college student binge drinking and related adverse consequences.

    PubMed

    Reslan, Summar; Saules, Karen K; Serras, Alisha

    2011-08-01

    The literature suggests that identity impairments play a role in certain forms of maladaptive behavior. Thus, this study was designed to evaluate the extent to which a "Partier" self-concept confers risk for adverse drinking-related consequences, mediating the well documented relationship between college student binge drinking and adverse outcomes. Participants completed an Internet survey examining binge drinking behaviors and related consequences, "Partier" self-concept, and demographic characteristics. This sample was comprised of 251 undergraduate psychology students (M(age)=19.90, SD(age)=1.80; 83% female). Results suggest that "Partier" self-concept partially mediates the relationship between binge drinking and adverse consequences, and it contributes unique variance beyond that explained by frequency of binge drinking and duration of alcohol consumed during binge episodes. Future research should explore whether, for undergraduate college students, binge drinking prevention efforts tailored towards self-concept may fare better than those that have traditionally focused on heavy alcohol use, negative consequences, and related sanctions. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. A Heuristic Decision Making Model to Mitigate Adverse Consequences in a Network Centric Warfare/Sense and Respond System

    DTIC Science & Technology

    2005-05-01

    made. 4. Do military decision makers identify / analyze adverse consequences presently? Few do based on this research and most don’t do it effectively ...A HEURISTIC DECISION MAKING MODEL TO MITIGATE ADVERSE CONSEQUENCES IN A NETWORK CENTRIC WARFARE / SENSE AND RESPOND SYSTEM...ENS/05-01 A HEURISTIC DECISION MAKING MODEL TO MITIGATE ADVERSE CONSEQUENCES IN A NETWORK CENTRIC WARFARE / SENSE AND RESPOND SYSTEM

  1. Clinical outcomes and adverse effect monitoring in allergic rhinitis.

    PubMed

    Juniper, Elizabeth F; Ståhl, Elisabeth; Doty, Richard L; Simons, F Estelle R; Allen, David B; Howarth, Peter H

    2005-03-01

    reduced or absent CNS sedative effects. Therefore, the CNS effects are entirely avoidable, and the first-generation H 1 -antihistamines should no longer be used in the management of allergic rhinitis. The considerably rarer but potentially very serious cardiac arrhythmogenic effects of H 1 -antihistamines are appreciated to be molecule-specific rather than class-specific. The in vitro screening of new compounds to eliminate the further development of those with cardiotoxicity ideally will lead to this adverse effect being historic. The incorporation of electrocardiogram recording in clinical trials provides direct information relating to prolongation of QT interval corrected for heart rate. Although administered at low doses, intranasal steroids still have the potential for systemic absorption and adverse consequences. However, it is appreciated that meaningful differences exist in the bioavailability of different steroid molecules, and although a small but statistically significant effect on growth in children has been identified with the long-term use of intranasal beclomethasone when administered twice daily for 1 year, this is not evident with all intranasal steroids. In addition, twice-daily intranasal steroid administration may have more effect--from the endocrinologic perspective--than once-daily administration in the morning, which coincides better with the natural diurnal variation in cortisol. Thus, once-daily intranasal steroid administration is preferable, and when used in studies in children, measurement of height change during the study period is an important outcome variable together with other indices of systemic steroid bioavailability (eg, tests of hypothalamic-pituitary-adrenal axis function). These considerations have even greater relevance if children are concurrently also receiving inhaled steroids for asthma, because the total steroid load will be greater.

  2. Unintended adverse consequences of introducing electronic health records in residential aged care homes.

    PubMed

    Yu, Ping; Zhang, Yiting; Gong, Yang; Zhang, Jiajie

    2013-09-01

    The aim of this study was to investigate the unintended adverse consequences of introducing electronic health records (EHR) in residential aged care homes (RACHs) and to examine the causes of these unintended adverse consequences. A qualitative interview study was conducted in nine RACHs belonging to three organisations in the Australian Capital Territory (ACT), New South Wales (NSW) and Queensland, Australia. A longitudinal investigation after the implementation of the aged care EHR systems was conducted at two data points: January 2009 to December 2009 and December 2010 to February 2011. Semi-structured interviews were conducted with 110 care staff members identified through convenience sampling, representing all levels of care staff who worked in these facilities. Data analysis was guided by DeLone and McLean Information Systems Success Model, in reference with the previous studies of unintended consequences for the introduction of computerised provider order entry systems in hospitals. Eight categories of unintended adverse consequences emerged from 266 data items mentioned by the interviewees. In descending order of the number and percentage of staff mentioning them, they are: inability/difficulty in data entry and information retrieval, end user resistance to using the system, increased complexity of information management, end user concerns about access, increased documentation burden, the reduction of communication, lack of space to place enough computers in the work place and increasing difficulties in delivering care services. The unintended consequences were caused by the initial conditions, the nature of the EHR system and the way the system was implemented and used by nursing staff members. Although the benefits of the EHR systems were obvious, as found by our previous study, introducing EHR systems in RACH can also cause adverse consequences of EHR avoidance, difficulty in access, increased complexity in information management, increased documentation

  3. Adverse childhood experiences of referred children exposed to intimate partner violence: consequences for their wellbeing.

    PubMed

    Lamers-Winkelman, Francien; Willemen, Agnes M; Visser, Margreet

    2012-02-01

    This study investigated the relationships among Adverse Childhood Experiences (ACEs) in a high risk clinical sample of Dutch children whose mothers were abused by an intimate partner, and the severity of behavioral and emotional problems and trauma symptoms. The study population comprised 208 children (M=7.81 years, SD=2.39, range 2-12) who were referred to mental health and welfare institutions after reported Intimate Partner Violence (IPV). At intake, caregivers, children, and teachers completed questionnaires on Adverse Childhood Experiences, behavior and emotional problems, and trauma symptoms. The results showed that child witnesses of IPV were also exposed to other adverse experiences, such as abuse, household dysfunction and neglect. The mean number of ACEs was 5.08 (range 2-9). Twenty percent of the children in this sample experienced seven ACEs or more. The number of ACEs children were exposed to was unrelated to the level of emotional and behavioral problems, except for trauma related symptoms reported by parents. This study shows that children who witnessed Intimate Partner Violence were also exposed to other adverse experiences. The results of this study may imply that in this high-risk clinical sample of children exposed to IPV, additional adverse experiences have a limited relationship to psychological outcomes. A thorough assessment and inclusion of all Adverse Childhood Experiences is necessary for a comprehensive treatment program. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Adverse Childhood Experiences of Referred Children Exposed to Intimate Partner Violence: Consequences for their Wellbeing

    ERIC Educational Resources Information Center

    Lamers-Winkelman, Francien; Willemen, Agnes M.; Visser, Margreet

    2012-01-01

    Objective: This study investigated the relationships among Adverse Childhood Experiences (ACEs) in a high risk clinical sample of Dutch children whose mothers were abused by an intimate partner, and the severity of behavioral and emotional problems and trauma symptoms. Methods: The study population comprised 208 children (M = 7.81 years, SD =…

  5. 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.

  6. Environmental Enteric Dysfunction: Pathogenesis, Diagnosis, and Clinical Consequences

    PubMed Central

    Keusch, Gerald T.; Denno, Donna M.; Black, Robert E.; Duggan, Christopher; Guerrant, Richard L.; Lavery, James V.; Nataro, James P.; Rosenberg, Irwin H.; Ryan, Edward T.; Tarr, Phillip I.; Ward, Honorine; Bhutta, Zulfiqar A.; Coovadia, Hoosen; Lima, Aldo; Ramakrishna, Balakrishnan; Zaidi, Anita K. M.; Hay Burgess, Deborah C.; Brewer, Thomas

    2014-01-01

    Stunting is common in young children in developing countries, and is associated with increased morbidity, developmental delays, and mortality. Its complex pathogenesis likely involves poor intrauterine and postnatal nutrition, exposure to microbes, and the metabolic consequences of repeated infections. Acquired enteropathy affecting both gut structure and function likely plays a significant role in this outcome, especially in the first few months of life, and serve as a precursor to later interactions of infection and malnutrition. However, the lack of validated clinical diagnostic criteria has limited the ability to study its role, identify causative factors, and determine cost-effective interventions. This review addresses these issues through a historical approach, and provides recommendations to define and validate a working clinical diagnosis and to guide critical research in this area to effectively proceed. Prevention of early gut functional changes and inflammation may preclude or mitigate the later adverse vicious cycle of malnutrition and infection. PMID:25305288

  7. Clinical consequences of diet-induced dysbiosis.

    PubMed

    Chan, Yee Kwan; Estaki, Mehrbod; Gibson, Deanna L

    2013-01-01

    Various disease states are associated with an imbalance of protective and pathogenic bacteria in the gut, termed dysbiosis. Current evidence reveals that dietary factors affect the microbial ecosystem in the gut. Changes to community structure of the intestinal microbiota are not without consequence considering the wide effects that the microbes have on both local and systemic immunity. The goal of this review is to give insight into the importance of gut microbiota in disease development and the possible therapeutic interventions in clinical settings. We introduce the complex tripartite relationship between diet, microbes and the gut epithelium. This is followed by a summary of clinical evidence of diet-induced dysbiosis as a contributing factor in the development of gastrointestinal diseases like inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Finally, the current dietary and microbial interventions to promote a healthy microbial profile will be reviewed. © 2013 S. Karger AG, Basel.

  8. Childhood adversities and clinical symptomatology in first-episode psychosis.

    PubMed

    Lindgren, Maija; Mäntylä, Teemu; Rikandi, Eva; Torniainen-Holm, Minna; Morales-Muñoz, Isabel; Kieseppä, Tuula; Mantere, Outi; Suvisaari, Jaana

    2017-12-01

    In addition to severe traumatic experiences, milder, more common childhood adversities reflecting psychosocial burden may also be common in people with psychotic disorders and have an effect on symptomatology and functioning. We explored eleven negative childhood experiences and their influence on clinical symptoms among young adults with first-episode psychosis (FEP, n = 75) and matched population controls (n = 51). Individuals with FEP reported more adversities than controls. Specifically serious conflicts within the family, bullying at school, maternal mental health problems, and one's own and parents' serious illness during childhood were experienced by the patients more often than by controls. In the FEP group, the severity of adversity was associated with increased anxiety, manic, and obsessive-compulsive symptoms, but not with the severity of positive psychotic symptoms. Adversity produced a more pronounced effect on symptoms in male patients than in female patients. To conclude, in line with earlier studies of more chronic psychosis, a majority of the participants with FEP reported exposure to childhood adversities, with the FEP group reporting more adversities than controls. High levels of mood and anxiety symptoms in patients with FEP may be related to cumulative exposure to childhood adversities. This should be taken into account in the treatment for FEP. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Adverse Health Consequences of Performance-Enhancing Drugs: An Endocrine Society Scientific Statement

    PubMed Central

    Pope, Harrison G.; Wood, Ruth I.; Rogol, Alan; Nyberg, Fred; Bowers, Larry

    2014-01-01

    Despite the high prevalence of performance-enhancing drug (PED) use, media attention has focused almost entirely on PED use by elite athletes to illicitly gain a competitive advantage in sports, and not on the health risks of PEDs. There is a widespread misperception that PED use is safe or that adverse effects are manageable. In reality, the vast majority of PED users are not athletes but rather nonathlete weightlifters, and the adverse health effects of PED use are greatly underappreciated. This scientific statement synthesizes available information on the medical consequences of PED use, identifies gaps in knowledge, and aims to focus the attention of the medical community and policymakers on PED use as an important public health problem. PED users frequently consume highly supraphysiologic doses of PEDs, combine them with other PEDs and/or other classical drugs of abuse, and display additional associated risk factors. PED use has been linked to an increased risk of death and a wide variety of cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders. Because randomized trials cannot ethically duplicate the large doses of PEDs and the many factors associated with PED use, we need observational studies to collect valid outcome data on the health risks associated with PEDs. In addition, we need studies regarding the prevalence of PED use, the mechanisms by which PEDs exert their adverse health effects, and the interactive effects of PEDs with sports injuries and other high-risk behaviors. We also need randomized trials to assess therapeutic interventions for treating the adverse effects of PEDs, such as the anabolic-androgen steroid withdrawal syndrome. Finally, we need to raise public awareness of the serious health consequences of PEDs. PMID:24423981

  10. Laws prohibiting the sale of tobacco to minors: impact and adverse consequences.

    PubMed

    Etter, Jean-François

    2006-07-01

    This paper discusses the consequences of laws that prohibit the sale of tobacco to minors. When enforced, such laws may decrease tobacco sales to minors, but local authorities are often reluctant to enforce these laws. However, the prohibition of tobacco sales to minors is often followed by an increase in the use of tobacco obtained from social sources, mainly family and friends. Importantly, these laws do not decrease smoking prevalence among minors. Several local laws prohibit youths from purchasing, using, and possessing tobacco. However, these laws shift responsibility from retailers to youth, criminalizing young smokers. Those who advocate this type of approach have not documented the adverse consequences of laws that prohibit minors from purchasing, using, or possessing tobacco. In conclusion, youth access laws are ineffective and are not based on sound science.

  11. Pathways to Disease: The Biological Consequences of Social Adversity on Asthma in Minority Youth

    DTIC Science & Technology

    2016-10-01

    the microbiome, and teleomere length and relate these biomarkers to the measured exposures to adversity and stress. The selection of and methods to...granted approval from the HRPO at the end of December 2015. After selecting a subset of our study population for evaluation, we experienced a second delay...of almost three months in setting up our account for Clinical lab testing. Since we were able to prepare the selected samples for biomarker testing

  12. Clinically assessed consequences of workplace physical violence.

    PubMed

    De Puy, Jacqueline; Romain-Glassey, Nathalie; Gut, Melody; Wild, Pascal; Pascal, Wild; Mangin, Patrice; Danuser, Brigitta

    2015-02-01

    To assess consequences of physical violence at work and identify their predictors. Among the patients in a medicolegal consultation from 2007 to 2010, the subsample of workplace violence victims (n = 185) was identified and contacted again in average 30 months after the assault. Eighty-six victims (47 %) participated. Ordinal logistic regression analyses assessed the effect of 9 potential risk factors on physical, psychological and work consequences summarized in a severity score (0-9). Severity score distribution was as follows: 4+: 14 %; 1-3: 42 %; and 0: 44 %. Initial psychological distress resulting from the violence was a strong predictor (p < 0.001) of the severity score both on work and long-term psychological consequences. Gender and age did not reach significant levels in multivariable analyses even though female victims had overall more severe consequences. Unexpectedly, only among workers whose jobs implied high awareness of the risk of violence, first-time violence was associated with long-term psychological and physical consequences (p = 0.004). Among the factors assessed at follow-up, perceived lack of employers' support or absence of employer was associated with higher values on the severity score. The seven other assessed factors (initial physical injuries; previous experience of violence; preexisting health problems; working alone; internal violence; lack of support from colleagues; and lack of support from family or friends) were not significantly associated with the severity score. Being a victim of workplace violence can result in long-term consequences on health and employment, their severity increases with the seriousness of initial psychological distress. Support from the employer can help prevent negative outcomes.

  13. Beyond drinking: differential effects of demographic and socioeconomic factors on alcohol-related adverse consequences across European countries.

    PubMed

    Kuendig, Hervé; Plant, Moira L; Plant, Martin A; Kuntsche, Sandra; Miller, Patrick; Gmel, Gerhard; Ahlström, Salme; Bergmark, Karin Helmersson; Olafsdóttir, Hildigunnur; Elekes, Zsuzsanna; Csemy, Ladislav; Knibbe, Ronald

    2008-01-01

    Evidence underlines the importance of drinking patterns and individual characteristics in experiencing adverse alcohol-related consequences; however, little research has been conducted to explore who does and who does not experience consequences with similar drinking patterns. Using data from seven European countries, this study assesses the association between demographic and socioeconomic characteristics and six adverse consequences. Conditional logistic regression models were estimated, cases (experiencing a consequence) being matched to controls (not experiencing the consequence) by drinking patterns. In general, protective effects with increasing age and being in a partnership were consistent. Gender effects were mixed, but mainly protective for women. Educational achievement and economic status showed consistent effects across countries, but different directions of effect across consequences. Consequences mostly associated with individual drinking pattern (injury, blackout, and loss of control over drinking) exhibited similar patterns of associations, but varying ones arose for consequences additionally influenced by societal reaction to drinking (guilt, role failure, and pressure to cut down drinking). Differences in strengths and directions of effects across consequences pointed to the possibility that the reporting of adverse consequences is not only influenced by alcohol consumption, but also by attributional processes related to demographic and socioeconomic statuses. Copyright 2008 S. Karger AG, Basel.

  14. Disclosing clinical adverse events to patients: can practice inform policy?

    PubMed Central

    Sorensen, Ros; Iedema, Rick; Piper, Donella; Manias, Elizabeth; Williams, Allison; Tuckett, Anthony

    2009-01-01

    Abstract Objectives  To understand patients’ and health professionals’ experience of Open Disclosure and how practice can inform policy. Background  Open Disclosure procedures are being implemented in health services worldwide yet empirical evidence on which to base models of patient–clinician communication and policy development is scant. Design, setting and participants  A qualitative method was employed using semi‐structured open‐ended interviews with 154 respondents (20 nursing, 49 medical, 59 clinical/administrative managerial, 3 policy coordinators, 15 patients and 8 family members) in 21 hospitals and health services in four Australian states. Results  Both patients and health professionals were positive about Open Disclosure, although each differed in their assessments of practice effectiveness. We found that five major elements influenced patients’ and professionals’ experience of openly disclosing adverse events namely: initiating the disclosure, apologizing for the adverse event, taking the patient’s perspective, communicating the adverse event and being culturally aware. Conclusions  Evaluating the impact of Open Disclosure refines policy implementation because it provides an evidence base to inform policy. Health services can use specific properties relating to each of the five Open Disclosure elements identified in this study as training standards and to assess the progress of policy implementation. However, health services must surmount their sensitivity to revealing the extent of error so that research into patient experiences can inform practice and policy development. PMID:19804555

  15. Types, Mechanisms, and Clinical Cardiovascular Consequences

    PubMed Central

    Javaheri, Shahrokh; Barbe, Ferran; Campos-Rodriguez, Francisco; Dempsey, Jerome A.; Khayat, Rami; Javaheri, Sogol; Malhotra, Atul; Martinez-Garcia, Miguel A.; Mehra, Reena; Pack, Allan I.; Polotsky, Vsevolod Y.; Redline, Susan; Somers, Virend K.

    2017-01-01

    Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke. Several discoveries in the pathogenesis, along with developments in the treatment of sleep apnea, have accumulated in recent years. In this review, we discuss the mechanisms of sleep apnea, the evidence that addresses the links between sleep apnea and cardiovascular disease, and research that has addressed the effect of sleep apnea treatment on cardiovascular disease and clinical endpoints. Finally, we review the recent development in sleep apnea treatment options, with special consideration of treating patients with heart disease. Future directions for selective areas are suggested. PMID:28209226

  16. Epilepsy genetics: clinical beginnings and social consequences.

    PubMed

    Johnston, J A; Rees, M I; Smith, P E M

    2009-07-01

    The approach to epilepsy care has transformed in the last 30 years, with more and better anti-epileptic medications, improved cerebral imaging and increased surgical options. Alongside this, developments in neuroscience and molecular genetics have furthered the understanding of epileptogenesis. Future developments in pharmacogenomics hold the promise of antiepileptic drugs matched to specific genotypes. Despite this rapid progress, one-third of epilepsy patients remain refractory to medication, with their seizures impacting upon day-to-day activity, social well-being, independence, economic output and quality of life. International genome collaborations, such as HapMap and the Welcome Trust Case-Control Consortium single nucleotide polymorphism (SNP) mapping project have identified common genetic variations in diseases of major public health importance. Such genetic signposts should help to identify at-risk populations with a view to producing more effective pharmaceutical treatments. Neurological disorders, despite comprising one-fifth of UK acute medical hospital admissions, are surprisingly under-represented in these projects. Epilepsy is the commonest serious neurological disorder worldwide. Although physically, psychologically, socially and financially disabling, it rarely receives deserved attention from physicians, scientists and governmental bodies. As outlined in this article, research into epilepsy genetics presents unique challenges. These help to explain why the identification of its complex genetic traits has lagged well behind other disciplines, particularly the efforts made in neuropsychiatric disorders. Clinical beginnings must underpin any genetic understanding in epilepsy. Success in identifying genetic traits in other disorders does not make the automatic case for genome-wide screening in epilepsy, but such is a desired goal. The essential clinical approach of accurately phenotyping, diagnosing and interpreting the dynamic nature of epilepsy

  17. Premature adrenarche: etiology, clinical findings, and consequences.

    PubMed

    Voutilainen, Raimo; Jääskeläinen, Jarmo

    2015-01-01

    Adrenarche means the morphological and functional change of the adrenal cortex leading to increasing production of adrenal androgen precursors (AAPs) in mid childhood, typically at around 5-8 years of age in humans. The AAPs dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the best serum markers of adrenal androgen (AA) secretion and adrenarche. Normal ACTH secretion and action are needed for adrenarche, but additional inherent and exogenous factors regulate AA secretion. Inter-individual variation in the timing of adrenarche and serum concentrations of DHEA(S) in adolescence and adulthood are remarkable. Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action (pubic/axillary hair, adult type body odor, oily skin or hair, comedones, acne, accelerated statural growth) before the age of 8 years in girls or 9 years in boys associated with AAP concentrations high for the prepubertal chronological age. To accept the diagnosis of PA, central puberty, adrenocortical and gonadal sex hormone secreting tumors, congenital adrenal hyperplasia, and exogenous source of androgens need to be excluded. The individually variable peripheral conversion of circulating AAPs to biologically more active androgens (testosterone, dihydrotestosterone) and the androgen receptor activity in the target tissues are as important as the circulating AAP concentrations as determinants of androgen action. PA has gained much attention during the last decades, as it has been associated with small birth size, the metabolic and polycystic ovarian syndrome (PCOS), and thus with an increased risk for type 2 diabetes and cardiovascular diseases in later life. The aim of this review is to describe the known hormonal changes and their possible regulators in on-time and premature adrenarche, and the clinical features and possible later health problems associating with PA. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Assistive devices for balance and mobility: benefits, demands, and adverse consequences.

    PubMed

    Bateni, Hamid; Maki, Brian E

    2005-01-01

    To provide information on the advantages and possible disadvantages of using canes and walkers. English-language articles were identified by searching MEDLINE and PubMed (1966-May 2003) for key words cane or walker , excluding articles unrelated to mobility aids. Bibliographies were reviewed and ISI Web of Science citation searches were run to identify additional references. Over 1000 articles were selected for further evaluation. We extracted all studies of single-tip canes or pickup walkers addressing: (1) functional, biomechanic, or neuromotor benefits; (2) biomechanic, attentional, neuromotor, metabolic, or physiologic demands; and (3) falls, injuries, or other problems. We included approximately 10% of the articles originally identified. The methodology of each selected article, and findings relevant to the benefits, demands, or adverse effects of cane or walker use were summarized. Findings were synthesized by considering their relation to basic biomechanic principles. Some biomechanic findings appear to support the clinical view that canes and walkers can improve balance and mobility for older adults and people with other clinical conditions. However, a large proportion of users experience difficulties, and the use of such devices is associated with increased risk of falling. A small number of studies have characterized some of the specific demands and problems associated with using mobility aids. Clinical and biomechanic evaluations of canes and walkers confirm that these devices can improve balance and mobility. However, they can also interfere with ones ability to maintain balance in certain situations, and the strength and metabolic demands can be excessive. More research is needed to identify and solve specific problems. Such research may lead to improved designs and guidelines for safer use of canes and walkers.

  19. Aloe vera: A review of toxicity and adverse clinical effects.

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-02

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex.

  20. Challenges in Coding Adverse Events in Clinical Trials: A Systematic Review

    PubMed Central

    Schroll, Jeppe Bennekou; Maund, Emma; Gøtzsche, Peter C.

    2012-01-01

    Background Misclassification of adverse events in clinical trials can sometimes have serious consequences. Therefore, each of the many steps involved, from a patient's adverse experience to presentation in tables in publications, should be as standardised as possible, minimising the scope for interpretation. Adverse events are categorised by a predefined dictionary, e.g. MedDRA, which is updated biannually with many new categories. The objective of this paper is to study interobserver variation and other challenges of coding. Methods Systematic review using PRISMA. We searched PubMed, EMBASE and The Cochrane Library. All studies were screened for eligibility by two authors. Results Our search returned 520 unique studies of which 12 were included. Only one study investigated interobserver variation. It reported that 12% of the codes were evaluated differently by two coders. Independent physicians found that 8% of all the codes deviated from the original description. Other studies found that product summaries could be greatly affected by the choice of dictionary. With the introduction of MedDRA, it seems to have become harder to identify adverse events statistically because each code is divided in subgroups. To account for this, lumping techniques have been developed but are rarely used, and guidance on when to use them is vague. An additional challenge is that adverse events are censored if they already occurred in the run-in period of a trial. As there are more than 26 ways of determining whether an event has already occurred, this can lead to bias, particularly because data analysis is rarely performed blindly. Conclusion There is a lack of evidence that coding of adverse events is a reliable, unbiased and reproducible process. The increase in categories has made detecting adverse events harder, potentially compromising safety. It is crucial that readers of medical publications are aware of these challenges. Comprehensive interobserver studies are needed. PMID

  1. EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

    EPA Science Inventory

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

  2. Consequences of Serotonin Transporter Genotype and Early Adversity on Behavioral Profile – Pathology or Adaptation?

    PubMed Central

    Heiming, Rebecca S.; Sachser, Norbert

    2010-01-01

    This review focuses on how behavioral profile is shaped by early adversity in individuals with varying serotonin transporter (5-HTT) genotype. In a recent study on 5-HTT knockout mice Heiming et al. (2009) simulated a ‘dangerous environment‘ by confronting pregnant and lactating females with odor cues of unfamiliar males, indicating the risk of infant killing. Growing up in a dangerous environment induced increased anxiety-related behavior and decreased exploratory locomotion in the offspring, the effects being most pronounced in mice lacking 5-HTT expression. We argue that these alterations in behavioral profile represent adaptive maternal effects that help the individuals to cope with adversity. In principle, such effects of adversity on behavioral profile should not automatically be regarded as pathological. Rather and in accordance with modern evolutionary theory they may represent adaptations, although individuals with 5-HTT genotype induced susceptibility to adversity may be at risk of developing pathologies. PMID:21151780

  3. Infectious Adverse Events Following Acupuncture: Clinical Progress and Microbiological Etiology.

    PubMed

    Kim, Youn-Jung; Kim, Sung-Han; Lee, Hak Jin; Kim, Won Young

    2018-06-11

    We investigated the clinical progress and bacteriological characteristics of infectious adverse events (AEs) following acupuncture and compared patient characteristics between serious and non-serious outcome groups. A retrospective observational study was conducted in 1,174 patients with infectious complications associated with acupuncture at the emergency department (ED) in a tertiary hospital in Korea between 2010 and 2014. Serious outcome was defined as development of septic shock, admission to intensive care unit (ICU) or attaining permanent morbidity. Forty-eight patients had certain causality and cellulitis, necrotizing fasciitis and osteomyelitis were common in order. Among them, 9 patients (18.8%) were categorized into serious outcome group, and they showed devastating outcomes such as septic shock (n = 2), ICU admission (n = 4), and permanent sequelae (n = 5). The serious group had delayed admission to the ED after acupuncture (30.0 [4.0-55.0] vs. 3.0 [1.0-10.0] days, P = 0.023). Methicillin-sensitive Staphylococcus aureus was the most frequently identified microorganism. The patients in the serious group required longer treatment duration (139.0 [49.0-183.5] vs. 14.0 [7.0-34.0] days, P < 0.001) as well as more operation with local (44.4% vs. 10.3%, P = 0.031) or general anaesthesia (33.3% vs. 2.6%, P = 0.017). The infectious AEs after acupuncture may cause serious outcomes. Patients and primary physicians should be aware of the risk of infectious complications and make efforts to prevent them.

  4. Gender inequality, economic growth, and the intergenerational transmission of adverse health consequences at birth.

    PubMed

    Qian, Mengcen; Chou, Shin-Yi; Deily, Mary E; Liu, Jin-Tan

    2018-03-01

    We estimate a gender differential in the intergenerational transmission of adverse birth outcomes. We link Taiwan birth certificates from 1978 to 2006 to create a sample of children born in the period 1999-2006 that includes information about their parents and their maternal grandmothers. We use maternal-sibling fixed effects to control for unobserved family-linked factors that may be correlated with birth outcomes across generations, and define adverse birth outcomes as small for gestational age. We find that when a mother is in the 5th percentile of birth weight for her gestational age, then her female children are 49-53% more likely to experience the same adverse birth outcome compared to other female children, while her male children are 27-32% more likely to experience this relative to other male children. We then investigate whether long-run improvements in local socio-economic conditions experienced by the child's family, as measured by intergenerational changes in town-level maternal education, affect the gender differential. We find no evidence that intergenerational improvements in socioeconomic conditions reduce the gender differential. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Use of proton pump inhibitors for the provision of stress ulcer prophylaxis: clinical and economic consequences.

    PubMed

    Barletta, Jeffrey F; Sclar, David A

    2014-01-01

    The provision of stress ulcer prophylaxis (SUP) for the prevention of clinically significant bleeding is widely recognized as a crucial component of care in critically ill patients. Nevertheless, SUP is often provided to non-critically ill patients despite a risk for clinically significant bleeding of roughly 0.1 %. The overuse of SUP therefore introduces added risks for adverse drug events and cost, with minimal expected benefit in clinical outcome. Historically, histamine-2-receptor antagonists (H2RAs) have been the preferred agent for SUP; however, recent data have revealed proton pump inhibitors (PPIs) as the most common modality (76 %). There are no high quality randomized controlled trials demonstrating superiority with PPIs compared with H2RAs for the prevention of clinically significant bleeding associated with stress ulcers. In contrast, PPIs have recently been linked to several adverse effects including Clostridium difficile diarrhea and pneumonia. These complications have substantial economic consequences and have a marked impact on the overall cost effectiveness of PPI therapy. Nevertheless, PPI use remains widespread in patients who are at both high and low risk for clinically significant bleeding. This article will describe the utilization of PPIs for SUP and present the clinical and economic consequences linked to their use/overuse.

  6. Social consequences of early socioeconomic adversity and youth BMI trajectories: gender and race/ethnicity differences.

    PubMed

    Bae, Dayoung; Wickrama, K A S; O'Neal, Catherine Walker

    2014-08-01

    The present study investigated the mediating effects of adolescent BMI trajectories on socioeconomic continuity over the early life course using a nationally representative sample of 11,075 respondents. This study considered both the initial severity as well as change over time in BMI as psycho-physiological mediators. Consistent with the life course pathway model and the cumulative advantage and disadvantage principle, the results suggested that early socioeconomic adversity is associated with youth BMI trajectories over time, which in turn, impair young adult socioeconomic attainment. The results also revealed important gender and racial/ethnic differences in the hypothesized associations. These findings elucidate how early adversity exerts an enduring long-term influence on social attainment in young adulthood. Further, the findings suggest that effective obesity intervention and prevention programs should focus not only on the severity of obesity but also on growth in BMI over the early years. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  7. Embryonic vascular disruption adverse outcomes: Linking high-throughput signaling signatures with functional consequences.

    PubMed

    Ellis-Hutchings, Robert G; Settivari, Raja S; McCoy, Alene T; Kleinstreuer, Nicole; Franzosa, Jill; Knudsen, Thomas B; Carney, Edward W

    2017-04-13

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High-throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Embryonic vascular disruption adverse outcomes: Linking high throughput signaling signatures with functional consequences.

    PubMed

    Ellis-Hutchings, Robert G; Settivari, Raja S; McCoy, Alene T; Kleinstreuer, Nicole; Franzosa, Jill; Knudsen, Thomas B; Carney, Edward W

    2017-06-01

    Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Adverse effects of orthodontic treatment: A clinical perspective

    PubMed Central

    Talic, Nabeel F.

    2011-01-01

    Orthodontic treatment is associated with a number of adverse effects, such as root resorption, pain, pulpal changes, periodontal disease, and temporomandibular dysfunction (TMD). Orthodontists should be aware of these effects and associated risk factors. Risk factors linked to root resorption include the duration of treatment, length, and shape of the root, trauma history, habits, and genetic predisposition. PMID:24151415

  10. Modifiable Resilience Factors to Childhood Adversity for Clinical Pediatric Practice.

    PubMed

    Traub, Flora; Boynton-Jarrett, Renée

    2017-05-01

    Childhood adversity is highly prevalent and associated with risk for poor health outcomes in childhood and throughout the life course. Empirical literature on resilience over the past 40 years has identified protective factors for traumatized children that improve health outcomes. Despite these empirical investigations of resilience, there is limited integration of these findings into proactive strategies to mitigate the impact of adverse childhood experiences. We review the state of resilience research, with a focus on recent work, as it pertains to protecting children from the health impacts of early adversity. We identify and document evidence for 5 modifiable resilience factors to improve children's long- and short-term health outcomes, including fostering positive appraisal styles in children and bolstering executive function, improving parenting, supporting maternal mental health, teaching parents the importance of good self-care skills and consistent household routines, and offering anticipatory guidance about the impact of trauma on children. We conclude with 10 recommendations for pediatric practitioners to leverage the identified modifiable resilience factors to help children withstand, adapt to, and recover from adversity. Taken together, these recommendations constitute a blueprint for a trauma-informed medical home. Building resilience in pediatric patients offers an opportunity to improve the health and well-being of the next generation, enhance national productivity, and reduce spending on health care for chronic diseases. Copyright © 2017 by the American Academy of Pediatrics.

  11. Automated Detection of Surgical Adverse Events from Retrospective Clinical Data

    ERIC Educational Resources Information Center

    Hu, Zhen

    2017-01-01

    The Detection of surgical adverse events has become increasingly important with the growing demand for quality improvement and public health surveillance with surgery. Event reporting is one of the key steps in determining the impact of postoperative complications from a variety of perspectives and is an integral component of improving…

  12. The health care work environment and adverse health and safety consequences for nurses.

    PubMed

    Geiger-Brown, Jeanne; Lipscomb, Jane

    2010-01-01

    Nurses' working conditions are inextricably linked to the quality of care that is provided to patients and patients' safety. These same working conditions are associated with health and safety outcomes for nurses and other health care providers. This chapter describes aspects of the nursing work environment that have been linked to hazards and adverse exposures for nurses, as well as the most common health and safety outcomes of nursing work. We include studies from 2000 to the present by nurse researchers, studies of nurses as subjects, and studies of workers under similar working conditions that could translate to nurses' work environment. We explore a number of work organization factors including shift work and extended work hours, safety climate and culture, teamwork, and communication. We also describe environmental hazards, including chemical hazards (e.g., waste anesthetics, hazardous drugs, cleaning compounds) and airborne and bloodborne pathogen exposure. Nurses' health and safety outcomes include physical (e.g., musculoskeletal disorders, gastrointestinal, slips, trips and falls, physical assault) and psychosocial outcomes (e.g., burnout, work-family conflict). Finally, we present recommendations for future research to further protect nurses and all health care workers from a range of hazardous working conditions.

  13. Adverse events of vaccines and the consequences of non-vaccination: a critical review

    PubMed Central

    Aps, Luana Raposo de Melo Moraes; Piantola, Marco Aurélio Floriano; Pereira, Sara Araujo; de Castro, Julia Tavares; Santos, Fernanda Ayane de Oliveira; Ferreira, Luís Carlos de Souza

    2018-01-01

    ABSTRACT OBJECTIVE: To analyze the risks related to vaccines and the impacts of non-vaccination on the world population. METHODS: This is a narrative review that has considered information present in the bibliographic databases NCBI-PubMed, Medline, Lilacs, and Scientific Electronic Library Online (SciELO), between November 2015 and November 2016. For the analysis of outbreaks caused by non-vaccination, we considered the work published between 2010 and 2016. RESULTS: We have described the main components of the vaccines offered by the Brazilian public health system and the adverse events associated with these elements. Except for local inflammatory reactions and rare events, such as exacerbation of autoimmune diseases and allergies, no causal relationship has been demonstrated between the administration of vaccines and autism, Alzheimer's disease, or narcolepsy. On the other hand, the lack of information and the dissemination of non-scientific information have contributed to the reemergence of infectious diseases in several countries in the world and they jeopardize global plans for the eradication of these diseases. CONCLUSIONS: The population should be well informed about the benefits of vaccination and health professionals should assume the role of disseminating truthful information with scientific support on the subject, as an ethical and professional commitment to society. PMID:29668817

  14. The impact of childhood adversity on suicidality and clinical course in treatment-resistant depression.

    PubMed

    Tunnard, Catherine; Rane, Lena J; Wooderson, Sarah C; Markopoulou, Kalypso; Poon, Lucia; Fekadu, Abebaw; Juruena, Mario; Cleare, Anthony J

    2014-01-01

    Childhood adversity is a risk factor for the development of depression and can also affect clinical course. We investigated this specifically in treatment-resistant depression (TRD). One hundred and thirty-seven patients with TRD previously admitted to an inpatient affective disorders unit were included. Clinical, demographic and childhood adversity (physical, sexual, emotional abuse; bullying victimization, traumatic events) data were obtained during admission. Associations between childhood adversity, depressive symptoms and clinical course were investigated. Most patients had experienced childhood adversity (62%), with traumatic events (35%) and bullying victimization (29%) most commonly reported. Childhood adversity was associated with poorer clinical course, including earlier age of onset, episode persistence and recurrence. Logistic regression analyses revealed childhood adversity predicted lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). The cross-sectional design and retrospective measurement of childhood adversity are limitations of the study. Childhood adversity was common amongst these TRD patients and was associated with poor clinical course, psychosis and suicide attempts. Routine assessment of early adversity may help identify at risk individuals and inform clinical intervention. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Metabolic and Clinical Consequences of Hyperthyroidism on Bone Density

    PubMed Central

    Gorka, Jagoda; Taylor-Gjevre, Regina M.

    2013-01-01

    In 1891, Von Recklinghausen first established the association between the development of osteoporosis in the presence of overt hyperthyroidism. Subsequent reports have demonstrated that BMD loss is common in frank hyperthyroidism, and, to a lesser extent, in subclinical presentations. With the introduction of antithyroid medication in the 1940s to control biochemical hyperthyroidism, the accompanying bone disease became less clinically apparent as hyperthyroidism was more successfully treated medically. Consequently, the impact of the above normal thyroid hormones in the pathogenesis of osteoporosis may be presently underrecognized due to the widespread effective treatments. This review aims to present the current knowledge of the consequences of hyperthyroidism on bone metabolism. The vast number of recent papers touching on this topic highlights the recognized impact of this common medical condition on bone health. Our focus in this review was to search for answers to the following questions. What is the mechanisms of action of thyroid hormones on bone metabolism? What are the clinical consequences of hyperthyroidism on BMD and fracture risk? What differences are there between men and women with thyroid disease and how does menopause change the clinical outcomes? Lastly, we report how different treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis. PMID:23970897

  16. Clinical trials bureaucracy: unintended consequences of well-intentioned policy.

    PubMed

    Califf, Robert M

    2006-01-01

    As randomized controlled trials have become the 'gold standard' for medical research, a complex regulatory structure for the conduct of clinical trials has emerged. However, this structure has not been adequately assessed to ensure that regulations governing human subjects research actually produce the desired effects. Our purpose is to identify some of the major shortcomings in the current regulatory system of human clinical trials oversight, and to propose some potential solutions to these problems. We discuss the evolution of the current US regulatory environment and its application in the context of several widely-used drug therapies. Despite numerous randomized controlled trials, performed within a structure of extensive documentation and data collection, serious shortcomings in a number of pharmaceutical therapies were not detected until after the drugs were approved and widely adopted by clinicians. The current system of regulatory bureaucracy in clinical trials has led to an extremely expensive research paradigm that, in spite of complex systems of oversight and exhaustive data collection, cannot be shown to adequately ensure the integrity of the research process and the protection of human research subjects. Some parts of the system, including Research Ethics Review Boards, may not be well-suited to carrying out their core mission of overseeing research conduct, and other aspects of clinical trials regulatory structure, such as monitoring/auditing review and adverse event reporting, may constitute a waste of money and resources. Misdirected data collection and adverse events reporting divert valuable resources and hamper development of large, simple clinical trials powered to definitively answer important research questions. Careful scrutiny of the utility of current or proposed regulatory schemes is required to ensure the integrity of human subjects research and to enhance the effectiveness of research dollars.

  17. Consequences of contextual factors on clinical reasoning in resident physicians.

    PubMed

    McBee, Elexis; Ratcliffe, Temple; Picho, Katherine; Artino, Anthony R; Schuwirth, Lambert; Kelly, William; Masel, Jennifer; van der Vleuten, Cees; Durning, Steven J

    2015-12-01

    Context specificity and the impact that contextual factors have on the complex process of clinical reasoning is poorly understood. Using situated cognition as the theoretical framework, our aim was to evaluate the verbalized clinical reasoning processes of resident physicians in order to describe what impact the presence of contextual factors have on their clinical reasoning. Participants viewed three video recorded clinical encounters portraying straightforward diagnoses in internal medicine with select patient contextual factors modified. After watching each video recording, participants completed a think-aloud protocol. Transcripts from the think-aloud protocols were analyzed using a constant comparative approach. After iterative coding, utterances were analyzed for emergent themes with utterances grouped into categories, themes and subthemes. Ten residents participated in the study with saturation reached during analysis. Participants universally acknowledged the presence of contextual factors in the video recordings. Four categories emerged as a consequence of the contextual factors: (1) emotional reactions (2) behavioral inferences (3) optimizing the doctor patient relationship and (4) difficulty with closure of the clinical encounter. The presence of contextual factors may impact clinical reasoning performance in resident physicians. When confronted with the presence of contextual factors in a clinical scenario, residents experienced difficulty with closure of the encounter, exhibited as diagnostic uncertainty. This finding raises important questions about the relationship between contextual factors and clinical reasoning activities and how this relationship might influence the cost effectiveness of care. This study also provides insight into how the phenomena of context specificity may be explained using situated cognition theory.

  18. Factors associated with adverse clinical outcomes among obstetric trainees

    PubMed Central

    Aiken PhD, Catherine E.; Aiken, Abigail; Park, Hannah; Brockelsby, Jeremy C.; Prentice, Andrew

    2016-01-01

    Objective To determine whether UK obstetric trainees transitioning from directly to indirectly-supervised practice have a higher likelihood of adverse patient outcomes from operative deliveries compared to other indirectly supervised trainees and to examine whether performing more procedures under direct supervision is associated with fewer adverse outcomes in initial indirect practice. Methods We examined all deliveries (13,861) conducted by obstetricians at a single centre over 5 years (2008-2013). Mixed-effects logistic regression models were used to compare estimated blood loss, maternal trauma, umbilical arterial pH, delayed neonatal respiration, failed instrumental delivery, and critical incidents for trainees in their first indirectly-supervised year with trainees in all other years of indirect practice. Outcomes for trainees in their first indirectly-supervised 3 months were compared to their outcomes for the remainder of the year. Linear regression was used to examine the relationship between number of procedures performed under direct supervision and initial outcomes under indirect supervision. Results Trainees in their first indirectly-supervised year had a higher likelihood of >2 litres estimated blood loss at any delivery (OR 1.32;CI(1.01-1.64) p<0.05) and of failed instrumental delivery (OR 2.33;CI(1.37-3.29) p<0.05) compared with other indirectly-supervised trainees. Other measured outcomes showed no significant differences. Within the first three months of indirect supervision, the likelihood of operative vaginal deliveries with >1litre estimated blood loss (OR 2.54;CI(1.88-3.20) p<0.05) was higher compared to the remainder of the first year. Performing more deliveries under direct supervision prior to beginning indirectly-supervised training was associated with decreased risk of >1litre estimated blood loss (p<0.05). Conclusions Obstetric trainees in their first year of indirectly-supervised practice have a higher likelihood of immediate adverse

  19. Exposure to Ambient Particulate Matter during Specific Gestational Periods Produces Adverse Obstetric Consequences in Mice

    PubMed Central

    Blum, Jason L.; Chen, Lung-Chi

    2017-01-01

    Background: Epidemiological studies associate inhalation of fine-sized particulate matter (PM2.5) during pregnancy with preterm birth (PTB) and low birth weight (LBW) but disagree over which time frames are most sensitive, or if effects are cumulative. Objectives: Our objective was to provide experimental plausibility for epidemiological observations by testing the hypothesis that exposure to PM2.5 during discrete periods of pregnancy results in PTB and LBW. Methods: For the first study, timed-pregnant B6C3F1 mice were exposed to concentrated ambient PM2.5 (CAPs) or filtered air (FA) throughout pregnancy [6 h/d from gestational day (GD) 0.5 through GD16.5]. A follow-up study examined the effects of CAPs exposure during discrete gestational periods (1: GD0.5–5.5; 2: GD6.5–14.5; 3: GD14.5–16.5; 4: GD0.5–16.5) aligning to milestones during human development. Results: In the first experiment, exposure to 160 μg CAPs/m3 throughout pregnancy decreased gestational term by 0.5 d (∼1.1  wk decrease for humans) and birth weight by 11.4% compared with FA. The follow-up experiment investigated timing of CAPs exposure (mean concentrations at 178, 193, 171, and 173 μg/m3 for periods 1–4, respectively). Pregnancy was significantly shortened (vs. FA) by ∼0.4d when exposure occurred during gestational periods 2 and 4, and by ∼0.5d if exposure occurred during period 3. Exposure during periods 1, 2, and 4 reduced birth weight by ∼10% compared with FA, and placental weight was reduced (∼8%) on GD17.5 if exposure occurred only during period 3. Conclusions: Adverse PM2.5-induced outcomes such as PTB and LBW are dependent upon the periods of maternal exposure. The results of these experimental studies could contribute significantly to air pollution policy decisions in the future. https://doi.org/10.1289/EHP1029 PMID:28893721

  20. Incomplete evidence: the inadequacy of databases in tracing published adverse drug reactions in clinical trials

    PubMed Central

    Derry, Sheena; Kong Loke, Yoon; Aronson, Jeffrey K

    2001-01-01

    Background We would expect information on adverse drug reactions in randomised clinical trials to be easily retrievable from specific searches of electronic databases. However, complete retrieval of such information may not be straightforward, for two reasons. First, not all clinical drug trials provide data on the frequency of adverse effects. Secondly, not all electronic records of trials include terms in the abstract or indexing fields that enable us to select those with adverse effects data. We have determined how often automated search methods, using indexing terms and/or textwords in the title or abstract, would fail to retrieve trials with adverse effects data. Methods We used a sample set of 107 trials known to report frequencies of adverse drug effects, and measured the proportion that (i) were not assigned the appropriate adverse effects indexing terms in the electronic databases, and (ii) did not contain identifiable adverse effects textwords in the title or abstract. Results Of the 81 trials with records on both MEDLINE and EMBASE, 25 were not indexed for adverse effects in either database. Twenty-six trials were indexed in one database but not the other. Only 66 of the 107 trials reporting adverse effects data mentioned this in the abstract or title of the paper. Simultaneous use of textword and indexing terms retrieved only 82/107 (77%) papers. Conclusions Specific search strategies based on adverse effects textwords and indexing terms will fail to identify nearly a quarter of trials that report on the rate of drug adverse effects. PMID:11591220

  1. Surgical adverse outcome reporting as part of routine clinical care.

    PubMed

    Kievit, J; Krukerink, M; Marang-van de Mheen, P J

    2010-12-01

    In The Netherlands, health professionals have created a doctor-driven standardised system to report and analyse adverse outcomes (AO). The aim is to improve healthcare by learning from past experiences. The key elements of this system are (1) an unequivocal definition of an adverse outcome, (2) appropriate contextual information and (3) a three-dimensional hierarchical classification system. First, to assess whether routine doctor-driven AO reporting is feasible. Second, to investigate how doctors can learn from AO reporting and analysis to improve the quality of care. Feasibility was assessed by how well doctors reported AO in the surgical department of a Dutch university hospital over a period of 9 years. AO incidence was analysed per patient subgroup and over time, in a time-trend analysis of three equal 3-year periods. AO were analysed case by case and statistically, to learn lessons from past events. In 19,907 surgical admissions, 9189 AOs were reported: one or more AO in 18.2% of admissions. On average, 55 lessons were learnt each year (in 4.3% of AO). More AO were reported in P3 than P1 (OR 1.39 (1.23-1.57)). Although minor AO increased, fatal AO decreased over time (OR 0.59 (0.45-0.77)). Doctor-driven AO reporting is shown to be feasible. Lessons can be learnt from case-by-case analyses of individual AO, as well as by statistical analysis of AO groups and subgroups (illustrated by time-trend analysis), thus contributing to the improvement of the quality of care. Moreover, by standardising AO reporting, data can be compared across departments or hospitals, to generate (confidential) mirror information for professionals cooperating in a peer-review setting.

  2. Surgical adverse outcome reporting as part of routine clinical care

    PubMed Central

    Krukerink, M; Marang-van de Mheen, P J

    2010-01-01

    Background In The Netherlands, health professionals have created a doctor-driven standardised system to report and analyse adverse outcomes (AO). The aim is to improve healthcare by learning from past experiences. The key elements of this system are (1) an unequivocal definition of an adverse outcome, (2) appropriate contextual information and (3) a three-dimensional hierarchical classification system. Objectives First, to assess whether routine doctor-driven AO reporting is feasible. Second, to investigate how doctors can learn from AO reporting and analysis to improve the quality of care. Methods Feasibility was assessed by how well doctors reported AO in the surgical department of a Dutch university hospital over a period of 9 years. AO incidence was analysed per patient subgroup and over time, in a time-trend analysis of three equal 3-year periods. AO were analysed case by case and statistically, to learn lessons from past events. Results In 19 907 surgical admissions, 9189 AOs were reported: one or more AO in 18.2% of admissions. On average, 55 lessons were learnt each year (in 4.3% of AO). More AO were reported in P3 than P1 (OR 1.39 (1.23–1.57)). Although minor AO increased, fatal AO decreased over time (OR 0.59 (0.45–0.77)). Conclusions Doctor-driven AO reporting is shown to be feasible. Lessons can be learnt from case-by-case analyses of individual AO, as well as by statistical analysis of AO groups and subgroups (illustrated by time-trend analysis), thus contributing to the improvement of the quality of care. Moreover, by standardising AO reporting, data can be compared across departments or hospitals, to generate (confidential) mirror information for professionals cooperating in a peer-review setting. PMID:20430928

  3. Standard Information Models for Representing Adverse Sensitivity Information in Clinical Documents.

    PubMed

    Topaz, M; Seger, D L; Goss, F; Lai, K; Slight, S P; Lau, J J; Nandigam, H; Zhou, L

    2016-01-01

    Adverse sensitivity (e.g., allergy and intolerance) information is a critical component of any electronic health record system. While several standards exist for structured entry of adverse sensitivity information, many clinicians record this data as free text. This study aimed to 1) identify and compare the existing common adverse sensitivity information models, and 2) to evaluate the coverage of the adverse sensitivity information models for representing allergy information on a subset of inpatient and outpatient adverse sensitivity clinical notes. We compared four common adverse sensitivity information models: Health Level 7 Allergy and Intolerance Domain Analysis Model, HL7-DAM; the Fast Healthcare Interoperability Resources, FHIR; the Consolidated Continuity of Care Document, C-CDA; and OpenEHR, and evaluated their coverage on a corpus of inpatient and outpatient notes (n = 120). We found that allergy specialists' notes had the highest frequency of adverse sensitivity attributes per note, whereas emergency department notes had the fewest attributes. Overall, the models had many similarities in the central attributes which covered between 75% and 95% of adverse sensitivity information contained within the notes. However, representations of some attributes (especially the value-sets) were not well aligned between the models, which is likely to present an obstacle for achieving data interoperability. Also, adverse sensitivity exceptions were not well represented among the information models. Although we found that common adverse sensitivity models cover a significant portion of relevant information in the clinical notes, our results highlight areas needed to be reconciled between the standards for data interoperability.

  4. Childhood adversity and social functioning in psychosis: Exploring clinical and cognitive mediators.

    PubMed

    Palmier-Claus, Jasper; Berry, Katherine; Darrell-Berry, Hannah; Emsley, Richard; Parker, Sophie; Drake, Richard; Bucci, Sandra

    2016-04-30

    Childhood adversity may increase risk of impaired social functioning across the continuum of psychosis. However, the pathways by which adversity dictates functional outcome remain underexplored. This study investigated the association between childhood adversity and social functioning, and the clinical and cognitive mediators of this relationship. Fifty-four clinical (20 chronic, 20 first episode, 14 at ultra-high risk) and 120 non-clinical participants completed standardised questionnaires, semi-structured interviews and tests of theory of mind ability. The authors used multiple group structural equation modelling to fit mediation models allowing for differential relationships between the clinical and non-clinical samples. When examining each pathway separately, depression, paranoia and anxious attachment mediated the effect of childhood adversity on social functioning. In a combined model, depression was the only significant mediating variable with greater adversity predicting lower mood across groups. Childhood adversity did not significantly predict theory of mind ability in any of the models. This is the first study to indicate that childhood adversity acts on social functioning by increasing levels of depression, suggesting a common mechanism across the spectrum of psychosis. Clinical interventions should target low mood in order to improve social functioning at all stages of psychotic disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey.

    PubMed

    Bush, Thomas M; Rayburn, Keith S; Holloway, Sandra W; Sanchez-Yamamoto, Deanna S; Allen, Blaine L; Lam, Tiffany; So, Brian K; Tran, De H; Greyber, Elizabeth R; Kantor, Sophia; Roth, Larry W

    2007-01-01

    Patients often combine prescription medications with herbal and dietary substances (herein referred to as herbal medicines). A variety of potential adverse herb-drug interactions exist based on the pharmacological properties of herbal and prescription medications. To determine the incidence of potential and observed adverse herb-drug interactions in patients using herbal medicines with prescription medications. Consecutive patients were questioned about their use of herbal medicines in 6 outpatient clinics. Patients reporting use of these products provided a list of their prescription medications, which were reviewed for any potential adverse herb-drug interactions using a comprehensive natural medicine database. Any potential adverse herb-drug interactions prompted a review of the patient's chart for evidence of an observed adverse herb-drug interaction. The rate of potential and observed adverse herb-drug interactions. Eight hundred four patients were surveyed, and 122 (15%) used herbal medicines. Eighty-five potential adverse herb-drug interactions were found in 49 patients (40% of herbal medicine users). Twelve possible adverse herb-drug interactions in 8 patients (7% of herbal medicine users) were observed. In all 12 cases, the severity scores were rated as mild, including 8 cases of hypoglycemia in diabetics taking nopal (prickly pear cactus). A substantial number of potential adverse herb-drug interactions were detected and a small number of adverse herb-drug interactions observed, particularly in diabetics taking nopal. Screening for herbal medicine usage in 804 patients did not uncover any serious adverse interactions with prescription medications.

  6. Improving Pediatric Adverse Drug Event Reporting through Clinical Pharmacy Services

    PubMed Central

    Crowther, David M.; Buck, Marcia L.; McCarthy, Michelle W.; Barton, Virginia W.

    2011-01-01

    OBJECTIVES The purpose of this study was to summarize adverse drug event (ADE) reporting and to characterize the type of healthcare practitioners involved in reporting over a 10-year period at a 120-bed university-affiliated children's hospital. METHODS The University of Virginia Children's Hospital ADE database was analyzed for records involving pediatric patients. Data from patients <18 years of age who were admitted to the University of Virginia Children's Hospital between January 1, 2000, and December 31, 2009, were analyzed. Data collected included drug name and therapeutic class of the suspected causative agent, description of the event, severity, causality, outcome, and the type of healthcare practitioner reporting the event. RESULTS A total of 863 ADEs were reported over the 10-year period. The 5 most common types reported were extravasation injury (10%), rash (8%), hypotension (5%), pruritus (5%), and renal failure (3%). A total of 196 (21%) cases were categorized as mild, 436 (47%) cases as moderate, and 296 (32%) cases as severe. Further characterization of extravasations was performed to identify trends relating to potential causes. In 45 (57%) reports, parenteral nutrition was identified as the causative agent. Full recovery was documented in 21 (47%) extravasations. Of the total events reported, 83% were reported by pharmacists, 16% by nurses, and <1% by other healthcare practitioners. CONCLUSIONS Results of this study are consistent with those of previous studies involving ADE reporting in children's hospitals. This consistency is due in part to system design and use of unit-based pharmacists as the primary reporters. PMID:22768013

  7. Correction to: Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in Clinical Trials.

    PubMed

    Ballow, Mark; Wasserman, Richard L; Jolles, Stephen; Chapel, Helen; Berger, Mel; Misbah, Siraj A

    2018-04-27

    The article Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in Clinical Trials, written by Mark Ballow, Richard L. Wasserman, Stephen Jolles, Helen Chapel, Mel Berger, Siraj A. Misbah, was originally published Online First without open access.

  8. ERA: Adverse Consequences

    ERIC Educational Resources Information Center

    Martin, Brian

    2011-01-01

    Excellence in Research for Australia has a number of limitations: inputs are counted as outputs, time is wasted, disciplinary research is favoured and public engagement is discouraged. Most importantly, by focusing on measurement and emphasising competition, ERA may actually undermine the cooperation and intrinsic motivation that underpin research…

  9. Estimating the scale of adverse animal welfare consequences of movement restriction and mitigation strategies in a classical swine fever outbreak.

    PubMed

    Yadav, Shankar; Weng, Hsin-Yi

    2017-04-04

    The study aim was to quantify the impact of movement restriction on the well-being of pigs and the associated mitigation responses during a classical swine fever (CSF) outbreak. We developed a stochastic risk assessment model and incorporated Indiana swine industry statistics to estimate the timing and number of swine premises that would encounter overcrowding or feed interruption resulting from movement restriction. Our model also quantified the amount of on-farm euthanasia and movement of pigs to slaughter plants required to alleviate those conditions. We simulated various single-site (i.e., an outbreak initiated from one location) and multiple-site (i.e., an outbreak initiated from more than one location) outbreak scenarios in Indiana to estimate outputs. The study estimated that 14% of the swine premises in Indiana would encounter overcrowding or feed interruption due to movement restriction implemented during a CSF outbreak. The number of premises that would experience animal welfare conditions was about 2.5 fold of the number of infected premises. On-farm euthanasia needed to be performed on 33% of those swine premises to alleviate adverse animal welfare conditions, and more than 90% of on-farm euthanasia had to be carried out within 2 weeks after the implementation of movement restriction. Conversely, movement of pigs to slaughter plants could alleviate 67% of adverse animal welfare conditions due to movement restriction, and only less than 1% of movement of pigs to slaughter plants had to be initiated in the first 2 weeks of movement restrictions. The risk of secondary outbreaks due to movement of pigs from movement restriction areas to slaughter plants was low and only seven pigs from each shipment needed to be tested for CSF infection to prevent a secondary outbreak. We found that the scale of adverse animal welfare consequences of movement restriction during a CSF outbreak in Indiana was substantial, and controlled movement of pigs to slaughter plants

  10. A survey of Ethiopian physicians' experiences of bedside rationing: extensive resource scarcity, tough decisions and adverse consequences.

    PubMed

    Defaye, Frehiwot Berhane; Desalegn, Dawit; Danis, Marion; Hurst, Samia; Berhane, Yemane; Norheim, Ole Frithjof; Miljeteig, Ingrid

    2015-10-14

    Resource scarcity in health care is a universal challenge. In high-income settings, bedside rationing is commonly discussed and debated as a means to addressing scarcity. However, little is known about physicians' experiences in resource-limited contexts in low- income countries. Here we describe physicians' experiences regarding scarcity of resources, bedside rationing, use of various strategies to save resources, and perceptions of the consequences of rationing in Ethiopia. A national survey was conducted amongst physicians from 49 public hospitals using stratified, multi-stage sampling in six regions. All physicians in the selected hospitals were invited to respond to a self-administered questionnaire. Data were weighted and analyzed using descriptive statistics. In total, 587 physicians responded (91% response rate). The majority had experienced system-wide shortages of various types of medical services. The services most frequently reported to be in short supply, either daily or weekly, were access to surgery, specialist and intensive care units, drug prescriptions and admission to hospital (52, 49, 46, 47 and 46% respectively). The most common rationing strategies used daily or weekly were limiting laboratory tests, hospital drugs, radiological investigations and providing second best treatment (47, 47, 47 and 39% respectively). Availability of institutional or national guidelines for whom to see and treat first was lacking. Almost all respondents had witnessed different adverse consequences of resource scarcity; 54% reported seeing patients who, in their estimation, had died due to resource scarcity. Almost 9 out of 10 physicians were so troubled by limited resources that they often regretted their choice of profession. This study provides the first glimpses of the untold story of resource shortage and bedside rationing in Ethiopia. Physicians encounter numerous dilemmas due to resource scarcity, and they report they lack adequate guidance for how to handle

  11. Do flexicurity policies protect workers from the adverse health consequences of temporary employment? A cross-national comparative analysis.

    PubMed

    Shahidi, Faraz Vahid; De Moortel, Deborah; Muntaner, Carles; Davis, Owen; Siddiqi, Arjumand

    2016-12-01

    Flexicurity policies comprise a relatively novel approach to the regulation of work and welfare that aims to combine labour market flexibility with social security. Advocates of this approach argue that, by striking the right balance between flexibility and security, flexicurity policies allow firms to take advantage of loose contractual arrangements in an increasingly competitive economic environment while simultaneously protecting workers from the adverse health and social consequences of flexible forms of employment. In this study, we use multilevel Poisson regression models to test the theoretical claim of the flexicurity approach using data for 23 countries across three waves of the European Social Survey. We construct an institutional typology of labour market regulation and social security to evaluate whether inequalities in self-reported health and limiting longstanding illness between temporary workers and their permanent counterparts are smaller in countries that most closely approximate the ideal type described by advocates of the flexicurity approach. Our results indicate that, while the association between temporary employment and health varies across countries, institutional configurations of labour market regulation and social security do not provide a meaningful explanation for this cross-national variation. Contrary to the expectations of the flexicurity hypothesis, our data do not indicate that employment-related inequalities are smaller in countries that approximate the flexicurity approach. We discuss potential explanations for these findings and conclude that there remains a relative lack of evidence in support of the theoretical claims of the flexicurity approach.

  12. Postoperative Tachycardia: Clinically Meaningful or Benign Consequence of Orthopedic Surgery?

    PubMed

    Sigmund, Alana E; Fang, Yixin; Chin, Matthew; Reynolds, Harmony R; Horwitz, Leora I; Dweck, Ezra; Iturrate, Eduardo

    2017-01-01

    To determine the clinical significance of tachycardia in the postoperative period. Individuals 18 years or older undergoing hip and knee arthroplasty were included in the study. Two data sets were collected from different time periods: development data set from January 1, 2011, through December 31, 2011, and validation data set from December 1, 2012, through September 1, 2014. We used the development data set to identify the optimal definition of tachycardia with the strongest association with the vascular composite outcome (pulmonary embolism and myocardial necrosis and infarction). The predictive value of this definition was assessed in the validation data set for each outcome of interest, pulmonary embolism, myocardial necrosis and infarction, and infection using multiple logistic regression to control for known risk factors. In 1755 patients in the development data set, a maximum heart rate (HR) greater than 110 beats/min was found to be the best cutoff as a correlate of the composite vascular outcome. Of the 4621 patients who underwent arthroplasty in the validation data set, 40 (0.9%) had pulmonary embolism. The maximum HR greater than 110 beats/min had an odds ratio (OR) of 9.39 (95% CI, 4.67-18.87; sensitivity, 72.5%; specificity, 78.0%; positive predictive value, 2.8%; negative predictive value, 99.7%) for pulmonary embolism. Ninety-seven patients (2.1%) had myocardial necrosis (elevated troponin). The maximum HR greater than 110 beats/min had an OR of 4.71 (95% CI, 3.06-7.24; sensitivity, 47.4%; specificity, 78.1%; positive predictive value, 4.4%; negative predictive value, 98.6%) for this outcome. Thirteen (.3%) patients had myocardial infarction according to our predetermined definition, and the maximum HR greater than 110 beats/min had an OR of 1.72 (95% CI, 0.47-6.27). Postoperative tachycardia within the first 4 days of surgery should not be dismissed as a postoperative variation in HR, but may precede clinically significant adverse outcomes

  13. 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.

  14. Acute hazardous substance releases resulting in adverse health consequences in children: Hazardous Substances Emergency Events Surveillance system, 1996-2003.

    PubMed

    Wattigney, Wendy A; Kaye, Wendy E; Orr, Maureen F

    2007-11-01

    Because of their small size and ongoing organ development, children may be more susceptible than adults to the harmful effects of toxic chemicals. The objective of the study reported here was to identify frequent locations, released substances, and factors contributing to short-term chemical exposures associated with adverse health consequences experienced by children. The study examined the Hazardous Substances Emergency Events Surveillance (HSEES) system data from 1996-2003. Eligible events involved the acute release of a hazardous substance associated with at least one child being injured. The study found that injured children were predominantly at school, home, or a recreational center when events took place. School-related events were associated with the accidental release of acids and the release of pepper spray by pranksters. Carbon monoxide poisonings occurring in the home, retail stores, entertainment facilities, and hotels were responsible for about 10 percent of events involving child victims. Chlorine was one of the top chemicals harmful to children, particularly at public swimming pools. Although human error contributed to the majority of releases involving child victims, equipment failure was responsible for most chlorine and ammonia releases. The authors conclude that chemical releases resulting in injury to children occur mostly in schools, homes, and recreational areas. Surveillance of acute hazardous chemical releases helped identify contributing causes and can guide the development of prevention outreach activities. Chemical accidents cannot be entirely prevented, but efforts can be taken to provide safer environments in which children can live, learn, and play. Wide dissemination of safety recommendations and education programs is required to protect children from needless environmental dangers.

  15. A path analysis of gender differences in adolescent onset of alcohol, tobacco and other drug use (ATOD), reported ATOD use and adverse consequences of ATOD use.

    PubMed

    Thomas, B S

    1996-01-01

    Gender differences in the ways a risk factor approach explains onset of using alcohol, tobacco and other drugs (ATOD), reported use of ATOD and adverse consequences from ATOD use were investigated by means of separate path analyses for male and female adolescents. A fully recursive model was specified in which alienation, trait anger, interaction anxiety and cognitive motivation for ATOD use comprised the first column variables which were used to predict earliness of onset. For the second step, column one variables plus onset were used to predict ATOD use. In the final step, column one variables plus onset and ATOD use were used to predict adverse consequences of ATOD use. An ex post facto design was used in surveying 796 high school students in a single Midwestern community. The data from this sample supported the predictive validity of the theoretical model. In addition to the expected indirect or mediated effects of the risk factors via onset of ATOD use on ATOD use and via onset and ATOD use on adverse consequences of ATOD use, there were direct effects of column on risk factors on both ATOD use and on adverse consequences of ATOD use for both males and females, lending support to the concept of multiple pathway risk factors. The three gender differences that emerged in the separate path analyses were entirely consistent with the gendered deviance model.

  16. Preadoption adversity and long-term clinical-range behavior problems in adopted Chinese girls.

    PubMed

    Tan, Tony Xing; Camras, Linda A; Kim, Eun Sook

    2016-04-01

    In this study, we report findings on the role of preadoption adversity on long-term clinical-range problems in adopted Chinese girls. Four waves (2005, 2007, 2009 and 2011) of problem behavior data on 1,223 adopted Chinese girls (M = 4.86 years, SD = 2.82 in 2005) were collected from the adoptive mothers with the Child Behavior Checklist (CBCL). At Wave 1 (2005), data on the following indicators of preadoption adversity was collected: age at adoption, physical signs/symptoms (e.g., sores) of preadoption adversity, developmental delays at arrival, refusal/avoidance behaviors and crying/clinging behaviors toward adoptive parents during the first 3 weeks of adoption. We found that the percentage of clinical-range internalizing problems was 11.1%, 16.5%, 11.3%, and 16.1% at Wave 1, Wave 2, Wave 3, and Wave 4, respectively; the corresponding percentage of clinical-range externalizing problems was 8.4%, 10.5%, 8.4% and 9.9% respectively; and the corresponding percentage of clinical-range total CBCL problems was 9.3%, 13.0%, 9.8% and 12.6% respectively. Analyses with Mplus showed that controlling for demographic variables, indicators of preadoption adversity, except age at adoption, increased the odds for clinical-range behavior problems. Longitudinal path models revealed that controlling for demographic variables and the children's adjustment status in the previous wave, refusal/avoidance remained significant in predicting clinical-range internalizing, externalizing and total CBCL problems at Wave 2, delays at arrival and signs/symptoms were significant in predicting clinical-range internalizing problems at Wave 3. Overall, adoptees with clinical-range CBCL problems in earlier waves were 9-28 times as likely to show clinical-range CBCL problems in subsequent waves. (c) 2016 APA, all rights reserved).

  17. 45 CFR 60.11 - Reporting adverse actions on clinical privileges.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... (5 U.S.C. 552a note), (v) Date of birth, (vi) Name of each professional school attended and year of... 45 Public Welfare 1 2012-10-01 2012-10-01 false Reporting adverse actions on clinical privileges. 60.11 Section 60.11 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...

  18. 45 CFR 60.11 - Reporting adverse actions on clinical privileges.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... (5 U.S.C. 552a note), (v) Date of birth, (vi) Name of each professional school attended and year of... 45 Public Welfare 1 2010-10-01 2010-10-01 false Reporting adverse actions on clinical privileges. 60.11 Section 60.11 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...

  19. 45 CFR 60.11 - Reporting adverse actions on clinical privileges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (5 U.S.C. 552a note), (v) Date of birth, (vi) Name of each professional school attended and year of... 45 Public Welfare 1 2011-10-01 2011-10-01 false Reporting adverse actions on clinical privileges. 60.11 Section 60.11 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...

  20. Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa

    PubMed Central

    Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C

    2014-01-01

    Purpose Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. Methods We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Key Findings Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. Significance There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and

  1. Clinical features, proximate causes, and consequences of active convulsive epilepsy in Africa.

    PubMed

    Kariuki, Symon M; Matuja, William; Akpalu, Albert; Kakooza-Mwesige, Angelina; Chabi, Martin; Wagner, Ryan G; Connor, Myles; Chengo, Eddie; Ngugi, Anthony K; Odhiambo, Rachael; Bottomley, Christian; White, Steven; Sander, Josemir W; Neville, Brian G R; Newton, Charles R J C; Twine, Rhian; Gómez Olivé, F Xavier; Collinson, Mark; Kahn, Kathleen; Tollman, Stephen; Masanja, Honratio; Mathew, Alexander; Pariyo, George; Peterson, Stefan; Ndyomughenyi, Donald; Bauni, Evasius; Kamuyu, Gathoni; Odera, Victor Mung'ala; Mageto, James O; Ae-Ngibise, Ken; Akpalu, Bright; Agbokey, Francis; Adjei, Patrick; Owusu-Agyei, Seth; Kleinschmidt, Immo; Doku, Victor C K; Odermatt, Peter; Nutman, Thomas; Wilkins, Patricia; Noh, John

    2014-01-01

    Epilepsy is common in sub-Saharan Africa (SSA), but the clinical features and consequences are poorly characterized. Most studies are hospital-based, and few studies have compared different ecological sites in SSA. We described active convulsive epilepsy (ACE) identified in cross-sectional community-based surveys in SSA, to understand the proximate causes, features, and consequences. We performed a detailed clinical and neurophysiologic description of ACE cases identified from a community survey of 584,586 people using medical history, neurologic examination, and electroencephalography (EEG) data from five sites in Africa: South Africa; Tanzania; Uganda; Kenya; and Ghana. The cases were examined by clinicians to discover risk factors, clinical features, and consequences of epilepsy. We used logistic regression to determine the epilepsy factors associated with medical comorbidities. Half (51%) of the 2,170 people with ACE were children and 69% of seizures began in childhood. Focal features (EEG, seizure types, and neurologic deficits) were present in 58% of ACE cases, and these varied significantly with site. Status epilepticus occurred in 25% of people with ACE. Only 36% received antiepileptic drugs (phenobarbital was the most common drug [95%]), and the proportion varied significantly with the site. Proximate causes of ACE were adverse perinatal events (11%) for onset of seizures before 18 years; and acute encephalopathy (10%) and head injury prior to seizure onset (3%). Important comorbidities were malnutrition (15%), cognitive impairment (23%), and neurologic deficits (15%). The consequences of ACE were burns (16%), head injuries (postseizure) (1%), lack of education (43%), and being unmarried (67%) or unemployed (57%) in adults, all significantly more common than in those without epilepsy. There were significant differences in the comorbidities across sites. Focal features are common in ACE, suggesting identifiable and preventable causes. Malnutrition and

  2. Intravenous infusion of haptoglobin for the prevention of adverse clinical outcome in Sickle Cell Disease.

    PubMed

    Quimby, Kim R; Hambleton, Ian R; Landis, R Clive

    2015-10-01

    Sickle Cell Disease (SCD) is a genetic condition which manifests as altered hemoglobin (Hb) protein that can aggregate under hypoxic conditions. The resultant sickled erythrocytes experience premature hemolysis, releasing an estimated 10g of free Hb (fHb) into the intravascular space. FHb participates in redox reactions creating various reactive oxygen species which rapidly and irreversibly scavenge nitric oxide, thereby attenuating its vasodilatory, antithrombotic, and anti-inflammatory properties. FHb also induces endothelial expression of adhesion molecules, triggering leukocyte margination at the vessel wall. These mechanisms participate in diverse SCD-associated clinical events including nephropathy, pulmonary hypertension, chronic leg ulceration, and ischemic events. FHb also exerts a direct reno-toxic effect contributing to albuminuria which is an early, frequent manifestation of glomerular injury. Under normal conditions, fHb is effectively scavenged by the Hb-scavenging mechanism (HSM); this involves binding to haptoglobin (Hp), uptake via the Hb-scavenging receptor (CD163) on monocytes and metabolism by heme-oxygenase-1. This culminates in increased CD163 expression and release of anti-inflammatory by-products e.g. interleukin-10 (IL-10). In SCD, the Hb-binding capacity is overwhelmed by chronic hemolysis; our previous research shows serum Hp as the depleted component. This deficiency could result in the harmful consequences of circulating fHb going unbridled. The hypothesis we explore here is that Hp infusions, in excess of fHb concentration, will allow the HSM to remain functional, and thereby achieve improved clinical outcomes, tracking albuminuria as a sentinel. Albuminuria was selected because of its high prevalence in SCD and its relative ease of diagnosis and monitoring. The hypothesis may be evaluated in four phases: Phase 1 will determine the concentration of Hp needed to trigger the HSM as measured by induction of CD163 and IL-10 and the

  3. Better Adherence to the Mediterranean Diet Could Mitigate the Adverse Consequences of Obesity on Cardiovascular Disease: The SUN Prospective Cohort.

    PubMed

    Eguaras, Sonia; Toledo, Estefanía; Hernández-Hernández, Aitor; Cervantes, Sebastián; Martínez-González, Miguel A

    2015-11-05

    Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (<6 points or ≥6 points in the Trichopoulou's Mediterranean Diet Score). We observed 152 incident cases of cardiovascular disease (CVD). An increased risk of CVD across categories of body mass index (BMI) was apparent if adherence to the MedDiet was low, with multivariable-adjusted hazard ratios (HRs): 1.44 (95% confidence interval: 0.93-2.25) for ≥25 - <30 kg/m² of BMI and 2.00 (1.04-3.83) for ≥30 kg/m² of BMI, compared to a BMI < 25 kg/m². In contrast, these estimates were 0.77 (0.35-1.67) and 1.15 (0.39-3.43) with good adherence to MedDiet. Better adherence to the MedDiet was associated with reduced CVD events (p for trend = 0.029). Our results suggest that the MedDiet could mitigate the harmful cardiovascular effect of overweight/obesity.

  4. [Designing a tool to describe drug interactions and adverse events for learning and clinical routine].

    PubMed

    Auzéric, M; Bellemère, J; Conort, O; Roubille, R; Allenet, B; Bedouch, P; Rose, F-X; Juste, M; Charpiat, B

    2009-11-01

    Pharmacists play an important role in prescription analysis. They are involved in therapeutic drug monitoring, particularly for drugs with a narrow therapeutic index, prevention and management of drug interactions, and may be called in to identify side effects and adverse events related to drug therapy. For the polymedicated patient, the medical file, the list of prescribed drugs and the history of their administration may be insufficient to adequately assign the responsibility of a given adverse effect to one or more drugs. Graphical representations can sometimes be useful to describe and clarify a sequence of events. In addition, as part of their academic course, students have many occasions to hear about "side effects" and "drug interactions". However, in the academic setting, there are few opportunities to observe the evolution and the consequences of these events. In the course of their hospital training, these students are required to perform patient follow-up for pharmacotherapeutic or educational purposes and to comment case reports to physicians. The aim of this paper is to present a tool facilitating the graphic display of drug interaction consequences and side effects. This tool can be a useful aid for causality assessment. It structures the students' training course and helps them better understand the commentaries pharmacists provide for physicians. Further development of this tool should contribute to the prevention of adverse drug events.

  5. Use of the adverse outcome pathway framework to represent cross-species consequences of specific pathway perturbations

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework has been developed as a means for assembling scientifically defensible descriptions of how particular molecular perturbations, termed molecular initiating events (MIEs), can evoke a set of predictable responses at different levels of bi...

  6. [Analysis of rational clinical uses of traditional Chinese medicine injections and factors influencing adverse drug reactions].

    PubMed

    Sun, Shi-Guang; Li, Zi-Feng; Xie, Yan-Ming; Liu, Jian; Lu, Yan; Song, Yi-Fei; Han, Ying-Hua; Liu, Li-Da; Peng, Ting-Ting

    2013-09-01

    To rationalize the clinical use and safety are some of the key issues in the surveillance of traditional Chinese medicine injections (TCMIs). In this 2011 study, 240 medical records of patients who had been discharged following treatment with TCMIs between 1 and 12 month previously were randomly selected from hospital records. Consistency between clinical use and the description of TCMIs was evaluated. Research on drug use and adverse drug reactions/events using logistic regression analysis was carried out. There was poor consistency between clinical use and best practice advised in manuals on TCMIs. Over-dosage and overly concentrated administration of TCMIs occurred, with the outcome of modifying properties of the blood. Logistic regression analysis showed that, drug concentration was a valid predictor for both adverse drug reactions/events and benefits associated with TCMIs. Surveillance of rational clinical use and safety of TCMIs finds that clinical use should be consistent with technical drug manual specifications, and drug use should draw on multi-layered logistic regression analysis research to help avoid adverse drug reactions/events.

  7. [Are non-clinical studies predictive of adverse events in humans?].

    PubMed

    Claude, N

    2007-09-01

    The predictibility of adverse events induced by drugs in non-clinical safety studies performed on in vitro and/or in vivo models is a key point for the safety of humans exposed to pharmaceuticals. The strength and the weakness of animal studies to predict human toxicity were assessed by an international study on the concordance of the toxicity of 150 pharmaceuticals observed in humans with that observed in experimental animals. The results showed a good correlation (70% of the adverse events in humans were detected in animal studies) and an early time to first appearance of concordant animal toxicity: 94% were first observed in studies of 1 month or less in duration. The highest incidence of overall concordance was seen in hematological and cardiovascular adverse effects and the least was seen in cutaneous and ophthalmological adverse effects. These studies, scientifically and regulatory standardized, need, in some cases to be adapted to specific problems linked to sensitive populations (young, old or with a pathology which could be worsened by the drug), or specific pharmaceuticals (produced by biotechnology). Some severe adverse events are not detected in conventional animal models (immuno-allergy, idiosyncrasy). Taken together, these elements support the value of toxicology studies to predict many human toxic events associated with pharmaceuticals. Nevertheless, a part of human toxicity is not detected by these experimental approaches, and new tools developed through progress in biology and bio-informatics should reduce this uncertainly margin.

  8. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions.

    PubMed

    Galli, Jonathan A; Pandya, Aloknath; Vega-Olivo, Michelle; Dass, Chandra; Zhao, Huaqing; Criner, Gerard J

    2017-08-01

    The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation. We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event. Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy. Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions. © 2017 Asian Pacific Society of Respirology.

  9. Adverse effects as a consequence of being the subject of orthopaedic manual therapy training, a worldwide retrospective survey.

    PubMed

    Thoomes-de Graaf, M; Thoomes, E; Carlesso, L; Kerry, R; Rushton, A

    2017-06-01

    Physical therapists (PTs) use a range of manual therapy techniques developed to an advanced level through postgraduate orthopaedic manipulative physical therapy (OMPT) programmes. The aim of this study was to describe the adverse effects experienced by students after having techniques performed on them as part of their OMPT training. A descriptive online survey of current students and recent graduates (≤5 years)m of OMPT programmes across the 22 Member Organisations of the International Federation of Orthopaedic Manipulative Physical Therapists. The questionnaire was completed by 1640 respondents across 22 countries (1263 graduates, 377 students. Some 60% of respondents reported never having experienced adverse effects during their manual therapy training. Of the 40% who did, 66.4% reported neck pain, 50.9% headache and 32% low back pain. Most reports of neck pain started after a manipulation and/or mobilisation, of which 53.4% lasted ≤24 h, 38.1% > 24 h but <3 months and 13.7% still experienced neck pain to date. A small percentage of respondents (3.3%) reported knowing of a fellow student experiencing a major adverse effect. Mild to moderate adverse effects after practising manual therapy techniques are commonly reported, but usually resolve within 24 h. However, this survey has identified the reported occurrence of major adverse effects that warrant further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Clinical roundtable monograph. New alternatives in CLL therapy: managing adverse events.

    PubMed

    Chanan-Khan, Asher; Kipps, Thomas; Stilgenbauer, Stephan

    2010-08-01

    Chronic lymphocytic leukemia (CLL) is a B-cell leukemia mainly affecting older adults. Historically, CLL has been regarded as an incurable disease, and treatment has been confined to cytotoxic chemotherapy regimens. However, prognosis for patients treated with these agents remained poor, prompting the development of new, targeted agents. The introduction of rituximab, a CD20-targeted monoclonal antibody, revolutionized the treatment for this disease. Rituximab in combination with fludarabine improved response rates and length of progression-free survival. The success of rituximab in this setting has prompted the development of many more investigational agents for CLL, including other antibody agents. However, as with any medication, the potential benefit achieved with CLL therapies is mitigated by the safety risk for the patient. These agents have been associated with adverse events such as immunosuppression, reactivation of cytomegalovirus, and infusion-related reactions that can occur with antibody administration. Adverse events can greatly affect the patient’s quality of life and ability to tolerate therapy. Management of adverse events is a critical component of the overall treatment strategy for CLL, particularly in elderly patients. In this clinical roundtable monograph, 3 expert physicians discuss the latest clinical studies evaluating the treatment of CLL, focusing on the adverse events associated with each agent and the potential interventions that can be used to manage their occurrence.

  11. Comorbidities and psychotic illness. Part 1: Philosophy and clinical consequences.

    PubMed

    Agius, Mark; Aquilina, Francesca Falzon

    2014-11-01

    This article aims at addressing the implications of defining 'comorbidity' within the field of psychiatry. We have looked at the standard definition of comorbidity and then discussed whether this definition can be applied to comorbidities in psychiatry. While comorbidities in physical illness are clearly the coexistence of two independent illnesses, Comorbidities in Mental illness are the result of the polygenic nature of mental illnesses, especially in psychotic illness whether schizophrenia or bipolar disorder. As a consequence, often the comorbidities of psychiatric illness are caused by two conditions which have in common the presence of particular single nucleotide polymorphisms (snps), which regulate the metabolism of neurotransmitters or the presence of neurotrophic factors . Thus inevitably, many such comorbidities are inextricably linked. We discuss the consequences of this form of comorbidity for the description, classification, and risk profile of mental illness.

  12. Consequences of Contextual Factors on Clinical Reasoning in Resident Physicians

    ERIC Educational Resources Information Center

    McBee, Elexis; Ratcliffe, Temple; Picho, Katherine; Artino, Anthony R., Jr.; Schuwirth, Lambert; Kelly, William; Masel, Jennifer; van der Vleuten, Cees; Durning, Steven J.

    2015-01-01

    Context specificity and the impact that contextual factors have on the complex process of clinical reasoning is poorly understood. Using situated cognition as the theoretical framework, our aim was to evaluate the verbalized clinical reasoning processes of resident physicians in order to describe what impact the presence of contextual factors have…

  13. 236 children with developmental hydrocephalus: causes and clinical consequences

    PubMed Central

    Tully, Hannah M; Ishak, Gisele E; Rue, Tessa C; Dempsey, Jennifer C; Browd, Samuel R; Millen, Kathleen J; Doherty, Dan; Dobyns, William B

    2016-01-01

    Few systematic assessments of developmental forms of hydrocephalus exist. We reviewed MRIs and clinical records of patients with infancy-onset hydrocephalus. Among 411 infants, 236 had hydrocephalus with no recognizable extrinsic cause. These children were assigned to one of five subtypes and compared on the basis of clinical characteristics, developmental and surgical outcomes. At an average age of 5.3 years, 72% of children were walking independently and 87% could eat by mouth. 18% had epilepsy. Distinct patterns of associated malformations and syndromes were observed within each subtype. On average, children with aqueductal obstruction, cysts and encephaloceles had worse clinical outcomes than those with other forms of developmental hydrocephalus. 53% of surgically-treated patients experienced at least one shunt failure, but hydrocephalus associated with posterior fossa crowding required fewer shunt revisions. We conclude that each subtype of developmental hydrocephalus is associated with distinct clinical characteristics, syndromology, and outcomes, suggesting differences in underlying mechanisms. PMID:26184484

  14. Area-Level Deprivation and Adverse Consequences in People With Substance Use Disorders: Findings From the Psychiatric and Addictive Dual Disorder in Italy (PADDI) Study.

    PubMed

    Carrà, Giuseppe; Crocamo, Cristina; Borrelli, Paola; Tabacchi, Tommaso; Bartoli, Francesco; Popa, Ioana; Montomoli, Cristina; Clerici, Massimo

    2017-03-21

    Environmental factors may operate with individual ones to influence the risk of substance use. Research has focused on severe adverse consequences influenced by contextual variables. However, the literature on community level factors influencing substance use behaviors is relatively limited across Europe so far. We capitalized on data from a National survey, exploring individual and contextual characteristics, to study adverse consequences among people with substance use disorders. The impact of area-level deprivation on nonfatal overdose, hepatitis C or B infections, and major involvement with the criminal justice system, was explored. Logistic regression models with cluster-robust errors, modeling subject-level and area-level effects, were used. Living in deprived and intermediate areas, as compared with affluent ones, was associated with greater likelihood of both nonfatal overdose and jail sentences longer than 6 months, though not of active viral hepatitis. Area-level deprivation may play an important role in determining adverse consequences in people with substance use disorders, also after controlling for individual-level characteristics. More research is needed to understand the aspects of social and physical environments that matter for drug outcomes before effective policy and research interventions can be developed.

  15. Adverse food reactions: Pathogenesis, clinical signs, diagnosis and alternatives to elimination diets.

    PubMed

    Mueller, R S; Unterer, S

    2018-06-01

    This review summarises available information about adverse food reactions in dogs and cats. Much of the published information on the pathogenesis of adverse food reactions in these species is transferred from what is known in mice and human beings. Clinical signs affect mostly the integument and gastrointestinal system. Pruritus of the distal limbs, face, ears and ventrum is the most common cutaneous presentation in dogs, although urticaria has also been reported. In cats, all so-called 'cutaneous reaction patterns' may be due to adverse food reactions. The most common gastrointestinal signs in both species are diarrhoea and vomiting. An elimination diet over several weeks using a protein source and a carbohydrate source previously not fed is still the diagnostic tool of choice. Improvement on such a diet, deterioration on re-challenge with the old food and improvement again on the elimination diet confirms the diagnosis of adverse food reaction, whereas alternative tests of blood, serum, saliva and hair have been found to be unsatisfactory. Patch testing with food antigens has been recommended as an aid to choose the elimination diet ingredients, since it has a reasonable negative predictability and likelihood ratio, but is laborious and costly. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive, behavioral, and emotional outcomes.

    PubMed

    Marusak, Hilary A; Iadipaolo, Allesandra S; Harper, Felicity W; Elrahal, Farrah; Taub, Jeffrey W; Goldberg, Elimelech; Rabinak, Christine A

    2018-06-01

    Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine's true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent "cure" that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer - namely, the presence of a life-threatening disease and endurance of invasive medical procedures - has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for

  17. The use-dependent, nicotinic antagonist BTMPS reduces the adverse consequences of morphine self-administration in rats in an abstinence model of drug seeking

    PubMed Central

    Hall, Brandon J.; Pearson, Laura S.; Terry, Alvin V.; Buccafusco, Jerry J.

    2011-01-01

    In this study, the use-dependent, nicotinic receptor antagonist bis (2, 2, 6, 6-tetramethyl-4-piperidinyl) sebacate (BTMPS) was evaluated for its ability to attenuate the adverse consequences associated with morphine in rats in all three phases of an abstinence model of drug seeking: self-administration, acute withdrawal, and delayed test of drug seeking. Rats were allowed to self-administer morphine (FR1 schedule) with an active response lever, on a 24hr basis inside operant chambers, for 14 days. Each rat was subsequently evaluated for stereotypical behaviors associated with spontaneous morphine withdrawal. Rats were then placed in standard housing cages for a six week period of protracted abstinence from morphine. After this period, each rat was placed back into its respective operant chamber for a 14 day assessment of unrewarded drug seeking responses. BTMPS was administered to the animals in all three clinically relevant phases in three separate sets of experiments. BTMPS treatment during the self-administration phase resulted in up to a 34% reduction of lever responses to morphine when compared to vehicle treated control animals, as well as a 32% reduction in the dose of morphine self-administered. When given during self-administration and acute withdrawal, BTMPS treatment decreased acute withdrawal symptoms (up to 64%) of morphine use and reduced (up to 45%) drug seeking responses after six weeks of protracted withdrawal compared to control animals. BTMPS treatment after six weeks of abstinence from morphine had no effect. These results offer insight into the role of central cholinergic receptors in the onset and maintenance of drug addiction. PMID:21651919

  18. Predicting the clinical efficacy and potential adverse effects of a humanized anticocaine monoclonal antibody

    PubMed Central

    Norman, Andrew B; Ball, William J

    2012-01-01

    The effects of a humanized monoclonal antibody (mAb) having high affinity and specificity for cocaine in animal models are reviewed. The mAb reduced the concentration of cocaine in the brain of mice after intravenous injection of cocaine. In addition, the mAb increased the concentration of cocaine required to reinstate cocaine self-administration. These effects may predict clinical efficacy of a passive immunotherapy for reducing the probability of cocaine-induced relapse. However, in the presence of the mAb, once cocaine self-administration was reinstated, the consumption rate of cocaine was increased. This effect is hypothesized to result from a pharmacokinetic/pharmacodynamic interaction. A humanized mAb should minimize adverse events related to the immunogenicity of the mAb protein, and the specificity for cocaine should avoid adverse events related to interactions with physiologically relevant endogenous proteins. PMID:22401638

  19. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation

    PubMed Central

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A.; Arima, Hisatomi; Wang, Dao Wen

    2016-01-01

    Abstract Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin–angiotensin–aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin–angiotensin–aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive. A pooled study of 6 randomized controlled trials assessing the efficacy of renin–angiotensin–aldosterone blockers on subjects with atrial fibrillation was performed. A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76– 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70–0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2–2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0–6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0–0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: –0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction. This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043

  20. Aggression on inpatient units: Clinical characteristics and consequences.

    PubMed

    Renwick, Laoise; Stewart, Duncan; Richardson, Michelle; Lavelle, Mary; James, Karen; Hardy, Claire; Price, Owen; Bowers, Len

    2016-08-01

    Aggression and violence are widespread in UK Mental Health Trusts, and are accompanied by negative psychological and physiological consequences for both staff and other patients. Patients who are younger, male, and have a history of substance use and psychosis diagnoses are more likely to display aggression; however, patient factors are not solely responsible for violence, and there are complex circumstances that lead to aggression. Indeed, patient-staff interactions lead to a sizeable portion of aggression and violence on inpatient units, thus they cannot be viewed without considering other forms of conflict and containment that occur before, during, and after the aggressive incident. For this reason, we examined sequences of aggressive incidents in conjunction with other conflict and containment methods used to explore whether there were particular profiles to aggressive incidents. In the present study, 522 adult psychiatric inpatients from 84 acute wards were recruited, and there were 1422 incidents of aggression (verbal, physical against objects, and physical). Cluster analysis revealed that aggressive incident sequences could be classified into four separate groups: solo aggression, aggression-rule breaking, aggression-medication, and aggression-containment. Contrary to our expectations, we did not find physical aggression dominant in the aggression-containment cluster, and while verbal aggression occurred primarily in solo aggression, physical aggression also occurred here. This indicates that the management of aggression is variable, and although some patient factors are linked with different clusters, these do not entirely explain the variation. © 2016 Australian College of Mental Health Nurses Inc.

  1. The predictive effect of insight on adverse clinical outcomes in bipolar I disorder: a two-year prospective study.

    PubMed

    Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Ko, Chih-Hung

    2008-05-01

    Research has revealed that a lack of insight is associated with poorer clinical outcomes in schizophrenia; however, the predictive value of insight on adverse clinical outcomes among bipolar patients is quite understudied. The aim of this prospective study was to examine the impact of insight on adverse clinical outcomes among the patients with bipolar I disorder over a 2-year period. Sixty-five remitted bipolar I disorder patients received follow-up assessments at 3, 6, 9, 12, 18, and 24 months to detect the adverse clinical outcomes defined by the incidence of bipolar-related psychiatric hospitalization, emergency room visits, violent or suicidal behavior. The Schedule of Assessment of Insight was used to provide a baseline insight score. Cox regression analysis was used to examine the predictive value of insight on the adverse clinical outcomes. Impaired insight into treatment and a greater number of previous hospitalizations significantly increased the risk of adverse clinical outcomes with bipolar disorder in the 2-year period. However, insight into recognition of the illness and re-labeling of psychotic phenomena did not have any significant effect on adverse clinical outcomes. Bipolar patients' insight into treatment is an independent predictor of adverse clinical outcomes. Improving insight into treatment might be a promising target for a better outcome.

  2. Right sided single coronary artery origin: surgical interventions without clinical consequences.

    PubMed

    Hamid, Tahir; Rose, Samman; Horner, Simon

    2011-11-01

    Congenital coronary anomalies are uncommon and are usually diagnosed incidentally during coronary angiogram or autopsy. Isolated coronary artery anomalies and the anomalous origin of left main stem (LMS) from the proximal portion of the right coronary artery or from the right sinus of valsalva are extremely rare. A 68 years old woman with atypical chest pains was referred for risk assessment for the general anaesthesia. A stress exercise treadmill test and myocardial perfusion scan revealed evidence of mild myocardial ischemia. Her coronary angiography revealed her left coronary artery to have a single origin with the right coronary artery. There were no flowlimiting lesions. A CT aortography confirmed a retro-aortic course of the left coronary artery. She successfully underwent multiple surgical procedures under general anaesthesia including total abdominal hysterectomy, Burch colposuspension (twice) for stress incontinence, intravesical botox injection for urge incontinence and haemorrhoidectomy for recurrent rectal mucosal prolapse. Various anaesthetic agents including halothane, thiopentone, suxamethonium, pancuronium, enflurane, fentanyl, propofol and isoflurane were used without any adverse clinical consequences. She remained well on 48 months follow-up.

  3. 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

  4. The vascularization of the os calcaneum and the clinical consequences.

    PubMed

    Andermahr, J; Helling, H J; Rehm, K E; Koebke, Z

    1999-06-01

    This study was conducted to analyze extraosseous and intraosseous vascularization of the os calcaneum and to elucidate possible clinical manifestations. The arteries of 13 lower leg and foot specimens of human cadavers were injected with a polymer and subjected to maceration or were embedded in plastic. The examination revealed that 45% of the bone is vascularized via medial arteries and 45% via lateral arteries, whereas the remaining 10% is supplied by the sinus tarsi artery. From the medial side, two or three vessels branch off the posterior tibial artery, penetrate the calcaneus below the sustentaculum, and supply the medial part of the posterior joint. The lateral calcaneal artery normally is a branch from the posterior tibial artery. In two of 13 specimens, this lateral supply comes from the peroneal artery. The medial and lateral intraosseous arterial supply for the calcaneus is equal. Inside the bone there is a water-shed zone where the medial and lateral arterial supply meet in the midline. Only 10% of the blood flow is supplied by vessels in the sinus tarsi. Clinically, interruption of the lateral calcaneal artery during the conventional lateral surgical approach for a calcaneus fracture may result in ischemic bone necrosis. The lateral calcaneal artery could supply a local microvascular flap to cover soft tissue defects of the heel. A compartment syndrome after a calcaneus fracture may be caused by bleeding from the medial calcaneal arteries into the quadratus plantae compartment.

  5. Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov.

    PubMed

    Su, Eric Wen; Sanger, Todd M

    2017-01-01

    Drug repositioning (i.e., drug repurposing) is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics) and PolyAnalyst (Megaputer) were utilized. An I2E query extracts "Serious Adverse Events" (SAE) data from randomized trials in ClinicalTrials.gov. Through a statistical algorithm, a PolyAnalyst workflow ranks the drugs where the treatment arm has fewer predefined SAEs than the control arm, indicating that potentially the drug is reducing the level of SAE. Hypotheses could then be generated for the new use of these drugs based on the predefined SAE that is indicative of disease (for example, cancer).

  6. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials

    PubMed Central

    Federer, Callie; Yoo, Minjae

    2016-01-01

    Abstract Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov (https://clinicaltrials.gov/), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov. Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs. PMID:27631620

  7. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

    PubMed

    Federer, Callie; Yoo, Minjae; Tan, Aik Choon

    2016-12-01

    Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

  8. The clinical consequences of an industrial aerosol plant explosion.

    PubMed

    Hull, D; Grindlinger, G A; Hirsch, E F; Petrone, S; Burke, J

    1985-04-01

    The factors relating to the clinical outcome of an industrial aerosol plant explosion are reviewed. Eighteen of 24 workers inside the plant required hospitalization and five died. Proximity to the blast was associated with extensive injuries unless workers were shielded by physical barriers or partitions. Burn severity and mortality were increased in those wearing synthetic garments compared to their counterparts wearing fiber clothing. Facial burns occurred in all unprotected workers. Forearm and hand burns in 11 patients required decompressive escharotomies. Topical treatment with silver sulfadiazine was associated with more significant leukopenia and neutropenia than treatment with silver nitrate. We conclude that industrial design should include safeguards which isolate workers from flammable materials, including isolation of explosive materials from working areas, alarm systems to detect leakage of flammable agents, protective barriers and shields, and the regulation and institution of flame and flash-resistant clothing.

  9. Clinical and physiological consequences of rapid tryptophan depletion.

    PubMed

    Moore, P; Landolt, H P; Seifritz, E; Clark, C; Bhatti, T; Kelsoe, J; Rapaport, M; Gillin, J C

    2000-12-01

    We review here the rapid tryptophan depletion (RTD) methodology and its controversial association with depressive relapse. RTD has been used over the past decade to deplete serotonin (5-hydroxy-tryptamine, or 5-HT) in humans and to probe the role of the central serotonin system in a variety of psychiatric conditions. Its current popularity was stimulated by reports that RTD reversed the antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs) in remitted patients with a history of depression but not in patients treated with antidepressants which promote catecholaminergic rather than serotonergic neurotransmission (such as tricyclic antidepressants or buproprion). However, RTD has inconsistent effects in terms of full clinical relapse in depressed patients. Pooling the data from all published reports, patients who are either unmedicated and/or fully remitted are much less likely to experience relapse (7 of 61, or approximately 9%) than patients who are recently medicated and partially remitted (63 of 133, or approximately 47%; although, the numbers here may reflect patient overlap between reports). Recently remitted patients who have been treated with non-pharmacological therapies such as total sleep deprivation, electroconvulsive therapy, or bright light therapy also do not commonly show full clinical relapse with RTD. We briefly review RTD effects in other psychiatric disorders, many of which are treated with SSRIs. There is accumulating evidence to suggest that RTD affects central serotonergic neurotransmission. Nevertheless, many questions remain about the ability of RTD to reverse the beneficial effects of SSRIs or MAOIs, or to induce symptoms in unmedicated symptomatic or asymptomatic patients.

  10. Scabies: important clinical consequences explained by new molecular studies.

    PubMed

    Fischer, Katja; Holt, Deborah; Currie, Bart; Kemp, David

    2012-01-01

    In 2004, we reviewed the status of disease caused by the scabies mite Sarcoptes scabiei at the time and pointed out that very little basic research had ever been done. The reason for this was largely the lack of availability of mites for experimental purposes and, to a degree, a consequent lack of understanding of its importance, resulting in the trivial name 'itch mite'. Scabies is responsible for major morbidity in disadvantaged communities and immunocompromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by bacterial pathogens such as Streptococcus pyogenes and Staphylococcus aureus via skin lesions, resulting in severe downstream disease such as in a high prevalence of rheumatic fever/heart disease in affected communities. We now have further evidence that in disadvantaged populations living in tropical climates, scabies rather than 'Strep throat' is an important source of S. pyogenes causing rheumatic fever and eventually rheumatic heart disease. In addition, our work has resulted in two fundamental research tools that facilitate much of the current biomedical research efforts on scabies, namely a public database containing ~45,000 scabies mite expressed sequence tags and a porcine in vivo model. Here we will discuss novel and unexpected proteins encountered in the database that appear crucial to mite survival with regard to digestion and evasion of host defence. The mode(s) of action of some of these have been at least partially revealed. Further, newly discovered molecules that may well have a similar role, such as a family of inactivated cysteine proteases, are yet to be investigated. Hence, there are now whole families of potential targets for chemical inhibitors of S. scabiei. These efforts put today's scabies research in a unique position to design and test small molecules that may specifically interfere with mite-derived molecules, such as digestive proteases and mite

  11. Clinical and Radiologic Outcomes of a Fully Hydroxyapatite-Coated Femoral Revision Stem: Excessive Stress Shielding Incidence and its Consequences.

    PubMed

    Sanli, Ilknur; Arts, Jacobus Johannes Christiaan; Geurts, Jan

    2016-01-01

    Stress shielding remains a concern in total hip arthroplasty. The consequences of stress shielding in hydroxyapatite-coated femoral component revisions were evaluated in a prospective cohort study. A total of 106 patients operated on by revision total hip arthroplasty were identified. Sixty-three patients were eligible for clinical and radiologic assessment of osseointegration, bone remodeling, and stress shielding. Five patients showed evidence of excessive stress shielding. One patient experienced a periprosthetic fracture. No adverse events occurred in the remaining patients with a low rate of thigh pain and reliable osseointegration. This is the only available study concerning mid- to long-term consequences of excessive stress shielding in hydroxyapatite-coated revision stems. We advocate surgeons using these stems to remain vigilant and be aware of possible stress shielding side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences.

    PubMed

    Fregonese, Laura; Stolk, Jan

    2008-06-19

    Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that manifests as pulmonary emphysema, liver cirrhosis and, rarely, as the skin disease panniculitis, and is characterized by low serum levels of AAT, the main protease inhibitor (PI) in human serum. The prevalence in Western Europe and in the USA is estimated at approximately 1 in 2,500 and 1 : 5,000 newborns, and is highly dependent on the Scandinavian descent within the population. The most common deficiency alleles in North Europe are PI Z and PI S, and the majority of individuals with severe AATD are PI type ZZ. The clinical manifestations may widely vary between patients, ranging from asymptomatic in some to fatal liver or lung disease in others. Type ZZ and SZ AATD are risk factors for the development of respiratory symptoms (dyspnoea, coughing), early onset emphysema, and airflow obstruction early in adult life. Environmental factors such as cigarette smoking, and dust exposure are additional risk factors and have been linked to an accelerated progression of this condition. Type ZZ AATD may also lead to the development of acute or chronic liver disease in childhood or adulthood: prolonged jaundice after birth with conjugated hyperbilirubinemia and abnormal liver enzymes are characteristic clinical signs. Cirrhotic liver failure may occur around age 50. In very rare cases, necrotizing panniculitis and secondary vasculitis may occur. AATD is caused by mutations in the SERPINA1 gene encoding AAT, and is inherited as an autosomal recessive trait. The diagnosis can be established by detection of low serum levels of AAT and isoelectric focusing. Differential diagnoses should exclude bleeding disorders or jaundice, viral infection, hemochromatosis, Wilson's disease and autoimmune hepatitis. For treatment of lung disease, intravenous alpha-1-antitrypsin augmentation therapy, annual flu vaccination and a pneumococcal vaccine every 5 years are recommended. Relief of breathlessness may be obtained with long

  13. Sleep Apnea: Types, Mechanisms, and Clinical Cardiovascular Consequences.

    PubMed

    Javaheri, Shahrokh; Barbe, Ferran; Campos-Rodriguez, Francisco; Dempsey, Jerome A; Khayat, Rami; Javaheri, Sogol; Malhotra, Atul; Martinez-Garcia, Miguel A; Mehra, Reena; Pack, Allan I; Polotsky, Vsevolod Y; Redline, Susan; Somers, Virend K

    2017-02-21

    Sleep apnea is highly prevalent in patients with cardiovascular disease. These disordered breathing events are associated with a profile of perturbations that include intermittent hypoxia, oxidative stress, sympathetic activation, and endothelial dysfunction, all of which are critical mediators of cardiovascular disease. Evidence supports a causal association of sleep apnea with the incidence and morbidity of hypertension, coronary heart disease, arrhythmia, heart failure, and stroke. Several discoveries in the pathogenesis, along with developments in the treatment of sleep apnea, have accumulated in recent years. In this review, we discuss the mechanisms of sleep apnea, the evidence that addresses the links between sleep apnea and cardiovascular disease, and research that has addressed the effect of sleep apnea treatment on cardiovascular disease and clinical endpoints. Finally, we review the recent development in sleep apnea treatment options, with special consideration of treating patients with heart disease. Future directions for selective areas are suggested. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Mitigation of adverse interactions in pairs of clinical practice guidelines using constraint logic programming.

    PubMed

    Wilk, Szymon; Michalowski, Wojtek; Michalowski, Martin; Farion, Ken; Hing, Marisela Mainegra; Mohapatra, Subhra

    2013-04-01

    We propose a new method to mitigate (identify and address) adverse interactions (drug-drug or drug-disease) that occur when a patient with comorbid diseases is managed according to two concurrently applied clinical practice guidelines (CPGs). A lack of methods to facilitate the concurrent application of CPGs severely limits their use in clinical practice and the development of such methods is one of the grand challenges for clinical decision support. The proposed method responds to this challenge. We introduce and formally define logical models of CPGs and other related concepts, and develop the mitigation algorithm that operates on these concepts. In the algorithm we combine domain knowledge encoded as interaction and revision operators using the constraint logic programming (CLP) paradigm. The operators characterize adverse interactions and describe revisions to logical models required to address these interactions, while CLP allows us to efficiently solve the logical models - a solution represents a feasible therapy that may be safely applied to a patient. The mitigation algorithm accepts two CPGs and available (likely incomplete) patient information. It reports whether mitigation has been successful or not, and on success it gives a feasible therapy and points at identified interactions (if any) together with the revisions that address them. Thus, we consider the mitigation algorithm as an alerting tool to support a physician in the concurrent application of CPGs that can be implemented as a component of a clinical decision support system. We illustrate our method in the context of two clinical scenarios involving a patient with duodenal ulcer who experiences an episode of transient ischemic attack. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. [Mental health of children, adolescents and young adults--part 1: prevalence, illness persistence, adversities, service use, treatment delay and consequences].

    PubMed

    Lambert, M; Bock, T; Naber, D; Löwe, B; Schulte-Markwort, M; Schäfer, I; Gumz, A; Degkwitz, P; Schulte, B; König, H H; Konnopka, A; Bauer, M; Bechdolf, A; Correll, C; Juckel, G; Klosterkötter, J; Leopold, K; Pfennig, A; Karow, A

    2013-11-01

    Numerous birth-control studies, epidemiological studies, and observational studies have investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use by children, adolescents and young adults is low, even lower than for adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for a poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the interface of child and adolescent and adult psychiatry. Emerging studies show that these health-care structures are effective and efficient. Part 1 of the present review summarises the current state of mental health in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, and treatment delay with consequences. © Georg Thieme Verlag KG Stuttgart · New York.

  16. Mechanisms of ring chromosome formation, ring instability and clinical consequences.

    PubMed

    Guilherme, Roberta S; Meloni, Vera F Ayres; Kim, Chong A; Pellegrino, Renata; Takeno, Sylvia S; Spinner, Nancy B; Conlin, Laura K; Christofolini, Denise M; Kulikowski, Leslie D; Melaragno, Maria I

    2011-12-21

    The breakpoints and mechanisms of ring chromosome formation were studied and mapped in 14 patients. Several techniques were performed such as genome-wide array, MLPA (Multiplex Ligation-Dependent Probe Amplification) and FISH (Fluorescent in situ Hybridization). The ring chromosomes of patients I to XIV were determined to be, respectively: r(3)(p26.1q29), r(4)(p16.3q35.2), r(10)(p15.3q26.2), r(10)(p15.3q26.13), r(13)(p13q31.1), r(13)(p13q34), r(14)(p13q32.33), r(15)(p13q26.2), r(18)(p11.32q22.2), r(18)(p11.32q21.33), r(18)(p11.21q23), r(22)(p13q13.33), r(22)(p13q13.2), and r(22)(p13q13.2). These rings were found to have been formed by different mechanisms, such as: breaks in both chromosome arms followed by end-to-end reunion (patients IV, VIII, IX, XI, XIII and XIV); a break in one chromosome arm followed by fusion with the subtelomeric region of the other (patients I and II); a break in one chromosome arm followed by fusion with the opposite telomeric region (patients III and X); fusion of two subtelomeric regions (patient VII); and telomere-telomere fusion (patient XII). Thus, the r(14) and one r(22) can be considered complete rings, since there was no loss of relevant genetic material. Two patients (V and VI) with r(13) showed duplication along with terminal deletion of 13q, one of them proved to be inverted, a mechanism known as inv-dup-del. Ring instability was detected by ring loss and secondary aberrations in all but three patients, who presented stable ring chromosomes (II, XIII and XIV). We concluded that the clinical phenotype of patients with ring chromosomes may be related with different factors, including gene haploinsufficiency, gene duplications and ring instability. Epigenetic factors due to the circular architecture of ring chromosomes must also be considered, since even complete ring chromosomes can result in phenotypic alterations, as observed in our patients with complete r(14) and r(22).

  17. Risk for Clinically Relevant Adverse Cardiac Events in Patients With Chest Pain at Hospital Admission.

    PubMed

    Weinstock, Michael B; Weingart, Scott; Orth, Frank; VanFossen, Douglas; Kaide, Colin; Anderson, Judy; Newman, David H

    2015-07-01

    Patients with potentially ischemic chest pain are commonly admitted to the hospital or observed after a negative evaluation in the emergency department (ED) owing to concern about adverse events. Previous studies have looked at 30-day mortality, but no current large studies have examined the most important information regarding ED disposition: the short-term risk for a clinically relevant adverse cardiac event (including inpatient ST-segment elevation myocardial infarction, life-threatening arrhythmia, cardiac or respiratory arrest, or death). To determine the incidence of clinically relevant adverse cardiac events in patients hospitalized for chest pain with 2 troponin-negative findings, nonconcerning initial ED vital signs, and nonischemic, interpretable electrocardiographic findings. We conducted a blinded data review of 45,416 encounters obtained from a prospectively collected database enrolling adult patients admitted or observed with the following inclusion criteria: (1) primary presenting symptom of chest pain, chest tightness, chest burning, or chest pressure and (2) negative findings for serial biomarkers. Data were collected and analyzed from July 1, 2008, through June 30, 2013, from the EDs of 3 community teaching institutions with an aggregate census of more than 1 million visits. We analyzed data extracted by hypothesis-blinded abstractors. The primary outcome was a composite of life-threatening arrhythmia, inpatient ST-segment elevation myocardial infarction, cardiac or respiratory arrest, or death during hospitalization. Of the 45,416 encounters, 11,230 met criteria for inclusion. Mean patient age was 58.0 years. Of the 11 230 encounters, 44.83% of patients arrived by ambulance and 55.00% of patients were women. Relevant history included hypertension in 46.00%, diabetes mellitus in 19.72%, and myocardial infarction in 13.16%. The primary end point occurred in 20 of the 11 230 patients (0.18% [95% CI, 0.11%-0.27%]). After excluding patients with

  18. Identifying adverse drug event information in clinical notes with distributional semantic representations of context.

    PubMed

    Henriksson, Aron; Kvist, Maria; Dalianis, Hercules; Duneld, Martin

    2015-10-01

    For the purpose of post-marketing drug safety surveillance, which has traditionally relied on the voluntary reporting of individual cases of adverse drug events (ADEs), other sources of information are now being explored, including electronic health records (EHRs), which give us access to enormous amounts of longitudinal observations of the treatment of patients and their drug use. Adverse drug events, which can be encoded in EHRs with certain diagnosis codes, are, however, heavily underreported. It is therefore important to develop capabilities to process, by means of computational methods, the more unstructured EHR data in the form of clinical notes, where clinicians may describe and reason around suspected ADEs. In this study, we report on the creation of an annotated corpus of Swedish health records for the purpose of learning to identify information pertaining to ADEs present in clinical notes. To this end, three key tasks are tackled: recognizing relevant named entities (disorders, symptoms, drugs), labeling attributes of the recognized entities (negation, speculation, temporality), and relationships between them (indication, adverse drug event). For each of the three tasks, leveraging models of distributional semantics - i.e., unsupervised methods that exploit co-occurrence information to model, typically in vector space, the meaning of words - and, in particular, combinations of such models, is shown to improve the predictive performance. The ability to make use of such unsupervised methods is critical when faced with large amounts of sparse and high-dimensional data, especially in domains where annotated resources are scarce. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation

    PubMed Central

    Su, Shih-Chi; Hung, Shuen-Iu; Fan, Wen-Lang; Dao, Ro-Lan; Chung, Wen-Hung

    2016-01-01

    Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine. PMID:27854302

  20. Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text.

    PubMed

    Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

    2013-01-01

    Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives.

  1. Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

    PubMed Central

    Miller, Paul E.; Mannis, Mark J.

    2015-01-01

    Abstract This article reviews ocular adverse events (AEs) reported in association with administration of antibody–drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID:26539624

  2. Meningitis With a Negative Cerebrospinal Fluid Gram Stain in Adults: Risk Classification for an Adverse Clinical Outcome

    PubMed Central

    Khoury, Nabil T.; Hossain, Md Monir; Wootton, Susan H.; Salazar, Lucrecia; Hasbun, Rodrigo

    2012-01-01

    Objective To derive and validate a risk score for an adverse clinical outcome in adults with meningitis and a negative cerebrospinal fluid (CSF) Gram stain. Patients and Methods We conducted a retrospective study of 567 adults from Houston, Texas, with meningitis evaluated between January 1, 2005, and January 1, 2010. The patients were divided into derivation (N=292) and validation (N=275) cohorts. An adverse clinical outcome was defined as a Glasgow Outcome Scale score of 4 or less. Results Of the 567 patients, 62 (11%) had an adverse clinical outcome. A predictive model was created using 3 baseline variables that were independently associated with an adverse clinical outcome (P<.05): age greater than 60 years, abnormal findings on neurologic examination (altered mental status, focal neurologic deficits, or seizures), and CSF glucose level of less than 2.4975 mmol/L (to convert CSF glucose to mmol/L, multiply by 0.05551). The model classified patients into 2 categories of risk for an adverse clinical outcome—derivation sample: low risk, 0.6% and high risk, 32.8%; P<.001; and validation sample: low risk, 0.5% and high risk, 21.1%; P<.001. Conclusion Adults with meningitis and a negative CSF Gram stain can be accurately stratified for the risk of an adverse clinical outcome using clinical variables available at presentation. PMID:23218086

  3. Interactive associations of depression and sleep apnea with adverse clinical outcomes after acute myocardial infarction

    PubMed Central

    Hayano, Junichiro; Carney, Robert M.; Watanabe, Eiichi; Kawai, Kiyohiro; Kodama, Itsuo; Stein, Phyllis K.; Watkins, Lana L.; Freedland, Kenneth E.; Blumenthal, James A.

    2012-01-01

    Objective Depression and sleep apnea (SA) are common among patients after acute myocardial infarction (AMI), and both are associated with increased risk for adverse outcomes. We tested the hypothesis that there is an interaction between depression and SA in relation to prognosis in post-AMI patients. Methods Participants were 337 depressed and 379 nondepressed post-AMI patients who participated in a substudy of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial. SA was identified from Holter ECG at the entry by an algorithm that detects cyclic variation of heart rate. Results During a median follow-up of 25 months, 43 (6.0%) of patients died and 83 (11.6%) either died or experienced a recurrent AMI. Among 94 patients with both depression and SA, these endpoints occurred in 20 (21.3%) and 25 (26.6%), the prevalence that was 6.9 and 3.9 times higher than predicted probabilities by ENRICHD clinical risk scores (P <.001 for both). In the patients with depression alone, SA alone, or neither, the frequencies did not differ significantly from the predicted probability. Although both depression and SA predicted death and the combined endpoint, we observed depression by SA interactions (P = .03 and .02). SA independently predicted these endpoints in depressed (P <.001 and P = .001), but not in nondepressed patients (P = .73 and .84). Similarly, depression independently predicted these endpoints in SA (P <.001 for both), but not in non-SA patients (P = .61 and .12). Conclusion The combination of depression and SA estimated by CVHR is associated with long-term adverse clinical outcomes after AMI. PMID:23023681

  4. Understanding Interrater Reliability and Validity of Risk Assessment Tools Used to Predict Adverse Clinical Events.

    PubMed

    Siedlecki, Sandra L; Albert, Nancy M

    This article will describe how to assess interrater reliability and validity of risk assessment tools, using easy-to-follow formulas, and to provide calculations that demonstrate principles discussed. Clinical nurse specialists should be able to identify risk assessment tools that provide high-quality interrater reliability and the highest validity for predicting true events of importance to clinical settings. Making best practice recommendations for assessment tool use is critical to high-quality patient care and safe practices that impact patient outcomes and nursing resources. Optimal risk assessment tool selection requires knowledge about interrater reliability and tool validity. The clinical nurse specialist will understand the reliability and validity issues associated with risk assessment tools, and be able to evaluate tools using basic calculations. Risk assessment tools are developed to objectively predict quality and safety events and ultimately reduce the risk of event occurrence through preventive interventions. To ensure high-quality tool use, clinical nurse specialists must critically assess tool properties. The better the tool's ability to predict adverse events, the more likely that event risk is mediated. Interrater reliability and validity assessment is relatively an easy skill to master and will result in better decisions when selecting or making recommendations for risk assessment tool use.

  5. A qualitative study evaluating causality attribution for serious adverse events during early phase oncology clinical trials.

    PubMed

    Mukherjee, Som D; Coombes, Megan E; Levine, Mitch; Cosby, Jarold; Kowaleski, Brenda; Arnold, Andrew

    2011-10-01

    In early phase oncology trials, novel targeted therapies are increasingly being tested in combination with traditional agents creating greater potential for enhanced and new toxicities. When a patient experiences a serious adverse event (SAE), investigators must determine whether the event is attributable to the investigational drug or not. This study seeks to understand the clinical reasoning, tools used and challenges faced by the researchers who assign causality to SAE's. Thirty-two semi-structured interviews were conducted with medical oncologists and trial coordinators at six Canadian academic cancer centres. Interviews were recorded and transcribed verbatim. Individual interview content analysis was followed by thematic analysis across the interview set. Our study found that causality assessment tends to be a rather complex process, often without complete clinical and investigational data at hand. Researchers described using a common processing strategy whereby they gather pertinent information, eliminate alternative explanations, and consider whether or not the study drug resulted in the SAE. Many of the interviewed participants voiced concern that causality assessments are often conducted quickly and tend to be highly subjective. Many participants were unable to identify any useful tools to help in assigning causality and welcomed more objectivity in the overall process. Attributing causality to SAE's is a complex process. Clinical trial researchers apply a logical system of reasoning, but feel that the current method of assigning causality could be improved. Based on these findings, future research involving the development of a new causality assessment tool specifically for use in early phase oncology clinical trials may be useful.

  6. [Perception of clinical practice derived risks compared to adverse effects detected in an internal medicine service].

    PubMed

    Jiménez Muñoz, A B; Muiño Miguez, A; Quintás Viqueira, A; Pinilla Llorente, B; Durán García, M E; Rodríguez Pérez, M P

    2008-01-01

    To know how the health care workers perceive the risks derived from the care practice. To estimate the most frequent adverse effects (AE) and establish differences and similarities between the perception of risks and the AE produced. A self-administered questionnaire was applied to all the workers of an Internal Medicine Department of a General University Hospital on perception of risks and safety of the patient. After, and by using the screening guide of the IDEA project, edition 1, the clinical histories of the patients selected were analyzed by medical residents of preventive Medicine and Internal Medicine. Questionnaire. Fifty questionnaires we sent with a 42% response rate. Risks prioritized by obtaining a lower mean score: there is not action plan against catastrophes (2.79/10) and lack of spaces to report (3/10); those having greater percentage of open questions: long maintenance of urinary probes (47.61%) and inadequate prescription of antibiotics (33.33%). Study of AE. Incidence of patients with AE: 25% (95% CI 11.06-38.9). Incidence of AE: 26.6% (95% CI 12.6-40.6). 41.6% of AE was related to medication, 25% to nosocomial infection, 16.66% to technical problems in procedures and 16.66% were related to nursing cares. The perception of the health care workers on health care practice derived risks is different from the adverse events that really appear. The professionals are concerned about the information to patients than about scientific and technical quality. The most frequent adverse events produced are those related with medication. The only common point is concern for nosocomial infection.

  7. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    PubMed

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. High Phosphohistone H3 Expression Correlates with Adverse Clinical, Biological, and Pathological Factors in Neuroblastomas

    PubMed Central

    Ramani, Pramila; Taylor, Scott; Miller, Elizabeth; Sowa-Avugrah, Emile; May, Margaret T.

    2015-01-01

    Phosphohistone H3 (pHH3), a biomarker of the late G2- and M-phase of the cell cycle, provides a powerful indication of the proliferative state of many cancers. We investigated the prognostic significance of pHH3 by immunostaining 80 neuroblastomas and counting the average number of strongly stained nuclei and mitotic figures. The median and 75th percentile pHH3 proliferation indices (PIs) were 0.54% and 1.06% (range, 0.01% to 2.23%) respectively. pHH3 expression was significantly higher in neuroblastomas from patients with adverse clinical characteristics, all unfavorable pathological factors including high mitosis karyorrhexis index (MKI), and adverse biological factors including MYCN oncogene amplification. High pHH3-PIs, at 1% threshold, were significantly associated with a shorter overall survival (OS) and event-free survival (EFS) in the univariable Cox regression analyses. In the multivariable models, high pHH3 counts were significantly associated with worse OS after adjustment for age but were not independent of either high MKI or MYCN amplification. In children less than 18 months of age, high MKIs and high PHH3-PIs were associated with significantly worse OS and EFS. In conclusion, high pHH3 expression correlates strongly with high MKI and MYCN amplification and indicates poor prognosis in neuroblastomas. PMID:25711230

  9. A knowledge engineering framework towards clinical support for adverse drug event prevention: the PSIP approach.

    PubMed

    Koutkias, Vassilis; Stalidis, George; Chouvarda, Ioanna; Lazou, Katerina; Kilintzis, Vassilis; Maglaveras, Nicos

    2009-01-01

    Adverse Drug Events (ADEs) are currently considered as a major public health issue, endangering patients' safety and causing significant healthcare costs. Several research efforts are currently concentrating on the reduction of preventable ADEs by employing Information Technology (IT) solutions, which aim to provide healthcare professionals and patients with relevant knowledge and decision support tools. In this context, we present a knowledge engineering approach towards the construction of a Knowledge-based System (KBS) regarded as the core part of a CDSS (Clinical Decision Support System) for ADE prevention, all developed in the context of the EU-funded research project PSIP (Patient Safety through Intelligent Procedures in Medication). In the current paper, we present the knowledge sources considered in PSIP and the implications they pose to knowledge engineering, the methodological approach followed, as well as the components defining the knowledge engineering framework based on relevant state-of-the-art technologies and representation formalisms.

  10. Advanced Clinical Decision Support for Vaccine Adverse Event Detection and Reporting.

    PubMed

    Baker, Meghan A; Kaelber, David C; Bar-Shain, David S; Moro, Pedro L; Zambarano, Bob; Mazza, Megan; Garcia, Crystal; Henry, Adam; Platt, Richard; Klompas, Michael

    2015-09-15

    Reporting of adverse events (AEs) following vaccination can help identify rare or unexpected complications of immunizations and aid in characterizing potential vaccine safety signals. We developed an open-source, generalizable clinical decision support system called Electronic Support for Public Health-Vaccine Adverse Event Reporting System (ESP-VAERS) to assist clinicians with AE detection and reporting. ESP-VAERS monitors patients' electronic health records for new diagnoses, changes in laboratory values, and new allergies following vaccinations. When suggestive events are found, ESP-VAERS sends the patient's clinician a secure electronic message with an invitation to affirm or refute the message, add comments, and submit an automated, prepopulated electronic report to VAERS. High-probability AEs are reported automatically if the clinician does not respond. We implemented ESP-VAERS in December 2012 throughout the MetroHealth System, an integrated healthcare system in Ohio. We queried the VAERS database to determine MetroHealth's baseline reporting rates from January 2009 to March 2012 and then assessed changes in reporting rates with ESP-VAERS. In the 8 months following implementation, 91 622 vaccinations were given. ESP-VAERS sent 1385 messages to responsible clinicians describing potential AEs. Clinicians opened 1304 (94.2%) messages, responded to 209 (15.1%), and confirmed 16 for transmission to VAERS. An additional 16 high-probability AEs were sent automatically. Reported events included seizure, pleural effusion, and lymphocytopenia. The odds of a VAERS report submission during the implementation period were 30.2 (95% confidence interval, 9.52-95.5) times greater than the odds during the comparable preimplementation period. An open-source, electronic health record-based clinical decision support system can increase AE detection and reporting rates in VAERS. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society

  11. Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text

    PubMed Central

    Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

    2013-01-01

    Objective Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Materials and methods Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. Results The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. Discussion The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. Conclusions The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives. PMID:23703825

  12. Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma.

    PubMed

    Chen, Kai; Cai, Yuanxia; Zhang, Min; Wu, Zhixiang; Wu, Yeming

    2018-05-24

    Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy. © 2018 Wiley Periodicals, Inc.

  13. Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials.

    PubMed

    Lebwohl, Mark G; Papp, Kim A; Marangell, Lauren B; Koo, John; Blauvelt, Andrew; Gooderham, Melinda; Wu, Jashin J; Rastogi, Shipra; Harris, Susan; Pillai, Radhakrishnan; Israel, Robert J

    2018-01-01

    Individuals with psoriasis are at increased risk for psychiatric comorbidities, including suicidal ideation and behavior (SIB). To distinguish between the underlying risk and potential for treatment-induced psychiatric adverse events in patients with psoriasis being treated with brodalumab, a fully human anti-interleukin 17 receptor A monoclonal antibody. Data were evaluated from a placebo-controlled, phase 2 clinical trial; the open-label, long-term extension of the phase 2 clinical trial; and three phase 3, randomized, double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis. The analysis included 4464 patients with 9161.8 patient-years of brodalumab exposure. The follow-up time-adjusted incidence rates of SIB events were comparable between the brodalumab and ustekinumab groups throughout the 52-week controlled phases (0.20 vs 0.60 per 100 patient-years). In the brodalumab group, 4 completed suicides were reported, 1 of which was later adjudicated as indeterminate; all patients had underlying psychiatric disorders or stressors. There was no comparator arm past week 52. Controlled study periods were not powered to detect differences in rare events such as suicide. Comparison with controls and the timing of events do not indicate a causal relationship between SIB and brodalumab treatment. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  14. Assessing the potential adverse consequences of supplemental calcium on cardiovascular outcomes: should we change our approach to bone health?

    PubMed

    Rojas-Fernandez, Carlos H; Maclaughlin, Eric J; Dore, Naomi L; Ebsary, Sally

    2012-05-01

    To assess cardiovascular risks associated with supplemental calcium use to assist clinicians with evidence-based recommendations for patients who have, or who are at risk for, osteoporosis or osteopenia. Literature was accessed through December 2011 using MEDLINE, Cochrane Library, and International Pharmaceutical Abstracts using the terms calcium compounds and cardiovascular disease. In addition, reference citations from the publications identified were reviewed. All English-language articles were evaluated. Randomized controlled trials, observational studies, and meta-analyses were included. While supplemental calcium and vitamin D have been demonstrated to improve bone mineral density and decrease the risk of fractures, there have been recent reports that calcium supplements may increase the risk for cardiovascular events. Nine clinical trials and/or meta-analyses were reviewed; 3 documented increases in cardiovascular risk associated with calcium supplements, and 6 did not. No studies were designed to assess cardiovascular outcomes as primary end points. Balancing the evidence from these analyses with the results of randomized controlled trials assessing the effect of calcium on fracture prevention suggests that the benefits of calcium outweigh the cardiovascular risk. At this time, there is no cause to change routine practice surrounding supplemental calcium use in patients who have, or are at risk for, osteoporosis or osteopenia.

  15. Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance.

    PubMed

    Fornasier, G; Taborelli, M; Francescon, S; Polesel, J; Aliberti, M; De Paoli, P; Baldo, P

    2018-05-21

    Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥ 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.

  16. Correlation of Clinical and Dosimetric Factors With Adverse Pulmonary Outcomes in Children After Lung Irradiation

    SciTech Connect

    Venkatramani, Rajkumar, E-mail: rvenkatramani@chla.usc.edu; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; Kamath, Sunil

    Purpose: To identify the incidence and the risk factors for pulmonary toxicity in children treated for cancer with contemporary lung irradiation. Methods and Materials: We analyzed clinical features, radiographic findings, pulmonary function tests, and dosimetric parameters of children receiving irradiation to the lung fields over a 10-year period. Results: We identified 109 patients (75 male patients). The median age at irradiation was 13.8 years (range, 0.04-20.9 years). The median follow-up period was 3.4 years. The median prescribed radiation dose was 21 Gy (range, 0.4-64.8 Gy). Pulmonary toxic chemotherapy included bleomycin in 58.7% of patients and cyclophosphamide in 83.5%. The followingmore » pulmonary outcomes were identified and the 5-year cumulative incidence after irradiation was determined: pneumonitis, 6%; chronic cough, 10%; pneumonia, 35%; dyspnea, 11%; supplemental oxygen requirement, 2%; radiographic interstitial lung disease, 40%; and chest wall deformity, 12%. One patient died of progressive respiratory failure. Post-irradiation pulmonary function tests available from 44 patients showed evidence of obstructive lung disease (25%), restrictive disease (11%), hyperinflation (32%), and abnormal diffusion capacity (12%). Thoracic surgery, bleomycin, age, mean lung irradiation dose (MLD), maximum lung dose, prescribed dose, and dosimetric parameters between V{sub 22} (volume of lung exposed to a radiation dose ≥22 Gy) and V{sub 30} (volume of lung exposed to a radiation dose ≥30 Gy) were significant for the development of adverse pulmonary outcomes on univariate analysis. MLD, maximum lung dose, and V{sub dose} (percentage of volume of lung receiving the threshold dose or greater) were highly correlated. On multivariate analysis, MLD was the sole significant predictor of adverse pulmonary outcome (P=.01). Conclusions: Significant pulmonary dysfunction occurs in children receiving lung irradiation by contemporary techniques. MLD rather than

  17. Rice seed priming with Se : A novel approach to mitigate As induced adverse consequences on growth, yield and As load in brown rice.

    PubMed

    Moulick, Debojyoti; Santra, Subhas Chandra; Ghosh, Dibakar

    2018-05-16

    The current investigation was laid down to investigate the consequences of cultivating selenium (Se) primed seedlings of two contrasting rice varieties in arsenic (As) free and As spiked pot soil. At maturity, Se primed seedlings (both tested varieties) cultivated alike the controls (in As free condition) were found to posses significantly (p < 0.001) greater amount of chlorophyll, biomass, tiller number, panicle weight and test weight beside these, also having longer plant height than the control. Adverse effects of As stress can be seen in the unprimed plants of both the tested varieties in accordance to dose in the above studied parameters. Compare to the unprimed varieties cultivated in As spiked soil, Se primed plants exhibited an upward trend in restoring adverse effects of As like longer height, greater biomass content, tiller number, test weight etc, in a low to highly significant manner. Brown rice and cooked rice of Se primed plants content significantly (p < 0.001) less As load than those of unprimed plants. Se primed plants were found to restrict As translocation into the aerial parts by confining As into its root in greater amount than those of unprimed plants in variety irrespective fashion. Copyright © 2018. Published by Elsevier B.V.

  18. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  19. 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

  20. Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis.

    PubMed

    Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C

    2016-08-01

    Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials. We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers

  1. [CLINICAL AND IMMUNOLOGICAL CRITERIA FOR THE ADVERSE COURSE OF INFECTIOUS MONONUCLEOSIS IN CHILDREN].

    PubMed

    Kolesnik, Ya; Zharkova, T; Rzhevskaya, O; Kvaratskheliya, T; Sorokina, O

    2018-05-01

    The article presents the results of our own studies to determine the criteria for the adverse variants of the course of infectious mononucleosis (IM) in children. The study was conducted in the regional children's infectious clinical hospital in Kharkov. 161 children aged three to fifteen years were under observation with diagnosis of infectious moninucleosis. Out of 161 ill children, 140 (86.9%) had moderate severity of disease, and 21 (13.1%) had severe forms. All children were prescribed standard clinical and laboratory-instrumental examinations. The diagnosis of IM was verified by PCR (detection of VEB DNA in the blood) and ELISA (anti-VEB Ig M and Ig G). In 140 children (86.9%) IM proceeded sharply, smoothly (the first group), in 21 (13.1%) - unfavorably (wave and / or prolonged course) - the second group. The groups were comparable according to age, the severity of the disease and other parameters. All children received therapy according to approved protocols (Order of the Ministry of Health of Ukraine No. 354 of 09.07.2004). Immune status of children was assessed by determining the relative contents of CD3 +, CD4 +, CD8 +, CD16 +, CD19 + blood cells with appropriate monoclonal antibodies, serum IgA, IgM, IgG concentration by Mancini and interleukin (IL) -1β cytokine response and - 4, tumor necrosis factor (TNF α) is a solid-phase enzyme-linked immunosorbent assay. Based on the results of observations, it was established that the prognostically unfavorable criteria of IМ at the stages of manifestation of disease include: generalized lymphadenopathy involving 5-6 groups of lymph nodes and a significant increasing of them, purulent tonsillitis, marked increasing of size of liver and spleen on the background of anemia, thrombocytopenia, neutropenia and the absence of atypical mononuclears in the complete blood count. There is a depression of the cellular link and an increase in the humoral mechanisms of immune responses in case of development of adverse

  2. A Systematic Review of Early Warning Systems' Effects on Nurses' Clinical Performance and Adverse Events Among Deteriorating Ward Patients.

    PubMed

    Lee, Ju-Ry; Kim, Eun-Mi; Kim, Sun-Aee; Oh, Eui Geum

    2018-04-25

    Early warning systems (EWSs) are an integral part of processes that aim to improve the early identification and management of deteriorating patients in general wards. However, the widespread implementation of these systems has not generated robust data regarding nurses' clinical performance and patients' adverse events. This review aimed to determine the ability of EWSs to improve nurses' clinical performance and prevent adverse events among deteriorating ward patients. The PubMed, CINAHL, EMBASE, and Cochrane Library databases were searched for relevant publications (January 1, 1997, to April 12, 2017). In addition, a grey literature search evaluated several guideline Web sites. The main outcome measures were nurses' clinical performance (vital sign monitoring and rapid response team notification) and patients' adverse events (in-hospital mortality, cardiac arrest, and unplanned intensive care unit [ICU] admission). The search identified 888 reports, although only five studies fulfilled the inclusion criteria. The findings of these studies revealed that EWSs implementation had a positive effect on nurses' clinical performance, based on their frequency of documenting vital signs that were related to the patient's clinical deterioration. In addition, postimplementation reductions were identified for cardiac arrest, unplanned ICU admission, and unexpected death. It seems that EWSs can improve nurses' clinical performance and prevent adverse events (e.g., in-hospital mortality, unplanned ICU admission, and cardiac arrest) among deteriorating ward patients. However, additional high-quality evidence is needed to more comprehensively evaluate the effects of EWSs on these outcomes.

  3. Seven basic dimensions of personality pathology and their clinical consequences: Are all personalities equally harmful?

    PubMed

    Vall, Gemma; Gutiérrez, Fernando; Peri, Josep M; Gárriz, Miguel; Ferraz, Liliana; Baillés, Eva; Obiols, Jordi E

    2015-11-01

    Dimensional pathology models are increasingly being accepted for the assessment of disordered personalities, but their ability to predict negative outcomes is yet to be studied. We examine the relative clinical impact of seven basic dimensions of personality pathology through their associations with a wide range of clinical outcomes. A sample of 960 outpatients was assessed through a 7-factor model integrating the Cloninger, the Livesley, and the DSM taxonomies. Thirty-six indicators of clinical outcome covering three areas - dissatisfaction, functional difficulties, and clinical severity - were also assessed. The unique contribution of each personality dimension to clinical outcome was estimated through multiple regressions. Overall, personality dimensions explained 17.6% of the variance of clinical outcome, but varied substantially in terms of their unique contributions. Negative Emotionality had the greatest impact in all areas, contributing 43.9% of the explained variance. The remaining dimensions led to idiosyncratic patterns of clinical outcomes but had a comparatively minor clinical impact. A certain effect was also found for combinations of dimensions such as Negative Emotionality × Impulsive Sensation Seeking, but most interactions were clinically irrelevant. Our findings suggest that the most relevant dimensions of personality pathology are associated with very different clinical consequences and levels of harmfulness. The relative clinical impact of seven basic dimensions of personality pathology is examined. Negative Emotionality (Neuroticism) is 6-14 times as harmful as other pathological dimensions. The remaining dimensions and their interactions have very specific and comparatively minor clinical consequences. We examine only a handful of clinical outcomes. Our results may not be generalizable to other clinical or life outcomes. Our variables are self-reported and hence susceptible to bias. Our design does not allow us to establish causal

  4. The Japanese Postmarketing Adverse Event Relief System: A Confluence of Regulatory Science, the Legal System, and Clinical Pharmacology.

    PubMed

    Tominaga, T; Miyazaki, S; Oniyama, Y; Weber, A D; Kondo, T

    2017-08-01

    The Japanese Postmarketing Relief System provides for compensation to patients with adverse reactions, based on the acknowledgment that unpredicted adverse events occur inevitably once a drug is marketed. The system also provides new knowledge about the benefit-risk profile of a drug that may be incorporated into product labeling. The system relies on causality assessments that are based on sound clinical pharmacology principles. The system may serve as a model for other countries' healthcare systems. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  5. Faster clinical response to the onset of adverse events: A wearable metacognitive attention aid for nurse triage of clinical alarms.

    PubMed

    McFarlane, Daniel C; Doig, Alexa K; Agutter, James A; Brewer, Lara M; Syroid, Noah D; Mittu, Ranjeev

    2018-01-01

    This study evaluates the potential for improving patient safety by introducing a metacognitive attention aid that enables clinicians to more easily access and use existing alarm/alert information. It is hypothesized that this introduction will enable clinicians to easily triage alarm/alert events and quickly recognize emergent opportunities to adapt care delivery. The resulting faster response to clinically important alarms/alerts has the potential to prevent adverse events and reduce healthcare costs. A randomized within-subjects single-factor clinical experiment was conducted in a high-fidelity 20-bed simulated acute care hospital unit. Sixteen registered nurses, four at a time, cared for five simulated patients each. A two-part highly realistic clinical scenario was used that included representative: tasking; information; and alarms/alerts. The treatment condition introduced an integrated wearable attention aid that leveraged metacognition methods from proven military systems. The primary metric was time for nurses to respond to important alarms/alerts. Use of the wearable attention aid resulted in a median relative within-subject improvement for individual nurses of 118% (W = 183, p = 0.006). The top quarter of relative improvement was 3,303% faster (mean; 17.76 minutes reduced to 1.33). For all unit sessions, there was an overall 148% median faster response time to important alarms (8.12 minutes reduced to 3.27; U = 2.401, p = 0.016), with 153% median improvement in consistency across nurses (F = 11.670, p = 0.001). Existing device-centric alarm/alert notification solutions can require too much time and effort for nurses to access and understand. As a result, nurses may ignore alarms/alerts as they focus on other important work. There has been extensive research on reducing alarm frequency in healthcare. However, alarm safety remains a top problem. Empirical observations reported here highlight the potential of improving patient safety by supporting the meta

  6. Accounting for interim safety monitoring of an adverse event upon termination of a clinical trial.

    PubMed

    Dallas, Michael J

    2008-01-01

    Upon termination of a clinical trial that uses interim evaluations to determine whether the trial can be stopped, a proper statistical analysis must account for the interim evaluations. For example, in a group-sequential design where the efficacy of a treatment regimen is evaluated at interim stages, and the opportunity to stop the trial based on positive efficacy findings exists, the terminal p-value, point estimate, and confidence limits of the outcome of interest must be adjusted to eliminate bias. While it is standard practice to adjust terminal statistical analyses due to opportunities to stop for "positive" findings, adjusting due to opportunities to stop for "negative" findings is also important. Stopping rules for negative findings are particularly useful when monitoring a specific rare serious adverse event in trials designed to show safety with respect to the event. In these settings, establishing conservative stopping rules are appropriate, and therefore accounting for the interim monitoring can have a substantial effect on the final results. Here I present a method to account for interim safety monitoring and illustrate its usefulness. The method is demonstrated to have advantages over methodology that does not account for interim monitoring.

  7. Clinical Symptoms and Adverse Effects Associated With Energy Drink Consumption in Adolescents.

    PubMed

    Bashir, Dalia; Reed-Schrader, Essie; Olympia, Robert P; Brady, Jodi; Rivera, Ruby; Serra, Theresa; Weber, Christopher

    2016-11-01

    The aims of the study were to determine the prevalence of energy drink consumption by adolescents, to identify associated clinical symptoms and adverse effects, and to gain an understanding to the motivation behind its consumption. A prospective, questionnaire-based study was conducted at 2 emergency departments from June 2011 to June 2013. The questionnaire was distributed to a convenience sample of adolescents aged 12 to 18 years. Stratification was performed on the basis of frequency of consumption: frequent consumption (at least once a month) and infrequent consumption (less frequent than once a month). Data analysis was performed on 612 completed questionnaires. Two hundred two responders (33%) were considered frequent energy drink consumers. Frequent consumers were more likely to be involved in high-risk behaviors and more likely to consume other caffeinated drinks. In the previous 6 months, frequent energy drink consumers were more likely to report headache (76%), anger (47%), and increased urination (24%) and were more likely to require medical evaluation for headache (41%) and difficulty breathing (22%). Frequent energy drink consumers were more likely to believe that energy drinks "help me do better in school" (12%), "help me do better in sports" (35%), "are just for fun" (46%), "help me stay up at night" (67%), and "make me concentrate/focus better" (34%). Clarifying common misconceptions associated with energy drink consumption, especially in high-risk adolescents and frequent energy drink consumers, may decrease the frequency of symptoms experienced by adolescents, such as headache and difficulty breathing, requiring medical evaluation.

  8. Optimizing collection of adverse event data in cancer clinical trials supporting supplemental indications.

    PubMed

    Kaiser, Lee D; Melemed, Allen S; Preston, Alaknanda J; Chaudri Ross, Hilary A; Niedzwiecki, Donna; Fyfe, Gwendolyn A; Gough, Jacqueline M; Bushnell, William D; Stephens, Cynthia L; Mace, M Kelsey; Abrams, Jeffrey S; Schilsky, Richard L

    2010-12-01

    Although much is known about the safety of an anticancer agent at the time of initial marketing approval, sponsors customarily collect comprehensive safety data for studies that support supplemental indications. This adds significant cost and complexity to the study but may not provide useful new information. The main purpose of this analysis was to assess the amount of safety and concomitant medication data collected to determine a more optimal approach in the collection of these data when used in support of supplemental applications. Following a prospectively developed statistical analysis plan, we reanalyzed safety data from eight previously completed prospective randomized trials. A total of 107,884 adverse events and 136,608 concomitant medication records were reviewed for the analysis. Of these, four grade 1 to 2 and nine grade 3 and higher events were identified as drug effects that were not included in the previously established safety profiles and could potentially have been missed using subsampling. These events were frequently detected in subsamples of 400 patients or larger. Furthermore, none of the concomitant medication records contributed to labeling changes for the supplemental indications. Our study found that applying the optimized methodologic approach, described herein, has a high probability of detecting new drug safety signals. Focusing data collection on signals that cause physicians to modify or discontinue treatment ensures that safety issues of the highest concern for patients and regulators are captured and has significant potential to relieve strain on the clinical trials system.

  9. Clinical audit in gynecological cancer surgery: development of a risk scoring system to predict adverse events.

    PubMed

    Kondalsamy-Chennakesavan, Srinivas; Bouman, Chantal; De Jong, Suzanne; Sanday, Karen; Nicklin, Jim; Land, Russell; Obermair, Andreas

    2009-12-01

    Advanced gynecological surgery undertaken in a specialized gynecologic oncology unit may be associated with significant perioperative morbidity. Validated risk prediction models are available for general surgical specialties but currently not for gynecological cancer surgery. The objective of this study was to evaluate risk factors for adverse events (AEs) of patients treated for suspected or proven gynecological cancer and to develop a clinical risk score (RS) to predict such AEs. AEs were prospectively recorded and matched with demographical, clinical and histopathological data on 369 patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center. Stepwise multiple logistic regression was used to determine the best predictors of AEs. For the risk score (RS), the coefficients from the model were scaled using a factor of 2 and rounded to the nearest integer to derive the risk points. Sum of all the risk points form the RS. Ninety-five patients (25.8%) had at least one AE. Twenty-nine (7.9%) and 77 (20.9%) patients experienced intra- and postoperative AEs respectively with 11 patients (3.0%) experiencing both. The independent predictors for any AE were complexity of the surgical procedure, elevated SGOT (serum glutamic oxaloacetic transaminase, > or /=35 U/L), higher ASA scores and overweight. The risk score can vary from 0 to 14. The risk for developing any AE is described by the formula 100 / (1 + e((3.697 - (RS /2)))). RS allows for quantification of the risk for AEs. Risk factors are generally not modifiable with the possible exception of obesity.

  10. Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder.

    PubMed

    Bai, Ya-Mei; Li, Cheng-Ta; Tsai, Shih-Jen; Tu, Pei-Chi; Chen, Mu-Hong; Su, Tung-Ping

    2016-12-15

    Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder. MetS may cause complications in the brain, but studies investigating MetS-associated clinical psychiatric outcomes remain scant. We enrolled clinically stable outpatients with bipolar disorder aged 18-65 years and performed anthropometric and fasting biochemical assessments to investigate MetS prevalence. We then performed clinical assessments by using the Young Mania Rating Scale for manic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Positive and Negative Symptom Scale for psychotic symptoms, the Involuntary Movement Scale for tardive dyskinesia, the Barnes Akathisia Rating Scale for akathisia, the Udvalg for Kliniske Undersogelser for general side effects, the Schedule for Assessment of Insight for insight, the Global Assessment of Functioning scale for global functioning, and the Wisconsin Card Sorting Test (WCST) for cognitive executive function. In total, 143 patients were enrolled and had a MetS prevalence of 29.4%. The patients treated with atypical antipsychotics plus mood stabilizers (36.3%) and atypical antipsychotics alone (36.0%) had a significantly higher prevalence of MetS than did those treated with mood stabilizers alone (10.5%; p = 0.012). According to multivariate regression analyses adjusted for age, sex, smoking status, bipolar disorder subtype (I or II), pharmacological treatment duration, and psychiatric medication, compared with patients without MetS, those with MetS had significantly more previous hospitalizations (p = 0.036), severer tardive dyskinesia (p = 0.030), poorer insight (p = 0.036), poorer global function (p = 0.046), and more impaired executive function (conceptual level response on the WCST; p = 0.042). Our results indicated that patients with comorbid bipolar disorder and MetS have more adverse clinical outcomes than those without, with more hospitalizations, severer tardive

  11. The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.

    PubMed

    Shaikh, W A

    2000-07-01

    Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a

  12. Impact of drug cost sharing on service use and adverse clinical outcomes in elderly receiving antidepressants.

    PubMed

    Wang, Philip S; Patrick, Amanda R; Dormuth, Colin; Maclure, Malcolm; Avorn, Jerry; Canning, Claire F; Schneeweiss, Sebastian

    2010-03-01

    Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale "natural experiments'' in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a CAD 25 copay (CAD10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance. To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+. Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models. Neither policy affected the rates of visits to

  13. In-hospital death and adverse clinical events in elderly patients according to disease clustering: the REPOSI study.

    PubMed

    Marengoni, A; Bonometti, F; Nobili, A; Tettamanti, M; Salerno, F; Corrao, S; Iorio, A; Marcucci, M; Mannucci, P M

    2010-08-01

    The aim of the study was to recognize clusters of diseases among hospitalized elderly and to identify groups of patients at risk of in-hospital death and adverse clinical events according to disease clustering. This was a cross-sectional study conducted in 38 internal medicine and geriatric wards in Italy participating in the Registro Politerapie SIMI (REPOSI) study during 2008. The subjects were 1,332 inpatients aged 65 years or older. Clusters of diseases (i.e., two or more co-occurrent diseases) were identified using the odds ratios (OR) for the associations between pairs of conditions, followed by cluster analysis. Logistic regression models were used to evaluate the effect of disease clusters on in-hospital death and adverse clinical events. A total of 86.7% of the patients were discharged, 8.3% were transferred to another hospital unit, and 5.0% died during hospitalization; 36.4% of the patients had at least one adverse clinical event. Patients affected by the clusters, including heart failure (HF) and either chronic renal failure (CRF) or chronic obstructive pulmonary disease, had a significant association with in-hospital death (OR, 4.3;95% confidence interval [CI], 1.6-11.5; OR, 2.9; 95% CI, 1.1-8.3, respectively), as well as patients affected by CRF and anemia (OR, 6.1; 95% CI, 2.3-16.2). The cluster including HF and CRF was also associated with adverse clinical events (OR, 3.5; 95% CI, 1.5-7.8). The effect of both HF and CRF and anemia and CRF on in-hospital death was additive. Several groups of older patients at risk of in-hospital death and adverse clinical events were identified according to disease clustering. Knowledge of the relationship among co-occurring diseases may help developing strategies to improve clinical practice and preventative interventions.

  14. Clinical consequences and economic costs of untreated obstructive sleep apnea syndrome.

    PubMed

    Knauert, Melissa; Naik, Sreelatha; Gillespie, M Boyd; Kryger, Meir

    2015-09-01

    To provide an overview of the healthcare and societal consequences and costs of untreated obstructive sleep apnea syndrome. PubMed database for English-language studies with no start date restrictions and with an end date of September 2014. A comprehensive literature review was performed to identify all studies that discussed the physiologic, clinical and societal consequences of obstructive sleep apnea syndrome as well as the costs associated with these consequences. There were 106 studies that formed the basis of this analysis. Undiagnosed and untreated obstructive sleep apnea syndrome can lead to abnormal physiology that can have serious implications including increased cardiovascular disease, stroke, metabolic disease, excessive daytime sleepiness, work-place errors, traffic accidents and death. These consequences result in significant economic burden. Both, the health and societal consequences and their costs can be decreased with identification and treatment of sleep apnea. Treatment of obstructive sleep apnea syndrome, despite its consequences, is limited by lack of diagnosis, poor patient acceptance, lack of access to effective therapies, and lack of a variety of effective therapies. Newer modes of therapy that are effective, cost efficient and more accepted by patients need to be developed.

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

    PubMed

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

    2016-11-01

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

  16. Faster clinical response to the onset of adverse events: A wearable metacognitive attention aid for nurse triage of clinical alarms

    PubMed Central

    Doig, Alexa K.; Agutter, James A.; Brewer, Lara M.; Syroid, Noah D.; Mittu, Ranjeev

    2018-01-01

    Objective This study evaluates the potential for improving patient safety by introducing a metacognitive attention aid that enables clinicians to more easily access and use existing alarm/alert information. It is hypothesized that this introduction will enable clinicians to easily triage alarm/alert events and quickly recognize emergent opportunities to adapt care delivery. The resulting faster response to clinically important alarms/alerts has the potential to prevent adverse events and reduce healthcare costs. Materials and methods A randomized within-subjects single-factor clinical experiment was conducted in a high-fidelity 20-bed simulated acute care hospital unit. Sixteen registered nurses, four at a time, cared for five simulated patients each. A two-part highly realistic clinical scenario was used that included representative: tasking; information; and alarms/alerts. The treatment condition introduced an integrated wearable attention aid that leveraged metacognition methods from proven military systems. The primary metric was time for nurses to respond to important alarms/alerts. Results Use of the wearable attention aid resulted in a median relative within-subject improvement for individual nurses of 118% (W = 183, p = 0.006). The top quarter of relative improvement was 3,303% faster (mean; 17.76 minutes reduced to 1.33). For all unit sessions, there was an overall 148% median faster response time to important alarms (8.12 minutes reduced to 3.27; U = 2.401, p = 0.016), with 153% median improvement in consistency across nurses (F = 11.670, p = 0.001). Discussion and conclusion Existing device-centric alarm/alert notification solutions can require too much time and effort for nurses to access and understand. As a result, nurses may ignore alarms/alerts as they focus on other important work. There has been extensive research on reducing alarm frequency in healthcare. However, alarm safety remains a top problem. Empirical observations reported here highlight

  17. Adverse consequences of article 12 of the UN Convention on the Rights of Persons with Disabilities for persons with mental disabilities and an alternative way forward.

    PubMed

    Scholten, Matthé; Gather, Jakov

    2018-04-01

    It is widely accepted among medical ethicists that competence is a necessary condition for informed consent. In this view, if a patient is incompetent to make a particular treatment decision, the decision must be based on an advance directive or made by a substitute decision-maker on behalf of the patient. We call this the competence model. According to a recent report of the United Nations (UN) High Commissioner for Human Rights, article 12 of the UN Convention on the Rights of Persons with Disabilities (CRPD) presents a wholesale rejection of the competence model. The High Commissioner here adopts the interpretation of article 12 proposed by the Committee on the Rights of Persons with Disabilities. On this interpretation, CRPD article 12 renders it impermissible to deny persons with mental disabilities the right to make treatment decisions on the basis of impaired decision-making capacity and demands the replacement of all regimes of substitute decision-making by supported decision-making. In this paper, we explicate six adverse consequences of CRPD article 12 for persons with mental disabilities and propose an alternative way forward. The proposed model combines the strengths of the competence model and supported decision-making. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Adverse consequences of article 12 of the UN Convention on the Rights of Persons with Disabilities for persons with mental disabilities and an alternative way forward

    PubMed Central

    Gather, Jakov

    2018-01-01

    It is widely accepted among medical ethicists that competence is a necessary condition for informed consent. In this view, if a patient is incompetent to make a particular treatment decision, the decision must be based on an advance directive or made by a substitute decision-maker on behalf of the patient. We call this the competence model. According to a recent report of the United Nations (UN) High Commissioner for Human Rights, article 12 of the UN Convention on the Rights of Persons with Disabilities (CRPD) presents a wholesale rejection of the competence model. The High Commissioner here adopts the interpretation of article 12 proposed by the Committee on the Rights of Persons with Disabilities. On this interpretation, CRPD article 12 renders it impermissible to deny persons with mental disabilities the right to make treatment decisions on the basis of impaired decision-making capacity and demands the replacement of all regimes of substitute decision-making by supported decision-making. In this paper, we explicate six adverse consequences of CRPD article 12 for persons with mental disabilities and propose an alternative way forward. The proposed model combines the strengths of the competence model and supported decision-making. PMID:29070707

  19. Application of adverse outcome pathways (AOPs) in human health and ecotoxicology capturing divergent consequences of conserved molecular initiating events via AOP networks

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

  20. Application of Adverse Outcome Pathways (AOPs) in Human Health and Ecotoxicology Capturing Divergent Consequences of Conserved Molecular Initiating Events via AOP Networks (Presentation)

    EPA Science Inventory

    The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

  1. Potential consequences of clinical application of artificial gametes: a systematic review of stakeholder views.

    PubMed

    Hendriks, Saskia; Dondorp, Wybo; de Wert, Guido; Hamer, Geert; Repping, Sjoerd; Dancet, Eline A F

    2015-01-01

    Recent progress in the formation of artificial gametes, i.e. gametes generated from progenitors or somatic cells, has led to scientific and societal discussion about their use in medically assisted reproduction. In animals, live births have already been achieved using artificial gametes of varying (cell type) sources and biological research seems to be progressing steadily toward clinical application in humans. Artificial gametes could potentially help not only infertile heterosexual couples of reproductive age of which one or both partners lacks functional gametes, but also post-menopausal women and same-sex couples, to conceive a child who will be genetically related to them. But as clinical application of these new technologies may have wider societal consequences, a proactive consideration of the possible impact seems timely and important. This review aims to contribute to this by providing a systematic overview of the potential consequences of clinical application of artificial gametes anticipated by different stakeholders. The electronic database 'Medline/Pubmed' was systematically searched with medical subject heading terms (MesH) for articles published in English between January 1970 and December 2013. Articles were selected based on eligibility and reference lists of eligible studies were hand searched. The reported potential consequences of clinical application of artificial gametes were extracted from the articles and were grouped into categories by content analysis. Per category, we noted which stakeholders referred to which potential consequences, based on author affiliations and, if applicable, study participants. The systematic search yielded 2424 articles, and 84 studies were included after screening. Nine positive consequences, 21 specific consequences requiring consideration and 22 recommendations referring to clinical application of artificial gametes were documented. All positive consequences, consequences requiring consideration and

  2. Impact of Drug Cost Sharing on Service Use and Adverse Clinical Outcomes In Elderly Receiving Antidepressants

    PubMed Central

    Wang, Philip S.; Patrick, Amanda R.; Dormuth, Colin; Maclure, Malcolm; Avorn, Jerry; Canning, Claire F.; Schneeweiss, Sebastian

    2010-01-01

    Background Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) in have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale “natural experiments” in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a $25 Canadian copay ($10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance. Aims To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+. Methods Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models. Results Neither

  3. The nature, patterns, clinical outcomes, and financial impact of intraoperative adverse events in emergency surgery.

    PubMed

    Ramly, Elie P; Bohnen, Jordan D; Farhat, Maha R; Razmdjou, Shadi; Mavros, Michael N; Yeh, Daniel D; Lee, Jarone; Butler, Kathryn; De Moya, Marc; Velmahos, George C; Kaafarani, Haytham M A

    2016-07-01

    Little is known about intraoperative adverse events (iAEs) in emergency surgery (ES). We sought to describe iAEs in ES and to investigate their clinical and financial impact. The 2007 to 2012 administrative and American College of Surgeons-National Surgical Quality Improvement Program databases at our tertiary academic center were: (1) linked, (2) queried for all ES procedures, and then (3) screened for iAEs using the ICD-9-CM-based Patient Safety Indicator "accidental puncture/laceration". Flagged cases were systematically reviewed to: (1) confirm or exclude the occurrence of iAEs (defined as inadvertent injuries during the operation) and (2) extract additional variables such as procedure type, approach, complexity (measured by relative value units), need for adhesiolysis, and extent of repair. Univariate and multivariate analyses were performed to assess the independent impact of iAEs on 30-day morbidity, mortality, and hospital charges. Of a total of 9,288 patients, 1,284 (13.8%) patients underwent ES, of which 23 had iAEs (1.8%); 18 of 23 (78.3%) of the iAEs involved the small bowel or spleen, 10 of 23 (43.5%) required suture repair, and 8 of 23 (34.8%) required tissue or organ resection. Compared with those without iAEs, patients with iAEs were older (median age 62 vs 50; P = .04); their procedures were more complex (total relative value unit 46.7, interquartile range [27.5 to 52.6] vs 14.5 [.5 to 30.2]; P < .001), longer in duration (>3 hours: 52% vs 8%; P < .001), and more often required adhesiolysis (39.1% vs 13.5% P = .001). Patients with iAEs had increased total charges ($31,080 vs $11,330, P < .001), direct charges ($20,030 vs $7,387, P < .001), and indirect charges ($11,460 vs $4,088, P < .001). On multivariable analyses, iAEs were independently associated with increased 30-day morbidity (odds ratio, 3.56 [CI, 1.10 to 11.54]; P = .03) and prolonged postoperative length of stay (LOS; LOS >7 days; odds ratio, 5.60 [1.54 to 20.35]; P = .01]. A trend

  4. Adverse adult consequences of different alcohol use patterns in adolescence: An integrative analysis of data to age 30 years from four Australasian cohorts.

    PubMed

    Silins, Edmund; John Horwood, L; Najman, Jake M; Patton, George C; Toumbourou, John W; Olsson, Craig A; Hutchinson, Delyse M; Degenhardt, Louisa; Fergusson, David; Becker, Denise; Boden, Joseph M; Borschmann, Rohan; Plotnikova, Maria; Youssef, George J; Tait, Robert J; Clare, Philip; Hall, Wayne D; Mattick, Richard P

    2018-05-10

    Studies have linked adolescent alcohol use with adverse consequences in adulthood; yet it is unclear how strong the associations are and to what extent they may be due to confounding. Our aim was to estimate the strength of association between different patterns of adolescent drinking and longer-term psychosocial harms taking into account individual, family, and peer factors. Participant-level data were integrated from four long running longitudinal studies: Australian Temperament Project; Christchurch Health and Development Study; Mater Hospital and University of Queensland Study of Pregnancy; Victorian Adolescent Health Cohort Study. Australia and New Zealand. Participants were assessed on multiple occasions between ages 13 and 30 years (from 1991-2012). Number of participants varied (up to N=9453) by analysis. Three patterns of alcohol use (frequent, heavy episodic, and problem drinking) were assessed prior to age 17. Thirty outcomes were assessed to age 30 spanning substance use and related problems, antisocial behavior, sexual risk-taking, accidents, socioeconomic functioning, mental health, and partner relationships. After covariate adjustment, weekly drinking prior to age 17 was associated with a two to three-fold increase in the odds of binge drinking (OR: 2.14; 95%CI: 1.57-2.90), drink driving (OR: 2.78; 95%CI: 1.84-4.19), alcohol-related problems (OR: 3.04; 95%CI: 1.90-4.84), and alcohol dependence (OR: 3.30; 95%CI: 1.69-6.47) in adulthood. Frequency of drinking accounted for a greater proportion of the rate of most adverse outcomes than the other measures of alcohol use. Associations between frequent, heavy episodic, and problem drinking in adolescence and most non-alcohol outcomes were largely explained by shared risk factors for adolescent alcohol use and poor psychosocial functioning. Frequency of adolescent drinking predicts substance use problems in adulthood as much as, and possibly more than, heavy episodic and problem drinking independent of

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

    PubMed

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

    2006-03-01

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

  6. Hyaluronidase: Understanding Its Properties and Clinical Application for Cosmetic Injection Adverse Events.

    PubMed

    Harrison, Jeanine; Rhodes, Oriol

    The recent global consensus on the management of cosmetic aesthetic injectable complications from hyaluronic acid (HA) has increased the focus on the use of hyaluronidase more than ever before (M. Signorini et al., 2016). A comprehensive knowledge of facial anatomy, including structural positioning of facial arteries and veins, and an extensive knowledge of HA products available for injection procedures, combined with best practice protocols, will assist to prevent adverse events. Despite the growing number of patients using cosmetic fillers for facial restoration, the incidents incidence of adverse events remains low. Indeed, the avoidance of complications through safe and effective injection practice remains the key to preventing the need to use hyaluronidase.

  7. Adverse external ocular effects of topical ophthalmic therapy: an epidemiologic, laboratory, and clinical study.

    PubMed Central

    Wilson, F M

    1983-01-01

    New knowledge of adverse external ocular reactions to topical ophthalmic medications was obtained by means of a computerized epidemiologic study, laboratory studies, and clinical observations. Listed below are the major findings and conclusions that represent facts or concepts that were previously unknown, uncertain, misunderstood, or forgotten: The incidence of clinically important drug reactions among all cases was at least 13.09% and may have been as high as 16.02%. Among treated patients it was at least 16.26% to 19.90%. Taken together, drug reactions were the second most common external disease diagnosis. The incidence of each kind of drug reaction was determined. Toxic papillary reactions accounted for 79.10% of drug cases and 10.35% of all cases. Toxic papillary keratoconjunctivitis was the third most common single diagnosis. The following epidemiologic factors were found to be related to the development or presence of drug reactions: number and variety of treating practitioners, number of practitioners consulted, number of practitioners consulted who treated, specific ophthalmologist consulted (8.24% of ophthalmologists referred 39.55% of all drug cases and showed a tendency habitually to overtreat), number and kinds of patients' symptomatic complaints, number of medications prescribed and used, number of days of treatment, particular drugs and preservatives used (but not their strengths or vehicles), underlying (primary) diagnoses, and inaccuracy of referring ophthalmologists' diagnoses. Patients with dry eyes were especially at risk for the development of toxic papillary reactions. Among all cases, the incidence of reactions to preservatives (mainly thimerosal) in contact lens solutions was 0.39% to 1.95%, depending on whether definite or probable cases, respectively, were considered. The incidence among the 54 patients who used daily-wear lenses (excluding extended-wear therapeutic and optical contacts) was 7.41% for definite reactions and 37.04% for

  8. Vast Rise of Unconventional Hydraulic Fracturing in the United States, and the Extensive Adverse Ecological and Legal Consequences, Resulting from Failed Federal and State Regulatory Policies

    NASA Astrophysics Data System (ADS)

    Krokus, A.

    2017-12-01

    The quantity of unconventional HF campaigns has increased immensely, predominantly in the US, over the past decade. Numerous scholars have published research pertaining to the negative consequences resulting from HF. The principal contributor of the detrimental damage sustained, is the regulations administering HF, fail to protect against adverse externalities such as the increased frequency and intensity of injection induced seismicity. Induced earthquakes are now associated within the scope of civil litigation. Historically, seismicity has been perceived as an unpredictable catastrophic event. Currently, there is a plethora of litigation transpiring due to induced seismicity. These credible cases pose as a peril to existing legal theory, generating the potential to manifest profound consequences. Conducting qualitative policy oriented research indicated that regulations which protect against unfavorable repercussions, are administered by state authorities and corporations, who provide absolute governance. The EPA of 2005, 42 USCS § 15801 exempted HF from CWA, 33 USCS § 1251 and SWDA, 42 USCS § 300f. Applying an analytical jurisprudence approach, utilizing qualitative, longitudinal, and explanatory indagation, this study reviewed judicial dictum, orbiter dictum, along with transcripts related to every pending, dismissed, or settled litigated claim, related to damages involving induced seismicity in the states of AR, OK, and TX. Concluding that plaintiffs seeking declaratory and injunctive relief under RCRA, 42 U.S.C. § 6972(a)(1)(B) will be unsuccessful. District judges have followed precedent established by 319 U.S. 315 (1943), recently demonstrated in Sierra Club v. Chesapeake Operating, 5:16-CV-00134, and Pawnee Nation v. Eagle Road Oil, No. CIV-2017-803. Federal legislators can enact safe regulations under U.S. Const. art. I, § 8, cl. 3, articulated in 312 U.S. 100 (1941), reaffirmed by 317 U.S. 111 (1942), and 514 U.S. 549 (1995). OR has predicted a 40

  9. Comparison of serious adverse events posted at ClinicalTrials.gov and published in corresponding journal articles.

    PubMed

    Tang, Eve; Ravaud, Philippe; Riveros, Carolina; Perrodeau, Elodie; Dechartres, Agnes

    2015-08-14

    The reporting of serious adverse events (SAEs) in clinical trials is crucial to assess the balance between benefits and risks. For trials with serious adverse events posted at ClinicalTrials.gov, we assessed the consistency between SAEs posted at ClinicalTrials.gov and those published in corresponding journal articles. All records from ClinicalTrials.gov up to February 2014 were automatically exported in XML format. Among these, we identified all phase III or IV randomized controlled trials with at least one SAE posted. For a random sample of 300 of these trials, we searched for corresponding publications using MEDLINE via PubMed and extracted safety results from the articles. Among the sample of 300 trials with SAEs posted at ClinicalTrials.gov, 78 (26%) did not have a corresponding publication, and 20 (7%) had a publication that did not match the ClinicalTrials.gov record. For the 202 remaining trials, 26 published articles (13%) did not mention SAEs, 4 (2%) reported no SAEs, and 33 (16%) did not report the total number of SAEs per treatment group. Among the remaining 139 trials, for 44 (32%), the number of SAEs per group published did not match those posted at ClinicalTrials.gov. For 31 trials, the number of SAEs was greater at ClinicalTrials.gov than in the published article, with a difference ≥30 % for at least one group for 21. Only 33 trials (11%) had a publication reporting matching numbers of SAE and describing the type of SAE. Many trials with SAEs posted at ClinicalTrials.gov are not yet published, omit the reporting of these SAEs in corresponding publications, or report a discrepant number of SAEs as compared with ClinicalTrials.gov. These results underline the need to consult ClinicalTrials.gov for more information on serious harms.

  10. Common data elements for secondary use of electronic health record data for clinical trial execution and serious adverse event reporting.

    PubMed

    Bruland, Philipp; McGilchrist, Mark; Zapletal, Eric; Acosta, Dionisio; Proeve, Johann; Askin, Scott; Ganslandt, Thomas; Doods, Justin; Dugas, Martin

    2016-11-22

    Data capture is one of the most expensive phases during the conduct of a clinical trial and the increasing use of electronic health records (EHR) offers significant savings to clinical research. To facilitate these secondary uses of routinely collected patient data, it is beneficial to know what data elements are captured in clinical trials. Therefore our aim here is to determine the most commonly used data elements in clinical trials and their availability in hospital EHR systems. Case report forms for 23 clinical trials in differing disease areas were analyzed. Through an iterative and consensus-based process of medical informatics professionals from academia and trial experts from the European pharmaceutical industry, data elements were compiled for all disease areas and with special focus on the reporting of adverse events. Afterwards, data elements were identified and statistics acquired from hospital sites providing data to the EHR4CR project. The analysis identified 133 unique data elements. Fifty elements were congruent with a published data inventory for patient recruitment and 83 new elements were identified for clinical trial execution, including adverse event reporting. Demographic and laboratory elements lead the list of available elements in hospitals EHR systems. For the reporting of serious adverse events only very few elements could be identified in the patient records. Common data elements in clinical trials have been identified and their availability in hospital systems elucidated. Several elements, often those related to reimbursement, are frequently available whereas more specialized elements are ranked at the bottom of the data inventory list. Hospitals that want to obtain the benefits of reusing data for research from their EHR are now able to prioritize their efforts based on this common data element list.

  11. Male Hypogonadism and Osteoporosis: The Effects, Clinical Consequences, and Treatment of Testosterone Deficiency in Bone Health

    PubMed Central

    Houdek, Devon

    2017-01-01

    It is well recognized that bone loss accelerates in hypogonadal states, with female menopause being the classic example of sex hormones affecting the regulation of bone metabolism. Underrepresented is our knowledge of the clinical and metabolic consequences of overt male hypogonadism, as well as the more subtle age-related decline in testosterone on bone quality. While menopause and estrogen deficiency are well-known risk factors for osteoporosis in women, the effects of age-related testosterone decline in men on bone health are less well known. Much of our knowledge comes from observational studies and retrospective analysis on small groups of men with variable causes of primary or secondary hypogonadism and mild to overt testosterone deficiencies. This review aims to present the current knowledge of the consequences of adult male hypogonadism on bone metabolism. The direct and indirect effects of testosterone on bone cells will be explored as well as the important differences in male osteoporosis and assessment as compared to that in females. The clinical consequence of both primary and secondary hypogonadism, as well as testosterone decline in older males, on bone density and fracture risk in men will be summarized. Finally, the therapeutic options and their efficacy in male osteoporosis and hypogonadism will be discussed. PMID:28408926

  12. Cost and clinical consequence of antibiotic non-adherence in acute exacerbations of chronic bronchitis.

    PubMed

    Sorensen, S V; Baker, T; Fleurence, R; Dixon, J; Roberts, C; Haider, S; Hughes, D

    2009-08-01

    To quantify the impact of non-adherence on the clinical effectiveness of antibiotics for acute exacerbations of chronic bronchitis (AECB) and to estimate the economic consequences for Spain, Italy and the United States. Standard systematic reviewing procedures were followed to identify randomised controlled clinical trials of antibiotic treatment for acute respiratory tract infection for which adherence was reported. A decision-analytic model was then constructed to evaluate the impact of non-adherence to antibiotic treatment on clinical effectiveness and costs per AECB episode. The model compared the total treatment costs, cure rates and incremental costs per cure for a poor compliance group (PCG) against a good compliance group (GCG). Clinical and resource use estimates were from the published literature and physician surveys. Twenty-five articles met the criteria of the systematic review, although only one reported treatment success by adherence status. The relative risk of clinical effectiveness if non-adherent was 0.75 (95%CI 0.73-0.78). Based on this single study, the model predicted that 16-29% more patients would be cured in the GCG vs. the PCG, and payers would save up to euro122, euro179 and US$141 per AECB episode in Spain, Italy and the United States, respectively. Non-adherence to antibiotics for AECB may have an impact on clinical effectiveness, which is associated with increased costs.

  13. Adverse childhood experiences (ACE) and adult attachment interview (AAI) in a non-clinical population.

    PubMed

    Thomson, Paula; Jaque, S Victoria

    2017-08-01

    Adverse childhood experiences (ACE) tend to be interrelated rather than independently occurring. There is a graded effect associated with ACE exposure and pathology, with an increase when ACE exposure is four or more. This study examined a sample of active individuals (n=129) to determine distribution patterns and relationships between ACEs, attachment classification, unresolved mourning (U), and disclosure difficulty. The results of this study demonstrated a strong relationship between increased ACEs and greater unresolved mourning. Specifically, the group differences for individuals who experienced no ACE (n=42, 33%), those with 1-3 ACEs (n=48, 37.8%), and those with ≥4 ACEs (n=37, 29.1%) revealed a pattern in which increased group ACE exposure was associated with greater lack of resolution for past trauma/loss experiences, more adult traumatic events, and more difficulty disclosing past trauma. Despite ≥4 ACEs, 51.4% of highly exposed individuals were classified as secure in the Adult Attachment Interview. Resilience in this group may be related to a combination of attachment security, college education, and engagement in meaningful activities. Likewise, adversity may actually encourage the cultivation of more social support, goal efficacy, and planning behaviors; factors that augment resilience to adversity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Adverse Effects of Grape Seed Extract Supplement: A Clinical Case and Long-Term Follow-Up.

    PubMed

    Berry, Andrew C; Nakshabendi, Rahman; Abidali, Hussein; Atchaneeyasakul, Kunakorn; Dholaria, Kevin; Johnson, Cassandra; Kishore, Varsha A; Baltz, Aaron C

    2016-01-01

    Grape seed extract (GSE) supplement use is becoming more popular today for its potential chemopreventive and chemotherapeutic role. We report a 49-year-old male who presented with recurrent nausea, vomiting, diarrhea, and acute weakness following GSE use. A thorough medical workup ensued and no causes were identified clinically, procedurally, or with imaging. Symptoms resolved after GSE discontinuation and the patient remained symptom-free 5 years later. This case illustrates the paucity of documented detailed clinical cases and lack of controlled trials detailing a thorough and reproducible adverse effect profile of GSE supplement.

  15. Exploring the perception of nursing students about consequences of reflection in clinical settings

    PubMed Central

    Karimi, Shahnaz; Haghani, Fariba; Yamani, Nikoo; Kalyani, Majid Najafi

    2017-01-01

    Background Reflection on practical experiences is a key element that enables students to recognize their own strengths and weaknesses and develop nursing skills. Whilst reflection may enhance students’ learning in practice, there is little evidence about nursing students’ perception of the consequences of reflection in clinical settings. Objective This study aimed to explore Iranian nursing students’ perception regarding the consequences of reflection during clinical practices. Methods This qualitative study was conducted by a conventional content analysis approach in two nursing schools at Shiraz and Fasa Universities of Medical Sciences in Iran. Data were collected through in-depth semi-structured interviews during 2015–2016, from 20 students selected by purposive sampling. All the interviews were tape-recorded, transcribed verbatim, and analyzed by content analysis method. Rigor of this study was approved by member check and external audit. Results Two categories emerged from the data analysis, including movement toward professionalism and self-actualization of emotions. The former consisted of three subcategories of function modification, sharing experiences and generalizing experiences. The latter consisted of two subcategories of inner satisfaction and peace of mind. Conclusion The results indicated that nursing students’ reflection in clinical settings is effective in personal and professional levels. Reflection in a personal level led to positive emotions that increased the quality of care in patients. Accordingly, nursing educators need to create a nurturing climate as well as supporting reflective behaviors of nursing students. PMID:29038696

  16. Clinical outcomes and predictors of fetal and maternal consequences of pregnancy in lupus nephritis patients.

    PubMed

    Lv, Jiaxuan; Wang, Wei; Li, Yuehong

    2015-08-01

    To define the outcomes and risk predictors of fetal and maternal consequences of pregnancy in lupus nephritis (LN) patients. Maternal and fetal outcomes of pregnancy in 52 systemic lupus erythematosus (SLE) patients were observed. Patients were allocated into two groups according to the presence or absence of LN. LN patients were subject to a higher risk of fetal complications, including fetal loss (7/24, 29.2 %, P = 0.001), lower birth weight (2548.2 ± 540.8 vs. 2949.1 ± 592.6 g, P = 0.028) and a higher frequency of small for gestational age births (33.3 vs. 10.7 %, P = 0.002). Higher rates of lupus flares (83.3 vs. 21.4 %, P = 0.001) and increased LAI-P scores (0.65 ± 0.36 vs. 0.21 ± 0.27, P = 0.001) during pregnancy were observed in LN patients. Multivariate analysis showed that increased SLE activity (P = 0.02, OR 4.2, 95 % CI 1.2-14.5), renal damage (P = 0.001, OR 8.4, 95 % CI 2.2-31.8), hypocomplementemia (P = 0.05, OR 3.23, 95 % CI 1.0-10.7), hypoalbuminemia (P = 0.011, OR 5.62, 95 % CI 1.4-23.0) and hypertension (P = 0.021, OR 6.0, 95 % CI 1.5-24.2) during pregnancy were predictors of adverse fetal outcomes. Pregnancy in LN patients should be monitored before and during pregnancy because of poor fetal and maternal outcomes. Increased LAI-P scores, renal damage, hypocomplementemia, hypoalbuminemia and hypertension are predictors of adverse fetal outcomes for SLE patients.

  17. 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.

  18. 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.

  19. Genomic scar signatures associated with homologous recombination deficiency predict adverse clinical outcomes in patients with ovarian clear cell carcinoma.

    PubMed

    Chao, Angel; Lai, Chyong-Huey; Wang, Tzu-Hao; Jung, Shih-Ming; Lee, Yun-Shien; Chang, Wei-Yang; Yang, Lan-Yang; Ku, Fei-Chun; Huang, Huei-Jean; Chao, An-Shine; Wang, Chin-Jung; Chang, Ting-Chang; Wu, Ren-Chin

    2018-05-03

    We investigated whether genomic scar signatures associated with homologous recombination deficiency (HRD), which include telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH), can predict clinical outcomes in patients with ovarian clear cell carcinoma (OCCC). We enrolled patients with OCCC (n = 80) and high-grade serous carcinoma (HGSC; n = 92) subjected to primary cytoreductive surgery, most of whom received platinum-based adjuvant chemotherapy. Genomic scar signatures based on genome-wide copy number data were determined in all participants and investigated in relation to prognosis. OCCC had significantly lower genomic scar signature scores than HGSC (p < 0.001). Near-triploid OCCC specimens showed higher TAI and LST scores compared with diploid tumors (p < 0.001). While high scores of these genomic scar signatures were significantly associated with better clinical outcomes in patients with HGSC, the opposite was evident for OCCC. Multivariate survival analysis in patients with OCCC identified high LOH scores as the main independent adverse predictor for both cancer-specific (hazard ratio [HR] = 3.22, p = 0.005) and progression-free survival (HR = 2.54, p = 0.01). In conclusion, genomic scar signatures associated with HRD predict adverse clinical outcomes in patients with OCCC. The LOH score was identified as the strongest prognostic indicator in this patient group. Genomic scar signatures associated with HRD are less frequent in OCCC than in HGSC. Genomic scar signatures associated with HRD have an adverse prognostic impact in patients with OCCC. LOH score is the strongest adverse prognostic factor in patients with OCCC.

  20. The association of admission hyperglycaemia and adverse clinical outcome in medical emergencies: the multinational, prospective, observational TRIAGE study.

    PubMed

    Kutz, A; Struja, T; Hausfater, P; Amin, D; Amin, A; Haubitz, S; Bernard, M; Huber, A; Mueller, B; Schuetz, P

    2017-07-01

    The clinical relevance of hyperglycaemia in an emergency department population remains incompletely understood. We investigated the association between admission blood glucose levels and adverse clinical outcomes in a large emergency department cohort. We prospectively enrolled 7132 adult medical patients seeking emergency department care in three tertiary care hospitals in Switzerland, France and the USA. We used adjusted multivariable logistic regression models to examine the association between admission blood glucose levels and 30-day mortality, as well as adverse clinical course stratified by pre-existing diabetes and principal medical diagnoses. In 6044 people without diabetes (84.7%), severe hyperglycaemia, defined as a glucose level of > 11.1 mmol/l (200 mg/dl), was associated with a doubling in the risk of 30-day mortality [adjusted odds ratio (OR) 1.9; 95% confidence interval (95% CI), 1.1 to 3.3; P = 0.018] and a three-fold increase in the risk of intensive care unit admission (adjusted OR 3.0; 95% CI, 1.9 to 4.9; P < 0.001). These associations were similar among different diagnoses. In the population with diabetes (n = 1088), no association with 30-day mortality was found (adjusted OR 1.0; 95% CI, 0.6 to 1.8; P for interaction = 0.001), whereas the association with intensive care unit admission was weaker (adjusted OR 2.4; 95% CI, 1.5 to 4.1; P for interaction = 0.011). Overall 30-day mortality was higher in those with diabetes than in those without (6.1 vs. 4.4%, P = 0.015). In this large medical emergency department patient cohort, admission hyperglycaemia was strongly associated with adverse clinical course in people without diabetes. (Clinical Trial Registry No: NCT01768494). © 2017 Diabetes UK.

  1. QR in V1--an ECG sign associated with right ventricular strain and adverse clinical outcome in pulmonary embolism.

    PubMed

    Kucher, Nils; Walpoth, Nazan; Wustmann, Kerstin; Noveanu, Markus; Gertsch, Marc

    2003-06-01

    To test the hypothesis that Qr in V(1)is a predictor of pulmonary embolism, right ventricular strain, and adverse clinical outcome. ECG's from 151 patients with suspected pulmonary embolism were blindly interpreted by two observers. Echocardiography, troponin I, and pro-brain natriuretic peptide levels were obtained in 75 patients with pulmonary embolism. Qr in V(1)(14 vs 0 in controls; p<0.0001) and ST elevation in V(1)> or =1 mV (15 vs 1 in controls; p=0.0002) were more frequently present in patients with pulmonary embolism. Sensitivity and specificity of Qr in V(1)and T wave inversion in V(2)for predicting right ventricular dysfunction were 31/97% and 45/94%, respectively. Three of five patients who died in-hospital and 11 of 20 patients with a complicated course, presented with Qr in V(1). After adjustment for right ventricular strain including ECG, echocardiography, pro-brain natriuretic peptide and troponin I levels, Qr in V(1)(OR 8.7, 95%CI 1.4-56.7; p=0.02) remained an independent predictor of adverse outcome. Among the ECG signs seen in patients with acute pulmonary embolism, Qr in V(1)is closely related to the presence of right ventricular dysfunction, and is an independent predictor of adverse clinical outcome.

  2. Hemorheological alterations in sickle cell anemia and their clinical consequences - The role of genetic modulators.

    PubMed

    Silva, Marisa; Vargas, Sofia; Coelho, Andreia; Dias, Alexandra; Ferreira, Teresa; Morais, Anabela; Maia, Raquel; Kjöllerström, Paula; Lavinha, João; Faustino, Paula

    2016-01-01

    Sickle cell anemia (SCA) is an autosomal recessive disease caused by the HBB:c.20A>T mutation that leads to hemoglobin S synthesis. The disease presents with high clinical heterogeneity characterized by chronic hemolysis, recurrent episodes of vaso-oclusion and infection. This work aimed to characterize by in silico studies some genetic modulators of severe hemolysis and stroke risk in children with SCA, and understand their consequences at the hemorheological level.Association studies were performed between hemolysis biomarkers as well as the degree of cerebral vasculopathy and the inheritance of several polymorphic regions in genes related with vascular cell adhesion and vascular tonus in pediatric SCA patients. In silico tools (e.g. MatInspector) were applied to investigate the main variant consequences.Variants in vascular adhesion molecule-1 (VCAM1) gene promoter and endothelial nitric oxide synthase (NOS3) gene were significantly associated with higher degree of hemolysis and stroke events. They potentially modify transcription factor binding sites (e.g. VCAM1 rs1409419_T allele may lead to an EVI1 gain) or disturb the corresponding protein structure/function. Our findings emphasize the relevance of genetic variation in modulating the disease severity due to their effect on gene expression or modification of protein biological activities related with sickled erythrocyte/endothelial interactions and consequent hemorheological abnormalities.

  3. From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?

    PubMed

    McGregor, I S; Callaghan, P D; Hunt, G E

    2008-05-01

    Addictive drugs can profoundly affect social behaviour both acutely and in the long-term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the 'social neuropeptide' oxytocin and its possible role in acute and long-term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.

  4. The costs associated with adverse event procedures for an international HIV clinical trial determined by activity-based costing.

    PubMed

    Chou, Victoria B; Omer, Saad B; Hussain, Hamidah; Mugasha, Christine; Musisi, Maria; Mmiro, Francis; Musoke, Philippa; Jackson, J Brooks; Guay, Laura A

    2007-12-01

    To determine costs for adverse event (AE) procedures for a large HIV perinatal trial by analyzing actual resource consumption using activity-based costing (ABC) in an international research setting. The AE system for an ongoing clinical trial in Uganda was evaluated using ABC techniques to determine costs from the perspective of the study. Resources were organized into cost categories (eg, personnel, patient care expenses, laboratory testing, equipment). Cost drivers were quantified, and unit cost per AE was calculated. A subset of time and motion studies was performed prospectively to observe clinic personnel time required for AE identification. In 18 months, there were 9028 AEs, with 970 (11%) reported as serious adverse events. Unit cost per AE was $101.97. Overall, AE-related costs represented 32% ($920,581 of $2,834,692) of all study expenses. Personnel ($79.30) and patient care ($11.96) contributed the greatest proportion of component costs. Reported AEs were predominantly nonserious (mild or moderate severity) and unrelated to study drug(s) delivery. Intensive identification and management of AEs to conduct clinical trials ethically and protect human subjects require expenditure of substantial human and financial resources. Better understanding of these resource requirements should improve planning and funding of international HIV-related clinical trials.

  5. 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

  6. 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

  7. 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

  8. Clinical consequences of iron overload in patients with myelodysplastic syndromes: the case for iron chelation therapy.

    PubMed

    Shammo, Jamile M; Komrokji, Rami S

    2018-06-14

    Patients with myelodysplastic syndromes (MDS) are at increased risk of iron overload due to ineffective erythropoiesis and chronic transfusion therapy. The clinical consequences of iron overload include cardiac and/or hepatic failure, endocrinopathies, and infection risk. Areas covered: Iron chelation therapy (ICT) can help remove excess iron and ultimately reduce the clinical consequences of iron overload. The authors reviewed recent (last five years) English-language articles from PubMed on the topic of iron overload-related complications and the use of ICT (primarily deferasirox) to improve outcomes in patients with MDS. Expert Commentary: While a benefit of ICT has been more firmly established in other transfusion-dependent conditions such as thalassemia, its role in reducing iron overload in MDS remains controversial due to the lack of prospective controlled data demonstrating a survival benefit. Orally administered chelation agents (e.g., deferasirox), are now available, and observational and/or retrospective data support a survival benefit of using ICT in MDS. The placebo-controlled TELESTO trial (NCT00940602) is currently examining the use of deferasirox in MDS patients with iron overload, and is evaluating specifically whether use of ICT to alleviate iron overload can also reduce iron overload-related complications in MDS and improve survival.

  9. Bitopic Binding Mode of an M1 Muscarinic Acetylcholine Receptor Agonist Associated with Adverse Clinical Trial Outcomes

    PubMed Central

    Bradley, Sophie J.; Molloy, Colin; Bundgaard, Christoffer; Mogg, Adrian J.; Thompson, Karen J.; Dwomoh, Louis; Sanger, Helen E.; Crabtree, Michael D.; Brooke, Simon M.; Sexton, Patrick M.; Felder, Christian C.; Christopoulos, Arthur; Broad, Lisa M.

    2018-01-01

    The realization of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (mAChR) for the treatment of cognitive decline in Alzheimer’s disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702 (7-fluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1H-benzimidazol-2-one), described previously as a potent M1 receptor allosteric agonist, which showed procognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702, together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. Although they impart beneficial effects on learning and memory, we conclude that these properties are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data support the notion that “pure” positive allosteric modulators showing selectivity for the M1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses. PMID:29695609

  10. Bitopic Binding Mode of an M1 Muscarinic Acetylcholine Receptor Agonist Associated with Adverse Clinical Trial Outcomes.

    PubMed

    Bradley, Sophie J; Molloy, Colin; Bundgaard, Christoffer; Mogg, Adrian J; Thompson, Karen J; Dwomoh, Louis; Sanger, Helen E; Crabtree, Michael D; Brooke, Simon M; Sexton, Patrick M; Felder, Christian C; Christopoulos, Arthur; Broad, Lisa M; Tobin, Andrew B; Langmead, Christopher J

    2018-06-01

    The realization of the therapeutic potential of targeting the M 1 muscarinic acetylcholine receptor (mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M 1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702 (7-fluoro-5-methyl-3-[1-(oxan-4-yl)piperidin-4-yl]-1 H -benzimidazol-2-one), described previously as a potent M 1 receptor allosteric agonist, which showed procognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side effects. Here we provide evidence using ligand binding, chemical biology and functional assays to establish that rather than the allosteric mechanism claimed, GSK1034702 interacts in a bitopic manner at the M 1 mAChR such that it can concomitantly span both the orthosteric and an allosteric binding site. The bitopic nature of GSK1034702, together with the intrinsic agonist activity and a lack of muscarinic receptor subtype selectivity reported here, all likely contribute to the adverse effects of this molecule in clinical trials. Although they impart beneficial effects on learning and memory, we conclude that these properties are undesirable in a clinical candidate due to the likelihood of adverse side effects. Rather, our data support the notion that "pure" positive allosteric modulators showing selectivity for the M 1 mAChR with low levels of intrinsic activity would be preferable to provide clinical efficacy with low adverse responses. Copyright © 2018 by The Author(s).

  11. Mild orotic aciduria in UMPS heterozygotes: a metabolic finding without clinical consequences.

    PubMed

    Wortmann, Saskia B; Chen, Margaret A; Colombo, Roberto; Pontoglio, Alessandro; Alhaddad, Bader; Botto, Lorenzo D; Yuzyuk, Tatiana; Coughlin, Curtis R; Descartes, Maria; Grűnewald, Stephanie; Maranda, Bruno; Mills, Philippa B; Pitt, James; Potente, Catherine; Rodenburg, Richard; Kluijtmans, Leo A J; Sampath, Srirangan; Pai, Emil F; Wevers, Ron A; Tiller, George E

    2017-05-01

    Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life. If not treated with the pyrimidine precursor uridine, neutropenia, failure to thrive, growth retardation, developmental delay, and intellectual disability may ensue. We identified mild and isolated orotic aciduria in 11 unrelated individuals with diverse clinical signs and symptoms, the most common denominator being intellectual disability/developmental delay. Of note, none had blood count abnormalities, relevant hyperammonemia or altered plasma amino acid profile. All individuals were found to have heterozygous alterations in UMPS. Four of these variants were predicted to be null alleles with complete loss of function. The remaining variants were missense changes and predicted to be damaging to the normal encoded protein. Interestingly, family screening revealed heterozygous UMPS variants in combination with mild orotic aciduria in 19 clinically asymptomatic family members. We therefore conclude that heterozygous UMPS-mutations can lead to mild and isolated orotic aciduria without clinical consequence. Partial UMPS-deficiency should be included in the differential diagnosis of mild orotic aciduria. The discovery of heterozygotes manifesting clinical symptoms such as hypotonia and developmental delay are likely due to ascertainment bias.

  12. [Clinical consequences of replacing milk with yogurt in persistent infantile diarrhea].

    PubMed

    Touhami, M; Boudraa, G; Mary, J Y; Soltana, R; Desjeux, J F

    1992-02-01

    Persistent diarrhea is an episode of diarrhea that begins acutely but lasts longer than expected for this usually self-limited disease. Treatment of this ill-defined syndrome is not well standardized but immediate intervention is required to minimize the risk of malnutrition with its various consequences. This randomized clinical trial was undertaken to evaluate the clinical efficacy of substituting yogurt for milk, as the only treatment. After a one to two-day observation period during which a standard milk diet was given, 78 children aged 3 to 36 months with confirmed persistent diarrhea of more than 15 days but less than one month duration and negative tests for fecal blood were fed either milk (infant formula) or yogurt (infant formula fermented with Lactobacillus bulgaricus and Streptococcus thermophilus). At inclusion both groups were comparable for age, nutritional status, diarrhea, and lactose hydrogen breath test results. Clinical treatment failure (weight loss greater than 5% in one day or persistent diarrhea after 5 days) was significantly less common in children fed yogurt (15 +/- 6%) than in children fed milk (45 +/- 8%). The beneficial effects of feeding yogurt were apparent within 48 hours in 67 +/- 8% of infants. In conclusion, these data confirm the clinical efficacy of substituting yogurt for milk in young children with persistent diarrhea. They also suggest that yogurt may be a good alternative for the initial treatment of persistent diarrhea.

  13. Volume overload and adverse outcomes in chronic kidney disease: clinical observational and animal studies.

    PubMed

    Hung, Szu-Chun; Lai, Yi-Shin; Kuo, Ko-Lin; Tarng, Der-Cherng

    2015-05-05

    Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume overload and adverse outcomes in CKD is not fully understood. A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end-stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high-salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor-α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes. Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

    PubMed

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

    2017-12-22

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

  15. 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

  16. OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

    PubMed

    Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

    2016-01-01

    Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

  17. A randomized clinical trial on the effects of remote intercessory prayer in the adverse outcomes of pregnancies.

    PubMed

    da Rosa, Maria Inês; Silva, Fabio Rosa; Silva, Bruno Rosa; Costa, Luciana Carvalho; Bergamo, Angela Mendes; Silva, Napoleão Chiaramonte; Medeiros, Lidia Rosi de Freitas; Battisti, Iara Denise Endruweit; Azevedo, Rafael

    2013-08-01

    The scope of this article was to investigate whether intercessory prayer (IP) influences the adverse outcomes of pregnancies. A double-blind, randomized clinical trial was conducted with 564 pregnant women attending a prenatal public health care service. The women were randomly assigned to an IP group or to a control group (n = 289 per group). They were simultaneously and randomly assigned to practice prayer off-site or not. The following parameters were evaluated: Apgar scores, type of delivery and birth weight. The mean age of the women was 25.1 years of age (± 7.4), and the average gestational age was 23.4 weeks (± 8.1). The average number of years of schooling for the women was 8.1 years (± 3.1). The women in the IP and control groups presented a similar number of adverse medical events with non-significant p. No significant differences were detected in the frequency of adverse outcomes in pregnant women who practiced IP and those in the control group.

  18. Clinical Consequences of Mutations in Thyroid Hormone Receptor-α1

    PubMed Central

    van Mullem, Alies A.; Visser, Theo J.; Peeters, Robin P.

    2014-01-01

    Thyroid hormone (TH) exerts its biological activity via the TH receptors TRα1 and TRβ1/2, which are encoded by the THRA and THRB genes. The first patients with mutations in THRB were identified decades ago. These patients had a clinical syndrome of resistance to TH associated with high serum TH and nonsuppressed thyroid-stimulating hormone levels. Until recently, no patients with mutations in THRA had been identified. In an attempt to predict the clinical phenotype of such patients, different TRα1 mutant mouse models have been generated. These mice have a variable phenotype depending on the location and severity of the mutation. Recently, the first humans with mutations in THRA were identified. Their phenotype consists of relatively low serum T4 and high serum T3 levels (and thus an elevated T3/T4 ratio), growth retardation, delayed mental and bone development, and constipation. While, in retrospect, certain features present in humans can also be found in mouse models, the first humans carrying a defect in TRα1 were not suspected of having a THRA gene mutation initially. The current review focuses on the clinical consequences of TRα1 mutations. PMID:24847461

  19. [Emotional consequences of sterilization. Clinical comments on the methodology of psychological studies].

    PubMed

    Petersen, P

    1983-04-01

    72 detailed psychiatric and psychological retrospective and prospective investigations (from 1928-1975) on the emotional consequences of male and female sterilization were reviewed and the international literature is summarized. Favorable conditions for sterilization are clear and decisive motivation, freedom of decision making, throrough understanding of the decision of the sexual partner, a harmonious relationship with that partner, a stable and sensitive personality, and thorough preoperative individual counseling. Integration of the procedure may take from 1-4 years and occurs in both partners. This is a dynamic process which brings with it a crisis during which the disturbance may be integrated. Consequently, surgical contraception is a challenge to the relationship of the partners. Investigations to date point to coveted motivation. Personal ambition of the investigator, justification for the operation, political motives in favor of widespread surgical sterilization, and pragmatic clinical motives are often found. Rarely is the motive in the investigation the mere search for scientific truth. Frequently, perfectionistic objectivisim and positivism are found and the subjectivity of the investigator and client is eliminated. In future investigations, the transparency in the relationship of the investigator and client and anthropological concepts should be considered. Part of the investigation must consider transcultural comparisons in the significance of liberty, love, and loyality in reproduction and family planning. (author's)

  20. Gaps in clinical prevention and treatment for alcohol use disorders: costs, consequences, and strategies.

    PubMed

    Willenbring, Mark L

    2013-01-01

    Heavy drinking causes significant morbidity, premature mortality, and other social and economic burdens on society, prompting numerous prevention and treatment efforts to avoid or ameliorate the prevalence of heavy drinking and its consequences. However, the impact on public health of current selective (i.e., clinical) prevention and treatment strategies is unclear. Screening and brief counseling for at-risk drinkers in ambulatory primary care has the strongest evidence for efficacy, and some evidence indicates this approach is cost-effective and reduces excess morbidity and dysfunction. Widespread implementation of screening and brief counseling of nondependent heavy drinkers outside of the medical context has the potential to have a large public health impact. For people with functional dependence, no appropriate treatment and prevention approaches currently exist, although such strategies might be able to prevent or reduce the morbidity and other harmful consequences associated with the condition before its eventual natural resolution. For people with alcohol use disorders, particularly severe and recurrent dependence, treatment studies have shown improvement in the short term. However, there is no compelling evidence that treatment of alcohol use disorders has resulted in reductions in overall disease burden. More research is needed on ways to address functional alcohol dependence as well as severe and recurrent alcohol dependence.

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

    PubMed

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

    2014-12-17

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

  2. Clinical review: kinase inhibitors: adverse effects related to the endocrine system.

    PubMed

    Lodish, Maya B

    2013-04-01

    The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.

  3. Clinical consequences of initial duloxetine dosing strategies: Comparison of 30 and 60 mg QD starting doses

    PubMed Central

    Dunner, David L.; Wohlreich, Madelaine M.; Mallinckrodt, Craig H.; Watkin, John G.; Fava, Maurizio

    2005-01-01

    Background: To reduce the risk for treatment-emergent adverse events and increase patient compliance, clinicians frequently prescribe a suboptimal starting dose of antidepressants, with the goal of increasing the dose once the patient has demonstrated tolerability. Objective: The aim of this study was to examine the tolerability and effectiveness associated with an initial week of duloxetine hydrochloride treatment at 30 mg QD and subsequent dose increase to 60 mg QD, compared with a starting dose of 60 mg QD. Methods: In this open-label study, all patients met the criteria for major depressive disorder (MDD) described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were required to wash out from previous antidepressant medications for 21 days, and were then randomized to receive duloxetine 30 or 60 mg QD for 1 week. After 1 week, patients receiving duloxetine 30 mg QD had their dose increased to 60 mg QD. Patients returned for assessments at weeks 2, 4, 6, 8, and 12. During the remainder of the 12-week study period, the duloxetine dose could be titrated based on the degree of response from 60 mg QD (minimum) to 120 mg QD (maximum), with 90 mg QD as an intermediate dose. Tolerability was assessed by means of discontinuation rates, spontaneously reported adverse events, changes in vital signs, and laboratory tests. Effectiveness measures included the 17-item Hamilton Rating Scale for Depression (HAMD17) total score, HAMD17 core and Maier subscales, individual HAMD17 items, the Hamilton Rating Scale for Anxiety total score, and the Clinical Global Impression of Severity. Results: One hundred thirty-seven patients were enrolled (82 women, 55 men; mean age, 42 years; duloxetine 30 mg QD, 67 patients; duloxetine 60 mg QD, 70 patients). The rate of discontinuation due to adverse events did not differ significantly between patients starting duloxetine at 30 mg QD and 60 mg QD (13

  4. 45 CFR 60.12 - Reporting adverse actions taken against clinical privileges.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... privileges of a physician or dentist for a period longer than 30 days, (ii) Acceptance of the surrender of clinical privileges or any restriction of such privileges by a physician or dentist: (A) While the physician or dentist is under investigation by the health care entity relating to possible incompetence or...

  5. 45 CFR 60.12 - Reporting adverse actions taken against clinical privileges.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... privileges of a physician or dentist for a period longer than 30 days, (ii) Acceptance of the surrender of clinical privileges or any restriction of such privileges by a physician or dentist: (A) While the physician or dentist is under investigation by the health care entity relating to possible incompetence or...

  6. Clinical events in coronary patients who report low distress: adverse effect of repressive coping.

    PubMed

    Denollet, Johan; Martens, Elisabeth J; Nyklícek, Ivan; Conraads, Viviane M; de Gelder, Beatrice

    2008-05-01

    Coronary artery disease (CAD) patients who report low distress are considered to be at low psychological risk for clinical events. However, patients with a repressive coping style may fail to detect and report signals of emotional distress. The authors hypothesized that repressive CAD patients are at risk for clinical events, despite low self-rated distress. This was a prospective 5- to 10-year follow-up study, with a mean follow-up of 6.6 years. At baseline, 731 CAD patients filled out Trait-Anxiety (distress), Marlowe-Crowne (defensiveness), and Type D scales; 159 patients were classified as "repressive," 360 as "nonrepressive," and 212 as "Type D." The primary endpoint was a composite of total mortality or myocardial infarction (MI); the secondary endpoint was cardiac mortality/MI. No patients were lost to follow-up; 91 patients had a clinical event (including 35 cardiac death and 32 MI). Repressive patients reported low levels of anxiety, anger and depression at baseline, but were at increased risk for death/MI (21/159 = 13%) compared with nonrepressive patients (22/360 = 6%), p = .009. Poor systolic function, poor exercise tolerance, 3-vessel disease, index MI and Type-D personality--but not depression, anxiety or anger--also independently predicted clinical events. After controlling for these variables, repressive patients still had a twofold increased risk of death/MI, OR = 2.17, 95% CI = 1.10-4.08, p = .025). These findings were replicated for cardiac mortality/MI. CAD patients who use a repressive coping style are at increased risk for clinical events, despite their claims of low emotional distress. This phenomenon may cause an underestimation of the effect of stress on the heart. (PsycINFO Database Record (c) 2008 APA, all rights reserved).

  7. Evaluating statistical approaches to leverage large clinical datasets for uncovering therapeutic and adverse medication effects.

    PubMed

    Choi, Leena; Carroll, Robert J; Beck, Cole; Mosley, Jonathan D; Roden, Dan M; Denny, Joshua C; Van Driest, Sara L

    2018-04-18

    Phenome-wide association studies (PheWAS) have been used to discover many genotype-phenotype relationships and have the potential to identify therapeutic and adverse drug outcomes using longitudinal data within electronic health records (EHRs). However, the statistical methods for PheWAS applied to longitudinal EHR medication data have not been established. In this study, we developed methods to address two challenges faced with reuse of EHR for this purpose: confounding by indication, and low exposure and event rates. We used Monte Carlo simulation to assess propensity score (PS) methods, focusing on two of the most commonly used methods, PS matching and PS adjustment, to address confounding by indication. We also compared two logistic regression approaches (the default of Wald vs. Firth's penalized maximum likelihood, PML) to address complete separation due to sparse data with low exposure and event rates. PS adjustment resulted in greater power than propensity score matching, while controlling Type I error at 0.05. The PML method provided reasonable p-values, even in cases with complete separation, with well controlled Type I error rates. Using PS adjustment and the PML method, we identify novel latent drug effects in pediatric patients exposed to two common antibiotic drugs, ampicillin and gentamicin. R packages PheWAS and EHR are available at https://github.com/PheWAS/PheWAS and at CRAN (https://www.r-project.org/), respectively. The R script for data processing and the main analysis is available at https://github.com/choileena/EHR. leena.choi@vanderbilt.edu. Supplementary data are available at Bioinformatics online.

  8. Postoperative tricuspid regurgitation after adult congenital heart surgery is associated with adverse clinical outcomes.

    PubMed

    Lewis, Matthew J; Ginns, Jonathan N; Ye, Siqin; Chai, Paul; Quaegebeur, Jan M; Bacha, Emile; Rosenbaum, Marlon S

    2016-02-01

    Many patients with adult congenital heart disease will require cardiac surgery during their lifetime, and some will have concomitant tricuspid regurgitation. However, the optimal management of significant tricuspid regurgitation at the time of cardiac surgery remains unclear. We assessed the determinants of adverse outcomes in patients with adult congenital heart disease and moderate or greater tricuspid regurgitation undergoing cardiac surgery for non-tricuspid regurgitation-related indications. All adult patients with congenital heart disease and greater than moderate tricuspid regurgitation who underwent cardiac surgery for non-tricuspid regurgitation-related indications were included in a retrospective study at the Schneeweiss Adult Congenital Heart Center. Cohorts were defined by the type of tricuspid valve intervention at the time of surgery. The primary end point of interest was a composite of death, heart transplantation, and reoperation on the tricuspid valve. A total of 107 patients met inclusion criteria, and 17 patients (17%) reached the primary end point. A total of 68 patients (64%) underwent tricuspid valve repair, 8 patients (7%) underwent tricuspid valve replacement, and 31 patients (29%) did not have a tricuspid valve intervention. By multivariate analysis, moderate or greater postoperative tricuspid regurgitation was associated with a hazard ratio of 6.12 (1.84-20.3) for the primary end point (P = .003). In addition, failure to perform a tricuspid valve intervention at the time of surgery was associated with an odds ratio of 4.17 (1.26-14.3) for moderate or greater postoperative tricuspid regurgitation (P = .02). Moderate or greater postoperative tricuspid regurgitation was associated with an increased risk of death, transplant, or reoperation in adult patients with congenital heart disease undergoing cardiac surgery for non-tricuspid regurgitation-related indications. Concomitant tricuspid valve intervention at the time of cardiac surgery should

  9. Clinical Outcome Score Predicts Adverse Neurodevelopmental Outcome After Infant Heart Surgery.

    PubMed

    Mackie, Andrew S; Vatanpour, Shabnam; Alton, Gwen Y; Dinu, Irina A; Ryerson, Lindsay; Moddemann, Diane M; Thomas Petrie, Julie

    2015-06-01

    The purpose of this study was to determine whether a clinical outcome score derived from early postoperative events is associated with Bayley-III scores at 18 to 24 months among infants undergoing cardiopulmonary bypass surgery. Included were infants aged 6 weeks or less who underwent surgery between 2005 and 2009, all of whom were referred for neurodevelopmental evaluation at 18 to 24 months. We excluded children with chromosomal abnormalities. The prespecified clinical outcome score had a range of 0 to 7. Lower scores indicated a more rapid postoperative recovery. Patients requiring extracorporeal life support were assigned a score of 7. One hundred and ninety-nine subjects were included. Surgical procedures were arterial switch (72), Norwood (60), repair of total anomalous pulmonary venous connection (29), and other (38). Nine subjects had postoperative extracorporeal life support. Mean clinical outcome score in the Norwood group was 4.0 ± 1.4 versus the arterial switch group (2.6 ± 1.5, p < 0.001), total anomalous pulmonary venous connection group (2.8 ± 1.8, p < 0.01), and other group (4.0 ± 1.8, p = not significant). Among children who had a clinical outcome score of 4 or greater, there was a decrease in Bayley-III cognitive score of 5.7 (95% confidence interval: 1.5 to 9.9, p = 0.009), a decrease in language score of 10.0 (95% confidence interval: 4.9 to 15.1, p < 0.001), and a decrease in motor score of 9.7 (95% confidence interval: 4.8 to 14.5, p < 0.001). Time until lactate of 2.0 mmol/L or less and highest 24-hour inotrope score increased with increasing clinical outcome score (p < 0.0001). Clinical outcome scores of 4 or greater were associated with significantly lower Bayley-III scores at 18 to 24 months. This score may be valuable as an endpoint when evaluating novel potential therapies for this high-risk population. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Overview of the Clinical Consult Case Review of Adverse Events Following Immunization: Clinical Immunization Safety Assessment Network (CISA) 2004-2009

    PubMed Central

    Williams, S Elizabeth; Klein, Nicola P; Halsey, Neal; Dekker, Cornelia L; Baxter, Roger P; Marchant, Colin D; LaRussa, Philip S; Sparks, Robert C; Tokars, Jerome I; Pahud, Barbara A; Aukes, Laurie; Jakob, Kathleen; Coronel, Silvia; Choi, Howard; Slade, Barbara A; Edwards, Kathryn M

    2016-01-01

    Background In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). Methods Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. Results CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. Conclusions The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations. PMID:21801776

  11. Red blood cell antibodies in pregnancy and their clinical consequences: synergistic effects of multiple specificities.

    PubMed

    Nordvall, Maria; Dziegiel, Morten; Hegaard, Hanne Kristine; Bidstrup, Mogens; Jonsbo, Finn; Christensen, Birgit; Hedegaard, Morten

    2009-10-01

    The objective was to determine clinical consequences of various specificities for the infant/fetus. The population was patients referred between 1998 and 2005 to the tertiary center because of detected red blood cell (RBC) alloimmunization. Altogether 455 infants were delivered by 390 alloimmunized women. This was a retrospective cohort study. Data were obtained from the blood bank register and the obstetric and neonatal database. As indicators of hemolytic activity of the antibodies, the frequency of the therapeutic interventions intrauterine transfusion, exchange transfusion, and simple transfusion was used. Anti-D was the most common antibody (46.6%), followed by anti-K (15.4%). A combination of antibodies was detected in 27%. All three types of therapeutic intervention were significantly more frequent in women with anti-D plus an additional antibody than in women with anti-D as the sole antibody. The anti-D titer closely paralleled the clinical importance of the antibody. One case of anti-s with a titer of 512 required all three types of transfusion. Anti-D was the single most frequent and harmful specificity closely followed by anti-K. Combinations of antibody specificities were more harmful than single specificities, and a potentially synergistic effect should be considered.

  12. Molecular outcomes, clinical consequences, and genetic diagnosis of Oculocutaneous Albinism in Pakistani population.

    PubMed

    Shahzad, Mohsin; Yousaf, Sairah; Waryah, Yar M; Gul, Hadia; Kausar, Tasleem; Tariq, Nabeela; Mahmood, Umair; Ali, Muhammad; Khan, Muzammil A; Waryah, Ali M; Shaikh, Rehan S; Riazuddin, Saima; Ahmed, Zubair M

    2017-03-07

    Nonsyndromic oculocutaneous Albinism (nsOCA) is clinically characterized by the loss of pigmentation in the skin, hair, and iris. OCA is amongst the most common causes of vision impairment in children. To date, pathogenic variants in six genes have been identified in individuals with nsOCA. Here, we determined the identities, frequencies, and clinical consequences of OCA alleles in 94 previously unreported Pakistani families. Combination of Sanger and Exome sequencing revealed 38 alleles, including 22 novel variants, segregating with nsOCA phenotype in 80 families. Variants of TYR and OCA2 genes were the most common cause of nsOCA, occurring in 43 and 30 families, respectively. Twenty-two novel variants include nine missense, four splice site, two non-sense, one insertion and six gross deletions. In vitro studies revealed retention of OCA proteins harboring novel missense alleles in the endoplasmic reticulum (ER) of transfected cells. Exon-trapping assays with constructs containing splice site alleles revealed errors in splicing. As eight alleles account for approximately 56% (95% CI: 46.52-65.24%) of nsOCA cases, primarily enrolled from Punjab province of Pakistan, hierarchical strategies for variant detection would be feasible and cost-efficient genetic tests for OCA in families with similar origin. Thus, we developed Tetra-primer ARMS assays for rapid, reliable, reproducible and economical screening of most of these common alleles.

  13. Lost in Translation: The Unintended Consequences of Advance Directive Law on Clinical Care

    PubMed Central

    Castillo, Lesley S.; Williams, Brie A.; Hooper, Sarah M.; Sabatino, Charles P.; Weithorn, Lois A.; Sudore, Rebecca L.

    2011-01-01

    Background Advance directive law may compromise the clinical effectiveness of advance directives. Purpose To identify unintended legal consequences of advance directive law that may prevent patients from communicating end-of-life preferences. Data Sources Advance directive legal statutes for all 50 U.S. states and the District of Columbia and English-language searches of LexisNexis, Westlaw, and MEDLINE from 1966 to August 2010. Study Selection Two independent reviewers selected 51 advance directive statutes and 20 articles. Three independent legal reviewers selected 105 legal proceedings. Data Extraction Two reviewers independently assessed data sources and used critical content analysis to determine legal barriers to the clinical effectiveness of advance directives. Disagreements were resolved by consensus. Data Synthesis Legal and content-related barriers included poor readability (that is, laws in all states were written above a 12th-grade reading level), health care agent or surrogate restrictions (for example, 40 states did not include same-sex or domestic partners as default surrogates), and execution requirements needed to make forms legally valid (for example, 35 states did not allow oral advance directives, and 48 states required witness signatures, a notary public, or both). Vulnerable populations most likely to be affected by these barriers included patients with limited literacy, limited English proficiency, or both who cannot read or execute advance directives; same-sex or domestic partners who may be without legally valid and trusted surrogates; and unbefriended, institutionalized, or homeless patients who may be without witnesses and suitable surrogates. Limitation Only appellate-level legal cases were available, which may have excluded relevant cases. Conclusion Unintended negative consequences of advance directive legal restrictions may prevent all patients, and particularly vulnerable patients, from making and communicating their end

  14. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

    PubMed Central

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

  15. First experiences with a tool to measure the level of clinical information present in adverse drug reaction reports.

    PubMed

    Oosterhuis, Ingrid; Rolfes, Leàn; Ekhart, Corine; Muller-Hansma, Annemarie; Härmark, Linda

    2018-02-01

    To make a proper causality assessment of an adverse drug reaction (ADR) report, a certain level of clinical information is necessary. A tool was developed to measure the level of clinical information present in ADR reports. The aim of this study was to test the validity and reliability of the clinical documentation tool (ClinDoc) in an international setting. The tool was developed by a panel of pharmacovigilance experts. It includes four domains: ADR, chronology of the ADR, suspected drug and patient characteristics. The final score categorizes reports into: excellent, well, moderately or poorly documented. In two rounds, eight pharmacovigilance assessors of different countries made a total of 224 assessments using the tool, with the expert panels judgement as a standard. Sensitivity and specificity were calculated. The tool with four outcome-categories demonstrated low sensitivity. A lack of distinctiveness was demonstrated between the categories moderate and well. Results for the second round were re-analysed using three categories. This demonstrated a better validity. This is the first tool to give insight in the level of relevant clinical information present in ADR reports. It can be used internationally to compare reports coming from different reporting methods and different types of reporters in pharmacovigilance.

  16. Potential adverse cardiac remodelling in highly trained athletes: still unknown clinical significance.

    PubMed

    Gabrielli, Luigi; Sitges, Marta; Chiong, Mario; Jalil, Jorge; Ocaranza, María; Llevaneras, Silvana; Herrera, Sebastian; Fernandez, Rodrigo; Saavedra, Rodrigo; Yañez, Fernando; Vergara, Luis; Diaz, Alexis; Lavandero, Sergio; Castro, Pablo

    2018-06-12

    Moderate endurance exercise has long been considered an essential element to maintain cardiovascular health, and sedentary behaviour in the general population has been related to a significant increase in all-causes of mortality, cardiovascular disease mortality and cardiovascular disease incidence. However, a growing group of people performs an intense exercise that leads to multiple heart adaptive changes that are collectively called "athlete's heart". In this review, we discussed the evidence of cardiac remodelling process secondary to repetitive and strenuous exercise in some predisposed athletes that produces intense and probably deleterious changes in cardiac morphology and function with no clear clinical significance in long-term follow-up. Moreover, we also discussed the individual biological response to exercise assessed by myocardial damage, inflammation, oxidative stress, fibrosis and ventricular hypertrophy biomarkers showing different intensities with equivalent exertion.

  17. 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

  18. Intestinal Microbiota-Dependent Phosphatidylcholine Metabolites, Diastolic Dysfunction and Adverse Clinical Outcomes in Chronic Systolic Heart Failure

    PubMed Central

    Wilson Tang, W. H.; Wang, Zeneng; Shrestha, Kevin; Borowski, Allen G; Wu, Yuping; Troughton, Richard W; Klein, Allan L; Hazen, Stanley L

    2014-01-01

    Background Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aim to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). Methods and Results In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median TMAO levels, choline, and betaine levels were 5.8 [3.6, 12.1] μM, 10.9 [8.4, 14.0] μM, 43.8 [37.1, 53.0] μM, respectively, and were correlated with each other (all p<0.0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9, 13.2] vs 4.8 [3.4, 9.8] μM, p=0.005) and in subjects with New York Heart Association (NYHA) class III or greater (7.0 [4.7, 14.8] vs 4.7 [3.4, 11.3] μM, p=0.02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma NT-proBNP levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (Hazard ratio (HR) 1.64 [95% CI: 1.22 2.20], p=0.001), betaine (HR 1.51 [1.10–2.08], p=0.01), and TMAO (HR 1.48 [1.10–1.96], p=0.01) predicted increased risk for 5-year adverse clinical events (death/transplant). Only higher TMAO levels predicted incident adverse clinical events independent of age, eGFR, mitral E/septal Ea, and NT-proBNP levels (HR 1.46 [1.03 2.14], p=0.03). Conclusion Elevated plasma TMAO, choline and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO levels was associated with poor prognosis after adjustment for cardio-renal indices. PMID:25459686

  19. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure.

    PubMed

    Tang, W H Wilson; Wang, Zeneng; Shrestha, Kevin; Borowski, Allen G; Wu, Yuping; Troughton, Richard W; Klein, Allan L; Hazen, Stanley L

    2015-02-01

    Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aimed to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median (interquartile range) TMAO levels, choline, and betaine levels were 5.8 (3.6-12.1) μmol/L, 10.9 (8.4-14.0) μmol/L, and 43.8 (37.1-53.0) μmol/L, respectively, and were correlated with each other (all P < .0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9-13.2] vs 4.8 [3.4-9.8] μmol/L; P = .005) and in subjects with New York Heart Association functional class III or greater (7.0 [4.7-14.8] vs 4.7 [3.4-11.3] μmol/L; P = .02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (hazard ratio [HR] 1.64, 95% CI 1.22-2.20; P = .001), betaine (HR 1.51, 95% CI 1.10-2.08; P = .01), and TMAO (HR 1.48, 95% CI 1.10-1.96; P = .01) predicted increased risk for 5-year adverse clinical events (death/transplantation). Only higher TMAO levels predicted incident adverse clinical events independently from age, estimated glomerular filtration rate, mitral E/septal Ea, and NT-proBNP levels (HR 1.46, 95% CI 1.03-2.14; P = .03). Elevated plasma TMAO, choline, and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO was associated with poor prognosis after adjustment for cardiorenal indices. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. The Quality of Clinical Information in Adverse Drug Reaction Reports by Patients and Healthcare Professionals: A Retrospective Comparative Analysis.

    PubMed

    Rolfes, Leàn; van Hunsel, Florence; van der Linden, Laura; Taxis, Katja; van Puijenbroek, Eugène

    2017-07-01

    Clinical information is needed to assess the causal relationship between a drug and an adverse drug reaction (ADR) in a reliable way. Little is known about the level of relevant clinical information about the ADRs reported by patients. The aim was to determine to what extent patients report relevant clinical information about an ADR compared with their healthcare professional. A retrospective analysis of all ADR reports on the same case, i.e., cases with a report from both the patient and the patient's healthcare professional, selected from the database of the Dutch Pharmacovigilance Center Lareb, was conducted. The extent to which relevant clinical information was reported was assessed by trained pharmacovigilance assessors, using a structured tool. The following four domains were assessed: ADR, chronology, suspected drug, and patient characteristics. For each domain, the proportion of reported information in relation to information deemed relevant was calculated. An average score of all relevant domains was determined and categorized as poorly (≤45%), moderately (from 46 to 74%) or well (≥75%) reported. Data were analyzed using a paired sample t test and Wilcoxon signed rank test. A total of 197 cases were included. In 107 cases (54.3%), patients and healthcare professionals reported a similar level of clinical information. Statistical analysis demonstrated no overall differences between the groups (p = 0.126). In a unique study of cases of ADRs reported by patients and healthcare professionals, we found that patients report clinical information at a similar level as their healthcare professional. For an optimal pharmacovigilance, both healthcare professionals and patient should be encouraged to report.

  1. Major adverse cardiovascular event reduction with GLP-1 and SGLT2 agents: evidence and clinical potential

    PubMed Central

    Røder, Michael E.

    2017-01-01

    Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes. However, these drugs seem to have other effects such as weight reduction, low risk of hypoglycemia, and blood pressure reduction. Emerging evidence suggests pleiotropic effects, which potentially could be important in reducing cardiovascular risk. Prompted by regulatory authorities demanding cardiovascular outcome trials (CVOTs) assessing the cardiovascular safety of new antihyperglycemic drug candidates, many CVOTs are ongoing and a few of these are finalized. Somewhat surprising recent CVOTs in both drug classes have shown promising data on cardiovascular morbidity and mortality in patients with a very high risk of cardiovascular events. It is uncertain whether this is a class effect of the two drug classes, and it is yet unproven whether long-term cardiovascular benefits of these drugs can be extrapolated to populations at lower risk of cardiovascular disease. The aim of the present review is to give an overview of our current knowledge of the GLP-1RA and SGLT2-i classes, with specific focus on mechanisms of action, effects on cardiovascular risk factors and cardiovascular morbidity and mortality from the CVOTs presently available. The clinical potential of these data is discussed. PMID:29344329

  2. Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

    PubMed

    Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

    2018-05-01

    Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

  3. Retinoids: a journey from the molecular structures and mechanisms of action to clinical uses in dermatology and adverse effects.

    PubMed

    Khalil, Samar; Bardawil, Tara; Stephan, Carla; Darwiche, Nadine; Abbas, Ossama; Kibbi, Abdul Ghani; Nemer, Georges; Kurban, Mazen

    2017-12-01

    Retinoids are a class of compounds derived from vitamin A or having structural and/or functional similarities with vitamin A. They are classified into three generations based on their molecular structures. Inside the body, retinoids bind to several classes of proteins including retinoid-binding proteins and retinoid nuclear receptors. This eventually leads to the activation of specific regulatory regions of DNA - called the retinoic acid response elements - involved in regulating cell growth, differentiation and apoptosis. Several clinical trials have studied the role of topical and systemic retinoids in disease, and research is still ongoing. Currently, retinoids are used in several fields of medicine. This paper aims to review the structure, mechanisms of action, and adverse effects of retinoids, as well as some of their current uses in Dermatology.

  4. Bayesian inference on risk differences: an application to multivariate meta-analysis of adverse events in clinical trials.

    PubMed

    Chen, Yong; Luo, Sheng; Chu, Haitao; Wei, Peng

    2013-05-01

    Multivariate meta-analysis is useful in combining evidence from independent studies which involve several comparisons among groups based on a single outcome. For binary outcomes, the commonly used statistical models for multivariate meta-analysis are multivariate generalized linear mixed effects models which assume risks, after some transformation, follow a multivariate normal distribution with possible correlations. In this article, we consider an alternative model for multivariate meta-analysis where the risks are modeled by the multivariate beta distribution proposed by Sarmanov (1966). This model have several attractive features compared to the conventional multivariate generalized linear mixed effects models, including simplicity of likelihood function, no need to specify a link function, and has a closed-form expression of distribution functions for study-specific risk differences. We investigate the finite sample performance of this model by simulation studies and illustrate its use with an application to multivariate meta-analysis of adverse events of tricyclic antidepressants treatment in clinical trials.

  5. Prevalence, predictors, and clinical consequences of medical adherence in IBD: How to improve it?

    PubMed Central

    Lakatos, Peter Laszlo

    2009-01-01

    Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment. However, non-adherence has been reported in over 40% of patients, especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism, hospitalization risk, and the health care costs in chronic conditions, is enormous. The causes of medication non-adherence are complex, where the patient-doctor relationship, treatment regimen, and other disease-related factors play key roles. Moreover, subjective assessment might underestimate adherence. Poor adherence may result in more frequent relapses, a disabling disease course, in ulcerative colitis, and an increased risk for colorectal cancer. Improving medication adherence in patients is an important challenge for physicians. Understanding the different patient types, the reasons given by patients for non-adherence, simpler and more convenient dosage regimens, dynamic communication within the health care team, a self-management package incorporating enhanced patient education and physician-patient interaction, and identifying the predictors of non-adherence will help devise suitable plans to optimize patient adherence. This editorial summarizes the available literature on frequency, predictors, clinical consequences, and strategies for improving medical adherence in patients with IBD. PMID:19750566

  6. Prevalence, predictors, and clinical consequences of medical adherence in IBD: how to improve it?

    PubMed

    Lakatos, Peter Laszlo

    2009-09-14

    Inflammatory bowel diseases (IBD) are chronic diseases with a relapsing-remitting disease course necessitating lifelong treatment. However, non-adherence has been reported in over 40% of patients, especially those in remission taking maintenance therapies for IBD. The economical impact of non-adherence to medical therapy including absenteeism, hospitalization risk, and the health care costs in chronic conditions, is enormous. The causes of medication non-adherence are complex, where the patient-doctor relationship, treatment regimen, and other disease-related factors play key roles. Moreover, subjective assessment might underestimate adherence. Poor adherence may result in more frequent relapses, a disabling disease course, in ulcerative colitis, and an increased risk for colorectal cancer. Improving medication adherence in patients is an important challenge for physicians. Understanding the different patient types, the reasons given by patients for non-adherence, simpler and more convenient dosage regimens, dynamic communication within the health care team, a self-management package incorporating enhanced patient education and physician-patient interaction, and identifying the predictors of non-adherence will help devise suitable plans to optimize patient adherence. This editorial summarizes the available literature on frequency, predictors, clinical consequences, and strategies for improving medical adherence in patients with IBD.

  7. Molecular pathogenesis and clinical consequences of iron overload in liver cirrhosis.

    PubMed

    Sikorska, Katarzyna; Bernat, Agnieszka; Wroblewska, Anna

    2016-10-01

    The liver, as the main iron storage compartment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Excessive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease progression. We have also included literature on adjuvant therapeutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identification of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause significant improvement of liver functions in patients with iron overload. Phlebotomy can have beneficial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and available data suggest that it can be considered as target for adjuvant therapy in this condition.

  8. Symptoms, diagnoses, and sporting consequences among athletes referred to a Danish sports cardiology clinic.

    PubMed

    Kaiser-Nielsen, L V; Tischer, S G; Prescott, E B; Rasmusen, H K

    2017-01-01

    As the number of recreational athletes performing exercise and participating in competitions at a high-level increases, exercise-induced cardiac symptoms may become a more common problem, not least because recreational athletes often continue high-level exercise programs into advanced ages. We investigated the prevalence of cardiac symptoms and diagnoses among 201 athletes referred for cardiac evaluation at a Sports Cardiology Clinic in Denmark. To our knowledge, this is the first systematic study of athletes referred for suspected cardiac disease. The athletes were all well-trained recreational to elite athletes who participated in various sports with different training loads and a wide age span (13-66 years). All patients were referred by physicians, primarily their general practitioner (38%), and palpitations were the most common cardiac symptom (40%). Cardiac symptoms had a sensitivity of 86% in detecting cardiac disease and a specificity of 13%. Cardiac disease was diagnosed in 44% of the patients, and atrial fibrillation was the most prevalent diagnosis (7.5%). Cardiac diseases with therapeutic- or sports-related consequences for the patients were diagnosed in 28% of the population, but only 1% received a recommendation to avoid high-level sports indefinitely. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Retraumatization Mediates the Effect of Adverse Childhood Experiences on Clinical Training-Related Secondary Traumatic Stress Symptoms.

    PubMed

    Butler, Lisa D; Maguin, Eugene; Carello, Janice

    2018-01-01

    Previous research (Butler, Carello, & Maguin, 2016) has found that exposure to trauma-related material in graduate clinical coursework and field training can put students at risk for reactivations of feelings/memories from negative past experiences (retraumatization) and for secondary traumatic stress (STS) symptoms. The present report sought to examine the role, if any, of adverse childhood experiences (ACEs) in these outcomes. Using the Butler et al. (2016) sample, we examined: (1) rates of ACEs in 195 graduate social work students, (2) whether the total number of ACEs was associated with training-related retraumatization (TRT) and/or STS symptoms, and (3) if TRT mediated the relationship between ACEs and STS symptoms. The results indicate that more than three quarters of the sample had experienced one or more ACEs before age 18 and almost one third endorsed 4 or more. The most commonly reported ACEs were household mental illness, parental separation/divorce, household alcohol/substance abuse, and emotional abuse or neglect by a parent or household member. Higher ACE scores were associated with increased likelihood of TRT experiences and STS symptoms during training. A mediation analysis confirmed that TRT mediated the effect of ACE scores on STS symptoms; this finding also provides support for the role of proximal emotional reactions in mediating the effects of distal adverse experiences on the development of trauma symptoms. In summary, despite the evident resilience of this graduate student sample, those with ACE histories were at heightened risk for training-related distress. These results underscore the need for a trauma-informed approach to clinical training.

  10. 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

  11. Evaluation of clinically significant adverse events in patients discharged from a tertiary-care emergency department in Taiwan

    PubMed Central

    Wang, Lee-Min; How, Chorng-Kuang; Yang, Ming-Chin; Su, Syi

    2013-01-01

    Objective To investigate the reasons for the occurrence of clinically significant adverse events (CSAEs) in emergency department-discharged patients through emergency physicians' (EPs) subjective reasoning and senior EPs' objective evaluation. Design This was a combined prospective follow-up and retrospective review of cases of consecutive adult non-traumatic patients who presented to a tertiary-care emergency department in Taiwan between 1 September 2005 and 31 July 2006. Data were extracted from ‘on-duty EPs' subjective reasoning for discharging patients with CSAEs (study group) and without CSAEs (control group)’ and ‘objective evaluation of CSAEs by senior EPs, using clinical evidences such as recording history, physical examinations, laboratory/radiological examinations and observation of inadequacies in the basic management process (such as recording history, physical examinations, laboratory/radiological examinations and observation) as the guide’. Subjective reasons for discharging patients’ improvement of symptoms, and the certainty of safety of the discharge were compared in the two groups using χ2 statistics or t test. Results Of the 20 512 discharged cases, there were 1370 return visits (6.7%, 95% CI 6.3% to 7%) and 165 CSAEs due to physicians' factors (0.82%, 95% CI 0.75% to 0.95%). In comparisons between the study group and the control group, only some components of discharge reasoning showed a significant difference (p<0.001). Inadequacies in the basic management process were the main cause of CSAEs (164/165). Conclusion The authors recommended that EP follow-up of the basic management processes (including history record, physical examination, laboratory and radiological examinations, clinical symptoms/signs and treatment) using clinical evidence as a guideline should be made mandatory. PMID:22433586

  12. Factors affecting the causality assessment of adverse events following immunisation in paediatric clinical trials: An online survey.

    PubMed

    Voysey, Merryn; Tavana, Rahele; Farooq, Yama; Heath, Paul T; Bonhoeffer, Jan; Snape, Matthew D

    2015-12-16

    Serious adverse events (SAEs) in clinical trials require reporting within 24h, including a judgment of whether the SAE was related to the investigational product(s). Such assessments are an important component of pharmacovigilance, however classification systems for assigning relatedness vary across study protocols. This on-line survey evaluated the consistency of SAE causality assessment among professionals with vaccine clinical trial experience. Members of the clinical advisory forum of experts (CAFÉ), a Brighton Collaboration online-forum, were emailed a survey containing SAEs from hypothetical vaccine trials which they were asked to classify. Participants were randomised to either two classification options (related/not related to study immunisation) or three options (possibly/probably/unrelated). The clinical scenarios, were (i) leukaemia diagnosed 5 months post-immunisation with a live RSV vaccine, (ii) juvenile idiopathic arthritis (JIA) 3 months post-immunisation with a group A streptococcal vaccine, (iii) developmental delay diagnosed at age 10 months after infant capsular group B meningococcal vaccine, (iv) developmental delay diagnosed at age 10 months after maternal immunisation with a group B streptococcal vaccine. There were 140 respondents (72 two options, 68 three options). Across all respondents, SAEs were considered related to study immunisation by 28% (leukaemia), 74% (JIA), 29% (developmental delay after infant immunisation) and 42% (developmental delay after maternal immunisation). Having only two options made respondents significantly less likely to classify the SAE as immunisation-related for two scenarios (JIA p=0.0075; and maternal immunisation p=0.045). Amongst study investigators (n=43) this phenomenon was observed for three of the four scenarios: (JIA p=0.0236; developmental delay following infant immunisation p=0.0266; and developmental delay after maternal immunisation p=0.0495). SAE causality assessment is inconsistent amongst study

  13. Clinical consequences of untreated dental caries in German 5- and 8-year-olds.

    PubMed

    Grund, Katrin; Goddon, Inka; Schüler, Ina M; Lehmann, Thomas; Heinrich-Weltzien, Roswitha

    2015-11-04

    About half of all carious lesions in primary teeth of German 6- to 7-year-old children remain untreated, but no data regarding the clinical consequences of untreated dental caries are available. Therefore, this cross-sectional observational study aimed to assess the prevalence and experience of caries and odontogenic infections in the primary dentition of 5- and 8-year-old German children. Dental examinations were performed in 5-year-old pre-school children (n = 496) and in 8-year-old primary school children (n = 608) living in the Westphalian Ennepe-Ruhr district. Schools and preschools were selected by sociodemographic criteria including size, area, ownership, socio-economic status. Caries was recorded according to WHO criteria (1997). The Lorenz curves were used to display the polarisation of dental caries. Caries pattern in 5-year-olds was categorized by Wyne's (1997) definition of early childhood caries (ECC). Odontogenic infections as clinical consequence of untreated dental caries were assessed by the pufa index. The 'untreated caries-pufa ratio' was calculated, and the Spearman's rank correlation coefficient (ρ) was used for evaluating the correlation between dmft and pufa scores. Categorical data were compared between groups using the chi-square test and continuous data were analysed by t-test. Caries prevalence and experience in the primary dentition was 26.2 %/0.9 ± 2.0 dmft in 5-year-olds and 48.8 %/2.1 ± 2.8 dmft in 8-year-olds. ECC type I (22 %) was the prevalent caries pattern in 5-year-olds. About 30 % of the tooth decay was treated (5y: 29.7 %/8y: 39.3 %). The Lorenz curves showed a strong caries polarisation on 20 % of the children. Pufa prevalence and experience was 4.4 %/0.1 ± 0.5 pufa in 5-year-olds and 16.6 %/0.3 ± 0.9 pufa in 8-year-olds. In 5-year-olds 14.2 % and in 8-year-olds 34.2 % of the d-component had progressed mainly to the pulp. A significant correlation between dmft and pufa scores exists in

  14. Long-Term Clinical and Electroencephalography (EEG) Consequences of Idiopathic Partial Epilepsies.

    PubMed

    Dörtcan, Nimet; Tekin Guveli, Betul; Dervent, Aysin

    2016-05-03

    BACKGROUND Idiopathic partial epilepsies of childhood (IPE) affect a considerable proportion of children. Three main electroclinical syndromes of IPE are the Benign Childhood Epilepsy with Centro-temporal Spikes (BECTS), Panayiotopoulos Syndrome (PS), and Childhood Epilepsy with Occipital Paroxysms (CEOP). In this study we investigated the long-term prognosis of patients with IPE and discussed the semiological and electroencephalography (EEG) data in terms of syndromic characteristics. MATERIAL AND METHODS This study included a group of consecutive patients with IPE who had been followed since 1990. Demographic and clinical variables were investigated. Patients were divided into 3 groups - A: Cases suitable for a single IPE (BECTS, PS and CEOP); B: cases with intermediate characteristics within IPEs; and C: cases with both IPE and IGE characteristics. Long-term data regarding the individual seizure types and EEG findings were re-evaluated. RESULTS A total of 61 patients were included in the study. Mean follow-up duration was 7.8 ± 4.50 years. The mean age at onset of seizures was 7.7 years. There were 40 patients in group A 40, 14 in group B, and 7 in group C. Seizure and EEG characteristics were also explored independently from the syndromic approach. Incidence of autonomic seizures is considerably high at 2-5 years and incidence of oromotor seizures is high at age 9-11 years. The EEG is most abnormal at 6-8 years. The vast majority (86%) of epileptic activity (EA) with parietooccipital is present at 2-5 years, whereas EA with fronto-temporal or multiple sites become more abundant between ages 6 and 11. CONCLUSIONS Results of the present study provide support for the age-related characteristics of the seizures and EEGs in IPE syndromes. Acknowledgement of those phenomena may improve the management of IPEs and give a better estimate of the future consequences.

  15. Clinical and economic consequences of early discharge of patients following supratentorial stereotactic brain biopsy.

    PubMed

    Kaakaji, W; Barnett, G H; Bernhard, D; Warbel, A; Valaitis, K; Stamp, S

    2001-06-01

    The goal of this study was to determine the clinical and economic consequences of early discharge (< 8 hours) of patients following stereotactic brain biopsy (SBB). The records of all patients who underwent percutaneous SBB at The Cleveland Clinic Foundation, a tertiary care teaching hospital, during 1994 and 1995 (Group A) were retrospectively reviewed to collect data on the nature and timing of perioperative (< 48 hours) clinical and radiological complications. Biopsies were performed using image-guided stereotaxy either with or without a frame. Based on the results, guidelines for early discharge of patients following SBB were implemented. Information on the nature and timing of perioperative complications was also collected prospectively in all patients who underwent percutaneous SBB from January 1996 through July 1998 (Group B). Hospital financial records for patients who underwent SBB in 1997 and 1998 were also reviewed and assessed for net revenue stratified by discharge status: early discharge (< 8 hours), extended outpatient observation (> or = 8 and < 24 hours). and inpatient hospitalization (> or = 24 hours). In Group A, 130 biopsies were performed. There were five serious complications (3.8%), of which four were transient, and there was one death (0.8%). The death and any sustained deficit occurred in patients in whom a clot had been demonstrated on postoperative CT scans. All complications were detected within 6 hours after surgery. Intraoperative bleeding occurred in 12 patients (9.2%), but was associated with only 40% of cases in which hemorrhage appeared on postoperative CT scans. Guidelines for early discharge (< 8 hours) following SBB were developed and stipulated the absence of the following: 1) intraoperative hemorrhage; 2) new postoperative deficit; and 3) clot on a postoperative CT scan. In Group B, 139 biopsies were performed. There were three serious complications (2.2%), one of which was sustained due to a clot that had been demonstrated on

  16. Analysis of the adverse events reported to the office of the clinical director at a dental school in Bogotá, Colombia.

    PubMed

    Huertas, María F; Gonzalez, Juliana; Camacho, Sandra; Sarralde, Ana L; Rodríguez, Adriana

    2017-04-01

    Dentistry is interested in identifying and controlling adverse events, understood as involuntary injuries to the patient during dental care. The aim of this study was to analyze the adverse events reported to the Office of the Clinical Director at the School of Dentistry at Pontificia Universidad Javeriana (Colombia) during 2011-2012. It was an observational, descriptive study that evaluated 227 dental clinical records of patients who filed a complaint with the Office of the Clinical Director. Of these, 43 were adverse events and were used as the basis for this study. Of the 16,060 patients who received care during 2011 - 2012, 0.26% (43) filed a complaint involving an adverse event, of which 97.7 % were considered preventable. Most of these (76.18%, n= 32) occurred during clinical management of treatments in different specialties, 9.5% (4) were the result of deficient external dental laboratory quality, and 14.32% (6) were due to failure in document management, soft tissue injury, misdiagnosis and swallowing foreign objects. Of the patients involved, 65.2% (28) received care from postgraduate students, with the highest number of cases in the Oral Rehabilitation speciality. The occurrence of adverse events during dental care, indicates the need for information about their origin in order to establish protection barriers and prevent their incidence, particularly in the educational area under the student dental clinic service model. Sociedad Argentina de Investigación Odontológica.

  17. Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

    PubMed

    Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

    2017-07-01

    Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Alcohol, drugs, caffeine, tobacco, and environmental contaminant exposure: reproductive health consequences and clinical implications.

    PubMed

    Sadeu, J C; Hughes, Claude L; Agarwal, Sanjay; Foster, Warren G

    2010-08-01

    Reproductive function and fertility are thought to be compromised by behaviors such as cigarette smoking, substance abuse, and alcohol consumption; however, the strength of these associations are uncertain. Furthermore, the reproductive system is thought to be under attack from exposure to environmental contaminants, particularly those chemicals shown to affect endocrine homeostasis. The relationship between exposure to environmental contaminants and adverse effects on human reproductive health are frequently debated in the scientific literature and these controversies have spread into the lay press drawing increased public and regulatory attention. Therefore, the objective of the present review was to critically evaluate the literature concerning the relationship between lifestyle exposures and adverse effects on fertility as well as examining the evidence for a role of environmental contaminants in the purported decline of semen quality and the pathophysiology of subfertility, polycystic ovarian syndrome, and endometriosis. The authors conclude that whereas cigarette smoking is strongly associated with adverse reproductive outcomes, high-level exposures to other lifestyle factors are only weakly linked with negative fertility impacts. Finally, there is no compelling evidence that environmental contaminants, at concentrations representative of the levels measured in contemporary biomonitoring studies, have any effect, positive or negative, on reproductive health in the general population. Further research using prospective study designs with robust sample sizes are needed to evaluate testable hypotheses that address the relationship between exposure and adverse reproductive health effects.

  19. 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.

  20. German guideline for the management of adverse reactions to ingested histamine: Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Association of Allergologists (AeDA), and the Swiss Society for Allergology and Immunology (SGAI).

    PubMed

    Reese, Imke; Ballmer-Weber, Barbara; Beyer, Kirsten; Fuchs, Thomas; Kleine-Tebbe, Jörg; Klimek, Ludger; Lepp, Ute; Niggemann, Bodo; Saloga, Joachim; Schäfer, Christiane; Werfel, Thomas; Zuberbier, Torsten; Worm, Margitta

    2017-01-01

    Adverse food reactions are far more often perceived than objectively verified. In our scientific knowledge on non-allergic adverse reactions including the so called histamine intolerance, there are large deficits. Due to the fact that this disorder is increasingly discussed in the media and the internet, more and more people suspect it to be the trigger of their symptoms. The scientific evidence to support the postulated link between ingestion of histamine and adverse reactions is limited, and a reliable laboratory test for objective diagnosis is lacking. This position paper by the "Food Allergy" Working Group of the German Society for Allergology and Clinical Immunology (DGAKI) in collaboration with the German Association of Allergologists (AeDA), the Society for Pediatric Allergology and Environmental Medicine (GPA), and the Swiss Society for Allergology and Immunology (SGAI) reviews the data on the clinical picture of adverse reactions to ingested histamine, summarizes important aspects and their consequences, and proposes a practical diagnostic and therapeutic approach.

  1. 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

  2. Association of antenatal depression with adverse consequences for the mother and newborn in rural Ghana: findings from the DON population-based cohort study.

    PubMed

    Weobong, Benedict; ten Asbroek, Augustinus H A; Soremekun, Seyi; Manu, Alexander A; Owusu-Agyei, Seth; Prince, Martin; Kirkwood, Betty R

    2014-01-01

    Whilst there is compelling evidence of an almost 2-fold increased risk of still births, and suggestive evidence of increased mortality among offspring of mothers with psychotic disorders, only three studies have addressed the role of antenatal depression (AND) on survival of the baby. We examined these associations in a large cohort of pregnant women in Ghana. A Cohort study nested within 4-weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths in the Kintampo Health Research Centre study area of Ghana. Women were screened for AND using the Patient Health Questionnaire (PHQ-9) to ascertain DSM-IV major or minor depression. Outcomes were adverse birth outcomes, maternal/infant morbidity, and uptake of key newborn care practices, examined using logistic regression; effect sizes reported as relative risks with 95% confidence intervals. 20679 (89.6%) pregnant women completed the PHQ-9. The prevalence of AND was 9.9% (n = 2032) (95% confidence interval 9.4%-10.2%). AND was associated with: prolonged labour (RR 1.25, 95% CI 1.02-1.53); peripartum complications (RR 1.11, 95% CI 1.07-1.15); postpartum complications (RR 1.27, 96% CI 1.21-1.34); non-vaginal delivery (RR 1.19, 95% CI 1.02-1.40); newborn illness (RR 1.52, 95% CI 1.16-1.99); and bed net use during pregnancy (RR 0.93, 95% CI 0.89-0.98), but not neonatal deaths, still births, low birth weight, immediate breast feeding initiation, or exclusive breastfeeding. AND was marginally associated with preterm births (RR 1.32, 95% CI 0.98-1.76). This paper has contributed important evidence on the role of antenatal depression as a potential contributor to maternal and infant morbidity. Non-pharmacological treatments anchored on primary care delivery structures are recommended as an immediate step. We further recommend that trials are designed to assess if treating antenatal depression in conjunction with improving the quality of obstetric care results in

  3. [Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)].

    PubMed

    Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

    2018-06-20

      The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2,576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

  4. Quantifying Risk of Adverse Clinical Events With One Set of Vital Signs Among Primary Care Patients with Hypertension

    PubMed Central

    Tierney, William M; Brunt, Margaret; Kesterson, Joseph; Zhou, Xiao-Hua; L’Italien, Gil; Lapuerta, Pablo

    2004-01-01

    BACKGROUND Hypertension is often uncontrolled. One reason might be physicians’ reticence to modify therapy in response to single office measurements of vital signs. METHODS Using electronic records from an inner-city primary care practice, we extracted information about vital signs, diagnoses, test results, and drug therapy available on the first primary care visit in 1993 for patients with hypertension. We then identified multivariable predictors of subsequent vascular complications in the ensuing 5 years. RESULTS Of 5,825 patients (mean age 57 years) previously treated for hypertension for 5.6 years, 7% developed myocardial infarctions, 17% had strokes, 24% developed ischemic heart disease, 22% had heart failure, 12% developed renal insufficiency, and 13% died in 5 years. Controlling for other clinical data, a 10-mmHg increase in systolic blood pressure was associated with 13% increased risk (95% confidence interval [CI], 6%–21%) of renal insufficiency, 9% (95% CI, 3%–15%) increased risk of ischemic heart disease, 7% (95% CI, 3%–11%) increased risk of stroke, and 6% (95% CI, 2%–9%) increased risk of first stroke or myocardial infarction. A 10-mmHg elevation in mean blood pressure predicted a 12% (95% CI, 5%–20%) increased risk of heart failure. An increase in heart rate of 10 beats per minute predicted a 16% (95% CI, 2%–5%) increased risk of death. Diastolic blood pressure predicted only a 13% (95% CI, 4%–23%) increased risk of first stroke. CONCLUSIONS Vital signs—especially systolic blood pressure—recorded routinely during a single primary care visit had significant prognostic value for multiple adverse clinical events among patients treated for hypertension and should not be ignored by clinicians. PMID:15209196

  5. Quantifying risk of adverse clinical events with one set of vital signs among primary care patients with hypertension.

    PubMed

    Tierney, William M; Brunt, Margaret; Kesterson, Joseph; Zhou, Xiao-Hua; L'Italien, Gil; Lapuerta, Pablo

    2004-01-01

    Hypertension is often uncontrolled. One reason might be physicians' reticence to modify therapy in response to single office measurements of vital signs. Using electronic records from an inner-city primary care practice, we extracted information about vital signs, diagnoses, test results, and drug therapy available on the first primary care visit in 1993 for patients with hypertension. We then identified multivariable predictors of subsequent vascular complications in the ensuing 5 years. Of 5,825 patients (mean age 57 years) previously treated for hypertension for 5.6 years, 7% developed myocardial infarctions, 17% had strokes, 24% developed ischemic heart disease, 22% had heart failure, 12% developed renal insufficiency, and 13% died in 5 years. Controlling for other clinical data, a 10-mmHg increase in systolic blood pressure was associated with 13% increased risk (95% confidence interval [CI], 6%-21%) of renal insufficiency, 9% (95% CI, 3%-15%) increased risk of ischemic heart disease, 7% (95% CI, 3%-11%) increased risk of stroke, and 6% (95% CI, 2%-9%) increased risk of first stroke or myocardial infarction. A 10-mmHg elevation in mean blood pressure predicted a 12% (95% CI, 5%-20%) increased risk of heart failure. An increase in heart rate of 10 beats per minute predicted a 16% (95% CI, 2%-5%) increased risk of death. Diastolic blood pressure predicted only a 13% (95% CI, 4%-23%) increased risk of first stroke. Vital signs-especially systolic blood pressure-recorded routinely during a single primary care visit had significant prognostic value for multiple adverse clinical events among patients treated for hypertension and should not be ignored by clinicians.

  6. Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis.

    PubMed

    Tonstad, Serena; Davies, Simon; Flammer, Martina; Russ, Cristina; Hughes, John

    2010-04-01

    Varenicline (Chantix), Champix) has shown efficacy and tolerability as an aid to smoking cessation. In postmarketing surveillance, neuropsychiatric symptoms have appeared; however, their incidence and causal relationship to varenicline is not known. We assessed the incidence and relative risk (RR) of psychiatric disorders in ten randomized, double-blind, placebo-controlled trials of varenicline for smoking cessation. All smoking cessation phase II, III and IV randomized controlled clinical trials of varenicline versus placebo completed as of 31 December 2008, on file with the manufacturer (Pfizer, Inc.), were included. All studies have been published. All 3091 participants who received at least one dose of varenicline and all 2005 participants who received placebo were included in this analysis. These were men and women smoking > or =10 cigarettes/day, aged 18-75 years and without current psychiatric disease who received varenicline or placebo for 6 (one study), 12 (eight studies) or 52 (one study) weeks. Adverse events were recorded at each study visit and classified according to standard Medical Dictionary for Regulatory Activities (MedDRA) terms (version 11.0). The incidence of psychiatric disorders other than solely sleep disorders and disturbances was 10.7% in subjects treated with varenicline and 9.7% in subjects treated with placebo, with an RR of 1.02 (95% CI 0.86, 1.22). The RRs (95% CI) versus placebo of psychiatric adverse events with an incidence > or =1% in the varenicline group were 0.86 (0.67, 1.12) for anxiety disorders and symptoms, 0.76 (0.42, 1.39) for changes in physical activity, 1.42 (0.96, 2.08) for depressed mood disorders and disturbances, 1.21 (0.79, 1.83) for mood disorders and disturbances not elsewhere classified and 1.70 (1.50, 1.92) for sleep disorders and disturbances. There were no cases of suicidal ideation or behaviour in varenicline-treated subjects in the ten placebo-controlled studies analysed. However, among three trials that

  7. High-Performing Families: Causes, Consequences, and Clinical Solutions. The Family Psychology and Counseling Series.

    ERIC Educational Resources Information Center

    Robinson, Bryan E., Ed.; Chase, Nancy D., Ed.

    This book explores the dilemma of the increasing obsession with work and the resulting imbalances between career and family life. Through theoretical frameworks and case examples it discusses the negative consequences of the societal phenomena of over-work and over-dedication to careers, which have been misdiagnosed or ignored by mental health…

  8. Adverse effects associated with the clinical use of 4% TiF₄ on teeth enamel: case report.

    PubMed

    Pedro, Rafael de Lima; Pomarico, Luciana; Villardi, Michele; Maia, Lucianne Cople

    2011-05-01

    Titanium tetrafluoride (TiF₄) has been studied in dentistry as a promissory alternative for prevention and treatment of carious lesions. However, there are few in vivo studies concerning the consequences of its use on tooth enamel. The goal of this study was to report the effects of a 4% TiF₄ application on the remineralization of an incipient carious lesion of a permanent tooth. This research found an unexpected clinical outcome. A patient with active white spots had two of these lesions treated with 4% TiF₄ associated with fluoridated dentifrice and another lesion treated with fluoridated dentifrice only, thus the remineralization of the two kinds of treatment administered could be observed and compared. An extrinsic pigment appeared in the regions that received the TiF₄ treatment, which was partially removed by professional prophylaxis. Also, regular recidivists of this pigmentation in the review consultations were noted. The authors concluded that although the use of 4% TiF₄ was effective in treating incipient carious lesions on enamel, it was also responsible for an undesired pigmented layer on the tooth to which it was applied. Beyond the varied fluoridated materials used in dentistry, titanium tetrafluoride (TiF₄) deserves attention. This compound has the common properties of fluorides, and researchers are exploring its role in carious lesion prevention, fissure sealing, and tooth erosion prevention in in vitro and in situ studies. Research is also exploring its use for microinfiltration prevention in tooth restoration and hypersensitivity treatment. However, when compared to other fluoridated products TiF₄ demonstrates additional, specific particularities, such as the formation of a titanium dioxide (TiO₂) layer, which is tough, hydrophobic, and resistant in acidic environments. Nevertheless, there are insufficient in vivo studies concerning the consequences of TiF₄-containing products affecting tooth enamel. Thus, the goals of this study

  9. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline.

    PubMed

    Brahmer, Julie R; Lacchetti, Christina; Schneider, Bryan J; Atkins, Michael B; Brassil, Kelly J; Caterino, Jeffrey M; Chau, Ian; Ernstoff, Marc S; Gardner, Jennifer M; Ginex, Pamela; Hallmeyer, Sigrun; Holter Chakrabarty, Jennifer; Leighl, Natasha B; Mammen, Jennifer S; McDermott, David F; Naing, Aung; Nastoupil, Loretta J; Phillips, Tanyanika; Porter, Laura D; Puzanov, Igor; Reichner, Cristina A; Santomasso, Bianca D; Seigel, Carole; Spira, Alexander; Suarez-Almazor, Maria E; Wang, Yinghong; Weber, Jeffrey S; Wolchok, Jedd D; Thompson, John A

    2018-06-10

    Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process. The systematic review focused on guidelines, systematic reviews and meta-analyses, randomized controlled trials, and case series published from 2000 through 2017. Results The systematic review identified 204 eligible publications. Much of the evidence consisted of systematic reviews of observational data, consensus guidelines, case series, and case reports. Due to the paucity of high-quality evidence on management of immune-related adverse events, recommendations are based on expert consensus. Recommendations Recommendations for specific organ system-based toxicity diagnosis and management are presented. While management varies according to organ system affected, in general, ICPi therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. ICPi therapy may be suspended for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or less. Corticosteroids may be administered. Grade 3 toxicities generally warrant suspension of ICPis and the initiation of high-dose corticosteroids (prednisone 1 to 2 mg/kg/d or methylprednisolone 1 to 2 mg/kg/d). Corticosteroids should be tapered over the course of at least 4 to 6 weeks. Some refractory cases may require infliximab or other immunosuppressive therapy. In general, permanent discontinuation of ICPis is

  10. Financial barriers and adverse clinical outcomes among patients with cardiovascular-related chronic diseases: a cohort study.

    PubMed

    Campbell, David J T; Manns, Braden J; Weaver, Robert G; Hemmelgarn, Brenda R; King-Shier, Kathryn M; Sanmartin, Claudia

    2017-02-15

    Some patients with cardiovascular-related chronic diseases such as diabetes and heart disease report financial barriers to achieving optimal health. Previous surveys report that the perception of having a financial barrier is associated with self-reported adverse clinical outcomes. We sought to confirm these findings using linked survey and administrative data to determine, among patients with cardiovascular-related chronic diseases, if there is an association between perceived financial barriers and the outcomes of: (1) disease-related hospitalizations, (2) all-cause mortality and (3) inpatient healthcare costs. We used ten cycles of the nationally representative Canadian Community Health Survey (administered between 2000 and 2011) to identify a cohort of adults aged 45 and older with hypertension, diabetes, heart disease or stroke. Perceived financial barriers to various aspects of chronic disease care and self-management were identified (including medications, healthful food and home care) from the survey questions, using similar questions to those used in previous studies. The cohort was linked to administrative data sources for outcome ascertainment (Discharge Abstract Database, Canadian Mortality Database, Patient Cost Estimator). We utilized Poisson regression techniques, adjusting for potential confounding variables (age, sex, education, multimorbidity, smoking status), to assess for associations between perceived financial barriers and disease-related hospitalization and all-cause mortality. We used gross costing methodology and a variety of modelling approaches to assess the impact of financial barriers on hospital costs. We identified a cohort of 120,752 individuals over the age of 45 years with one or more of the following: hypertension, diabetes, heart disease or stroke. One in ten experienced financial barriers to at least one aspect of their care, with the two most common being financial barriers to accessing medications and healthful food. Even

  11. Exploratory study of factors associated with adverse clinical features in patients presenting with non-fatal drug overdose/self-poisoning to the ambulance service.

    PubMed

    Gwini, Stella May; Shaw, Deborah; Iqbal, Mohammad; Spaight, Anne; Siriwardena, Aloysius Niroshan

    2011-10-01

    To investigate the factors associated with adverse clinical features presented by drug overdose/self-poisoning patients and the treatments provided. Historical patient records collected over 3 months from ambulance crews attending non-fatal overdoses/self-poisoning incidents were reviewed. Logistic regression was used to investigate predictors of adverse clinical features (reduced consciousness, obstructed airway, hypotension or bradycardia, hypoglycaemia) and treatment. Of 22,728 calls attended to over 3 months, 585 (rate 26/1000 calls) were classified as overdose or self-poisoning. In the 585 patients identified, paracetamol-containing drugs were most commonly involved (31.5%). At least one adverse clinical feature occurred in 103 (17.7%) patients, with higher odds in men and opiate overdose or illegal drugs. Older patients and patients with reduced consciousness were more likely to receive oxygen. The latter also had a greater chance of receiving saline. Non-fatal overdose/self-poisoning accounted for 2.6% of patients attended by an ambulance. Gender, illegal drugs or opiates were important predictors of adverse clinical features. The treatments most often provided to patients were oxygen and saline.

  12. Anxiety, Depression, and Adverse Clinical Outcomes in Patients With Atrial Fibrillation Starting Warfarin: Cardiovascular Research Network WAVE Study.

    PubMed

    Baumgartner, Christine; Fan, Dongjie; Fang, Margaret C; Singer, Daniel E; Witt, Daniel M; Schmelzer, John R; Williams, Marc S; Gurwitz, Jerry H; Sung, Sue Hee; Go, Alan S

    2018-04-14

    Anxiety and depression are associated with worse outcomes in several cardiovascular conditions, but it is unclear whether they affect outcomes in atrial fibrillation (AF). In a large diverse population of adults with AF, we evaluated the association of diagnosed anxiety and/or depression with stroke and bleeding outcomes. The Cardiovascular Research Network WAVE (Community-Based Control and Persistence of Warfarin Therapy and Associated Rates and Predictors of Adverse Clinical Events in Atrial Fibrillation and Venous Thromboembolism) Study included adults with AF newly starting warfarin between 2004 and 2007 within 5 health delivery systems in the United States. Diagnosed anxiety and depression and other patient characteristics were identified from electronic health records. We identified stroke and bleeding outcomes from hospitalization databases using validated International Classification of Diseases, Ninth Revision ( ICD-9 ), codes. We used multivariable Cox regression to assess the relation between anxiety and/or depression with outcomes after adjustment for stroke and bleeding risk factors. In 25 570 adults with AF initiating warfarin, 490 had an ischemic stroke or intracranial hemorrhage (1.52 events per 100 person-years). In multivariable analyses, diagnosed anxiety was associated with a higher adjusted rate of combined ischemic stroke and intracranial hemorrhage (hazard ratio, 1.52; 95% confidence interval, 1.01-2.28). Results were not materially changed after additional adjustment for patient-level percentage of time in therapeutic anticoagulation range on warfarin (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36). In contrast, neither isolated depression nor combined depression and anxiety were significantly associated with outcomes. Diagnosed anxiety was independently associated with increased risk of combined ischemic stroke and intracranial hemorrhage in adults with AF initiating warfarin that was not explained by differences in risk factors

  13. Knowledge of consequences of missing teeth in patients attending prosthetic clinic in u.C.h. Ibadan.

    PubMed

    Dosumu, O O; Ogunrinde, J T; Bamigboye, S A

    2014-06-01

    Various causes of tooth loss such as caries, trauma, periodontal diseases, and cancer have been documented in the literature. In addition, factors that can modify these causes such as level of education, age and sex have been studied. There is however paucity of information on whether patients or people with missing teeth are aware of the side effects of tooth loss on them or on the remaining teeth. This study investigated the knowledge of consequences of missing teeth among partially edentulous patients in a teaching hospital. Self-administered questionnaires were distributed to the patients to collect information relating to demography, cause and duration of tooth loss, awareness of the consequences of tooth loss and their sources of information. Four clinical conditions including supra-eruption, mastication, teeth drifting, and facial collapse were used to assess the level of awareness of consequences of missing teeth. Two hundred and three participants were included in the study. Their mean age was 45.5±1.8 years. There was no significant difference between the knowledge of the consequences of missing teeth and sex or on level of education (p(·) 0.05). Dentists constituted the largest source of information to these patients (25.6%) while the media constituted the least (0.5%). The result of this study showed poor knowledge of the consequences of missing teeth among partially edentulous patients and the media that should be of assistance were equally unaware, signifying urgent need for public awareness on this subject.

  14. [Consequences of the 12th AMG amendment on the conduct of non-commercial clinical trials].

    PubMed

    Rossion, I

    2005-12-01

    In 2004, the German Drug Law was reformed substantially putting into effect the European directive 2001/20/EG on Good Clinical Practice (GCP). Investigator initiated trials have to comply with the same requirements as clinical trials for drug development. When registered drugs are used in non-commercial clinical trials some simplifications are possible.Currently, all essential elements of GCP, such as financing of the trial, laying-down of sponsor responsibilities, establishing an extensive quality assurance system as well as immediate reporting of unexpected serious drug reactions, are stipulated by law. Since regulatory authorities and ethics committees have to approve every clinical trial, surveillance is reinforced. The new requirements cannot be met without sufficient financing, qualified personnel and professional structures for clinical trials. Compared to European partners, the research location Germany is at a disadvantage due to high administrative workload and costs.

  15. [Treatment of Epidermal Growth Factor Receptor Inhibitors Associated Adverse Skin Reactions by Zhiyang Pingfu Liquid: a Clinical Study].

    PubMed

    Wang, Hong-yan; Zou, Chao; Cui, Hui-juan; Bai, Yan-ping; Li, Yuan; Tan, Huang-ying; Wang, Wei; Ju, Hai

    2015-07-01

    To study the curative effect of Zhiyang Pingfu Liquid (ZPL) in treating epidermal growth factor receptor inhibitors (EGFRIs) associated adverse reactions of the skin. All 54 patients with pathologically confirmed malignant tumor had EGFRIs induced adverse reactions of the skin to various degrees. ZPL was externally applied for them all, once or twice per day, 14 days consisting of one therapeutic course. Changes of adverse skin reactions, time for symptoms relief, adverse skin reaction types suitable for ZPL were observed before and after treatment. EGFRIs associated skin adverse reactions were improved to various degrees after they used ZPL. The shortest symptoms relief time was 1 day while the longest was 12 days, with an average of 6.93 days and the median time 7 days. Compared with before treatment, itching, rash/scaling, acne/acneform eruptions were obviously improved (P < 0.05). ZPL could alleviate EGFRls associated adverse skin reactions, especially showed better effect on itching, rash/scaling, acne/acneform eruptions.

  16. Influence of Clinical Status on the Association Between Plasma Total and Unbound Bilirubin and Death or Adverse Neurodevelopmental Outcomes in Extremely Low Birth Weight Infants

    PubMed Central

    Oh, William; Stevenson, David K.; Tyson, Jon E.; Morris, Brenda H.; Ahlfors, Charles E.; Bender, G. Jesse; Wong, Ronald J.; Perritt, Rebecca; Vohr, Betty R.; Van Meurs, Krista P.; Vreman, Hendrik J.; Das, Abhik; Phelps, Dale L.; O’Shea, T. Michael; Higgins, Rosemary D.

    2010-01-01

    Objectives To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method Total plasma biirubin and unbound biirubin were measured in 1,101 extremely low birth weight infants at 5±1 day of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow-up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow-up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow-up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma and unbound bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants. PMID:20105142

  17. The Tendril Plot-a novel visual summary of the incidence, significance and temporal aspects of adverse events in clinical trials.

    PubMed

    Karpefors, Martin; Weatherall, James

    2018-03-21

    In contrast to efficacy, safety hypotheses of clinical trials are not always pre-specified, and therefore, the safety interpretation work of a trial tends to be more exploratory, often reactive, and the analysis more statistically and graphically challenging. We introduce a new means of visualizing the adverse event data across an entire clinical trial. The approach overcomes some of the current limitations of adverse event analysis and streamlines the way safety data can be explored, interpreted and analyzed. Using a phase II study, we describe and exemplify how the tendril plot effectively summarizes the time-resolved safety profile of two treatment arms in a single plot and how that can provide scientists with a trial safety overview that can support medical decision making. To our knowledge, the tendril plot is the only way to graphically show important treatment differences with preserved temporal information, across an entire clinical trial, in a single view.

  18. 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.

  19. The renal concentrating mechanism and the clinical consequences of its loss

    PubMed Central

    Agaba, Emmanuel I.; Rohrscheib, Mark; Tzamaloukas, Antonios H.

    2012-01-01

    The integrity of the renal concentrating mechanism is maintained by the anatomical and functional arrangements of the renal transport mechanisms for solute (sodium, potassium, urea, etc) and water and by the function of the regulatory hormone for renal concentration, vasopressin. The discovery of aquaporins (water channels) in the cell membranes of the renal tubular epithelial cells has elucidated the mechanisms of renal actions of vasopressin. Loss of the concentrating mechanism results in uncontrolled polyuria with low urine osmolality and, if the patient is unable to consume (appropriately) large volumes of water, hypernatremia with dire neurological consequences. Loss of concentrating mechanism can be the consequence of defective secretion of vasopressin from the posterior pituitary gland (congenital or acquired central diabetes insipidus) or poor response of the target organ to vasopressin (congenital or nephrogenic diabetes insipidus). The differentiation between the three major states producing polyuria with low urine osmolality (central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia) is done by a standardized water deprivation test. Proper diagnosis is essential for the management, which differs between these three conditions. PMID:23293407

  20. Changes and Clinical Consequences of Smoking Cessation in Patients With COPD: A Prospective Analysis From the CHAIN Cohort.

    PubMed

    Martínez-González, Cristina; Casanova, Ciro; de-Torres, Juan P; Marín, José M; de Lucas, Pilar; Fuster, Antonia; Cosío, Borja G; Calle, Myriam; Peces-Barba, Germán; Solanes, Ingrid; Agüero, Ramón; Feu-Collado, Nuria; Alfageme, Inmaculada; Romero Plaza, Amparo; Balcells, Eva; de Diego, Alfredo; Marín Royo, Margarita; Moreno, Amalia; Llunell Casanovas, Antonia; Galdiz, Juan B; Golpe, Rafael; Lacárcel Bautista, Celia; Cabrera, Carlos; Marin, Alicia; Soriano, Joan B; Lopez-Campos, Jose Luis

    2018-02-22

    Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD. CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. One thousand and eighty-one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV 1 , 60.2 [20.5]%). During the 2-year follow-up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points. In this real-life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD. ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov. Copyright © 2018 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  1. [Experiences and recommendations of the German Federal Institute for Drugs and Medical Devices (BfArM) concerning clinical investigation of medical devices and the evaluation of serious adverse events (SAE)].

    PubMed

    Renisch, B; Lauer, W

    2014-12-01

    An integral part of the conformity assessment process for medical devices is a clinical evaluation based on clinical data. Particularly in the case of implantable devices and products of risk class III clinical trials must be performed. Since March 2010 applications for the authorization of clinical trials as well as for the waiver of the authorization requirement must be submitted centrally in Germany to the appropriate federal authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (PEI). In addition to authorization, approval by the responsible ethics committee is also required under law in order to begin clinical testing of medical devices in Germany. In this paper, the legal framework for the clinical testing of medical devices as well as those involved and possible procedures including evaluation criteria for the initial application of a trial and subsequent amendments are presented in detail. In addition, the reporting requirements for serious adverse events (SAEs) are explained and possible consequences of the evaluation are presented. Finally, a summary of application and registration numbers for all areas of extensive experience of the BfArM as well as requests and guidance for applicants are presented.

  2. Adverse events in vaccinations for travelers - a 1-year prospective survey in a travel clinic in Germany.

    PubMed

    Slesak, Günther; Fleck, Ralf; Scherbaum, Helmut; Blumenstock, Gunnar; Schäfer, Johannes

    2018-01-01

    The study goal was to assess and compare adverse events (AE) of current vaccinations for travelers under 'real-life conditions'. A prospective observational online questionnaire study was performed from May 2015 till April 2016 in a travel clinic in Germany. Online questionnaire links were sent 1 week after the first vaccination date. Severity was rated on a scale from 1 to 5 (minor to very severe AE). Of 1357 vaccinees 781 (57.6%) responded to the questionnaire, corresponding to 1415 vaccinations (1-7 simultaneous vaccinations). Responders were more often female (f:m = 1.29:1). Main age groups were 20-29 years old (36.1%). Most frequent vaccinations were against rabies (277; chick embryo cell vaccine (CEC): 97, human diploid cell vaccine (HDC): 180), yellow fever (250), typhoid fever (198), meningococcal meningitis (126) and Japanese encephalitis (104). A total of 217 vaccinees (27.8%) reported AE; 82 (10.5%) rated AE as more severe (grade 3: 61, grade 4: 18, grade 5: 3). No life-threatening AE was reported. Of 157 systemic AE the most frequent were: fatigue (75), headaches (46) and pyrexia (31). Of 94 local AE most frequently reported were pain (66), myalgia (25) and swelling (12). AE after single vaccinations were more often associated with rabies vaccine (OR 2.2; 1.2-4.2). AE increased with the number of simultaneous vaccinations (single vaccination: 24.1%, 88/365; 2 vaccinations: 26.6%, 73/274, ≥3 vaccinations: 39.4%, 56/142, χ2 = 12.24, P = 0.002, CCorr = 0.18), but more severe AE showed no association with the number of vaccinations (χ2 = 5.55, P = 0.06, CCorr = 0.12). Single and simultaneous vaccinations were overall well tolerated. AE were reported more frequently with rabies vaccinations in single vaccinations. Increased numbers of simultaneous vaccinations led to some incremental AE but not to more severe AE. Simultaneous vaccinations should be encouraged to reduce missed opportunities for immunizations.

  3. Meta-analysis of associations between childhood adversity and hippocampus and amygdala volume in non-clinical and general population samples.

    PubMed

    Calem, Maria; Bromis, Konstantinos; McGuire, Philip; Morgan, Craig; Kempton, Matthew J

    2017-01-01

    Studies of psychiatric populations have reported associations between childhood adversity and volumes of stress-related brain structures. This meta-analysis investigated these associations in non-clinical samples and therefore independent of the effects of severe mental health difficulties and their treatment. The MEDLINE database was searched for magnetic resonance imaging studies measuring brain structure in adults with and without childhood adversity. Fifteen eligible papers (1781 participants) reporting hippocampal volumes and/or amygdala volumes were pooled using a random effects meta-analysis. Those with childhood adversity had lower hippocampus volumes (hedges g = - 0.15, p  = 0.010). Controlling for gender, this difference became less evident (hedges g = - 0.12, p  = 0.124). This association differed depending on whether studies included participants with some psychopathology, though this may be due to differences in the type of adversity these studies examined. There was no strong evidence of any differences in amygdala volume. Childhood adversity may have only a modest impact on stress-related brain structures in those without significant mental health difficulties.

  4. Two Hundred Thirty-Six Children With Developmental Hydrocephalus: Causes and Clinical Consequences.

    PubMed

    Tully, Hannah M; Ishak, Gisele E; Rue, Tessa C; Dempsey, Jennifer C; Browd, Samuel R; Millen, Kathleen J; Doherty, Dan; Dobyns, William B

    2016-03-01

    Few systematic assessments of developmental forms of hydrocephalus exist. We reviewed magnetic resonance images (MRIs) and clinical records of patients with infancy-onset hydrocephalus. Among 411 infants, 236 had hydrocephalus with no recognizable extrinsic cause. These children were assigned to 1 of 5 subtypes and compared on the basis of clinical characteristics and developmental and surgical outcomes. At an average age of 5.3 years, 72% of children were walking independently and 87% could eat by mouth; in addition, 18% had epilepsy. Distinct patterns of associated malformations and syndromes were observed within each subtype. On average, children with aqueductal obstruction, cysts, and encephaloceles had worse clinical outcomes than those with other forms of developmental hydrocephalus. Overall, 53% of surgically treated patients experienced at least 1 shunt failure, but hydrocephalus associated with posterior fossa crowding required fewer shunt revisions. We conclude that each subtype of developmental hydrocephalus is associated with distinct clinical characteristics, syndromology, and outcomes, suggesting differences in underlying mechanisms. © The Author(s) 2015.

  5. 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

  6. Using clinical symptoms to predict adverse maternal and perinatal outcomes in women with preeclampsia: data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study.

    PubMed

    Yen, Tin-Wing; Payne, Beth; Qu, Ziguang; Hutcheon, Jennifer A; Lee, Tang; Magee, Laura A; Walters, Barry N; von Dadelszen, Peter

    2011-08-01

    Preeclampsia is a leading cause of maternal morbidity. The clinical challenge lies in predicting which women with preeclampsia will suffer adverse outcomes and would benefit from treatment, while minimizing potentially harmful interventions. Our aim was to determine the ability of maternal symptoms (i.e., severe nausea or vomiting, headache, visual disturbance, right upper quadrant pain or epigastric pain, abdominal pain or vaginal bleeding, and chest pain or dyspnea) to predict adverse maternal or perinatal outcomes. We used data from the PIERS (Pre-eclampsia Integrated Estimate of RiSk) study, a multicentre, prospective cohort study designed to investigate the maternal risks associated with preeclampsia. Relative risks and receiver operating characteristic (ROC) curves were assessed for each preeclampsia symptom and outcome pair. Of 2023 women who underwent assessment, 52% experienced at least one preeclampsia symptom, with 5.2% and 5.3% respectively experiencing an adverse maternal or perinatal outcome. No symptom and outcome pair, in either of the maternal or perinatal groups, achieved an area under the ROC curve value > 0.7, which would be necessary to demonstrate a discriminatory predictive value. Maternal symptoms of preeclampsia are not independently valid predictors of maternal adverse outcome. Caution should be used when making clinical decisions on the basis of symptoms alone in the preeclamptic patient.

  7. Toward a Case Definition of Adverse Health Effects in the Environs of Industrial Wind Turbines: Facilitating a Clinical Diagnosis

    ERIC Educational Resources Information Center

    McMurtry, Robert Y.

    2011-01-01

    Internationally, there are reports of adverse health effects (AHE) in the environs of industrial wind turbines (IWT). There was multidisciplinary confirmation of the key characteristics of the AHE at the first international symposium on AHE/IWT. The symptoms being reported are consistent internationally and are characterized by crossover findings…

  8. Systematic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Chinese Herbal Decoction for the Treatment of Gout

    PubMed Central

    Liu, Xiaoyu; Chen, Pinyi; Liu, Ling; Zhang, Yanqi; Wu, Yazhou; Pettigrew, Julia Christine; Cheng, Dixiang; Yi, Dong

    2014-01-01

    Background In East Asia, numerous reports describe the utilization of traditional Chinese herbal decoctions to treat gout. However, the reported clinical effects vary. Objectives In this study, we reviewed and analyzed a large number of randomized controlled clinical trials to systematically assess the clinical efficacy and adverse reactions of Chinese herbal decoctions for treating gout. Methods We performed a comprehensive search of databases, such as PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, Chinese biomedical literature database, et al. In addition, we manually searched the relevant meeting information in the library of the Third Military Medical University. Results Finally, 17 randomized controlled trials with a sample size of 1,402 cases met the criteria and were included in the study. The results of the meta-analysis showed that when gout had progressed to the stage of acute arthritis, there was no significant difference in clinical efficacy between Chinese herbal decoctions and traditional Western medicine, as indicated based on the following parameters: serum uric acid (standardized mean difference (SMD):0.35, 95% confidence interval (CI): 0.03 to 0.67), C reactive protein (SMD: 0.25, 95% CI: −0.18 to 0.69), erythrocyte sedimentation rate (SMD: 0.21, 95% CI: −0.02 to 0.45) and overall clinical response (relative risk (RR): 1.05, 95% CI: 1.01 to 1.10). However, the Chinese herbal decoction was significantly better than traditional Western medicine in controlling adverse drug reactions (RR: 0.06, 95% CI: 0.03 to 0.13). Conclusions Through a systematic review of the clinical efficacy and safety of Chinese herbal decoctions and traditional Western medicine for the treatment of gout, we found that Chinese herbal decoction and traditional Western medicine led to similar clinical efficacy, but the Chinese herbal decoctions were superior to Western medicine in terms of controlling adverse drug reactions. PMID:24465466

  9. When obesity and chronic obstructive pulmonary disease collide. Physiological and clinical consequences.

    PubMed

    O'Donnell, Denis E; Ciavaglia, Casey E; Neder, J Alberto

    2014-05-01

    In many parts of the world, the prevalence of both chronic obstructive pulmonary disease (COPD) and obesity is increasing at an alarming rate. Such patients tend to have greater respiratory symptoms, more severe restriction of daily activities, poorer health-related quality of life, and greater health care use than their nonobese counterparts. Physiologically, increasing weight gain is associated with lung volume reduction effects in both health and disease, and this should be considered when interpreting common pulmonary function tests where lung volume is the denominator, such as FEV1/FVC and the ratio of diffusing capacity of carbon monoxide to alveolar volume, or indeed when evaluating the physiological consequences of emphysema in obese individuals. Contrary to expectation, the presence of mild to moderate obesity in COPD appears to have little deleterious effect on respiratory mechanics and muscle function, exertional dyspnea, and peak symptom-limited oxygen uptake during cardiopulmonary exercise testing. Thus, in evaluating obese patients with COPD reporting activity restriction, additional nonpulmonary factors, such as increased metabolic loading, cardiocirculatory impairment, and musculoskeletal abnormalities, should be considered. Care should be taken to recognize the presence of obstructive sleep apnea in obese patients with COPD, as effective treatment of the former condition likely conveys an important survival advantage. Finally, morbid obesity in COPD presents significant challenges to effective management, given the combined effects of erosion of the ventilatory reserve and serious metabolic and cardiovascular comorbidities that collectively predispose to an increased risk of death from respiratory failure.

  10. 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

  11. [Adverse effects of oxcarbazepine].

    PubMed

    Fang, Shu; Gong, Zhi-Cheng

    2015-04-01

    Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

  12. Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options.

    PubMed

    Konturek, Peter C; Brzozowski, T; Konturek, S J

    2011-12-01

    Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress

  13. Polygraphic respiratory events during sleep with noninvasive ventilation in children: description, prevalence, and clinical consequences.

    PubMed

    Caldarelli, Valeria; Borel, Jean Christian; Khirani, Sonia; Ramirez, Adriana; Cutrera, Renato; Pépin, Jean-Louis; Fauroux, Brigitte

    2013-04-01

    The optimal monitoring during sleep with noninvasive positive pressure ventilation (NPPV) has not been validated in children. The aim of the study was to describe on polygraphic (PG) recordings the respiratory events and associated autonomic arousals (AA) and/or 3 % desaturations (DS3%) during nocturnal NPPV. This was a prospective descriptive study performed in the pulmonology unit of a pediatric university hospital. Consecutive patients admitted for routine follow-up of long-term NPPV were enrolled. Nocturnal PG during sleep with NPPV was performed. A second PG was performed after adjustment of the ventilatory settings when a respiratory event occurred more than 50 times/h. The PG tracings of 39 patients (age range 1-18 years) were analyzed. Underlying diagnoses included neuromuscular disease (n = 13), obstructive sleep apnea (n = 15), and lung disease (n = 11). Unintentional leaks, patient-ventilator asynchronies, decrease in ventilatory drive, upper airway obstruction with or without reduction of ventilatory drive, and mixed events were observed in 27, 33, 10, 11, 12, and 3 % of the patients, respectively. A predominant respiratory event was observed in all patients. The mean duration spent with respiratory events was 32 ± 30 % (range 3-96 %) of total recording time. Unintentional leaks were the most frequently associated with AA, whereas patient-ventilator asynchronies were rarely associated with AA or DS3%. In eight re-evaluated patients, a decrease in the main event was observed (p = 0.005). Respiratory events during sleep with NPPV are common in children treated with long-term NPPV. Consequences of respiratory events vary according to the type of event with unintentional leaks being associated preferentially with AA.

  14. The Molecular, Cellular and Clinical Consequences of Targeting the Estrogen Receptor Following Estrogen Deprivation Therapy

    PubMed Central

    Fan, Ping; Maximov, Philipp Y.; Curpan, Ramona F.; Abderrahman, Balkees; Jordan, V. Craig

    2015-01-01

    During the past twenty years our understanding of the control of breast tumor development, growth and survival has changed dramatically. The once long forgotten application of high dose synthetic estrogen therapy as the first chemical therapy to treat any cancer has been resurrected, refined and reinvented as the new biology of estrogen-induced apoptosis. High dose estrogen therapy was cast aside once tamoxifen, from its origins as a failed “morning after pill”, was reinvented as the first targeted therapy to treat any cancer. The current understanding of the mechanism of estrogen-induced apoptosis is described as a consequence of acquired resistance to long term antihormone therapy in estrogen receptor (ER) positive breast cancer. The ER signal transduction pathway remains a target for therapy in breast cancer despite “antiestrogen” resistance, but becomes a regulator of resistance. Multiple mechanisms of resistance come into play: Selective ER Modulator (SERM) stimulated growth, growth factor/ER crosstalk, estrogen-induced apoptosis and mutations of ER. But it is with the science of estrogen-induced apoptosis that the next innovation in women’s health will be developed. Recent evidence suggests that the glucocorticoid properties of medroxyprogesterone acetate blunt estrogen-induced apoptosis in estrogen deprived breast cancer cell populations. As a result breast cancer develops during long-term Hormone Replacement Therapy (HRT). A new synthetic progestin with estrogen-like properties, such as the 19 nortestosterone derivatives used in oral contraceptives, will continue to protect the uterus from unopposed estrogen stimulation but at the same time, reinforce apoptosis in vulnerable populations of nascent breast cancer cells. PMID:26052034

  15. Variability of word discrimination scores in clinical practice and consequences on their sensitivity to hearing loss.

    PubMed

    Moulin, Annie; Bernard, André; Tordella, Laurent; Vergne, Judith; Gisbert, Annie; Martin, Christian; Richard, Céline

    2017-05-01

    Speech perception scores are widely used to assess patient's functional hearing, yet most linguistic material used in these audiometric tests dates to before the availability of large computerized linguistic databases. In an ENT clinic population of 120 patients with median hearing loss of 43-dB HL, we quantified the variability and the sensitivity of speech perception scores to hearing loss, measured using disyllabic word lists, as a function of both the number of ten-word lists and type of scoring used (word, syllables or phonemes). The mean word recognition scores varied significantly across lists from 54 to 68%. The median of the variability of the word recognition score ranged from 30% for one ten-word list down to 20% for three ten-word lists. Syllabic and phonemic scores showed much less variability with standard deviations decreasing by 1.15 with the use of syllabic scores and by 1.45 with phonemic scores. The sensitivity of each list to hearing loss and distortions varied significantly. There was an increase in the minimum effect size that could be seen for syllabic scores compared to word scores, with no significant further improvement with phonemic scores. The use of at least two ten-word lists, quoted in syllables rather than in whole words, contributed to a large decrease in variability and an increase in sensitivity to hearing loss. However, those results emphasize the need of using updated linguistic material for clinical speech score assessments.

  16. Proteomics in investigation of cancer metastasis: functional and clinical consequences and methodological challenges.

    PubMed

    Maryáš, Josef; Faktor, Jakub; Dvořáková, Monika; Struhárová, Iva; Grell, Peter; Bouchal, Pavel

    2014-03-01

    Metastases are responsible for most of the cases of death in patients with solid tumors. There is thus an urgent clinical need of better understanding the exact molecular mechanisms and finding novel therapeutics targets and biomarkers of metastatic disease of various tumors. Metastases are formed in a complicated biological process called metastatic cascade. Up to now, proteomics has enabled the identification of number of metastasis-associated proteins and potential biomarkers in cancer tissues, microdissected cells, model systems, and secretomes. Expression profiles and biological role of key proteins were confirmed in verification and functional experiments. This communication reviews these observations and analyses the methodological aspects of the proteomics approaches used. Moreover, it reviews contribution of current proteomics in the field of functional characterization and interactome analysis of proteins involved in various events in metastatic cascade. It is evident that ongoing technical progress will further increase proteome coverage and sample capacity of proteomics technologies, giving complex answers to clinical and functional questions asked. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Patient-reported outcomes (PRO) focused on adverse events (PRO-AEs) in adjuvant and metastatic breast cancer: clinical and translational implications.

    PubMed

    Stefanovic, Stefan; Wallwiener, Markus; Karic, Uros; Domschke, Christoph; Katic, Luka; Taran, Florin-Andrei; Pesic, Aleksandra; Hartkopf, Andreas; Hadji, Peyman; Teufel, Martin; Schuetz, Florian; Sohn, Christof; Fasching, Peter; Schneeweiss, Andreas; Brucker, Sara

    2017-02-01

    The capture of adequate treatment outcomes and quality of life (QOL) of advanced breast cancer patients in clinical routine represents a great challenge. Patient-reported outcomes (PROs) are data elements directly reported by patients about experiences with care, including symptoms, functional status, or quality of life. There is growing interest in the medical community for the evaluation and implementation of PROs of adverse events (PRO-AEs). Recent interest in PROs in health care has evolved in the context of patient centeredness. Our primary objective was to identify trials that had implemented PRO-AEs in the breast cancer treatment setting, thereby demonstrating its feasibility. We aimed to identify published studies that used patient reports to assess AEs during and after breast cancer treatment, to identify clinician underreported and modifiable AEs that are important to patients, and to analyze the feasibility and usefulness of PRO instrument implementation in everyday oncological practice with special attention given to electronic-based PRO instruments. We conducted a systematic search of PubMed for studies that used PRO instruments to assess AEs of breast cancer treatment in the metastatic and adjuvant settings. Two authors independently reviewed the search results and decided which studies fully met the predefined inclusion criteria. The search yielded 606 publications. The two reviewers found that 9 studies met the inclusion criteria. Three AEs were identified as important to patients but inadequately reported by health care providers, namely hot flushes, vaginal dryness, and weight gain. PROs and PRO-AEs are the consequence of contemporary concepts of patient-centered medicine and the growing feasibility, utility, and implications of collecting data using modern technology. Furthermore, the willingness of patients to utilize innovative applications for their own health has been increasing in parallel to the enhanced impact of the World Wide Web

  18. Consequences of orthodontic treatment in malocclusion patients: clinical and microbial effects in adults and children.

    PubMed

    Guo, Li; Feng, Ying; Guo, Hong-Gang; Liu, Bo-Wen; Zhang, Yang

    2016-10-28

    Malocclusion is a common disease of oral and maxillofacial region. The study was aimed to investigate levels changes of periodontal pathogens in malocclusion patients before, during and after orthodontic treatments, and to confirm the difference between adults and children. One hundred and eight malocclusion patients (46 adults and 62 children at the school-age) were randomly selected and received orthodontic treatment with fixed orthodontic appliances. Subgingival plaques were Porphyromonas gingivalis (P.gingivalis), Fusobacterium nucleatum (F. nucleatum), Prevotella intermedia (P. intermedia) and Tannerella forsythensis (T. forsythensis) collected from the observed regions before and after treatment. Clinical indexes, including plaque index (PLI), gingival index (GI), sulcus bleeding index (SBI), probing depth (PD) and attachment loss (AL) of observed teeth were examined. The detection rates of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis increased from baseline to the third month without significant difference, and then returned to pretreatment levels 12 month after applying fixed orthodontic appliances. Adults' percentage contents of P.gingivalis, F. nucleatum, P. intermedia and T. forsythensis were significantly higher than those of children at baseline and the first month, but not obvious at the third month. PLI and SBI were increased from baseline to the first and to the third month both in adults and children groups. Besides, PD were increased from baseline to first month, followed by a downward trend in the third month; however, all patients were failed to detect with AL. Periodontal and microbiological statuses of malocclusion patients may be influenced by fixed orthodontic appliances in both adults and children, more significant in children than in adults. Some microbiological indexes have synchronous trend with the clinical indexes. Long-term efficacy of fixed orthodontic appliances for malocclusion should be confirmed by future

  19. Clinical characteristics and economic consequence of Klebsiella pneumoniae liver abscess in Taiwan.

    PubMed

    Wu, Ping-Feng; Chang, Yea-Yuan; Lin, Yi-Tsung; Wang, Fu-Der; Chan, Yu-Jiun; Fung, Chang-Phone

    2015-04-01

    Klebsiella pneumoniae liver abscess (KPLA) has emerged as an endemic disease in Taiwan, and its prevalence has been increasing in east Asian countries in the past three decades. The utilization of healthcare resources associated with KPLA is assumed to be substantial, and may be of future concern. This study investigated the clinical characteristics and economic burden of KPLA in Taiwan in 2011 and 2012. Adult patients with KPLA were identified retrospectively in a tertiary medical center in Taiwan from January 2011 to December 2012. The clinical characteristics, total and daily hospitalization expenditure, and the risk factors for the costs of KPLA were analyzed. Among patients with KPLA, the median cost was $5290.80 in US dollars, and the mean cost was $6337.50 ± $4363.40. Length of hospital stay was the only independent risk factor for the high total hospitalization expenditure. The duration of antibiotic use was nearly the same as the length of hospital stay. The prolonged stay in the general ward (≥21 days) also contributed to the high total cost of hospitalization. The independent risk factors for the high average daily cost of hospitalization were a higher Charlson Comorbidity Index and the requirement of intensive care on admission. The current study is the first to demonstrate the high economic burden resulting from KPLA in a medical center in Taiwan. Standardizing the treatment protocol for KPLA inpatients and introducing an outpatient parenteral antimicrobial therapy center to reduce the length of stay may reduce costs, whereas development of a vaccine may be necessary to tackle endemic KPLA in the future. Copyright © 2013. Published by Elsevier B.V.

  20. Ginger for Prevention of Antituberculosis-induced Gastrointestinal Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical Trial.

    PubMed

    Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

    2016-06-01

    In this study, the potential benefits of ginger in preventing antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)(®) or placebo one-half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug-induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug-induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug-induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug-induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Predictive value of self-stigma, insight, and perceived adverse effects of medication for the clinical outcomes in patients with depressive disorders.

    PubMed

    Yen, Cheng-Fang; Lee, Yu; Tang, Tze-Chun; Yen, Ju-Yu; Ko, Chih-Hung; Chen, Cheng-Chung

    2009-03-01

    The aims of this prospective study were to examine the predictive values of self-stigma, insight, and perceived adverse effects of medication for remission of depressive symptoms, suicidal risk, and medication adherence in patients with depressive disorders over a 1-year follow-up period. One hundred seventy-four participants who were in a state of obvious depression underwent an index interview to determine their degree of self-stigma, insight, and perceived adverse effects of medication. One year later, they were reassessed to determine the severity of their depressive symptoms, suicidal risk, and the level of the medication adherence, and their associations with the 3 possible predictors at the index interview were examined. The results of this study indicated that perceiving more severe adverse effects of medication at the index interview increased the risks of the nonremission of depressive symptoms, occurrence of suicidal ideation or attempt, and medication nonadherence in patients with depressive disorders in the 1-year period. However, the degrees of self-stigma and insight did not predict the severity of depressive symptoms, suicidal risk, or the level of the medication adherence. Based on the results of this study, we suggest that it is important for clinicians to prevent the occurrence of and to help patients manage the adverse effects of medication. We also suggest that further prospective studies are needed to examine the predictive values of self-stigma and insight for clinical outcomes and medication adherence.

  2. Unsatisfactory Glucose Management and Adverse Pregnancy Outcomes of Gestational Diabetes Mellitus in the Real World of Clinical Practice: A Retrospective Study.

    PubMed

    Feng, Ru; Liu, Lu; Zhang, Yuan-Yuan; Yuan, Zhong-Shang; Gao, Ling; Zuo, Chang-Ting

    2018-05-05

    Facing the increasing prevalence of gestational diabetes mellitus (GDM), this study aimed to evaluate the management of GDM and its association with adverse pregnancy outcomes. The data of 996 inpatients with GDM who terminated pregnancies in our hospital from January 2011 to December 2015 were collected. Treatments during pregnancy and the last hospital admission before delivery were analyzed. Pregnancy outcomes of the GDM patients were compared with 996 nondiabetic subjects matched by delivery year and gestational age. The association between fasting plasma glucose (FPG) and adverse pregnancy outcomes was examined by logistic regression analyses. The average prevalence of GDM over the 5 years was 4.4% (1330/30,191). Within the GDM patients, 42.8% (426/996) received dietary intervention, whereas 19.1% (190/996) received insulin treatment. Adverse outcomes were more likely to occur in patients with unsatisfactory control of blood glucose such as respiratory distress syndrome (RDS, χ 2 = 13.373, P < 0.01). Elevated FPG was identified as an independent risk factor for premature birth (odds ratio [OR] = 1.460, P < 0.001), neonatal care unit admission (OR = 1.284, P < 0.001), RDS (OR = 1.322, P = 0.001), and stillbirth (OR = 1.427, P < 0.001). Management of GDM in the real world of clinical practice was unsatisfactory, which might have contributed to adverse pregnancy outcomes.

  3. [Potential antimicrobial drug interactions in clinical practice: consequences of polypharmacy and multidrug resistance].

    PubMed

    Martínez-Múgica, Cristina

    2015-12-01

    Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.

  4. Cytochrome P450 pharmacogenetics in drug development: in vitro studies and clinical consequences.

    PubMed

    Rodrigues, A David; Rushmore, Thomas H

    2002-06-01

    Members of the human cytochrome P450 (CYP) superfamily play a role in the metabolism of many drugs and several of them, CYP2D6, CYP2C9 and CYP2C19, have been shown to be polymorphic as a result of single nucleotide polymorphisms (SNPs), gene deletions, and gene duplications. These polymorphisms can impact the pharmacokinetics (PK), metabolism, safety and efficacy of drugs, and because of the availability of automation, genotyped human tissue, recombinant CYP preparations (rCYPs) and reagents, most pharmaceutical companies have increasingly screened out compounds that are metabolized solely by polymorphic CYPs. In the absence of suitable animal models, it has been widely accepted that such in vitro data are useful because one can obtain information prior to dosing in man and select the most appropriate clinical studies with prospectively genotyped and phenotyped subjects. Overall, current trends in the industry have been fueled by increased managed healthcare, the desire to minimize the need for therapeutic drug monitoring and CYP genotyping in medical practice, and a very competitive market place. In the past, such paradigms have not been as influential and there are numerous examples of marketed drugs that are metabolized by polymorphic CYPs.

  5. Anatomical variations within the deep posterior compartment of the leg and important clinical consequences.

    PubMed

    Hislop, M; Tierney, P

    2004-09-01

    The management of musculoskeletal conditions makes up a large part of a sports medicine practitioner's practice. A thorough knowledge of anatomy is an essential component of the armament necessary to decipher the large number of potential conditions that may confront these practitioners. To cloud the issue further, anatomical variations may be present, such as supernumerary muscles, thickened fascial bands or variant courses of nerves and blood vessels, which can themselves manifest as acute or chronic conditions that lead to significant morbidity or limitation of activity. There are a number of contentious areas within the literature surrounding the anatomy of the leg, particularly involving the deep posterior compartment. Conditions such as chronic exertional compartment syndrome, tibial periostitis (shin splints), peripheral nerve entrapment and tarsal tunnel syndrome may all be affected by subtle anatomical variations. This paper primarily focuses on the deep posterior compartment of the leg and uses the gross dissection of cadaveric specimens to describe definitively the anatomy of the deep posterior compartment. Variant fascial attachments of flexor digitorum longus are documented and potential clinical sequelae such as chronic exertional compartment syndrome and tarsal tunnel syndrome are discussed.

  6. The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes.

    PubMed

    Wu, Vin-Cent; Wang, Shuo-Meng; Chueh, Shih-Chieh Jeff; Yang, Shao-Yu; Huang, Kuo-How; Lin, Yen-Hung; Wang, Jian-Jhong; Connolly, Rory; Hu, Ya-Hui; Gomez-Sanchez, Celso E; Peng, Kang-Yung; Wu, Kwan-Dun

    2017-01-19

    Constitutive activation of the Wnt pathway/β-catenin signaling may be important in aldosterone-producing adenoma (APA). However, significant gaps remain in our understanding of the prevalence and clinical outcomes after adrenalectomy in APA patients harboring CTNNB1 mutations. The molecular expression of CYP11B2 and gonadal receptors in adenomas were also explored. Adenomas from 219 APA patients (95 men; 44.2%; aged 50.5 ± 11.9 years) showed a high rate of somatic mutations (n = 128, 58.4%). The majority of them harbored KCNJ5 mutations (n = 116, 52.9%); 8 patients (3.7%, 6 women) had CTNNB1 mutations. Patients with APAs harboring CTNNB1 mutations were older and had shorter duration of hypertension. After adrenalectomy, CTNNB1 mutation carriers had a higher possibility (87.5%) of residual hypertension than other APA patients. APAs harboring CTNNB1 mutations have heterogeneous staining of β-catenin and variable expression of gonadal receptors and both CYP11B1 and CYP11B2. This suggests that CTNNB1 mutations may be more related to tumorigenesis rather than excessive aldosterone production.

  7. Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

    SciTech Connect

    Basch, Ethan, E-mail: ebasch@med.unc.edu; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; Pugh, Stephanie L.

    Purpose: To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials: Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visitsmore » when an expected PRO-CTCAE assessment was completed. Results: Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling “too sick.” Conclusions: Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be

  8. Feasibility of Patient Reporting of Symptomatic Adverse Events via the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial.

    PubMed

    Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O'Mara, Ann M; Denicoff, Andrea M; Minasian, Lori M; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

    2017-06-01

    To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Patients enrolled in NRG Oncology's RTOG 1012 (Prophylactic Manuka Honey for Reduction of Chemoradiation Induced Esophagitis-Related Pain during Treatment of Lung Cancer) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly ×4 during treatment; 12 weeks after treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Among 226 study sites participating in RTOG 1012, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients, of which 34 (43%) required tablet computers to be provided. All 152 patients in RTOG 1012 agreed to self-report using the PRO-CTCAE (median age 66 years; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range, 30-240 minutes), and median time for CRAs to teach a patient to self-report was 10 minutes (range, 2-60 minutes). Compliance was high, particularly during active treatment, when patients self-reported at 86% of expected time points, although compliance was lower after treatment (72%). Common reasons for noncompliance were institutional errors, such as forgetting to provide computers to participants; patients missing clinic visits; Internet connectivity; and patients feeling "too sick." Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic AEs at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between

  9. Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences.

    PubMed

    Cope, Emily K; Goldberg, Andrew N; Pletcher, Steven D; Lynch, Susan V

    2017-05-12

    Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients. Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2  = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2  = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, T H 1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045). A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response-features which may inform strategies for tailored therapy in this patient population.

  10. Clinical and economic consequences of antibiotic-impregnated cerebrospinal fluid shunt catheters.

    PubMed

    Eymann, Regina; Chehab, Somar; Strowitzki, Martin; Steudel, Wolf-Ingo; Kiefer, Michael

    2008-06-01

    The authors evaluated the safety and efficacy of antibiotic-impregnated shunt catheters (AISCs) and determined the cost-benefit ratio related to the fact that AISCs increase the implant costs of a shunt procedure by approximately $400 per patient. The control group comprised 98 adults with chronic hydrocephalus and 22 children, who were treated without AISCs (non-AISCs). In the treatment group, AISCs (Bactiseal, Codman, Johnson & Johnson) were implanted in 171 adults and 26 children. The minimum follow-up period was 6 months. Important risk factors for shunt infections (such as age, comorbidity, cause of hydrocephalus, operating time, and duration of external cerebrospinal fluid drainage prior to shunt placement) did not differ between the study and control groups. In the pediatric AISC group, the frequency of premature, shunt-treated infants and the incidence of external ventricular drainage prior to shunt insertion were actually higher than those in the non-AISC group. When using AISCs, the shunt infection rate dropped from 4 to 0.6% and from 13.6 to 3.8% in the adult and the pediatric cohort, respectively. Overall the infection rate decreased from 5.8 to 1%, which was statistically significant (p = 0.0145). The average costs of a single shunt infection were $17,300 and $13,000 in children and adults, respectively. The cost-benefit calculation assumed to have saved shunt infection-related costs of approximately $50,000 in 197 AISC-treated patients due to the reduction in shunt infection rate in this group compared with costs in the control group. Despite the incremental implant costs associated with the use of AISCs, the overall reduction in infection-related costs made the use of AISCs cost beneficial in the authors' department. From clinical and economic perspectives, AISCs are seemingly a valuable addition in hydrocephalus therapy.

  11. No association between anxiety and depression and adverse clinical outcome among patients with cardiovascular disease: findings from the DANREHAB trial.

    PubMed

    Kornerup, Henriette; Zwisler, Ann-Dorthe Olsen; Prescott, Eva

    2011-10-01

    Anxiety and depression have been linked to adverse prognostic outcome in patients with cardiovascular disease (CVD) with mixed results. The timing of anxiety and depression measurement has received little attention so far. The study sample consisted of 536 patients admitted to hospital for CVD and followed in a rehabilitation trial. Symptoms were assessed using the Hospital Anxiety and Depression Scale at baseline and after 1 year. Cox proportional hazards model was used to describe the association between anxiety and depression and adverse outcome (myocardial infarction (MI), heart failure (HF), stroke, death and a combined endpoint) after 5 years. Prevalence of anxiety and depression at baseline was 32% and 13%, respectively. There were 303 combined events; 140 deaths, 60 patients had MI, 177 patients were admitted to hospital with HF and 60 patients had a stroke. Neither anxiety nor depression at any time was associated with mortality or the combined endpoint. Anxiety in IHD patients at baseline and at 1 year was associated with increased risk of MI (HR 2.74; 95% CI: 1.10-6.83) but was attenuated after adjusting for other risk factors (HR 1.18; 95% CI: 0.39-3.55). Both anxiety and depression at 1 year were associated with increased risk of stroke: HR 2.25 (95% CI: 1.05-4.82) and 2.34 (95% CI: 0.99-5.50), respectively, but risk associated with anxiety was attenuated after adjustment. There were no gender differences. Contrary to conclusions from recent meta-analyses, anxiety and depression measured at baseline and after 1 year were not associated with adverse outcome in CVD patients after multivariable adjustment. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Sun protection behavior and knowledge of patients attending laser clinic to prevent adverse events of laser: A Cross-sectional, Single Center, Tertiary Care Study.

    PubMed

    Tempark, Therdpong; Lueangarun, Suparuj; Chatproedprai, Susheera; Panchaprateep, Ratchathorn; Pongprutthipan, Marisa; Wananukul, Siriwan

    2018-06-08

    Limited data of sun protection knowledge in laser treatment patients exists therefore, preventative information should be provided by dermatologists to minimize harmful effects. To assess sun protection knowledge-behavior and knowledge to prevent adverse events from laser therapy among patients who visited a laser clinic at a tertiary university hospital in Bangkok, Thailand. This is a self-reported questionnaire, cross-sectional survey. All participants from the Laser Clinic in KCMH were recruited into the study. A Total of 385 patients were enrolled into the study; 80.5% female participants. Patients who never received laser treatment significantly lacked proper sun protection knowledge to prevent adverse events of lasers when compared to those who previous received laser treatments regarding the application of sunscreen after laser treatment (56.6% vs 17.4%, p < 0.001), consistent application of sunscreen 4-6 weeks prior to receiving laser treatment (60.5% vs 18.9%, p < 0.001), application of topical corticosteroid after laser (67.1% vs 54.1%, p = 0.048), and sun protection in the post laser area (41.9% vs 20.4%, p < 0.001). The attitude and knowledge of sun protection to prevent adverse events were significantly different among the group of educational levels and previous history of laser treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. Polysensitivity in delayed cutaneous adverse drug reactions to macrolides, clindamycin, and pristinamycin: clinical history and patch testing.

    PubMed

    El Khoury, M; Assier, H; Gener, G; Paul, M; Haddad, C; Chosidow, O; Wolkenstein, P; Ingen-Housz-Oro, S

    2018-05-10

    Although they have different biochemical structures, macrolides, lincosamides (including clindamycin) and streptogramins (including pristinamycin) share a similar mechanism of action on Gram-positive bacteria and are grouped into the MLS family. 1 Cross-allergies induced by drugs of similar mechanism of action but different chemical structure (polysensitivity) are poorly described. Our objectives were to investigate the possibility of polysensitivity among MLS antibiotics, and to compare the value of patch tests (PTs) in MLS-induced delayed-cutaneous adverse drug reactions (D-CADRs). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  14. Neurobiological consequences of childhood trauma.

    PubMed

    Nemeroff, Charles B

    2004-01-01

    There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.

  15. Feasibility of Patient Reporting of Symptomatic Adverse Events via the PRO-CTCAE in a Chemoradiotherapy Cooperative Group Multicenter Clinical Trial

    PubMed Central

    Basch, Ethan; Pugh, Stephanie L; Dueck, Amylou C; Mitchell, Sandra A; Berk, Lawrence; Fogh, Shannon; Rogak, Lauren J; Gatewood, Marcha; Reeve, Bryce B; Mendoza, Tito R; O’Mara, Ann; Denicoff, Andrea; Minasian, Lori; Bennett, Antonia V; Setser, Ann; Schrag, Deborah; Roof, Kevin; Moore, Joan K; Gergel, Thomas; Stephans, Kevin; Rimner, Andreas; DeNittis, Albert; Bruner, Deborah Watkins

    2017-01-01

    Purpose To assess the feasibility of measuring symptomatic adverse events (AEs) in a multicenter clinical trial using the National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Methods and Materials Patients enrolled in Trial XXXX (XXXX) were asked to self-report 53 PRO-CTCAE items representing 30 symptomatic AEs at 6 time points (baseline; weekly x4 during treatment; 12-weeks post-treatment). Reporting was conducted via wireless tablet computers in clinic waiting areas. Compliance was defined as the proportion of visits when an expected PRO-CTCAE assessment was completed. Results Among 226 study sites participating in Trial XXXX, 100% completed 35-minute PRO-CTCAE training for clinical research associates (CRAs); 80 sites enrolled patients of which 34 (43%) required tablet computers to be provided. All 152 patients in Trial XXXX agreed to self-report using the PRO-CTCAE (median age 66; 47% female; 84% white). Median time for CRAs to learn the system was 60 minutes (range 30–240), and median time for CRAs to teach a patient to self-report was 10 minutes (range 2–60). Compliance was high, particularly during active treatment when patients self-reported at 86% of expected time points, although compliance was lower post-treatment (72%). Common reasons for non-compliance were institutional errors such as forgetting to provide computers to participants; patients missing clinic visits; internet connectivity; and patients feeling “too sick”. Conclusions Most patients enrolled in a multicenter chemoradiotherapy trial were willing and able to self-report symptomatic adverse events at visits using tablet computers. Minimal effort was required by local site staff to support this system. The observed causes of missing data may be obviated by allowing patients to self-report electronically between-visits, and by employing central compliance monitoring. These approaches are being incorporated

  16. Effect of RAAS blockers on adverse clinical outcomes in high CVD risk subjects with atrial fibrillation: A meta-analysis and systematic review of randomized controlled trials.

    PubMed

    Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A; Arima, Hisatomi; Wang, Dao Wen

    2016-06-01

    Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin-angiotensin-aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin-angiotensin-aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive.A pooled study of 6 randomized controlled trials assessing the efficacy of renin-angiotensin-aldosterone blockers on subjects with atrial fibrillation was performed.A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76- 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70-0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2-2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0-6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0-0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: -0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction.This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation.

  17. Study of adverse events following immunisation with universal and newer vaccines in the Serampore IMA Child Clinic over a period of 7 years.

    PubMed

    Das, Pradip Kumar

    2013-04-01

    Immunisation is an important part of childcare practice. It is one of the most beneficial and cost effective measures for the prevention of diseases. From the previous retrospective studies, it was evident that smallpox has been completely eradicated throughout now-a-days with the wholehearted and sincere efforts of healthcare providers by applying efficient and safe vaccine against smallpox, same is true also to polio which is now close to worldwide eradication and measles and rubella are no longer endemic in certain parts of the world. Not only has that with the introduction of safer and more efficient newer vaccines, the incidence of most other vaccine preventable disease of childhood also reduced considerably. The aim of the present study is to estimate the incidence and clinical presentation of adverse events following immunisation with universal and newer vaccines for a period of seven years using prospective active surveillance. Children under the age of 7 years were taken for universal and newer scheduled vaccinations given in the Serampore IMA Child Clinic under the supervision of the clinicians maintaining strictly the guidelines of Expanded Programme of Immunisation (Government of India). This study of adverse events following immunisation in the Serampore IMA Child Clinic confirms that the adverse events such as fever (0.37%), pain and swelling at the site of injection (0.32%0, urticarial rash (0.02%), anaphylactic shock (0.003%) are negligible. There were only two reports of anaphylaxis following preschool and infant schedule vaccines, including measles, mumps and rubella (MMR), Haemophilus influenzae type B vaccines and typhoid vaccines in approximately 52,000 infants received over a period of 7 years starting from 1st April, 2005 to 31st March, 2012 and there were no deaths or longterm effects reported during the post follow-up period in the Serampore IMA Child Clinic.

  18. Prevalence of clinical consequences of untreated dental caries and its relation to dental fear among 12-15-year-old schoolchildren in Bangalore city, India.

    PubMed

    Murthy, A K; Pramila, M; Ranganath, S

    2014-02-01

    To investigate the prevalence of clinical consequences of untreated dental caries and its relation to dental fear among public schoolchildren in India. A cross-sectional study of 1,452 schoolchildren aged 12-15-years in Bangalore city using a three-stage stratified random sample was conducted. Caries was scored by WHO (World Health Organisation) criteria (1997) and clinical consequences of untreated dental caries using the PUFA index. Dental fear was assessed by a single item dental fear questionnaire. The overall prevalence of caries was 57.9% and of untreated dental caries was 19.4%. Children with high dental fear had 2.05 times the risk of untreated caries as compared to children with low fear. This study showed that the prevalence of clinical consequences of untreated dental caries was low, and dental fear was shown to be a significant determinant of clinical consequences of untreated dental caries.

  19. Effect of Continued Support of Midwifery Students in Labour on the Childbirth and Labour Consequences: A Randomized Controlled Clinical Trial

    PubMed Central

    Bolbol-Haghighi, Nahid; Masoumi, Seyedeh Zahra

    2016-01-01

    Introduction Childbirth experience is a process throughout women’s life and the most important consequence of labour. Support is the key factor to have a positive experience of childbirth. In order to improve and reduce the stress and anxiety levels in women during labour and cope with the childbirth pain, the emotional, physical and educational support of doulas can be used. Aim This study was aimed to evaluate the effect of continued support of midwifery students in labour on the childbirth and labour consequences. Materials and Methods The present study was conducted using a randomized controlled clinical trial design on 100 pregnant women referred to the maternity ward at Fatemieh Hospital, Shahroud, Iran. The participants were assigned to the supportive or non-supportive group based on allocation sequence using a randomized block design and table of computer-generated random numbers prior to beginning the study. Supportive care was provided by the trained midwifery students. Childbirth and labour consequences were analysed by chi-square test, Fisher-exact test, independent t-test, Mann-Whitney U-test using SPSS-21 software. Results The results showed a significantly lower duration of the first stage of labour in the supportive group, as compared to that in the non-supportive group (p <0.001). Moreover, Apgar scores in the supportive group, compared to those in the non-supportive group, significantly increased at minutes 1 and 5 (p <0.001 and p = 0.04, respectively). Conclusion The findings of this study showed that the supportive care provided by the midwifery students shortens duration of the first stage of labour and improves the Apgar scores in the first and fifth minutes. PMID:27790526

  20. Clinical and Immunological Insights on Severe, Adverse Neurotropic and Viscerotropic Disease following 17D Yellow Fever Vaccination▿

    PubMed Central

    Silva, Maria Luiza; Espírito-Santo, Luçandra Ramos; Martins, Marina Angela; Silveira-Lemos, Denise; Peruhype-Magalhães, Vanessa; Caminha, Ricardo Carvalho; de Andrade Maranhão-Filho, Péricles; Auxiliadora-Martins, Maria; de Menezes Martins, Reinaldo; Galler, Ricardo; da Silva Freire, Marcos; Marcovistz, Rugimar; Homma, Akira; Teuwen, Dirk E.; Elói-Santos, Silvana Maria; Andrade, Mariléia Chaves; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis

    2010-01-01

    Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-γR in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3+ CD16+/− CD56+/−/CD3+ ratio), activated T cells (CD4+ and CD8+ cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-γ+], tumor necrosis factor alpha positive [TNF-α+], and IL-4 positive [IL-4+]), CD8+ T cells (IL-4+ and IL-5+), and B lymphocytes (TNF-α+, IL-4+, and IL-10+). The analysis of CD4+ T cells revealed a complex profile that consisted of an increased frequency of IL-12+ and IFN-γ+ cells and a decreased percentage of TNF-α+, IL-4+, and IL-5+ cells. Depressed cytokine synthesis was observed in monocytes (TNF-α+) following the provision of antigenic stimuli in vitro. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD. PMID:19906894

  1. Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan.

    PubMed

    Ichikura, Kanako; Okumura, Yasuyuki; Takeuchi, Takashi

    2016-01-01

    Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of ≥4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine-promethazine-phenobarbital combination drug (Vegetamin®) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new-generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60-5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18-6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose.

  2. The AFFORD clinical decision aid to identify emergency department patients with atrial fibrillation at low risk for 30-day adverse events.

    PubMed

    Barrett, Tyler W; Storrow, Alan B; Jenkins, Cathy A; Abraham, Robert L; Liu, Dandan; Miller, Karen F; Moser, Kelly M; Russ, Stephan; Roden, Dan M; Harrell, Frank E; Darbar, Dawood

    2015-03-15

    There is wide variation in the management of patients with atrial fibrillation (AF) in the emergency department (ED). We aimed to derive and internally validate the first prospective, ED-based clinical decision aid to identify patients with AF at low risk for 30-day adverse events. We performed a prospective cohort study at a university-affiliated tertiary-care ED. Patients were enrolled from June 9, 2010, to February 28, 2013, and followed for 30 days. We enrolled a convenience sample of patients in ED presenting with symptomatic AF. Candidate predictors were based on ED data available in the first 2 hours. The decision aid was derived using model approximation (preconditioning) followed by strong bootstrap internal validation. We used an ordinal outcome hierarchy defined as the incidence of the most severe adverse event within 30 days of the ED evaluation. Of 497 patients enrolled, stroke and AF-related death occurred in 13 (3%) and 4 (<1%) patients, respectively. The decision aid included the following: age, triage vitals (systolic blood pressure, temperature, respiratory rate, oxygen saturation, supplemental oxygen requirement), medical history (heart failure, home sotalol use, previous percutaneous coronary intervention, electrical cardioversion, cardiac ablation, frequency of AF symptoms), and ED data (2 hours heart rate, chest radiograph results, hemoglobin, creatinine, and brain natriuretic peptide). The decision aid's c-statistic in predicting any 30-day adverse event was 0.7 (95% confidence interval 0.65, 0.76). In conclusion, in patients with AF in the ED, Atrial Fibrillation and Flutter Outcome Risk Determination provides the first evidence-based decision aid for identifying patients who are at low risk for 30-day adverse events and candidates for safe discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

    PubMed

    Pradhan, Richeek; Singh, Sonal

    2018-04-11

    Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.

  4. Estimation of the clinical and economic consequences of non-compliance with antimicrobial treatment of canine skin infections.

    PubMed

    Van Vlaenderen, Ilse; Nautrup, Barbara Poulsen; Gasper, Sabina M

    2011-05-01

    The goal of this study was to estimate the health and economic consequences of non-compliance with oral antimicrobial treatment in dogs with superficial pyoderma, wounds or abscesses in the US. A mathematical model (Markov model) which simulated treatment with long-term injectable cefovecin versus oral amoxicillin/clavulanic acid was developed and accounted for the effect of non-compliance on clinical outcomes and mean total treatment costs per patient. Efficacy parameters considered in the model were derived from clinical studies. Treatment failure due to oral antimicrobial treatment non-compliance was approximated from published data at 13.6%. US cost data for 2009 were derived from public sources. When non-compliance was considered as a cause of treatment failure with oral medication, the long-term injectable antibiotic was more effective than oral comparator (162 versus 158 days without clinical signs). Mean total treatment costs were lower with cefovecin (USD 376.74) versus amoxicillin/clavulanic acid (USD 382.34) in dogs of 25 kg; and cefovecin remained cost-saving up to a body weight of 31 kg. In large dogs, cefovecin was more costly; however, total therapy costs were less than 6% greater than with amoxicillin/clavulanic acid. Accordingly the higher drug and administration costs of the long-term injectable antibiotic were totally or substantially offset when non-compliance was considered as reason for treatment failure with oral medication. The model also allowed for the estimation of the impact of various non-compliance scenarios. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Highly Prevalent Hyperuricaemia is Associated with Adverse Clinical Outcomes Among Ghanaian Stroke Patients: An Observational Prospective Study.

    PubMed

    Sarfo, F S; Akassi, J; Antwi, N K B; Obese, V; Adamu, S; Akpalu, A; Bedu-Addo, G

    2015-09-01

    Although a direct causal relationship between hyperuricaemia and stroke continues to be debated, strong associations between serum uric acid (SUA) and cerebrovascular disease exist. Very few studies have been conducted to evaluate the frequency and association between this potentially modifiable biomarker of vascular risk and stroke in sub-Saharan Africa. Therefore the aim of this study was to examine the association between hyperuricaemia and the traditional risk factors and the outcomes of stroke in Ghanaian patients. In this prospective observational study, 147 patients presenting with stroke at a tertiary referral centre in Ghana were consecutively recruited. Patients were screened for vascular risk factors and SUA concentrations measured after an overnight fast. Associations between hyperuricaemia and stroke outcomes were analysed using Kaplan-Meier and Cox proportional hazards regression analysis. The frequency of hyperuricaemia among Ghanaian stroke patients was 46.3%. Non-significant associations were observed between hyperuricaemia and the traditional risk factors of stroke. SUA concentration was positively correlated with stroke severity and associated with early mortality after an acute stroke with unadjusted hazards ratio of 2.3 (1.4 - 4.2, p=0.001). A potent and independent dose-response association between increasing SUA concentration and hazard of mortality was found on Cox proportional hazards regression, aHR (95% CI) of 1.65 (1.14-2.39), p=0.009 for each 100µmol/l increase in SUA. Hyperuricaemia is highly frequent and associated with adverse functional outcomes among Ghanaian stroke patients. Further studies are warranted to determine whether reducing SUA levels after a stroke would be beneficial within our setting.

  6. The Complement System and Adverse Pregnancy Outcomes

    PubMed Central

    Regal, Jean F.; Gilbert, Jeffrey S.; Burwick, Richard M.

    2015-01-01

    Adverse pregnancy outcomes significantly contribute to morbidity and mortality for mother and child, with lifelong health consequences for both. The innate and adaptive immune system must be regulated to insure survival of the feta allograft, and the complement system is no exception. An intact complement system optimizes placental development and function and is essential to maintain host defense and fetal survival. Complement regulation is apparent at the placental interface from early pregnancy with some degree of complement activation occurring normally throughout gestation. However, a number of pregnancy complications including early pregnancy loss, fetal growth restriction, hypertensive disorders of pregnancy and preterm birth are associated with excessive or misdirected complement activation, and are more frequent in women with inherited or acquired complement system disorders or complement gene mutations. Clinical studies employing complement biomarkers in plasma and urine implicate dysregulated complement activation in components of each of the adverse pregnancy outcomes. In addition, mechanistic studies in rat and mouse models of adverse pregnancy outcomes address the complement pathways or activation products of importance and allow critical analysis of the pathophysiology. Targeted complement therapeutics are already in use to control adverse pregnancy outcomes in select situations. A clearer understanding of the role of the complement system in both normal pregnancy and complicated or failed pregnancy will allow a rational approach to future therapeutic strategies for manipulating complement with the goal of mitigating adverse pregnancy outcomes, preserving host defense, and improving long term outcomes for both mother and child. PMID:25802092

  7. German cardiac CT registry: indications, procedural data and clinical consequences in 7061 patients undergoing cardiac computed tomography.

    PubMed

    Marwan, Mohamed; Achenbach, Stephan; Korosoglou, Grigorios; Schmermund, Axel; Schneider, Steffen; Bruder, Oliver; Hausleiter, Jörg; Schroeder, Stephen; Barth, Sebastian; Kerber, Sebastian; Leber, Alexander; Moshage, Werner; Senges, Jochen

    2018-05-01

    Cardiac computed tomography permits quantification of coronary calcification as well as detection of coronary artery stenoses after contrast enhancement. Moreover, cardiac CT offers high-resolution morphologic and functional imaging of cardiac structures which is valuable for various structural heart disease interventions and electrophysiology procedures. So far, only limited data exist regarding the spectrum of indications, image acquisition parameters as well as results and clinical consequences of cardiac CT examinations using state-of-the-art CT systems in experienced centers. Twelve cardiology centers with profound expertise in cardiovascular imaging participated in the German Cardiac CT Registry. Criteria for participation included adequate experience in cardiac CT as well of the availability of a 64-slice or newer CT system. Between 2009 and 2014, 7061 patients were prospectively enrolled. For all cardiac CT examinations, patient parameters, procedural data, indication and clinical consequences of the examination were documented. Mean patient age was 61 ± 12 years, 63% were males. The majority (63%) of all cardiac CT examinations were performed in an outpatient setting, 37% were performed during an inpatient stay. 91% were elective and 9% were scheduled in an acute setting. In most examinations (48%), reporting was performed by cardiologists, in 4% by radiologists and in 47% of the cases as a consensus reading. Cardiac CT was limited to native acquisitions for assessment of coronary artery calcification in 9% of patients, only contrast-enhanced coronary CT angiography was performed in 16.6% and combined native and contrast-enhanced coronary CT angiography was performed in 57.7% of patients. Non-coronary cardiac CT examinations constituted 16.6% of all cases. Coronary artery calcification assessment was performed using prospectively ECG-triggered acquisition in 76.9% of all cases. The median dose length product (DLP) was 42 mGy cm (estimated effective

  8. Correlates of syphilis seropositivity and risk for syphilis-associated adverse pregnancy outcomes among women attending antenatal care clinics in the Democratic Republic of Congo.

    PubMed

    Taylor, Melanie M; Ebrahim, Shahul; Abiola, Nadine; Kinkodi, Didine Kaba; Mpingulu, Minlangu; Kabuayi, Jean Pierre; Ekofo, Felly; Newman, Daniel R; Peterman, Thomas A; Kamb, Mary L; Sidibe, Kassim

    2014-09-01

    Screening and treatment for syphilis among pregnant women is the primary means of prevention of congenital syphilis. Sentinel surveillance for syphilis can inform these prevention efforts. We reviewed antenatal syphilis screening results to assess trends and to identify correlates of seropositivity among women attending antenatal care clinics in the Democratic Republic of Congo during 2011. Syphilis seropositivity among the 17,669 women attending the antenatal care clinics during 2011 was 4.2% (range 0.4%-16.9%). Syphilis seropositivity was significantly higher among women attending rural clinics (5.0%) as compared to urban clinics (3.0%) and those tested in antenatal care clinics in the provinces of Equateur (7.6%) and Orientale (7.7%) as compared to other provinces (p < 0.001). Based on the antenatal care syphilis seroprevalence and national pregnancy estimates, we estimate that approximately 128,591 pregnant women countrywide would have tested seropositive for syphilis during 2011. Over 85,000 adverse pregnancy outcomes would have resulted from these maternal infections, assuming prenatal syphilis diagnosis and treatment were not available. The prevalence of syphilis was highest in rural areas, but exceeded 1% in every area, indicating a need to assure screening and treatment throughout Democratic Republic of Congo. These sentinel surveillance estimates can be used to guide national congenital syphilis prevention efforts. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. Peri-procedural ST segment resolution during Primary Percutaneous Coronary Intervention (PPCI) for acute myocardial infarction: predictors and clinical consequences.

    PubMed

    Karamasis, Grigoris V; Russhard, Paul; Al Janabi, Firas; Parker, Michael; Davies, John R; Keeble, Thomas R; Clesham, Gerald J

    ECG ST segment resolution (STR) has been used to assess myocardial perfusion in STEMI patients undergoing PPCI. However, in most of the studies ECGs recorded at different time points after the actual procedure have been used, limiting the options of therapeutic interventions while the patient is still in the catheterisation laboratory. The aim of this study was to investigate the presence and clinical consequences of intra-procedural STR during PPCI. We analysed 12 lead ECGs recorded at the onset and the end of the PPCI procedure, measuring STR in the lead with maximum ST elevation on the initial recording. STR was defined as good when > 50% compared to baseline. Pre and immediately post PPCI ECGs were recorded in 467 STEMI cases whilst the patient was on the catheter lab table. Mean patient age was 63 (+/- 12) years old and 75% were men. Mean duration of symptoms to admission was 3.8 (+/- 3.4) hours and 51% of infarcts were anterior. Good ST resolution at the end of the procedure was seen in 46.5% of patients and was observed more commonly in inferior compared to anterior infarcts (60.1% vs. 32.6%, p<0.001), and in current smokers (53.2% vs. 42.4%, p=0.031). In patients presenting with symptoms for < 4 hours, good STR was more common (74% vs. 66%, p=0.019). Thrombus aspiration was used more frequently in patients who had good STR (88.5% vs 79.8% p=0.011). Patients with good ST resolution had a shorter mean hospital length of stay (3.8 vs. 4.5 days, p=0.009) and a higher left ventricular ejection fraction (49.9% vs. 44.2%, p<0.001) measured by transthoracic echocardiography prior to discharge. Good peri-procedural ST resolution was seen in less than half of STEMI patients undergoing PPCI. There were important clinical consequences of good ST resolution. Identification of suboptimal peri-procedural ST resolution could help identify patients who may benefit from new treatments aimed at protecting the microcirculation, whilst the patients are still in the angiography

  10. The feasibility, perceived satisfaction, and value of using synchronous webinars to educate clinical research professionals on reporting adverse events in clinical trials: a report from the Children's Oncology Group.

    PubMed

    Borgerson, Dawn; Dino, Jennifer

    2012-01-01

    Clinical research professionals are faced with decreased funding and increased workloads; innovative methods of professional development programs are necessary to accommodate these factors. This study evaluated the feasibility, perceived satisfaction, and value of using webinars to educate clinical research professionals on reporting adverse events commonly experienced in pediatric oncology clinical trials. The setting incorporated synchronous web-based educational technology. Constructivist learning provides the theoretical framework for this study. Participants evaluated the professional development program at 2 time points: (a) at the conclusion and (b) 4 to 6 weeks afterward, using survey method. Synchronous webinars were both economical and effective in educating clinical research professionals across institutional sites. Participants reported exceptionally high levels of satisfaction with the accessibility, scope, quality, and interactivity of the professional development program. The vast majority of participants reported that the education would assist with reporting adverse events in pediatric oncology clinical trials and this perception persisted into clinical practice. Although the results of this study were intended to guide future educational efforts of the Children's Oncology Group, they may also apply to other cooperative groups.

  11. Linking MedDRA®-coded Clinical Phenotypes to Biological Mechanisms by The Ontology of Adverse Events: A pilot study on Tyrosine Kinase Inhibitors (TKIs)

    PubMed Central

    Sarntivijai, Sirarat; Zhang, Shelley; Jagannathan, Desikan G.; Zaman, Shadia; Burkhart, Keith K.; Omenn, Gilbert S.; He, Yongqun; Athey, Brian D.; Abernethy, Darrell R.

    2016-01-01

    Introduction A translational bioinformatics challenge lies in connecting population and individual’s clinical phenotypes in various formats to biological mechanisms. The Medical Dictionary for Regulatory Activities (MedDRA®) is the default dictionary for Adverse Event (AE) reporting in the FDA Adverse Event Reporting System (FAERS). The Ontology of Adverse Events (OAE) represents AEs as pathological processes occurring after drug exposures. Objectives The aim is to establish a semantic framework to link biological mechanisms to phenotypes of AEs by combining OAE with MedDRA® in FAERS data analysis. We investigated the AEs associated with Tyrosine Kinase Inhibitors (TKIs) and monoclonal antibodies (mAbs) targeting tyrosine kinases. The selected 5 TKIs/mAbs (i.e., dasatinib, imatinib, lapatinib, cetuximab, and trastuzumab) are known to induce impaired ventricular function (non-QT) cardiotoxicity. Results Statistical analysis of FAERS data identified 1,053 distinct MedDRA® terms significantly associated with TKIs/mAbs, where 884 did not have corresponding OAE terms. We manually annotated these terms, added them to OAE by the standard OAE development strategy, and mapped them to MedDRA®. The data integration to provide insights into molecular mechanisms for drug-associated AEs is performed by including linkages in OAE for all related AE terms to MedDRA® and existing ontologies including Human Phenotype Ontology (HP), Uber Anatomy Ontology (UBERON), and Gene Ontology (GO). Sixteen AEs are shared by all 5 TKIs/mAbs, and each of 17 cardiotoxicity AEs was associated with at least one TKI/mAb. As an example, we analyzed ‘cardiac failure’ using the relations established in OAE with other ontologies, and demonstrated that one of the biological processes associated with cardiac failure maps to the genes associated with heart contraction. Conclusion By expanding existing OAE ontological design, our TKI use case demonstrates that the combination of OAE and Med

  12. Critical thinking about adverse drug effects: lessons from the psychology of risk and medical decision-making for clinical psychopharmacology.

    PubMed

    Nierenberg, Andrew A; Smoller, Jordan W; Eidelman, Polina; Wu, Yelena P; Tilley, Claire A

    2008-01-01

    Systematic biases in decision-making have been well characterized in medical and nonmedical fields but mostly ignored in clinical psychopharmacology. The purpose of this paper is to sensitize clinicians who prescribe psychiatric drugs to the issues of the psychology of risk, especially as they pertain to the risk of side effects. Specifically, the present analysis focuses on heuristic organization and framing effects that create cognitive biases in medical practice. Our purpose is to increase the awareness of how pharmaceutical companies may influence physicians by framing the risk of medication side effects to favor their products. (c) 2008 S. Karger AG, Basel.

  13. Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

    PubMed

    Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

    2016-08-01

    Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

  14. Adverse impact of marijuana use on clinical outcomes among psychiatry patients with depression and alcohol use disorder.

    PubMed

    Bahorik, Amber L; Campbell, Cynthia I; Sterling, Stacy A; Leibowitz, Amy; Travis, Adam; Weisner, Constance M; Satre, Derek D

    2018-01-01

    This study examined whether marijuana use was associated with clinically problematic outcomes for patients with depression and alcohol use disorder (AUD). The sample consisted of 307 psychiatry outpatients with mild to severe depression and past 30-day hazardous drinking/drug use, who participated in a trial of substance use treatment. Participants were assessed for AUD based on DSM-IV criteria. Measures of marijuana use, depression symptoms, and functional status related to mental health were collected at baseline, 3, and 6 months. Differences in these outcomes were analyzed among patients with and without AUD using growth models, adjusting for treatment effects. Marijuana was examined as both an outcome (patterns of use) and a predictor (impact on depression and functioning). Forty percent used marijuana and about half the sample met AUD criteria. Fewer patients with AUD used marijuana than those without AUD at baseline. Over 6 months, the proportion of patients with AUD using marijuana increased compared to those without AUD. Patients with AUD using marijuana had greater depressive symptoms and worse functioning than those without AUD. These findings indicate that marijuana use is clinically problematic for psychiatry outpatients with depression and AUD. Addressing marijuana in the context of psychiatry treatment may help improve outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Clinical and economic consequences of vancomycin and fidaxomicin for the treatment of Clostridium difficile infection in Canada.

    PubMed

    Wagner, Monika; Lavoie, Louis; Goetghebeur, Mireille

    2014-03-01

    Clostridium difficile infection (CDI) represents a public health problem with increasing incidence and severity. To evaluate the clinical and economic consequences of vancomycin compared with fidaxomicin in the treatment of CDI from the Canadian health care system perspective. A decision-tree model was developed to compare vancomycin and fidaxomicin for the treatment of severe CDI. The model assumed identical initial cure rates and included first recurrent episodes of CDI (base case). Treatment of patients presenting with recurrent CDI was examined as an alternative analysis. Costs included were for study medication, physician services and hospitalization. Cost effectiveness was measured as incremental cost per recurrence avoided. Sensitivity analyses of key input parameters were performed. In a cohort of 1000 patients with an initial episode of severe CDI, treatment with fidaxomicin led to 137 fewer recurrences at an incremental cost of $1.81 million, resulting in an incremental cost of $13,202 per recurrence avoided. Among 1000 patients with recurrent CDI, 113 second recurrences were avoided at an incremental cost of $18,190 per second recurrence avoided. Incremental costs per recurrence avoided increased with increasing proportion of cases caused by the NAP1/B1/027 strain. Results were sensitive to variations in recurrence rates and treatment duration but were robust to variations in other parameters. The use of fidaxomicin is associated with a cost increase for the Canadian health care system. Clinical benefits of fidaxomicin compared with vancomycin depend on the proportion of cases caused by the NAP1/B1/027 strain in patients with severe CDI.

  16. Gene transfer as a strategy to achieve permanent cardioprotection II: rAAV-mediated gene therapy with heme oxygenase-1 limits infarct size 1 year later without adverse functional consequences.

    PubMed

    Li, Qianhong; Guo, Yiru; Ou, Qinghui; Wu, Wen-Jian; Chen, Ning; Zhu, Xiaoping; Tan, Wei; Yuan, Fangping; Dawn, Buddhadeb; Luo, Li; Hunt, Gregory N; Bolli, Roberto

    2011-11-01

    Extensive evidence indicates that heme oxygenase-1 (HO-1) exerts potent cytoprotective effects in response to stress. Previous studies have shown that gene therapy with HO-1 protects against myocardial ischemia/reperfusion injury for up to 8 weeks after gene transfer. However, the long-term effects of HO-1 gene therapy on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the HO-1 gene (rAAV/HO-1) that enables long-lasting transgene expression. Mice received injections in the anterior LV wall of rAAV/LacZ (LacZ group) or rAAV/HO-1 (HO-1 group); 1 year later, they were subjected to a 30-min coronary occlusion (O) and 4 h of reperfusion (R). Cardiac HO-1 gene expression was confirmed at 1 month and 1 year after gene transfer by immunoblotting and immunohistochemistry analyses. In the HO-1 group, infarct size (% of risk region) was dramatically reduced at 1 year after gene transfer (11.2 ± 2.1%, n = 12, vs. 44.7 ± 3.6%, n = 8, in the LacZ group; P < 0.05). The infarct-sparing effects of HO-1 gene therapy at 1 year were as powerful as those observed 24 h after ischemic PC (six 4-min O/4-min R cycles) (15.0 ± 1.7%, n = 10). There were no appreciable changes in LV fractional shortening, LV ejection fraction, or LV end-diastolic or end-systolic diameter at 1 year after HO-1 gene transfer as compared to the age-matched controls or with the LacZ group. Histology showed no inflammation in the myocardium 1 year after rAAV/HO-1-mediated gene transfer. These results demonstrate, for the first time, that rAAV-mediated HO-1 gene transfer confers long-term (1 year), possibly permanent, cardioprotection without adverse functional consequences, providing proof of principle for the concept of achieving prophylactic cardioprotection (i.e., "immunization against infarction").

  17. Impact of untreated dental caries and its clinical consequences on the oral health-related quality of life of schoolchildren aged 8-10 years.

    PubMed

    Mota-Veloso, Isabella; Soares, Maria Eliza C; Alencar, Bruna Mota; Marques, Leandro Silva; Ramos-Jorge, Maria Letícia; Ramos-Jorge, Joana

    2016-01-01

    This study aims to evaluate the impact of untreated dental caries and its clinical consequences on the quality of life of Brazilian schoolchildren aged 8-10 years. A randomly selected sample of 587 children underwent a clinical oral examination for the assessment of untreated dental caries and clinical consequences. The WHO criteria (decayed component of the decayed, missing, and filled teeth--D-DMFT in permanent teeth or d-dfmt in primary teeth) and the PUFA index, which records the presence of severely decayed permanent (upper case) and primary (lower case) teeth with visible pulpal involvement (P/p), as well as ulceration caused by dislocated tooth fragments (U/u), fistula (F/f), and abscesses (A/a), were used for the oral examination. Oral health-related quality of life (OHRQoL) was evaluated using the Child's Perception Questionnaire (CPQ8-10). Poisson regression was employed to test unadjusted and adjusted associations between untreated dental caries/clinical consequences and OHRQoL. The prevalence of untreated dental caries was 64.6% (D/d component of DMFT/dmft > 0) and 17.9% of children exhibited clinical consequences of caries (PUFA/pufa index >0). In the adjusted models, untreated caries was significantly associated with the total CPQ8-10 score and all subscale scores. The clinical consequences of dental caries (PUFA/pufa index >0) were significantly associated with the total CPQ8-10 as well as the oral symptoms and functional limitations' subscales. Untreated dental caries and its clinical consequences exerted a negative impact on the OHRQoL of the schoolchildren analyzed.

  18. P2Y12 Polymorphisms and the Risk of Adverse Clinical Events in Patients Treated with Clopidogrel: A Meta-Analysis.

    PubMed

    Zhao, Kun; Yang, Ming; Lu, Yanxia; Sun, Shusen; Li, Wei; Li, Xingang; Zhao, Zhigang

    2018-05-23

    Some studies have reported an association between P2Y12 gene polymorphisms and clopidogrel adverse outcomes with inconsistent results. We aimed to explore the relationship between P2Y12 polymorphisms and the risk of adverse clinical events in patients treated with clopidogrel through a meta-analysis. A systematic search of PubMed, Web of Science and the Cochrane Library was conducted. Retrieved articles were comprehensively reviewed and eligible studies were included, and the relevant data was extracted for this meta-analysis. All statistical tests were performed by the Review Manager 5.3 software. A total of 14 studies involving 8,698 patients were included. In the Han Chinese population, ischemic events were associated with P2Y12 T744C polymorphism in the CC vs TT+CT genetic model (OR=3.32, 95%CI=1.62-6.82, P =0.001), and the events were associated with P2Y12 C34T polymorphism in the TT+TC vs CC genetic model (OR=1.70, 95%CI=1.22-2.36, P =0.002). However, ischemic events were not related to P2Y12 G52T polymorphism (TT+TG vs GG: OR=1.13, 95%CI=0.76-1.68, P =0.56; TT vs GG+TG: OR=2.02, 95%CI=0.65-6.28, P =0.22). The associations between the P2Y12 polymorphism and ischemic events were not significant in T744C, G52T and C34T genotype for another subgroup of the Caucasian population ( P >0.05). Only two studies referring to bleeding events were included in this analysis of C34T polymorphism, and no significant association was found (TT+TC vs CC: OR=1.07, 95%CI=0.37-3.15, P =0.90). In the Caucasian population, P2Y12 gene polymorphisms are not associated with clinical events. However, in the Chinese Han population, P2Y12 T744C and C34T polymorphisms are significantly associated with adverse clinical events. © Georg Thieme Verlag KG Stuttgart · New York.

  19. PTEN deletion and heme oxygenase-1 overexpression cooperate in prostate cancer progression and are associated with adverse clinical outcome.

    PubMed

    Li, Yunru; Su, Jie; DingZhang, Xiao; Zhang, Jianguo; Yoshimoto, Maisa; Liu, Shuhong; Bijian, Krikor; Gupta, Ajay; Squire, Jeremy A; Alaoui Jamali, Moulay A; Bismar, Tarek A

    2011-05-01

    Overexpression of the pro-survival protein heme oxygenase-1 (HO-1) and loss of the pro-apoptotic tumour suppressor PTEN are common events in prostate cancer (PCA). We assessed the occurrence of both HO-1 expression and PTEN deletion in two cohorts of men with localized and castration-resistant prostate cancer (CRPC). The phenotypic cooperation of these markers was examined in preclinical and clinical models. Overall, there was a statistically significant difference in HO-1 epithelial expression between benign, high-grade prostatic intraepithelial neoplasia (HGPIN), localized PCA, and CRPC (p < 0.0001). The highest epithelial HO-1 expression was noted in CRPC (2.00 ± 0.89), followed by benign prostate tissue (1.49 ± 1.03) (p = 0.0003), localized PCA (1.20 ± 0.95), and HGPIN (1.07 ± 0.87) (p < 0.0001). However, the difference between HGPIN and PCA was not statistically significant (p = 0.21). PTEN deletions were observed in 35/55 (63.6%) versus 68/183 (37.1%) cases of CRPC and localized PCA, respectively. Although neither HO-1 overexpression nor PTEN deletions alone in localized PCA showed a statistically significant association with PSA relapse, the combined status of both markers correlated with disease progression (log-rank test, p = 0.01). In a preclinical model, inhibition of HO-1 by shRNA in PTEN-deficient PC3M cell line and their matched cells where PTEN is restored strongly reduced cell growth and invasion in vitro and inhibited tumour growth and lung metastasis formation in mice compared to cells where only HO-1 is inhibited or PTEN is restored. In summary, we provide clinical and experimental evidence for cooperation between epithelial HO-1 expression and PTEN deletions in relation to the PCA patient's outcome. These findings could potentially lead to the discovery of novel therapeutic modalities for advanced PCA. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  20. A systematic review of the evidence of reduced allergenicity and clinical benefit of food hydrolysates in dogs with cutaneous adverse food reactions.

    PubMed

    Olivry, Thierry; Bizikova, Petra

    2010-02-01

    Several hydrolysate-based diets have been commercialized for helping diagnose or treat dogs with cutaneous adverse food reactions (CAFR). This systematic review was performed to examine the evidence in favour of reduced immunological and clinical allergenicity of hydrolysates in dogs with CAFR. Citation databases, meeting abstracts and article bibliographies were scanned for relevant citations, and companies were contacted to provide unpublished reports. Eleven studies relevant to this study were identified. Some evidence of reduced serum IgE binding to a soy hydrolysate (1 study) and decreased intradermal test reactivity to hydrolysed proteins (three studies) was found. In four reports, the feeding of dogs suspected of having CAFR with hydrolysate-based diets reduced or eliminated clinical signs in a variable proportion of subjects. The percentage of dogs with CAFR that still reacted to these hydrolysate-based diets could not be assessed, however. Importantly, up to 50% of dogs with CAFR enrolled in three controlled studies exhibited increases in clinical signs after ingesting partial hydrolysates derived from foods to which they were hypersensitive. In conclusion, the limited number of studies undertaken point to reduced - but not eliminated - immunological and clinical allergenicity of hydrolysate-based commercial diets. A variable proportion of dogs with CAFR will exhibit a worsening of clinical signs when fed partial hydrolysates. Clinicians must weigh the clinical benefit of these diets versus their high cost and low risk of reduced appetence or gastrointestinal sign development. At this time, hydrolysate-containing diets are probably best used in dogs suspected not to be hypersensitive to their individual components.

  1. Clinical Evidence of Increase in Hair Growth and Decrease in Hair Loss without Adverse Reactions Promoted by the Commercial Lotion ECOHAIR®.

    PubMed

    Alonso, María Rosario; Anesini, Claudia

    2017-01-01

    Hair exerts protection, sensory functions, thermoregulation, and sexual attractiveness. Hair loss (alopecia) is caused by several diseases, drug intake, hormone imbalance, stress, and infections (Malassesia furfur). Drugs usually used in alopecia produce irreversible systemic and local side effects. An association of extracts of Coffea arabica and Larrea divaricata (ECOHAIR®) is successfully being commercialized in Argentina for hair growth. The aim of this study was to provide scientific support for the efficacy and innocuousness of ECOHAIR® in patients with noncicatricial alopecia during a 3-month treatment. The efficacy was determined through the assessment of an increase in hair volume, improvement in hair looks, growth of new hair, and a decrease in hair loss by the test of hair count and hair traction. The capacity to decrease the amount of dandruff was also evaluated as well as the adverse local effects caused by the treatment. ECOHAIR® spray improved the overall hair volume and appearance; it increased its thickness, induced hair growth, and decreased hair loss. Besides, no adverse local reactions were observed upon treatment with the product. This study provides scientific support for the clinical use of ECOHAIR® as a treatment to be used in noncicatricial alopecia. © 2017 S. Karger AG, Basel.

  2. Model-based decision making in early clinical development: minimizing the impact of a blood pressure adverse event.

    PubMed

    Stroh, Mark; Addy, Carol; Wu, Yunhui; Stoch, S Aubrey; Pourkavoos, Nazaneen; Groff, Michelle; Xu, Yang; Wagner, John; Gottesdiener, Keith; Shadle, Craig; Wang, Hong; Manser, Kimberly; Winchell, Gregory A; Stone, Julie A

    2009-03-01

    We describe how modeling and simulation guided program decisions following a randomized placebo-controlled single-rising oral dose first-in-man trial of compound A where an undesired transient blood pressure (BP) elevation occurred in fasted healthy young adult males. We proposed a lumped-parameter pharmacokinetic-pharmacodynamic (PK/PD) model that captured important aspects of the BP homeostasis mechanism. Four conceptual units characterized the feedback PD model: a sinusoidal BP set point, an effect compartment, a linear effect model, and a system response. To explore approaches for minimizing the BP increase, we coupled the PD model to a modified PK model to guide oral controlled-release (CR) development. The proposed PK/PD model captured the central tendency of the observed data. The simulated BP response obtained with theoretical release rate profiles suggested some amelioration of the peak BP response with CR. This triggered subsequent CR formulation development; we used actual dissolution data from these candidate CR formulations in the PK/PD model to confirm a potential benefit in the peak BP response. Though this paradigm has yet to be tested in the clinic, our model-based approach provided a common rational framework to more fully utilize the limited available information for advancing the program.

  3. Clinical features and risk factors for adverse outcome in Ebola virus disease in Moyamba District Sierra Leone.

    SciTech Connect

    Haaskjold, Yngvar Lunde; Bolkan, Hakon Angell; Krogh, Kurt Østhuus

    BACKGROUND The current outbreak of Ebola virus disease (EVD) in West Africa has attacked 24000 people, killed more than 10000 and disrupted social life. METHODS We studied retrospectively the clinical presentation and risk factors for fatal outcome in EVD among all patients admitted to the Ebola Treatment Center in Moyamba District, Sierra Leone. RESULTS Among a total of 88 admitted patients, eighty-two were tested by PCR and 31 (38%) were positive for Ebola virus. Ninety percent reported previous contact with EVD patients and 35% had participated in burials of EVD suspect deceased. No healthworkers were admitted. The most common symptomsmore » on admission were weakness (97%), diarrhea (68%), fever (62%), loss of appetite (62%), vomiting (58%), pain in muscles (62%) and joints (55%), headache (55%), abdominal pain (45%) and conjunctivitis (42%). On admission, bleeding was present in one-third (11/31), while more than half (17/31) bled during the hospital stay. Fifty-eight percent (18/31) died, most within 4-11 days of onset. Significant predictors for fatal outcome were shorter time from onset to admission (P=0.02), high initial viral load (P<0.001), bleeding (P=0.004), and severe pain (P=0.001). The only two patients with hiccups died. CONCLUSIONS Bleeding was more common in our cohort than reported elsewhere during this epidemic, and predicted poor prognosis. Severe pain was common, particularly in fatal cases, and calls for improved and safe palliation, for instance with transdermal opiates. The lack of fever in one third of EBV cases may have implications for screening procedures and case definitions.« less

  4. Adverse reactions to sulfites

    PubMed Central

    Yang, William H.; Purchase, Emerson C.R.

    1985-01-01

    Sulfites are widely used as preservatives in the food and pharmaceutical industries. In the United States more than 250 cases of sulfite-related adverse reactions, including anaphylactic shock, asthmatic attacks, urticaria and angioedema, nausea, abdominal pain and diarrhea, seizures and death, have been reported, including 6 deaths allegedly associated with restaurant food containing sulfites. In Canada 10 sulfite-related adverse reactions have been documented, and 1 death suspected to be sulfite-related has occurred. The exact mechanism of sulfite-induced reactions is unknown. Practising physicians should be aware of the clinical manifestations of sulfite-related adverse reactions as well as which foods and pharmaceuticals contain sulfites. Cases should be reported to health officials and proper advice given to the victims to prevent further exposure to sulfites. The food industry, including beer and wine manufacturers, and the pharmaceutical industry should consider using alternative preservatives. In the interim, they should list any sulfites in their products. PMID:4052897

  5. Management of adverse events in patients with hormone receptor-positive breast cancer treated with everolimus: observations from a phase III clinical trial.

    PubMed

    Peterson, Mary E

    2013-08-01

    Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, renal angiomyolipoma and tuberous sclerosis complex, and, in combination with exemestane, for hormone receptor-positive HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. Results from the phase III BOLERO-2 trial demonstrated that everolimus in combination with exemestane provided significant clinical benefit to patients with advanced hormone receptor-positive breast cancer. Although everolimus is generally well tolerated, as with most therapies administered in an advanced cancer setting, drug-related adverse events (AEs) inevitably occur. Most common AEs observed in the everolimus studies include stomatitis, rash, infection, noninfectious pneumonitis, and hyperglycemia. Clinical awareness and early identification of such AEs by oncology nurses are essential to dosing (interruptions, reduction, and treatment discontinuation); quality of life; and, ultimately, patient outcomes. Because everolimus has already been shown to significantly improve clinical efficacy in patients with advanced breast cancer, a proactive approach to the practical management of AEs associated with this mTOR inhibitor as well as other most common AEs observed in this patient population has been reviewed and outlined here.

  6. Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events.

    PubMed

    Martini, Dylan J; Hamieh, Lana; McKay, Rana R; Harshman, Lauren C; Brandao, Raphael; Norton, Craig K; Steinharter, John A; Krajewski, Katherine M; Gao, Xin; Schutz, Fabio A; McGregor, Bradley; Bossé, Dominick; Lalani, Aly-Khan A; De Velasco, Guillermo; Michaelson, M Dror; McDermott, David F; Choueiri, Toni K

    2018-04-01

    The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti-PD-1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7-46.5) and median TTP was 18.4 months (95% CI, 4.7-54.3) per Kaplan-Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients ( n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% ( n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti-PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti-PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402-8. ©2018 AACR . ©2018 American Association for Cancer Research.

  7. Current data on acute haematogenous osteomyelitis in children in Southern Israel: epidemiology, microbiology, clinics and therapeutic consequences.

    PubMed

    Cohen, Eugen; Lifshitz, Karin; Fruchtman, Yariv; Eidelman, Mark; Leibovitz, Eugene

    2016-09-01

    Acute haematogenous osteomyelities (AHO) is the most common form of osteomyelitis, occurring when bone is infected secondary to transient bacteremia. The prevalence, aetiology and outcome of AHO may vary from region to region and period to period. The study objectives were to define the epidemiology, clinical, laboratory and imaging characteristics and treatment consequences of AHO in children in southern Israel. This was a retrospective cohort study, enrolling all children <16 years of age hospitalized with AHO. Epidemiologic, clinical, laboratory and imaging data were recorded from medical charts. Ninety-one patients were diagnosed with AHO (52.7 % <4 years of age). Most children (80.24 %) did not receive antibiotic treatment prior to diagnosis. During 2005-2012 the AHO incidence was 5.6:100,000; the AHO incidence in the Bedouin and Jewish population was 7.3 and 4.1:100,000, respectively. Fifty-four (57.8 %) patients were afebrile at admission and 34 (37.4 %) showed leukocytosis >15,000/mm(3). The most involved bone was tibia (39.6 %), followed by femur (19.8 %), humerus (8.8 %) and pelvis (8.8 %). Positive cultures were reported in 26 (28.6 %) patients. The most common pathogen was methicillin-susceptible Staphylococcus aureus (MSSA, 18 patients, 19.8 %). There was only one case of MRSA. More positive cultures were recorded among children requiring surgery compared to children treated conservatively (P < 0.01). MSSA representation in cases requiring surgical intervention was higher than in cases treated conservatively (P = 0.01). There were nine bone biopsies and 33 bone aspirations (MSSA in 44.4 % and 24.2 %, respectively). The longest hospitalization was observed in patients with humerus-AHO (14.8 ± 12.2 days). There was no difference in the number of days of hospitalization between patients who received previous antibiotics compared with children who did not receive antibiotics before admission. Tibia was the most frequently

  8. ["Re-evaluation upon suspected event" is an approach for post-marketing clinical study: lessons from adverse drug events related to Bupleuri Radix preparations].

    PubMed

    Wu, Shu-Xin; Sun, Hong-Feng; Yang, Xiao-Hui; Long, Hong-Zhu; Ye, Zu-Guang; Ji, Shao-Liang; Zhang, Li

    2014-08-01

    We revisited the "Xiao Chaihu Decoction event (XCHDE)" occurred in late 1980s in Japan and the Bupleuri Radix related adverse drug reaction (ADR) reports in China After careful review, comparison, analysis and evaluation, we think the interstitial pneumonitis, drug induced Liver injury (DILI) and other severe adverse drug envents (ADEs) including death happened in Japan is probably results from multiple factors, including combinatory use of XCHDE with interferon, Kampo usage under modern medicine theory guidance, and use of XCHD on the basis of disease diagnosis instead of traditional Chinese syndrome complex differentiation. There are less ADE case reports related to XCHD preparation in China compared to Japan, mostly manifest with hypersensitivity responses of skin and perfuse perspiration. The symptoms of Radix Bupleuri injection related ADEs mainly manifest hypersensitivity-like response, 2 cases of intravenous infusion instead of intramuscular injection developed hypokalemia and renal failure. One case died from severe hypersensitivity shock. In Chinese literatures, there is no report of the interstitial pneumonitis and DILI associated with XCHDG in Japan. So far, there is no voluntary monitoring data and large sample clinical research data available. The author elaborated the classification of "reevaluation" and clarified "re-evaluation upon events" included the reaction to the suspected safety and efficacy events. Based on the current status of the clinical research on the Radix Bupleuri preparations, the author points out that post-marketing "re-evaluation upon suspected event" is not only a necessity of continuous evaluation of the safety, efficacy of drugs, it is also a necessity for providing objective clinical research data to share with the international and domestic drug administrations in the risk-benefit evaluation. It is also the unavoidable pathway to culture and push the excellent species and famous brands of TCM to the international market, in

  9. Gene transfer as a strategy to achieve permanent cardioprotection I: rAAV-mediated gene therapy with inducible nitric oxide synthase limits infarct size 1 year later without adverse functional consequences.

    PubMed

    Li, Qianhong; Guo, Yiru; Wu, Wen-Jian; Ou, Qinghui; Zhu, Xiaoping; Tan, Wei; Yuan, Fangping; Chen, Ning; Dawn, Buddhadeb; Luo, Li; O'Brien, Erin; Bolli, Roberto

    2011-11-01

    The ultimate goal of prophylactic gene therapy is to confer permanent protection against ischemia. Although gene therapy with inducible nitric oxide synthase (iNOS) is known to protect against myocardial infarction at 3 days and up to 2 months, the long-term effects on myocardial ischemic injury and function are unknown. To address this issue, we created a recombinant adeno-associated viral vector carrying the iNOS gene (rAAV/iNOS), which enables long-lasting transgene expression. The ability of rAAV/iNOS to direct the expression of functional iNOS protein was confirmed in COS-7 cells before in vivo gene transfer. Mice received injections in the anterior LV wall of rAAV/LacZ or rAAV/iNOS; 1 year later, they underwent a 30-min coronary occlusion (O) and 4 h of reperfusion (R). iNOS gene transfer resulted in elevated iNOS protein expression (+3-fold vs. the LacZ group, n = 6; P < 0.05) and iNOS activity (+4.4-fold vs. the LacZ group, n = 6; P < 0.05) 1 year later. Infarct size (% of risk region) was dramatically reduced at 1 year after iNOS gene transfer (13.5 ± 2.2%, n = 12, vs. 41.7 ± 2.9%, n = 10, in the LacZ group; P < 0.05). The infarct-sparing effect of iNOS gene therapy at 1 year was as powerful as that observed 24 h after ischemic preconditioning (six 4-min O/4-min R cycles) (19.3 ± 2.3%, n = 11; P < 0.05). Importantly, compared with the LacZ group (n = 11), iNOS gene transfer (n = 10) had no effect on LV dimensions or function for up to 1 year (at 1 year: FS 34.5 ± 2.0 vs. 34.6 ± 2.6%, EF 57.0 ± 2.0 vs. 59.7 ± 2.9%, LVEDD 4.3 ± 0.1 vs. 4.2 ± 0.2 mm, LVESD 2.8 ± 0.1 vs. 2.9 ± 0.2 mm) (echocardiography). These data demonstrate, for the first time, that rAAV-mediated iNOS gene transfer affords long-term, probably permanent (1 year), cardioprotection without adverse functional consequences, providing a strong rationale for further preclinical testing of prophylactic gene therapy.

  10. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

    This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

  11. Adverse effects of anticancer agents that target the VEGF pathway.

    PubMed

    Chen, Helen X; Cleck, Jessica N

    2009-08-01

    Antiangiogenesis agents that target the VEGF/VEGF receptor pathway have become an important part of standard therapy in multiple cancer indications. With expanded clinical experience with this class of agents has come the increasing recognition of the diverse adverse effects related to disturbance of VEGF-dependent physiological functions and homeostasis in the cardiovascular and renal systems, as well as wound healing and tissue repair. Although most adverse effects of VEGF inhibitors are modest and manageable, some are associated with serious and life-threatening consequences, particularly in high-risk patients and in certain clinical settings. This Review examines the toxicity profiles of anti-VEGF antibodies and small-molecule inhibitors. The potential mechanisms of the adverse effects, risk factors, and the implications for selection of patients and management are discussed.

  12. Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI: A Meta-Analysis

    PubMed Central

    Mega, Jessica L.; Simon, Tabassome; Collet, Jean-Philippe; Anderson, Jeffrey L.; Antman, Elliott M.; Bliden, Kevin; Cannon, Christopher P.; Danchin, Nicolas; Giusti, Betti; Gurbel, Paul; Horne, Benjamin D.; Hulot, Jean-Sebastian; Kastrati, Adnan; Montalescot, Gilles; Neumann, Franz-Josef; Shen, Lei; Sibbing, Dirk; Steg, P. Gabriel; Trenk, Dietmar; Wiviott, Stephen D.; Sabatine, Marc S.

    2011-01-01

    Content Clopidogrel, one of the most commonly prescribed medications, is a pro-drug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes. Objective In patients treated with clopidogrel, to define the risk of major adverse cardiovascular outcomes among carriers of one (∼26% prevalence in whites) and carriers of two (∼2% prevalence in whites) reduced-function CYP2C19 variants. Data Sources and Study Selection A literature search was conducted (January 2000-August 2010) of the MEDLINE, Cochrane, and EMBASE databases. Genetic studies were included where clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and where clinical outcomes were ascertained. Data Extraction Investigators from nine studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and their 95% confidence intervals (CI) for specific cardiovascular outcomes by genotype. Results Among 9685 patients [91.3% of whom underwent percutaneous coronary intervention (PCI) and 54.5% of whom had an acute coronary syndrome (ACS)], 863 experienced the composite endpoint of cardiovascular death, myocardial infarction, or stroke; 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were non-carriers, 26.3% had one, and 2.2% had two CYP2C19 reduced-function alleles. A significantly increased risk of the composite endpoint was evident in both carriers of one (HR 1.55, 95% CI 1.11-2.27, P=0.01) and two (HR 1.76, 95% CI 1.24-2.50, P=0.002) CYP2C19 reduced-function alleles. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of one (HR 2.67, 95% CI 1.69-4.22, P<0.0001) and two (HR 3.97, 95% CI 1.75-9.02, P=0.001) CYP2C19 reduced-function alleles

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

    PubMed

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

    2011-03-01

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

  14. SAMe-TT2R2 Score in the Outpatient Anticoagulation Clinic to Predict Time in Therapeutic Range and Adverse Events.

    PubMed

    Pivatto Junior, Fernando; Scheffel, Rafael Selbach; Ries, Lucas; Wolkind, Ricardo Roitman; Marobin, Roberta; Barkan, Sabrina Sigal; Amon, Luís Carlos; Biolo, Andréia

    2017-04-01

    The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events. To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs. Retrospective cohort study including patients with nonvalvular AF attending an outpatient anticoagulation clinic of a tertiary hospital. Visits to the outpatient clinic and emergency, as well as hospital admissions to the institution, during 2014 were evaluated. The TTR was calculated through the Rosendaal´s method. We analyzed 263 patients (median TTR, 62.5%). The low-risk group (score 0-1) had a better median TTR as compared with the high-risk group (score ≥ 2): 69.2% vs. 56.3%, p = 0.002. Similarly, the percentage of patients with TTR ≥ 60%, 65% or 70% was higher in the low-risk group (p < 0.001, p = 0.001 and p = 0.003, respectively). The high-risk group had a higher percentage of adverse events (11.2% vs. 7.2%), although not significant (p = 0.369). The SAMe-TT2R2 score proved to be effective to predict patients with a better TTR, but was not associated with adverse events. O escore SAMe-TT2R2 foi desenvolvido visando predizer quais pacientes em anticoagulação oral com antagonistas da vitamina K (AVKs) atingirão um tempo na faixa terapêutica (TFT) adequado (> 65%-70%) no seguimento. Estudos também o relacionaram com a ocorrência de eventos adversos. Descrever o TFT de acordo com o escore, além de relacionar a pontuação obtida com a ocorrência de eventos adversos adversos em pacientes com fibrilação atrial (FA) não valvar em anticoagulação oral com AVKs. Estudo de coorte retrospectivo incluindo pacientes com FA não valvar em acompanhamento em ambulat

  15. Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses.

    PubMed

    Cruz-Martinez, R; Savchev, S; Cruz-Lemini, M; Mendez, A; Gratacos, E; Figueras, F

    2015-03-01

    To assess the clinical value of third-trimester uterine artery (UtA) Doppler ultrasound in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses. UtA Doppler parameters, cerebroplacental ratio (CPR) and fetal middle cerebral artery (MCA) pulsatility index (PI) were evaluated weekly, starting from the time of SGA diagnosis until 24 h before induction of labor, in a cohort of 327 SGA fetuses with normal umbilical artery PI (< 95th centile), delivered at > 37 weeks' gestation. Differences in the sequence of CPR and MCA-PI changes < 5th centile, between the group with normal UtA Doppler indices at diagnosis and those with abnormal UtA indices, were analyzed by survival analysis. In addition, the use of UtA Doppler value, alone or in combination with a brain Doppler scan before delivery, to predict the risk of Cesarean section, Cesarean section for non-reassuring fetal status (NRFS), neonatal acidosis and neonatal hospitalization was evaluated by logistic regression analysis, adjusted for gestational age at birth and birth-weight percentile. Abnormal UtA Doppler at diagnosis of SGA was associated with a higher risk of developing abnormal brain Doppler indices before induction of labor than in those with a normal UtA at diagnosis (62.7% vs 34.6%, respectively; P < 0.01). Compared to those with normal UtA Doppler indices, those with abnormal UtA Doppler findings were associated with a higher risk of intrapartum Cesarean section (52.2% vs 37.3%, respectively; P = 0.03), Cesarean section for NRFS (35.8% vs 23.1%, respectively; P = 0.03), neonatal acidosis (10.4% vs 7.7%, respectively; P = 0.47) and neonatal hospitalization (23.9% vs 16.5%, respectively; P = 0.16). Logistic regression analysis indicated that UtA Doppler findings were not significantly associated with adverse perinatal outcome independent of brain Doppler findings. UtA Doppler indices predict adverse perinatal

  16. Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences

    PubMed Central

    Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Pang, Wing Fai; Leung, Chi Bon; Li, Philip Kam-Tao

    2016-01-01

    Background and objectives Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. Design, setting, participants, & measurements In this single–center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. Results Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3–62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0–65.8 days versus 27.5; IQR, 23.0–35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8–60.5 months versus 55.8; IQR

  17. Comparison of escitalopram vs. citalopram and venlafaxine in the treatment of major depression in Spain: clinical and economic consequences.

    PubMed

    Sicras-Mainar, Antoni; Navarro-Artieda, Ruth; Blanca-Tamayo, Milagrosa; Gimeno-de la Fuente, Victoria; Salvatella-Pasant, Jordi

    2010-12-01

    Population based study to determine the clinical consequences and economic impact of using escitalopram (ESC) vs. citalopram (CIT) and venlafaxine (VEN) in patients who initiate treatment for a new episode of major depression (MD) in real life conditions of outpatient practice. Observational, multicenter, retrospective study conducted using computerized medical records (administrative databases) of patients treated in six primary care centers and two hospitals between January 2003 and March 2007. patients >20 years of age diagnosed with a new episode of MD who initiate treatment with ESC, CIT or VEN who had not received any antidepressant treatment within the previous 6 months, and were followed for 18 months or more. socio-demographic variables, remission (defined as a patient completing 6 months of therapy), comorbidity, annual health care costs (medical visits, diagnostic and therapeutic tests, hospitalizations, emergency room and psychoactive drugs prescribed) and non-health care costs (productivity losses at work, mainly sick leave and disability). logistic regression and ANCOVA models. A total of 965 patients (ESC = 131; CIT = 491; VEN = 343) were identified and met study criteria. ESC-treated patients were younger, with a higher proportion of males, and had a lower specific comorbidity (p < 0.01). ESC-treated patients achieved higher remission rates compared to CIT (58.0% vs. 38.3%) or VEN patients (32.4%), p < 0.001, and had lower productivity work losses compared to VEN patients (32.7 vs. 43.8 days), p = 0.042. No differences in productivity work losses were observed between ESC and CIT patients. Compared to the ESC group, higher costs in average/unit of psychoactive drugs were found in the VEN group (€643.00), p = 0.003, whereas no differences were observed between the ESC and CIT groups (€294.70 vs. €265.20). In the corrected model, total costs (health care and non-health care cost) were lower with ESC (€2276.20) compared to CIT (

  18. Peritonitis before Peritoneal Dialysis Training: Analysis of Causative Organisms, Clinical Outcomes, Risk Factors, and Long-Term Consequences.

    PubMed

    Ma, Terry King-Wing; Chow, Kai Ming; Kwan, Bonnie Ching-Ha; Pang, Wing Fai; Leung, Chi Bon; Li, Philip Kam-Tao; Szeto, Cheuk Chun

    2016-07-07

    Peritonitis before peritoneal dialysis (PD) training (pretraining peritonitis [PTP]) is an uncommon event. The study aim was to examine the causative organisms, clinical outcomes, risk factors, and long-term consequences of PTP. In this single-center, retrospective, observational study involving all incident patients on PD who developed PTP between 1998 and 2012, we examined the causative organisms, primary response rate, complete cure rate, risk factors, and associations of PTP with peritoneal equilibration test (PET) and patient survival. For each patient in the PTP group, the patients who underwent catheter insertion immediately before and after the index case were identified as controls. Among 1252 incident patients on PD, 52 (4.2%) patients developed PTP, and 104 patients were identified as controls. The two groups were similar in age, sex distribution, comorbidities, and residual renal function, but the PTP group had significantly lower hemoglobin and serum albumin. Patients were followed up for a median of 37.5 months (interquartile range [IQR], 16.3-62.2 months). The most common causative organisms of PTP were Staphylococcus aureus (30.8%) and polymicrobial (21.2%); 25% had negative growth. The primary response and complete cure rates were 82.7% and 78.8%, respectively. In the PTP group, 7.7% of patients died, 9.6% of patients required catheter removal, and PD training was significantly delayed (median =42.0; IQR, 26.0-65.8 days versus 27.5; IQR, 23.0-35.0 days; P=0.01). Multivariate logistic regression analysis showed that serum albumin was the only predictor of PTP (adjusted odds ratio, 0.89 per 1-g/dl increase; 95% confidence interval, 0.82 to 0.97). There were no differences in PET results and dialysis adequacy (measured around 1 month after PD training). The PTP group had significantly worse patient survival (median =41.2; IQR, 21.8-60.5 months versus 55.8; IQR, 40.4-71.2 months; P=0.02). Technique failure occurred in 11.5% and 10.6% of patients in the

  19. Clinical consequences of untreated dental caries assessed using PUFA index and its covariates in children residing in orphanages of Pakistan.

    PubMed

    Kamran, Ramsha; Farooq, Warda; Faisal, Mehreen Riaz; Jahangir, Faisal

    2017-07-11

    The purpose of this study was to determine the prevalence and clinical effects of untreated dental caries in Pakistani children residing in orphanages using the DMFT and PUFA index; association of decay and untreated dental caries with demographics including type of orphanage; behavioural and dental visiting pattern; and association of dental pain experience and type of orphanage with dental visiting. A cross-sectional survey was conducted on a total of 753 orphan children belonging to 4-17 years of age group residing in twin cities of Rawalpindi and Islamabad, Pakistan. Clinical examination of children was performed using the DMFT and PUFA index for the assessment of dental caries and untreated decay, followed by questionnaire enquiring about eating and oral hygiene habits, dental visiting pattern and dental pain and swelling experience. Association between dental decay, child's dental visiting and pain as a consequence of untreated decay was carried out using chi square test and logistic regression analysis. The overall caries prevalence was 34.8% and overall prevalence of PUFA/pufa was 15.9%. The mean score of DMFT and dmft was 1.18 (SD 0.39) and 1.04 (SD 0.23), and mean PUFA was 1.18 (SD 0.57) and mean pufa score 1.14 (SD 0.35). Untreated caries ratio was found to be 49.1% indicating half the decay had progressed to involve the pulp. No significant association of gender was found with DMFT, dmft, PUFA and pufa (p > 0.05), however, when analysed individually, the 'D' component of DMFT was significantly associated with male gender (p = 0.05). Furthermore, no significant association of DMFT/dmft or PUFA/pufa in either dentition was found with behavioural characteristics such as dietary and oral hygiene habits. Also, 66.2% children who experienced pain had not been to the dentist in the past year (p = 0.013) and 52.6% children who mentioned experiencing pain at night had not been to the dentist in the past year (p = 0.009). Children with decay were more

  20. [Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

    PubMed

    Eckhardt, K; Cremer-Schaeffer, P; König, J; Paeschke, N

    2005-02-01

    With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member

  1. Large-scale adverse effects related to treatment evidence standardization (LAERTES): an open scalable system for linking pharmacovigilance evidence sources with clinical data.

    PubMed

    2017-03-07

    Integrating multiple sources of pharmacovigilance evidence has the potential to advance the science of safety signal detection and evaluation. In this regard, there is a need for more research on how to integrate multiple disparate evidence sources while making the evidence computable from a knowledge representation perspective (i.e., semantic enrichment). Existing frameworks suggest well-promising outcomes for such integration but employ a rather limited number of sources. In particular, none have been specifically designed to support both regulatory and clinical use cases, nor have any been designed to add new resources and use cases through an open architecture. This paper discusses the architecture and functionality of a system called Large-scale Adverse Effects Related to Treatment Evidence Standardization (LAERTES) that aims to address these shortcomings. LAERTES provides a standardized, open, and scalable architecture for linking evidence sources relevant to the association of drugs with health outcomes of interest (HOIs). Standard terminologies are used to represent different entities. For example, drugs and HOIs are represented in RxNorm and Systematized Nomenclature of Medicine -- Clinical Terms respectively. At the time of this writing, six evidence sources have been loaded into the LAERTES evidence base and are accessible through prototype evidence exploration user interface and a set of Web application programming interface services. This system operates within a larger software stack provided by the Observational Health Data Sciences and Informatics clinical research framework, including the relational Common Data Model for observational patient data created by the Observational Medical Outcomes Partnership. Elements of the Linked Data paradigm facilitate the systematic and scalable integration of relevant evidence sources. The prototype LAERTES system provides useful functionality while creating opportunities for further research. Future work will

  2. High truncated-O-glycan score predicts adverse clinical outcome in patients with localized clear-cell renal cell carcinoma after surgery.

    PubMed

    NguyenHoang, SonTung; Liu, Yidong; Xu, Le; Zhou, Lin; Chang, Yuan; Fu, Qiang; Liu, Zheng; Lin, Zongming; Xu, Jiejie

    2017-10-03

    Truncated O-glycans, including Tn-antigen, sTn-antigen, T-antigen, sT-antigen, are incomplete glycosylated structures and their expression occur frequently in tumor tissue. The study aims to evaluate the abundance of each truncated O-glycans and its clinical significance in postoperative patients with localized clear-cell renal cell carcinoma (ccRCC). We used immunohistochemical testing to analyze the expression of truncated O-glycans in tumor specimens from 401 patients with localized ccRCC. Truncated-O-glycan score was built by integrating the expression level of Tn-, sTn- and sT-antigen. Kaplan-Meier survival and Cox regression analysis were done to compare clinical outcomes in subgroups. Receiver operating characteristic (ROC) was applied to assess the impact of prognostic factors on overall survival (OS) and recurrence-free survival (RFS). The results identified Tn-, sTn-, sT-antigen as independent prognosticators. The OS and RFS were shortened among the 198 (49.4%) patients with high Truncated-O-glycan score than among the 203 (50.6%) patients with low score (hazard ratio for OS, 7.060; 95% confidence interval [CI]: 2.765 to 18.027; p <0.001; for RFS, 4.612; 95% CI: 2.141 to 9.931; p <0.001). There is no difference between low-risk patients and high-risk patients in low score group ( p = 0.987). High-risk patients with low score showed a better prognosis than low-risk patient with high score ( p = 0.029). The Truncated-O-glycan score showed better prognostic value for OS (AUC: 0.739, p = 0.003) and RFS (AUC: 0.719, p = 0.003) than TNM stage. In summary, the high Truncated-O-glycan score could predict adverse clinical outcome in localized ccRCC patients after surgery.

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

    PubMed

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

    2008-01-01

    Drug use increases with advancing age, and in older patients it is associated with an increase in adverse drug reactions (ADRs). ADRs are a primary cause of morbidity and mortality worldwide. To evaluate the prevalence, clinical characteristics and avoidability of ADR-related hospital admissions in elderly patients. From November 2004 to December 2005, all patients aged >or=65 years consecutively admitted to the Geriatric Unit of the Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo in Italy, were evaluated for enrolment in the study. ADRs were defined according to the WHO Adverse Reaction Terminology system. Drugs were classified according to Anatomical Therapeutic Chemical classification system. The Naranjo algorithm was used to evaluate the relationship between drug use and the ADR (definite, probable, possible or doubtful) and Hallas criteria were used to evaluate the avoidability of the ADR (definitely avoidable, possibly avoidable or unavoidable). All cases of a suspected ADR were discussed by a team trained in drug safety, including three geriatricians, one clinical pharmacologist and one pharmacist. Only cases of an ADR with an agreement >or=80% were included. Of the 1756 patients observed, 102 (5.8%, 42 males, 60 females, mean age 76.5 +/- 7.4 years, range 65-93 years) showed certain (6.8%) or probable (91.2%) ADR-related hospitalization. Gastrointestinal disorders (48 patients, 47.1%); platelet, bleeding and clotting disorders (20 patients, 19.6%); and cardiovascular disorders (13 patients, 12.7%) were the most frequent ADRs. NSAIDs (23.5%), oral anticoagulants (20.6%), low-dose aspirin (acetylsalicylic acid) [13.7%] and digoxin (12.7%) were the drugs most frequently involved in ADRs. Of the ADRs, 45.1% were defined as definitely avoidable, 31.4% as possibly avoidable, 18.6% as unavoidable and 4.9% as unclassifiable. Of 78 patients with definitely or possibly avoidable ADRs, 17 patients (21.8%) had received an inappropriate prescription, 29

  4. DNA and Protein Analyses to Confirm the Absence of Cross-Contamination and Support the Clinical Reliability of Extensively Hydrolysed Diets for Adverse Food Reaction-Pets.

    PubMed

    Lesponne, Isabelle; Naar, Jérôme; Planchon, Sébastien; Serchi, Tommaso; Montano, Mauricio

    2018-06-26

    Adverse food reactions (AFR) are a common cause of skin diseases in cats and dogs. The correct diagnosis and management of AFR relies upon clinical nutrition. The reliability of commercial hypoallergenic diets commonly used in AFR has been questioned because studies have shown the presence of proteins not declared on the label ingredients. It is proposed that extensively hydrolysed protein-based diets constitute a reliable nutritional solution. Royal Canin Anallergenic™ Canine and Feline diets are formulated with very low molecular weight feather protein and purified corn starch. Protein gel electrophoresis and thin layer paper chromatography were used to characterize protein hydrolysis in these diets and their hydrolysed raw materials; protein species were identified by mass spectrometry. To detect cross-contaminating protein, species-specific DNA was measured and correlated with ancillary protein content using calibration curves. The only protein components detected in the extensively hydrolysed feather protein raw material were amino acids and small oligopeptides. GBSS-I (Granule-bound starch synthase 1) was detected in the finished diets; this has not been reported as a clinically apparent allergen in dogs or cats. The DNA threshold corresponding to the maximum acceptable level of ancillary protein was not exceeded in 99.9% of more than 2150 product batches tested and no products were released to the market with cross-contaminating proteins. These results demonstrate the extensive level of protein hydrolysis in Royal Canin Anallergenic™ Canine and Feline diets and the absence of cross-contaminating protein, both key requirements for a diet to be used during diagnosis and for management of pets with AFR.

  5. Obesity is not an independent risk factor for adverse perioperative and long-term clinical outcomes following open AAA repair or EVAR.

    PubMed

    Park, Brian; Dargon, Phong; Binette, Christopher; Babic, Bruna; Thomas, Tina; Divinagracia, Thomas; Dahn, Michael S; Menzoian, James O

    2011-10-01

    Moderate (body mass index [BMI] ≥30) and morbid obesity (BMI ≥35) is increasing at an alarming rate in vascular surgery patients. The objective of this study was to determine the impact of obesity on perioperative and long-term clinical outcomes following open abdominal aortic aneurysm (AAA) repair or endovascular aneurysm repair (EVAR). This review includes patients that underwent open AAA repair (n = 403) or EVAR (n = 223) from 1999 to 2009. Specific patient characteristics such as comorbid diseases, medications, and body mass index (BMI) were assessed. Specific perioperative outcomes such as length of stay, myocardial infarctions, and mortality were reviewed. In addition, long-term outcomes such as rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days were also assessed. The incidence of obesity in open AAA patients was 25.3% (documented incidence 1.5%) and for EVAR was 24.6% (documented incidence 4%). Moderate and morbid obesity was associated with longer intensive care unit (ICU) admissions for both open AAA or EVAR patients (P < .05). However, no significant differences in perioperative outcomes in terms of overall length of stay, myocardial infarction, acute renal failure, wound infections, or mortality were noted between obese and nonobese patients underoing open AAA repair or EVAR (P > .05). Similarly, moderate and morbid obesity was not associated with significant differences in rates of reintervention, permanent renal dysfunction, and mortality beyond 30 days for patients undergoing open AAA repair or EVAR (P > .05). The results of this study indicate that moderate and morbid obesity are not independently associated with adverse perioperative and long-term clinical outcomes for patients undergoing open AAA repair or EVAR. Therefore, either open AAA repair or EVAR can be accomplished safely in moderately obese and morbidly obese patients.

  6. Medical management of the traumatic consequences of civil unrest incidents: causation, clinical approaches, needs and advanced planning criteria.

    PubMed

    Ballantyne, Bryan

    2006-01-01

    toxicity or introduce additional local and/or systemic toxicity. By the very circumstances of civil unrest incidents, injuries are inevitable, particularly when emotions are heightened and police and security forces have to resort to various chemical and/or physical means of control. Trauma may include slight to severe physical and/or chemical injuries, psychological problems and occasional deaths. Hospitals should be prepared for a wide range of casualties, and the fact that those seeking help will constitute a heterogeneous group, including wide age range, male, female, and individuals with pre-existing ill health. A major civil unrest incident necessitates that the local receiving hospital should be prepared and equipped for decontamination and triage processes. It is necessary to reassure patients who have been exposed to sensory irritants that the signs and symptoms are rapidly reversible, and do not result in long-term sequelae. With respect to chemical exposures, detailed evaluation should be given to possible ocular, cutaneous, respiratory and gastrointestinal effects. Also, exposure to chemosensory irritants results in transient increases in blood pressure, bradycardia and increased intraocular pressure. This indicates that those with cardiovascular diseases and glaucoma may be at increased risk for the development of complications. This article details the pharmacological, toxicological and clinical effects of chemicals used in civil disturbance control and discusses the management of contaminated individuals. Additionally, the potential for adverse effects from delivery systems and other physical restraint procedures is summarised. Due to the emergency and specialised circumstances and conditions of a civil unrest incident, there is a clear need for advanced planning by healthcare institutions in the event that such an incident occurs in their catchment area. This should include ensuring a good information base, preparations for medical and support staff

  7. USE OF CASE REPORTS IN ASSESSING ADVERSE OUTCOMES OF HUMAN PRENATAL DRUG EXPOSURES: AN APPROACH

    EPA Science Inventory

    The use of case reports for assessing the developmental consequences of prenatal drug exposure is limited by the inability to determine the incidence of adverse outcomes and by the high likelihood for bias. Yet, because it is impossible to conduct clinical trials for the assessme...

  8. Antiplatelet drug selection in PCI to vein grafts in patients with acute coronary syndrome and adverse clinical outcomes: Insights from the British Cardiovascular Intervention Society database.

    PubMed

    Sirker, Alex; Kwok, Chun Shing; Kontopantelis, Evangelos; Johnson, Tom; Freeman, Philip; de Belder, Mark A; Ludman, Peter; Zaman, Azfar; Mamas, Mamas A

    2018-01-22

    This study aims to evaluate outcomes associated with different P2Y12 agents in Saphenous Vein graft (SVG) percutaneous coronary intervention (PCI). SVG PCI is associated with greater risks of ischemic complications, compared with native coronary PCI. Outcomes associated with the use of potent P2Y12 blocking drugs, Prasugrel and Ticagrelor, in SVG PCI are unknown. Patients included in the study underwent SVG PCI in the United Kingdom between 2007 and 2014 for acute coronary syndrome and were grouped by P2Y12 antiplatelet use. In-hospital major adverse cardiac events, major bleeding and 30-day and 1-year mortality were examined. Multiple imputations with chained equations to impute missing data were used. Adjustment for baseline imbalances was performed using (1) multiple logistic regression (MLR) and (separately) (2) propensity score matching (PSM). Data weres analyzed from 8,119 patients and most cases were treated with Clopidogrel (n = 7,401), followed by Ticagrelor (n = 497) and Prasugrel (n = 221). In both MLR and PSM models, there was no significant evidence to suggest that either Prasugrel or Ticagrelor was associated with significantly lower 30-day mortality compared with Clopidogrel. The odds ratios reported from the multivariable analysis were 1.22 (95% CI: 0.60-2.51) for Prasugrel vs. Clopidogrel and 0.48 (95% CI: 0.20-1.16) for Ticagrelor vs. Clopidogrel. No significant differences were seen for in-hospital ischemic or bleeding events. Our real world national study provides no clear evidence to indicate that use of potent P2Y12 blockers in SVG PCI is associated with improved clinical outcomes. © 2018 Wiley Periodicals, Inc.

  9. Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors

    PubMed Central

    Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei

    2017-01-01

    Objective: To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Methods: Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. Results: The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s−1; p < 0.01). Conclusion: The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population. PMID:27928926

  10. Clinical observation of adverse drug reactions to non-ionic iodinated contrast media in population with underlying diseases and risk factors.

    PubMed

    Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei; Zhang, Weiguo

    2017-02-01

    To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s -1 ; p < 0.01). The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population.

  11. [Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].

    PubMed

    Wang, Xiao-Yun; Zhao, Yu-Liang

    2010-12-21

    To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.

  12. Differences in reporting serious adverse events in industry sponsored clinical trial registries and journal articles on antidepressant and antipsychotic drugs: a cross-sectional study

    PubMed Central

    Hughes, Shannon; Cohen, David; Jaggi, Rachel

    2014-01-01

    Objective To examine the degree of concordance in reporting serious adverse events (SAEs) from antidepressant and antipsychotic drug trials among journal articles and clinical trial summaries, and to categorise types of discrepancies. Design Cross-sectional study of summaries of all antidepressant and antipsychotic trials included in an online trial registry and their first associated stand-alone journal articles. Setting Clinicalstudyresults.org, sponsored by Pharmaceutical Research and Manufacturers of America; clinicaltrials.gov, administered by the US National Institutes of Health. Main outcome measure 3 coders extracted data on the numbers and types of SAEs. Results 244 trial summaries for six antidepressant and antipsychotic drugs were retrieved, 142 (58.2%) listing an associated article. Of 1608 SAEs in drug-treated participants according to trial summaries, 694 (43.2%) did not appear in associated articles. Nearly 60% of SAEs counted in articles and 41% in trial summaries had no description. Most cases of death (62.3%) and suicide (53.3%) were not reported in articles. Half or more of the 142 pairs were discordant in reporting the number (49.3%) or description (67.6%) of SAEs. These discrepancies resulted from journal articles’ (1) omission of complete SAE data, (2) reporting acute phase study results only and (3) more restrictive reporting criteria. Trial summaries with zero SAE were 2.35 (95% CI, 1.58 to 3.49; p<0.001) times more likely to be published with no discrepancy in their associated journal article. Since clinicalstudyresults.org was removed from the Internet in 2011, only 7.8% of retrieved trial summaries appear with results on clinicaltrials.gov. Conclusions Substantial discrepancies exist in SAE data found in journal articles and registered summaries of antidepressant and antipsychotic drug trials. Two main scientific sources accessible to clinicians and researchers are limited by incomplete, ambiguous and inconsistent reporting. Access to

  13. Tau elevations in the brain extracellular space correlate with reduced amyloid-β levels and predict adverse clinical outcomes after severe traumatic brain injury.

    PubMed

    Magnoni, Sandra; Esparza, Thomas J; Conte, Valeria; Carbonara, Marco; Carrabba, Giorgio; Holtzman, David M; Zipfel, Greg J; Stocchetti, Nino; Brody, David L

    2012-04-01

    Axonal injury is believed to be a major determinant of adverse outcomes following traumatic brain injury. However, it has been difficult to assess acutely the severity of axonal injury in human traumatic brain injury patients. We hypothesized that microdialysis-based measurements of the brain extracellular fluid levels of tau and neurofilament light chain, two low molecular weight axonal proteins, could be helpful in this regard. To test this hypothesis, 100 kDa cut-off microdialysis catheters were placed in 16 patients with severe traumatic brain injury at two neurological/neurosurgical intensive care units. Tau levels in the microdialysis samples were highest early and fell over time in all patients. Initial tau levels were >3-fold higher in patients with microdialysis catheters placed in pericontusional regions than in patients in whom catheters were placed in normal-appearing right frontal lobe tissue (P = 0.005). Tau levels and neurofilament light-chain levels were positively correlated (r = 0.6, P = 0.013). Neurofilament light-chain levels were also higher in patients with pericontusional catheters (P = 0.04). Interestingly, initial tau levels were inversely correlated with initial amyloid-β levels measured in the same samples (r = -0.87, P = 0.000023). This could be due to reduced synaptic activity in areas with substantial axonal injury, as amyloid-β release is closely coupled with synaptic activity. Importantly, high initial tau levels correlated with worse clinical outcomes, as assessed using the Glasgow Outcome Scale 6 months after injury (r = -0.6, P = 0.018). Taken together, our data add support for the hypothesis that axonal injury may be related to long-term impairments following traumatic brain injury. Microdialysis-based measurement of tau levels in the brain extracellular space may be a useful way to assess the severity of axonal injury acutely in the intensive care unit. Further studies with larger numbers of

  14. Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

    PubMed

    Berwanger, Otavio; Santucci, Eliana Vieira; de Barros E Silva, Pedro Gabriel Melo; Jesuíno, Isabella de Andrade; Damiani, Lucas Petri; Barbosa, Lilian Mazza; Santos, Renato Hideo Nakagawa; Laranjeira, Ligia Nasi; Egydio, Flávia de Mattos; Borges de Oliveira, Juliana Aparecida; Dall Orto, Frederico Toledo Campo; Beraldo de Andrade, Pedro; Bienert, Igor Ribeiro de Castro; Bosso, Carlos Eduardo; Mangione, José Armando; Polanczyk, Carisi Anne; Sousa, Amanda Guerra de Moraes Rego; Kalil, Renato Abdala Karam; Santos, Luciano de Moura; Sposito, Andrei Carvalho; Rech, Rafael Luiz; Sousa, Antônio Carlos Sobral; Baldissera, Felipe; Nascimento, Bruno Ramos; Giraldez, Roberto Rocha Corrêa Veiga; Cavalcanti, Alexandre Biasi; Pereira, Sabrina Bernardez; Mattos, Luiz Alberto; Armaganijan, Luciana Vidal; Guimarães, Hélio Penna; Sousa, José Eduardo Moraes Rego; Alexander, John Hunter; Granger, Christopher Bull; Lopes, Renato Delascio

    2018-04-03

    The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use

  15. Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006–2015

    PubMed Central

    Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

    2017-01-01

    Objectives To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. Setting The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. Design The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Results Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Conclusions Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. PMID:28619765

  16. Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006-2015.

    PubMed

    Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

    2017-06-15

    To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. 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 ...

  18. Clinical review: Cardiovascular consequences of ovarian disruption: a focus on functional hypothalamic amenorrhea in physically active women.

    PubMed

    O'Donnell, Emma; Goodman, Jack M; Harvey, Paula J

    2011-12-01

    Evidence indicates that hypoestrogenemia is linked with accelerated progression of atherosclerosis. Premenopausal women presenting with ovulatory disruption due to functional hypothalamic amenorrhea (FHA) are characterized by hypoestrogenemia. One common and reversible form of FHA in association with energy deficiency is exercise-associated amenorrhea (EAA). Articles were found via PubMed search for both original and review articles based on peer review publications between 1974 and 2011 reporting on cardiovascular changes in women with FHA, with emphasis placed on women with EAA. Despite participation in regular exercise training, hypoestrogenic women with EAA demonstrate paradoxical changes in cardiovascular function, including endothelial dysfunction, a known permissive factor for the progression and development of atherosclerosis. Such alterations suggest that the beneficial effects of regular exercise training on vascular function are obviated in the face of hypoestrogenemia. The long-term cardiovascular consequences of altered vascular function in response to ovulatory disruption in women with EAA remain to be determined. Retrospective data, however, suggest premature development and progression of coronary artery disease in older premenopausal women reporting a history of hypothalamic ovulatory disruption. Importantly, in women with EAA, estrogen therapy, folic acid supplementation without change in menstrual status, and resumption of menses restores endothelial function. In this review, we focus on the influence of hypoestrogenemia in association with energy deficiency in mediating changes in cardiovascular function in women with EAA, including endothelial function, regional blood flow, lipid profile, and autonomic control of blood pressure, heart rate, and baroreflex sensitivity. The influence of exercise training is also considered. With the premenopausal years typically considered to be cardioprotective in association with normal ovarian function

  19. 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

  20. Intravenous lipid emulsions in term infants: impact on laboratory and clinical outcomes and long-term consequences.

    PubMed

    Hartman, Corina; Shamir, Raanan

    2015-01-01

    Parenteral nutrition (PN) in term newborns and older infants is often required for nutritional support for temporary or permanent intestinal failure from any reason. Lipid emulsions (LEs) are an essential source of high-density energy, essential fatty acids, and fat-soluble vitamins. Depending on the fatty acid type, LEs may also have significant immunomodulatory effects. All LEs, starting with soybean oil-based LE and subsequently with medium-chain triglycerides-, olive oil- and fish oil-based LEs, have been investigated in newborns and infants. Laboratory data (mainly liver enzymes, plasma lipid profiles and some metabolic markers) have been investigated for some LEs. The outcome of intestinal failure-associated liver disease after switching to new fish oil-based LEs has been sporadically reported. Long-term outcome data have only looked at the relationship between PN and mortality/morbidity, especially liver disease, and a few studies have looked at growth. There are no controlled studies in this age group that investigated the relationship between different types of LEs and long-term outcomes. In spite of their contribution to understanding the use and indications of various LEs as well as their advantages and adverse effects, most studies in newborns and infants have been observational or retrospective, and the investigated population has been heterogeneous, either in terms of the degree of maturation, age or diagnoses. High-quality studies, preferably randomized and controlled, in this particular population are needed, especially with the widespread use of PN and the emergence of new LEs. © 2015 S. Karger AG, Basel.

  1. Learning from adverse incidents involving medical devices.

    PubMed

    Amoore, John; Ingram, Paula

    While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms.

  2. 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

  3. Unintended Consequences in Cancer Care Delivery Created by the Medicare Part B Proposal: Is the Clinical Rationale for the Experiment Flawed?

    PubMed

    Gordan, Lucio; Grogg, Amy; Blazer, Marlo; Fortner, Barry

    2017-02-01

    Medicare currently enrolls ≥ 45 million adults, and by 2030 this is projected to increase to ≥ 80 million beneficiaries. With this growth, the Centers for Medicare & Medicaid Services (CMS) issued a proposal, the Medicare Part B Drug Payment Model, to shrink drug expenditures, a major contributor to overall health care costs. For this to not adversely affect patient outcomes, lower-cost alternative medications with equivalent efficacy and no increased toxicity must be available. This is often not true in the treatment of cancer. Herein, we examine the flaws in the rationale of the CMS and the potential unintended consequences of this experiment. We identified the top three oncology expenditures (rituximab, bevacizumab, and trastuzumab) and their vetted alternatives (per the National Comprehensive Cancer Network guidelines) to ascertain whether lower-cost equivalent alternatives are available. Drug cost was based on April 2016 average sale price. We explored both efficacy of the agents and, when applicable, toxicity to compare alternatives to these high-dollar medications. For the largest Medicare oncology drug expenditures, there is not a lower-cost option with equal efficacy for their primary indications. Without lower-cost alternatives, the unintended consequence of this CMS experiment may include curtailing access to care or an increase in patient/program costs. The CMS proposal, by simply lowering reimbursement for drugs, does not acknowledge the value of these agents and could unintentionally reduce quality of care. Alternative approaches to value-based care, such as the Oncology Care Model and similar frameworks, should be explored.

  4. Evaluation of medium-term consequences of implementing commercial computerized physician order entry and clinical decision support prescribing systems in two ‘early adopter’ hospitals

    PubMed Central

    Cresswell, Kathrin M; Bates, David W; Williams, Robin; Morrison, Zoe; Slee, Ann; Coleman, Jamie; Robertson, Ann; Sheikh, Aziz

    2014-01-01

    Objective To understand the medium-term consequences of implementing commercially procured computerized physician order entry (CPOE) and clinical decision support (CDS) systems in ‘early adopter’ hospitals. Materials and methods In-depth, qualitative case study in two hospitals using a CPOE or a CDS system for at least 2 years. Both hospitals had implemented commercially available systems. Hospital A had implemented a CPOE system (with basic decision support), whereas hospital B invested additional resources in a CDS system that facilitated order entry but which was integrated with electronic health records and offered more advanced CDS. We used a combination of documentary analysis of the implementation plans, audiorecorded semistructured interviews with system users, and observations of strategic meetings and systems usage. Results We collected 11 documents, conducted 43 interviews, and conducted a total of 21.5 h of observations. We identified three major themes: (1) impacts on individual users, including greater legibility of prescriptions, but also some accounts of increased workloads; (2) the introduction of perceived new safety risks related to accessibility and usability of hardware and software, with users expressing concerns that some problems such as duplicate prescribing were more likely to occur; and (3) realizing organizational benefits through secondary uses of data. Conclusions We identified little difference in the medium-term consequences of a CPOE and a CDS system. It is important that future studies investigate the medium- and longer-term consequences of CPOE and CDS systems in a wider range of hospitals. PMID:24431334

  5. Clinical and economic consequences of wound sepsis after appendicectomy and their modification by metronidazole or povidone iodine.

    PubMed

    Foster, G E; Bourke, J B; Bolwell, J; Doran, J; Balfour, T W; Holliday, A; Hardcastle, J D; Marshall, D J

    1981-04-04

    The effects of intrarectal metronidazole and intraincisional povidone iodine on sepsis after emergency appendicectomy were compared in a double-blind randomised controlled trial in 496 patients. Wound sepsis occurred in 12.3% of metronidazole-treated patients compared with 24% in the povidone-iodine group and 23.5% in an untreated control group. The metronidazole-treated patients left hospital approximately 2 days earlier than patients in the other two groups. They returned to work sooner and receiver fewer visits from the district nursing service. A short six-dose course of metronidazole significantly reduces the wound-infection rate in patients over the age of 12 undergoing emergency appendicectomy. If the clinical and economic benefits of metronidazole shown by this study are confirmed, the drug should be considered for routine use in emergency appendicectomy.

  6. Health and Ethical Consequences of Outsourcing Pivotal Clinical Trials to Latin America: A Cross-Sectional, Descriptive Study.

    PubMed

    Homedes, Núria; Ugalde, Antonio

    2016-01-01

    The implications of conducting clinical trials in low and middle income countries on the financial accessibility and safety of the pharmaceutical products available in those markets have not been studied. Regulatory practices and ethical declarations lead to the commercialization of the new products, referred to as New Molecular Entities (NMEs), in the countries where tested as soon as they are approved in high surveillance countries. Patients and patients' associations use the Latin American courts to access new and expensive treatments, regardless of their safety profile and therapeutic value. Cross-sectional, descriptive study. To determine the therapeutic value and safety profile of the NMEs approved by the Food and Drug Administration (FDA) in 2011 and 2012 that had been tested in Latin America, and the implications of their market approval for the pharmaceutical budgets in the countries where tested. Latin America. To assess the therapeutic value and safety of the NMEs commercialized in the different countries we used f independent drug bulletins. The prices of the NMEs for the consumers were obtained from the pharmaceutical price observatories of the countries were the medicines had been tested. If the price was not available in the observatories, it was obtained from pharmaceutical distributors. We used the countries' minimum wage and per capita income to calculate the financial accessibility of a course of treatment with the NMEs. We found that 33 NMEs approved by the FDA in 2011 and 2012 have been tested in Latin America. Of these, 26 had been evaluated by independent drug bulletins and only five were found to add some value to a subset of patients and had significant side-effects. The pharmaceutical prices were very high, varied widely across countries and were unrelated to the countries' income per capita or minimum wage. The implementation of clinical trials in Latin America results in the commercialization of medicines with questionable safety

  7. Influence of the CYP2D6 Isoenzyme in Patients Treated with Venlafaxine for Major Depressive Disorder: Clinical and Economic Consequences

    PubMed Central

    Sicras-Mainar, Antoni; Guijarro, Pablo; Armada, Beatriz; Blanca-Tamayo, Milagrosa; Navarro-Artieda, Ruth

    2014-01-01

    Background Antidepressant drugs are the mainstay of drug therapy for sustained remission of symptoms. However, the clinical results are not encouraging. This lack of response could be due, among other causes, to factors that alter the metabolism of the antidepressant drug. Objective: to evaluate the impact of concomitant administration of CYP2D6 inhibitors or substrates on the efficacy, tolerability and costs of patients treated with venlafaxine for major depressive disorder in clinical practice. Methods We designed an observational study using the medical records of outpatients. Subjects aged ≥18 years who started taking venlafaxine during 2008–2010 were included. Three study groups were considered: no combinations (reference), venlafaxine-substrate, and venlafaxine-inhibitor. The follow-up period was 12 months. The main variables were: demographic data, comorbidity, remission (Hamilton <7), response to treatment, adverse events and costs. The statistical analysis included logistic regression models and ANCOVA, with p values <0.05 considered significant. Results A total of 1,115 subjects were recruited. The mean age was 61.7 years and 75.1% were female. Approximately 33.3% (95% CI: 30.5 to 36.1) were receiving some kind of drug combination (venlafaxine-substrate: 23.0%, and venlafaxine-inhibitor: 10.3%). Compared with the venlafaxine-substrate and venlafaxine-inhibitor groups, patients not taking concomitant drugs had a better response to therapy (49.1% vs. 39.9% and 34.3%, p<0.01), greater remission of symptoms (59.9% vs. 50.2% and 43.8%, p<0.001), fewer adverse events (1.9% vs. 7.0% and 6.1%, p<0.05) and a lower mean adjusted cost (€2,881.7 vs. €4,963.3 and €7,389.1, p<0.001), respectively. All cost components showed these differences. Conclusions The patients treated with venlafaxine alone showed a better response to anti-depressant treatment, greater remission of symptoms, a lower incidence of adverse events and lower healthcare costs. PMID:25369508

  8. Health and Ethical Consequences of Outsourcing Pivotal Clinical Trials to Latin America: A Cross-Sectional, Descriptive Study

    PubMed Central

    Homedes, Núria; Ugalde, Antonio

    2016-01-01

    Introduction The implications of conducting clinical trials in low and middle income countries on the financial accessibility and safety of the pharmaceutical products available in those markets have not been studied. Regulatory practices and ethical declarations lead to the commercialization of the new products, referred to as New Molecular Entities (NMEs), in the countries where tested as soon as they are approved in high surveillance countries. Patients and patients’ associations use the Latin American courts to access new and expensive treatments, regardless of their safety profile and therapeutic value. Design and Objectives Cross-sectional, descriptive study. To determine the therapeutic value and safety profile of the NMEs approved by the Food and Drug Administration (FDA) in 2011 and 2012 that had been tested in Latin America, and the implications of their market approval for the pharmaceutical budgets in the countries where tested. Setting Latin America. Measures To assess the therapeutic value and safety of the NMEs commercialized in the different countries we used f independent drug bulletins. The prices of the NMEs for the consumers were obtained from the pharmaceutical price observatories of the countries were the medicines had been tested. If the price was not available in the observatories, it was obtained from pharmaceutical distributors. We used the countries’ minimum wage and per capita income to calculate the financial accessibility of a course of treatment with the NMEs. Results We found that 33 NMEs approved by the FDA in 2011 and 2012 have been tested in Latin America. Of these, 26 had been evaluated by independent drug bulletins and only five were found to add some value to a subset of patients and had significant side-effects. The pharmaceutical prices were very high, varied widely across countries and were unrelated to the countries’ income per capita or minimum wage. Conclusion The implementation of clinical trials in Latin America

  9. Infectious mononucleosis in university students in the United kingdom: evaluation of the clinical features and consequences of the disease.

    PubMed

    Macsween, Karen F; Higgins, Craig D; McAulay, Karen A; Williams, Hilary; Harrison, Nadine; Swerdlow, Anthony J; Crawford, Dorothy H

    2010-03-01

    Infectious mononucleosis (IM) is common among university students. We undertook to analyze the clinical features and sequelae of the disease in a cohort of students at Edinburgh University. Consecutive IM case patients were recruited from 2000 through 2002 at the University Health Service after diagnosis of IM. IM resulted in marked reductions in student study time, physical exercise, and non-exercise-related social activities, and sustained increases in reported number of hours of sleep. The disease profile differed between the sexes, with significantly more females reporting fatigue, which was more likely to be prolonged (P = .003) and to lead to loss of study time (P = .013). Female case patients were more likely to discontinue their studies following IM (16% vs 0%; P = .056). Within the typically elevated lymphocyte counts in IM, we identified an elevated gammadelta T cell component that may contribute to the disease pathogenesis. IM results in substantial morbidity among university students, reported as more profound in females, and affecting academic studies, physical exercise, and social activities. Immunization to prevent IM and strategies to reduce post-IM disability would be beneficial in this population.

  10. Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

    SciTech Connect

    Kali, Avinash; Cokic, Ivan; Tang, Richard

    Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI tomore » characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse

  11. Late-onset immune-mediated adverse effects after poly-L-lactic acid injection in non-HIV patients: clinical findings and long-term follow-up.

    PubMed

    Alijotas-Reig, Jaume; Garcia-Gimenez, Victor; Vilardell-Tarres, Miquel

    2009-01-01

    It has been thought that poly-L-lactic acid (PLLA) injections do not have inflammatory side effects. Recent evidence shows that local/regional/systemic delayed adverse effects may appear with its use. To evaluate the clinical complaints, treatment response and long-term follow-up of non-HIV patients with delayed immune-mediated adverse effects related to PLLA injections. Prospective, case series study of 10 patients with delayed adverse effects related to PLLA injections. The inclusion criterion was defined as the onset at least 6 months after PLLA use, with 1 or more of the following clinical signs: oedema, skin induration, swelling/tender nodules with or without discharge of pus or filler material. Several systemic manifestations were also included. Patients with immediate side effects were excluded. Patients underwent clinical management and long-term follow-up. The average latency period to the onset of symptoms was 19.2 months (range: 6-60). Tender, inflammatory nodules and facial oedema were commonly seen. One case presented a systemic granulomatous disorder as a complication. After 50.2 months of average follow-up (range: 38-78), 5 patients are in remission, 4 have recurrent bouts and the last case has been lost to follow-up. Although infrequently, local and/or regional and/or systemic delayed and recurrent granulomatous reactions may complicate PLLA gel injections. Copyright 2009 S. Karger AG, Basel.

  12. Assessment of mental capacity to consent to treatment in anorexia nervosa: A comparison of clinical judgment and MacCAT-T and consequences for clinical practice.

    PubMed

    Elzakkers, Isis F F M; Danner, Unna N; Grisso, Thomas; Hoek, Hans W; van Elburg, Annemarie A

    Informed consent requires adequate mental capacity to consent to treatment. Mental capacity (MC) to consent to treatment refers to the ability to make medical decisions. MC is assessed in a general psychiatric interview, but this clinical assessment is known to overestimate mental capacity in patients and the inter rater reliability is low. The MacArthur Competence Assessment Tool for Treatment (MacCAT-T) has emerged as the gold standard to assess mental capacity to consent to treatment. The MacCAT-T is a semi-structured interview designed to aid clinicians in this assessment and has shown good inter rater reliability in patients with schizophrenia and other mental disorders, but has hardly been studied in patients with anorexia nervosa. Patients with anorexia nervosa (AN) regularly avoid treatment, even when severely ill and discussion includes assessing MC to consent to treatment. The aim of this study is to compare clinical judgment and the MacCAT-T in evaluating MC in patients with AN which in turn may influence use of the MacCAT-T in daily practice. In a sample of 70 consecutively referred severely ill patients with AN with a mean BMI of 15.5 kg/m 2 and a mean duration of illness of 8.6 years, clinical assessment of MC by experienced psychiatrists and the outcome of the MacCAT-T interview were compared. Agreement (κ-value) was calculated. Agreement between clinical assessment and outcome of the MacCAT-T was questionable (κ 0.23). Unlike in other psychiatric populations, clinicians judged a high proportion of patients with AN as having diminished MC. The MacCAT-T can be useful in assessing MC in AN when used in addition to clinical judgment to aid clinicians in complex cases. Why clinicians judge a relatively high proportion of patients with AN as having diminished MC, in contrast to lower proportions in other psychiatric disorders, is an area in need of further research. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Adverse effects of cannabis.

    PubMed

    2011-01-01

    establish a causal relationship in either direction, because of these methodological limitations. In Australia, the marked increase in cannabis use has not been accompanied by an increased incidence of schizophrenia. On the basis of the available data, we cannot reach firm conclusions on whether or not cannabis use causes psychosis. It seems prudent to inform apparently vulnerable individuals that cannabis may cause acute psychotic decompensation, especially at high doses. Users can feel dependent on cannabis, but this dependence is usually psychological. Withdrawal symptoms tend to occur within 48 hours following cessation of regular cannabis use, and include increased irritability, anxiety, nervousness, restlessness, sleep difficulties and aggression. Symptoms subside within 2 to 12 weeks. Driving under the influence of cannabis doubles the risk of causing a fatal road accident. Alcohol consumption plays an even greater role. A few studies and a number of isolated reports suggest that cannabis has a role in the occurrence of cardiovascular adverse effects, especially in patients with coronary heart disease. Numerous case-control studies have investigated the role of cannabis in the incidence of some types of cancer. Its role has not been ruled out, but it is not possible to determine whether the risk is distinct from that of the tobacco with which it is often smoked. Studies that have examined the influence of cannabis use on the clinical course of hepatitis C are inconclusive. Alcohol remains the main toxic agent that hepatitis C patients should avoid. In practice, the adverse effects of low-level, recreational cannabis use are generally minor, although they can apparently be serious in vulnerable individuals. The adverse effects of cannabis appear overall to be less serious than those of alcohol, in terms of neuropsychological and somatic effects, accidents and violence.

  14. Estimation of the Incidence of Bacterial Vaginosis and other Vaginal Infections and its Consequences on Maternal/Fetal Outcome in Pregnant Women Attending an Antenatal Clinic in a Tertiary Care Hospital in North India

    PubMed Central

    Lata, Indu; Pradeep, Yashodhara; Sujata; Jain, Amita

    2010-01-01

    Aims: This study was undertaken to estimate the incidence of bacterial vaginosis (BV) and other vaginal infections during pregnancy and its association with urinary tract infections (UTI) and its consequences on pregnancy outcome, maternal and fetal morbidity and mortality. Settings and Design: Prospective cohort study. Materials and Methods: The present prospective cohort study was conducted on 200 women attending the antenatal clinic (ANC) of a tertiary hospital. All pertinent obstetric and neonatal data covering antenatal events during the course of pregnancy, delivery, puerperium and condition of each newborn at the time of birth were collected. BV was detected by both Gram stain and gold standard clinical criteria (Amsel’s composite criteria). Statistical analysis used: Data were analyzed using SPSS version 9. Fischer’s exact test, chi square tests and Student’s’ test has been used for analysis. The probability of 5% was considered as significant for continuous variables such as age, period of gestation and birth weight. Odds ratio (OR) and confidence interval (CI) with 95% probability were determined. Results: The incidence of bacterial vaginosis was 41 in 200 patients. Adverse outcomes such as preterm labor, PROM and fetal complications were found more in pregnant women who had bacterial vaginosis (N=41), bacterial vaginosis with UTI (N=14) as compared to those without bacterial vaginosis (N=118). Conclusions: The incidence of poor pregnancy outcome was higher in bacterial vaginosis with UTI. Prevention of BV and UTI is cost effective to minimize the pregnancy-related complications and preterm labor to decrease in perinatal and maternal mortality and morbidity. We recommend all antenatal patients should be screened for the presence of bacterial vaginosis, other infections and UTI. PMID:20922108

  15. Estimation of the Incidence of Bacterial Vaginosis and other Vaginal Infections and its Consequences on Maternal/Fetal Outcome in Pregnant Women Attending an Antenatal Clinic in a Tertiary Care Hospital in North India.

    PubMed

    Lata, Indu; Pradeep, Yashodhara; Sujata; Jain, Amita

    2010-04-01

    This study was undertaken to estimate the incidence of bacterial vaginosis (BV) and other vaginal infections during pregnancy and its association with urinary tract infections (UTI) and its consequences on pregnancy outcome, maternal and fetal morbidity and mortality. Prospective cohort study. The present prospective cohort study was conducted on 200 women attending the antenatal clinic (ANC) of a tertiary hospital. All pertinent obstetric and neonatal data covering antenatal events during the course of pregnancy, delivery, puerperium and condition of each newborn at the time of birth were collected. BV was detected by both Gram stain and gold standard clinical criteria (Amsel's composite criteria). Data were analyzed using SPSS version 9. Fischer's exact test, chi square tests and Student's' test has been used for analysis. The probability of 5% was considered as significant for continuous variables such as age, period of gestation and birth weight. Odds ratio (OR) and confidence interval (CI) with 95% probability were determined. The incidence of bacterial vaginosis was 41 in 200 patients. Adverse outcomes such as preterm labor, PROM and fetal complications were found more in pregnant women who had bacterial vaginosis (N=41), bacterial vaginosis with UTI (N=14) as compared to those without bacterial vaginosis (N=118). The incidence of poor pregnancy outcome was higher in bacterial vaginosis with UTI. Prevention of BV and UTI is cost effective to minimize the pregnancy-related complications and preterm labor to decrease in perinatal and maternal mortality and morbidity. We recommend all antenatal patients should be screened for the presence of bacterial vaginosis, other infections and UTI.

  16. Systematic review of the clinical efficacy of sibutramine and orlistat in weigth loss, quality of life and its adverse effects in obese adolescents.

    PubMed

    García Díaz, E; Martín Folgueras, T

    2011-01-01

    The prevalence of obesity, a serious public health problem, is increasing among teenagers and thus also increases cardiovascular morbidity and mortality in adulthood. To provide a systematic review of the best evidence about the effect of sibutramine and orlistat in weight loss, quality of life and its adverse effects in adolescents diagnosed with obesity. We searched electronic databases and bibliographies of selected articles were inspected for any further reference. We included only randomized controlled trials that met a set of predefined criteria. The studies were reviewed by a narrative synthesis. We included 6 randomized controlled trials of sibutramine and 3 of orlistat. The majority reached a moderate to high methodological quality. Sibutramine and orlistat showed a reduction in body mass index (BMI) that was significantly higher compared with the placebo group. We also found a variation of weight with these drugs significantly better than placebo. Only one trial evaluated the quality of life. The incidence of adverse effects was similar for sibutramine and placebo, except for tachycardia. The most common adverse reactions associated with orlistat were gastrointestinal, mild to moderate. Sibutramine and orlistat in combination with a hypocaloric diet and changes in lifestyle in obese adolescents achieve a short-term loss of weight greater than that achieved through the dietary-behavioral therapy alone.

  17. The eye amputated - consequences of eye amputation with emphasis on clinical aspects, phantom eye syndrome and quality of life.

    PubMed

    Rasmussen, Marie Louise Roed

    2010-12-01

    In this thesis the term eye amputation (EA) covers the removing of an eye by: evisceration, enucleation and exenteration. Amputation of an eye is most frequently the end-stage in a complicated disease, or the primary treatment in trauma and neoplasm. In 2010 the literature is extensive due to knowledge about types of surgery, implants and surgical technique. However, not much is known about the time past surgery. To identify the number of EA, the causative diagnosis and the indication for surgical removal of the eye, the chosen surgical technique and to evaluate a possible change in surgical technique in Denmark from 1996 until 2003 (paper I); To describe the phantom eye syndrome and its prevalence of visual hallucinations, phantom pain and phantom sensations (paper II); To characterise the quality of phantom eye pain, including its intensity and frequency among EA patients. We attempted to identify patients with increased risk of developing pain after EA and investigated if preoperative pain is a risk factor for a later development of phantom pain (paper III); In addition we wanted to investigate the health related quality of life, perceived stress, self rated health, job separation due to illness or disability and socio-economic position of the EA in comparison with the general Danish population (paper IV). Records on 431 EA patients, clinical ophthalmological examination and an interview study of 173 EA patients and a questionnaire answered by 120 EA patients. The most frequent indications for EA in Denmark were painful blind eye (37%) and neoplasm (34%). During the study period 1996-2003, the annual number of eye amputations was stable, but an increase in bulbar eviscerations was noticed. Orbital implants were used with an increasing tendency until 2003. The Phantom eye syndrome is frequent among EA patients. Visual hallucinations were described by 42% of the patients. The content were mainly elementary visual hallucinations, with white or colored light as a

  18. Diverse cutaneous adverse eruptions caused by anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies: clinical features and management.

    PubMed

    Shen, John; Chang, Jason; Mendenhall, Melody; Cherry, Grace; Goldman, Jonathan W; Kulkarni, Rajan P

    2018-01-01

    The anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) immunotherapies have shown exceptional activity in many cancers. However, these immunotherapies can also result in diverse adverse cutaneous eruptions that need to be better characterized for ongoing management. The objective was to provide clinical and histopathologic descriptions of the variety of cutaneous adverse events seen in patients who received anti-PD-1/PD-L1 treatment and discuss their management. Patients with advanced cancers in clinical trials at University of California Los Angeles (UCLA), receiving anti-PD-1/PD-L1 treatment between 2012 and 2016 who developed cutaneous eruptions and were evaluated in the dermatology clinic were included in this retrospective case series study. A total of 16 patients were included in this study; of these, five were treated with pembrolizumab alone, two with avelumab alone, eight with nivolumab plus ipilimumab and one with nivolumab plus T-Vec. Of these 16 patients, eight had received systemic chemotherapy, six had received radiotherapy, and one had received trememlimumab prior to the immunotherapies described in this study. Cutaneous eruptions occurred at variable times, from week 1 to 88, with a median of 11.5 weeks; the morphologies included lichenoid, bullous, psoriasiform, macular, morbiliform appearances, and alopecia which were confirmed histopathologically in several of the cases. All cutaneous immune-related adverse events were either grade 1 or 2. Ten patients were treated with topical corticosteroids, and one also received NBUVB. Four patients eventually required systemic steroids. Three required discontinuation of their anti-PD-1/PD-L1 therapy secondary to the cutaneous eruptions. There are several different types of adverse cutaneous morphologies that may be seen with administration of PD-1 and PD-L1 inhibitors. Identifying the patterns of eruption may assist in prompt treatment. Most eruptions could be managed with

  19. The clinical and diagnostic consequences of Poly Implant Prothèse silicone breast implants, recalled from the European market in 2010.

    PubMed

    Maijers, Maria C; Niessen, Francisus B

    2013-03-01

    Recently, Poly Implant Prothèse silicone breast implants were recalled from the European market. The authors studied 112 women and previously published data on rupture prevalence. Women are presenting with symptoms they feel may be a result of ruptured implants. The authors' aim was to study the clinical consequences of Poly Implant Prothèse implants. One hundred twelve women with 224 proven Poly Implant Prothèse implants after 10 years of implantation were enrolled in this study. All women underwent physical examination and magnetic resonance imaging and were interviewed regarding symptoms. Details of the explantations of 35 women with at least one ruptured implant were documented. Tissue from 10 women was sent for pathologic investigation. Of 112 women, 34 (30.4 percent) had symptoms attributable to their implants. Physical examination showed that 12 of the 121 women (10.7 percent) had findings suggestive of rupture, most commonly pain. Three had lymphadenopathy that seemed to correlate with implant rupture or excessive "gel bleed." Pathologic findings showed no malignancies. Eight women who underwent explantation had no implant rupture. Excessive gel bleed was documented in half of them. Clinical consequences of women with Poly Implant Prothèse implants are comparable to those reported in the literature of other manufacturers. Neither complaints nor findings at physical examination had a significant correlation with implant rupture at explantation. Magnetic resonance imaging is still the preferred method compared with physical examination for diagnosing rupture. The low specificity was probably caused by the difficulty in differentiating between rupture and excessive gel bleed in these implants.

  20. Adverse event reporting in patients treated with levothyroxine: results of the pharmacovigilance task force survey of the american thyroid association, american association of clinical endocrinologists, and the endocrine society.

    PubMed

    Hennessey, James V; Malabanan, Alan O; Haugen, Bryan R; Levy, Elliot G

    2010-01-01

    To survey physicians to determine whether potency and consistency issues with levothyroxine sodium (LT4) have been resolved and to assess current experience regarding safety of substituting LT4 products. Members of the American Association of Clinical Endocrinologists, American Thyroid Association, and The Endocrine Society collaborated to create a survey instrument that would effectively sample the clinical experience of their society members and frequent prescribers of LT4. More than 18,000 e-mailed requests for information were generated, and the Web sites of each society provided links to the data collection form. The survey provided an opportunity to collect clinical observations of adverse events or product availability problems from physicians caring for patients with thyroid disease who required use of contemporary LT4 preparations. After adjustment for known reasons for unstable results from thyroid function tests, 199 reports of adverse events associated with changes in thyrotropin values were further analyzed. One hundred seventy-seven reports (88.9%) were associated with a change in the source of LT4; no change was noted in 21 (10.6%). Details regarding the circumstances of the change were provided in 167 of the 177 reports (94.4%), The reporting physicians themselves or their office staff had changed the LT4 preparation in only 1 of the 167 cases (0.6%). The remainder of changes had been made by the patient's pharmacy, either with the physician's knowledge (in 13 of 167 cases [7.8%]) or without his/her knowledge (in 153 of 167 cases [91.6%]). Fifty-four of 199 cases (27.1%) described serious adverse events; 52 of these (96.3%) were associated with a substitution of one LT4 preparation for another. The clinical use of contemporary LT4 products continues to be associated with some adverse outcomes. A small number of reports were associated with continued use of the same LT4 products. The most frequently reported adverse outcomes were associated with the

  1. Biomarkers of adverse drug reactions.

    PubMed

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

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

  2. Cardiac imaging with multi-sector data acquisition in volumetric CT: variation of effective temporal resolution and its potential clinical consequences

    NASA Astrophysics Data System (ADS)

    Tang, Xiangyang; Hsieh, Jiang; Taha, Basel H.; Vass, Melissa L.; Seamans, John L.; Okerlund, Darin R.

    2009-02-01

    With increasing longitudinal detector dimension available in diagnostic volumetric CT, step-and-shoot scan is becoming popular for cardiac imaging. In comparison to helical scan, step-and-shoot scan decouples patient table movement from cardiac gating/triggering, which facilitates the cardiac imaging via multi-sector data acquisition, as well as the administration of inter-cycle heart beat variation (arrhythmia) and radiation dose efficiency. Ideally, a multi-sector data acquisition can improve temporal resolution at a factor the same as the number of sectors (best scenario). In reality, however, the effective temporal resolution is jointly determined by gantry rotation speed and patient heart beat rate, which may significantly lower than the ideal or no improvement (worst scenario). Hence, it is clinically relevant to investigate the behavior of effective temporal resolution in cardiac imaging with multi-sector data acquisition. In this study, a 5-second cine scan of a porcine heart, which cascades 6 porcine cardiac cycles, is acquired. In addition to theoretical analysis and motion phantom study, the clinical consequences due to the effective temporal resolution variation are evaluated qualitative or quantitatively. By employing a 2-sector image reconstruction strategy, a total of 15 (the permutation of P(6, 2)) cases between the best and worst scenarios are studied, providing informative guidance for the design and optimization of CT cardiac imaging in volumetric CT with multi-sector data acquisition.

  3. Plasma Levels of Aminothiols, Nitrite, Nitrate, and Malondialdehyde in Myelodysplastic Syndromes in the Context of Clinical Outcomes and as a Consequence of Iron Overload

    PubMed Central

    Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

    2014-01-01

    The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001) , homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease. PMID:24669287

  4. Plasma levels of aminothiols, nitrite, nitrate, and malondialdehyde in myelodysplastic syndromes in the context of clinical outcomes and as a consequence of iron overload.

    PubMed

    Pimková, Kristýna; Chrastinová, Leona; Suttnar, Jiří; Štikarová, Jana; Kotlín, Roman; Čermák, Jaroslav; Dyr, Jan Evangelista

    2014-01-01

    The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteine (P < 0.001), homocysteine (P < 0.001), and cysteinylglycine (P < 0.006) and significantly depressed levels of total and oxidized forms of glutathione (P < 0.03) and nitrite (P < 0.001) in MDS patients compared to healthy donors. Moreover, total (P < 0.032) and oxidized cysteinylglycine (P = 0.029) and nitrite (P = 0.021) differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels (r = 0.78, P = 0.001) and serum free iron levels (r = 0.60, P = 0.001) and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease.

  5. Human-Computer Interactions: Are There Adverse Health Consequences?

    ERIC Educational Resources Information Center

    Emurian, Henry H.

    1989-01-01

    Discusses the hypothesis that similarities may exist between laboratory research paradigms evoking elevated blood pressure during task performance by normal subjects and video display terminal (VDT) work done by data clerks and college students. Type A behavior and the development of coronary heart disease are discussed, and further research needs…

  6. Neutropenia during HIV Infection: Adverse Consequences and Remedies

    PubMed Central

    Shi, Xin; Sims, Matthew D; Hanna, Michel M; Xie, Ming; Gulick, Peter G; Zheng, Yong-Hui; Basson, Marc D; Zhang, Ping

    2016-01-01

    Neutropenia frequently occurs in patients with Human immunodeficiency virus (HIV) infection. Causes for neutropenia during HIV infection are multifactoral, including the viral toxicity to hematopoietic tissue, the use of myelotoxic agents for treatment, complication with secondary infections and malignancies, as well as the patient’s association with confounding factors which impair myelopoiesis. An increased prevalence and severity of neutropenia is commonly seen in advanced stages of HIV disease. Decline of neutrophil phagocytic defense in combination with the failure of adaptive immunity renders the host highly susceptible to developing fatal secondary infections. Neutropenia and myelosuppression also restrict the use of many antimicrobial agents for treatment of infections caused by HIV and opportunistic pathogens. In recent years, HIV infection has increasingly become a chronic disease because of progress in antiretroviral therapy (ART). Prevention and treatment of severe neutropenia becomes critical for improving the survival of HIV-infected patients. PMID:24654626

  7. Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

    SciTech Connect

    Chiang, Andrew; Department of Radiation Oncology, Princess Margaret Hospital, University of Toronto, Toronto, ON; Zeng, Liang

    Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesicmore » intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.« less

  8. Adverse Effects of Plasma Transfusion

    PubMed Central

    Pandey, Suchitra; Vyas, Girish N.

    2012-01-01

    Plasma utilization has increased over the last two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions following infusion of fresh frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: (1) transfusion related acute lung injury; (2) transfusion associated circulatory overload, and (3) allergic/anaphylactic reactions. Other less common risks include (1) transmission of infections, (2) febrile non-hemolytic transfusion reactions, (3) RBC allo-immunization, and (4) hemolytic transfusion reactions. The affect of pathogen inactivation/reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

  9. Positive effects, side effects, and adverse events of clinical holistic medicine. A review of Gerda Boyesen's nonpharmaceutical mind-body medicine (biodynamic body-psychotherapy) at two centers in the United Kingdom and Germany.

    PubMed

    Allmer, Charlotte; Ventegodt, Søren; Kandel, Isack; Merrick, Joav

    2009-01-01

    To review adverse events of intensive, clinical holistic medicine (CHM) as it is practiced in holistic body-psychotherapy in England and Germany. Gerda Boyesen's "biodynamic body-psychotherapy" (BBP) is an intensive type of holistic mind-body medicine used by Boyesen at two centers. About 13,500 patients were treated during 1985-2005 period and studied for side effects and adverse events. The first author worked closely with Boyesen 1995-2005 with full insight in all aspects of the therapy and provided the data on side-effects. Therapy helped chronic patients with physical, psychological, sexual, psychiatric and existential problems to improve health, ability, and quality of life (NNT (number needed to treat) = 1-3). Effective in the treatment of mentally ill patients (schizophrenia, anxiety, poor mental health, low general ability). For retraumatization, brief reactive psychosis, depression, depersonalization and derealization, implanted memories, side effects from manipulations of the body, suicide/suicide attempts, hospitalization for physical and mental health problem during or 90 days after treatment, NNH (number needed to harm) > 13,500. Intensive, holistic non-drug medicine is helpful for physical, sexual, psychological, psychiatric and existential problems and is completely safe for the patient. The therapeutic value TV = NNH/NNT > 5,000. Altogether about 18,000 patients treated with different subtypes of CHM in four different countries have now been evaluated for effects, side effects and adverse events, with similar results.

  10. Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences-Comorbidities Network Study.

    PubMed

    Houben-Wilke, Sarah; Jörres, Rudolf A; Bals, Robert; Franssen, Frits M E; Gläser, Sven; Holle, Rolf; Karch, Annika; Koch, Armin; Magnussen, Helgo; Obst, Anne; Schulz, Holger; Spruit, Martijn A; Wacker, Margarethe E; Welte, Tobias; Wouters, Emiel F M; Vogelmeier, Claus; Watz, Henrik

    2017-01-15

    Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. The ankle-brachial index was used to diagnose PAD (ankle-brachial index ≤ 0.9). The 6-minute-walk distance, health status (St. George's Respiratory Questionnaire), COPD Assessment Test, and EuroQol-5-Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences-Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I-IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences-Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6-minute-walk distance (356 [108] vs. 422 [103] m, P < 0.001) and worse health status (St. George's Respiratory Questionnaire: 49.7 [20.1] vs. 42.7 [20.0] points, P < 0.001; COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol-5-Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P < 0.001). Differences remained significant after correction for several confounders. In a large cohort of patients with COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

  11. Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

    PubMed Central

    Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R.; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B.; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

    2017-01-01

    Objectives To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. Methods and findings We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Conclusion Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found. PMID:28617801

  12. Gastrointestinal adverse events during methylphenidate treatment of children and adolescents with attention deficit hyperactivity disorder: A systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials.

    PubMed

    Holmskov, Mathilde; Storebø, Ole Jakob; Moreira-Maia, Carlos R; Ramstad, Erica; Magnusson, Frederik Løgstrup; Krogh, Helle B; Groth, Camilla; Gillies, Donna; Zwi, Morris; Skoog, Maria; Gluud, Christian; Simonsen, Erik

    2017-01-01

    To study in more depth the relationship between type, dose, or duration of methylphenidate offered to children and adolescents with attention deficit hyperactivity disorder and their risks of gastrointestinal adverse events based on our Cochrane systematic review. We use data from our review including 185 randomised clinical trials. Randomised parallel-group trials and cross-over trials reporting gastrointestinal adverse events associated with methylphenidate were included. Data were extracted and quality assessed according to Cochrane guidelines. Data were summarised as risk ratios (RR) with 95% confidence intervals (CI) using the inverse variance method. Bias risks were assessed according to domains. Trial Sequential Analysis (TSA) was used to control random errors. Eighteen parallel group trials and 43 cross-over trials reported gastrointestinal adverse events. All trials were at high risk of bias. In parallel group trials, methylphenidate decreased appetite (RR 3.66, 95% CI 2.56 to 5.23) and weight (RR 3.89, 95% CI 1.43 to 10.59). In cross-over trials, methylphenidate increased abdominal pain (RR 1.61, 95% CI 1.27 to 2.04). We found no significant differences in the risk according to type, dose, or duration of administration. The required information size was achieved in three out of four outcomes. Methylphenidate increases the risks of decreased appetite, weight loss, and abdominal pain in children and adolescents with attention deficit hyperactivity disorder. No differences in the risks of gastrointestinal adverse events according to type, dose, or duration of administration were found.

  13. 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

  14. Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis

    PubMed Central

    Jeon, Tae Joo; Park, Ji Young

    2017-01-01

    AIM To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. METHODS We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. RESULTS Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P < 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d (median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P < 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88 in predicting organ failure in acute pancreatitis. CONCLUSION Elevated baseline NLR correlates with severe acute pancreatitis and organ failure. PMID:28638228

  15. Clinical significance of the neutrophil-lymphocyte ratio as an early predictive marker for adverse outcomes in patients with acute pancreatitis.

    PubMed

    Jeon, Tae Joo; Park, Ji Young

    2017-06-07

    To investigated the prognostic value of the neutrophil-lymphocyte ratio (NLR) in patients with acute pancreatitis and determined an optimal cut-off value for the prediction of adverse outcomes in these patients. We retrospectively analyzed 490 patients with acute pancreatitis diagnosed between March 2007 and December 2012. NLRs were calculated at admission and 24, 48, and 72 h after admission. Patients were grouped according to acute pancreatitis severity and organ failure occurrence, and a comparative analysis was performed to compare the NLR between groups. Among the 490 patients, 70 had severe acute pancreatitis with 31 experiencing organ failure. The severe acute pancreatitis group had a significantly higher NLR than the mild acute pancreatitis group on all 4 d (median, 6.14, 6.71, 5.70, and 4.00 vs 4.74, 4.47, 3.20, and 3.30, respectively, P < 0.05). The organ failure group had a significantly higher NLR than the group without organ failure on all 4 d (median, 7.09, 6.72, 6.27, and 6.24 vs 4.85, 4.49, 3.35, and 2.34, respectively, P < 0.05). The optimal cut-off value for baseline NLR was 4.76 in predicting severity and 4.88 in predicting organ failure in acute pancreatitis. Elevated baseline NLR correlates with severe acute pancreatitis and organ failure.

  16. Clinical Application and Psychometric Properties of a Norwegian Questionnaire for the Self-Assessment of Communication in Quiet and Adverse Conditions Using Two Revised APHAB Subscales.

    PubMed

    Heggdal, Peder O Laugen; Nordvik, Øyvind; Brännström, Jonas; Vassbotn, Flemming; Aarstad, Anne Kari; Aarstad, Hans Jørgen

    2018-01-01

    Difficulty in following and understanding conversation in different daily life situations is a common complaint among persons with hearing loss. To the best of our knowledge, there is currently no published validated Norwegian questionnaire available that allows for a self-assessment of unaided communication ability in a population with hearing loss. The aims of the present study were to investigate a questionnaire for the self-assessment of communication ability, examine the psychometric properties of this questionnaire, and explore how demographic variables such as degree of hearing loss, age, and sex influence response patterns. A questionnaire based on the subscales of the Norwegian translation of the Abbreviated Profile of Hearing Aid Benefit was applied to a group of hearing aid users and normal-hearing controls. A total of 108 patients with bilateral hearing loss, and 101 controls with self-reported normal hearing. The psychometric properties were evaluated. Associations and differences between outcome scores and descriptive variables were examined. A regression analysis was performed to investigate whether descriptive variables could predict outcome. The measures of reliability suggest that the questionnaire has satisfactory psychometric properties, with the outcome of the questionnaire correlating to hearing loss severity, thus indicating that the concurrent validity of the questionnaire is good. The findings indicate that the proposed questionnaire is a valid measure of self-assessed communication ability in both quiet and adverse listening conditions in participants with and without hearing loss. American Academy of Audiology

  17. Effect of Agaricus sylvaticus supplementation on nutritional status and adverse events of chemotherapy of breast cancer: a randomized, placebo-controlled, double-blind clinical trial.

    PubMed

    Valadares, Fabiana; Garbi Novaes, Maria Rita Carvalho; Cañete, Roberto

    2013-01-01

    Breast cancer (BC) represents the highest incidence of malignancy in women throughout the world. Medicinal fungi can stimulate the body, reduce side-effects associated with chemotherapy and improve the quality of life in patients with cancer. To evaluate the effects of dietary supplementation of Agaricus sylvaticus on clinical and nutritional parameters in BC patients undergoing chemotherapy. A randomized, placebo-controlled, double-blind, clinical trial was carried out at the Oncology Clinic, Hospital of the Federal District-Brazil from September 2007 to July 2009. Forty six patients with BC, Stage II and III, were randomly assigned to receive either nutritional supplement with A. sylvaticus (2.1 g/day) or placebo. Patients were evaluated during treatment period. Patient supplemented with A. sylvaticus improved in clinical parameters and gastrointestinal functions. Poor appetite decreased by 20% with no changes in bowel functions (92.8%), nausea and vomiting (80%). Dietary supplementation with A. sylvaticus improved nutritional status and reduced abnormal bowel functions, nausea, vomiting, and anorexia in patients with BC receiving chemotherapy.

  18. The perfect storm: obesity, adipocyte dysfunction, and metabolic consequences.

    PubMed

    de Ferranti, Sarah; Mozaffarian, Dariush

    2008-06-01

    As the prevalence of adiposity soars in both developed and developing nations, appreciation of the close links between obesity and disease increases. The strong relationships between excess adipose tissue and poor health outcomes, including cardiovascular disease, diabetes, and cancer, mandate elucidation of the complex cellular, hormonal, and molecular pathophysiology whereby adiposity initiates and maintains adverse health effects. In this report we review adipocyte metabolism and function in the context of energy imbalance and postprandial nutrient excess, including adipocyte hypertrophy and hyperplasia, adipocyte dysfunction, and other systemic consequences. We also discuss implications for laboratory evaluation and clinical care, including the role of lifestyle modifications. Chronic energy imbalance produces adipocyte hypertrophy and hyperplasia, endoplasmic reticulum stress, and mitochondrial dysfunction. These processes lead to increased intracellular and systemic release of adipokines, free fatty acids, and inflammatory mediators that cause adipocyte dysfunction and induce adverse effects in the liver, pancreatic beta-cells, and skeletal muscle as well as the heart and vascular beds. Several specialized laboratory tests can quantify these processes and predict clinical risk, but translation to the clinical setting is premature. Current and future pharmacologic interventions may target these pathways; modest changes in diet, physical activity, weight, and smoking are likely to have the greatest impact. Adipocyte endoplasmic reticulum and mitochondrial stress, and associated changes in circulating adipokines, free fatty acids, and inflammatory mediators, are central to adverse health effects of adiposity. Future investigation should focus on these pathways and on reversing the adverse lifestyle behaviors that are the fundamental causes of adiposity.

  19. Continuous distal migration and internal rotation of the C-stem prosthesis without any adverse clinical effects: an RSA study of 33 primary total hip arthroplasties followed for up to ten years.

    PubMed

    von Schewelov, T; Carlsson, A; Sanzén, L; Besjakov, J

    2014-05-01

    In 2005, we demonstrated that the polished triple-tapered C-stem at two years had migrated distally and rotated internally. From that series, 33 patients have now been followed radiologically, clinically and by radiostereometric analysis (RSA) for up to ten years. The distal migration within the cement mantle had continued and reached a mean of 2 mm (0.5 to 4.0) at ten years. Internal rotation, also within the cement mantle, was a mean 3.8° (external 1.6° to internal 6.6°) The cement mantle did not show any sign of migration or loosening in relation to the femoral bone. There were no clinical or radiological signs indicating that the migration or rotation within the cement mantle had had any adverse effects for the patients.

  20. Identification of adverse events that have a negative impact on quality of life in a clinical trial comparing docetaxel versus S-1 with cisplatin in lung cancer.

    PubMed

    Aotani, Eriko; Hamano, Tetsutaro; Gemma, Akihiko; Takeuchi, Masahiro; Takebayashi, Toru; Kobayashi, Kunihiko

    2016-10-01

    In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL. QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student's t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05). As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis (p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning (p = 0.0002), cognitive functioning (p < 0.0001), and financial problems (p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm. An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy.

  1. Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon

    PubMed Central

    Boussinesq, Michel; Gardon, Jacques; Gardon-Wendel, Nathalie; Chippaux, Jean-Philippe

    2003-01-01

    In August 2002, 65 cases of Loa-associated neurological Serious Adverse Events were reported after ivermectin treatment. The first signs, occurring within the 12–24 hours following treatment, included fatigue, generalized arthralgia, and sometimes agitation, mutism, and incontinence. Disorders of consciousness, including coma, generally appeared between 24 and 72 hours, and showed a rapid variation with time. The most frequent objective neurological signs were extrapyramidal. The patients presented with haemorrhages of the conjunctiva and of the retina. Biological examinations showed a massive Loa microfilaruria, the passage of Loa microfilariae into the cerebrospinal fluid, haematuria, and an increase in the C-reactive protein, all of which have been correlated with the high intensity of the initial Loa microfilaraemia. Eosinophil counts decreased dramatically within the first 24 hours, and then rose again rapidly. Electroencephalograms suggested the existence of a diffuse pathological process within the first weeks; the abnormalities disappearing after 3–6 months. Death may occur when patients are not properly managed, i.e. in the absence of good nursing. However, some patients who recovered showed sequelae such as aphasia, episodic amnesia, or extrapyramidal signs. The main risk factor for these encephalopathies is the intensity of the initial Loa microfilaraemia. The disorders of consciousness may occur when there are >50,000 Loa microfilariae per ml. The possible roles of co-factors, such as Loa strains, genetic predisposition of individuals, co-infestations with other parasites, or alcohol consumption, seem to be minor but they should be considered. The mechanisms of the post-ivermectin Loa-related encephalopathies should be investigated to improve the management of patients developing the condition. PMID:14975061

  2. 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.

  3. 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.

  4. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

    Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses.

  5. Adverse reactions associated with acetylcysteine.

    PubMed

    Sandilands, E A; Bateman, D N

    2009-02-01

    Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and

  6. Understanding the nature of errors in nursing: using a model to analyse critical incident reports of errors which had resulted in an adverse or potentially adverse event.

    PubMed

    Meurier, C E

    2000-07-01

    Human errors are common in clinical practice, but they are under-reported. As a result, very little is known of the types, antecedents and consequences of errors in nursing practice. This limits the potential to learn from errors and to make improvement in the quality and safety of nursing care. The aim of this study was to use an Organizational Accident Model to analyse critical incidents of errors in nursing. Twenty registered nurses were invited to produce a critical incident report of an error (which had led to an adverse event or potentially could have led to an adverse event) they had made in their professional practice and to write down their responses to the error using a structured format. Using Reason's Organizational Accident Model, supplemental information was then collected from five of the participants by means of an individual in-depth interview to explore further issues relating to the incidents they had reported. The detailed analysis of one of the incidents is discussed in this paper, demonstrating the effectiveness of this approach in providing insight into the chain of events which may lead to an adverse event. The case study approach using critical incidents of clinical errors was shown to provide relevant information regarding the interaction of organizational factors, local circumstances and active failures (errors) in producing an adverse or potentially adverse event. It is suggested that more use should be made of this approach to understand how errors are made in practice and to take appropriate preventative measures.

  7. The Public Health Burden of Early Adversity

    ERIC Educational Resources Information Center

    Schlueter, Lisa J.; Watamura, Sarah Enos

    2017-01-01

    Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…

  8. Childhood adversity and insomnia in adolescence.

    PubMed

    Wang, Yan; Raffeld, Miriam R; Slopen, Natalie; Hale, Lauren; Dunn, Erin C

    2016-05-01

    , timing, and accumulation of exposure and did not appear to be driven by psychiatric disorders. Given the well-documented physical and mental health consequences of insomnia, such findings further support the need for practitioners to screen children for exposure to childhood adversity and insomnia symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Metabolomic analysis of 92 pulmonary embolism patients from a nested case-control study identifies metabolites associated with adverse clinical outcomes.

    PubMed

    Zeleznik, O A; Poole, E M; Lindstrom, S; Kraft, P; Van Hylckama Vlieg, A; Lasky-Su, J A; Harrington, L B; Hagan, K; Kim, J; Parry, B A; Giordano, N; Kabrhel, C

    2018-03-01

    Essentials Risk-stratification often fails to predict clinical deterioration in pulmonary embolism (PE). First-ever high-throughput metabolomics analysis of risk-stratified PE patients. Changes in circulating metabolites reflect a compromised energy metabolism in PE. Metabolites play a key role in the pathophysiology and risk stratification of PE. Background Patients with acute pulmonary embolism (PE) exhibit wide variation in clinical presentation and outcomes. Our understanding of the pathophysiologic mechanisms differentiating low-risk and high-risk PE is limited, so current risk-stratification efforts often fail to predict clinical deterioration and are insufficient to guide management. Objectives To improve our understanding of the physiology differentiating low-risk from high-risk PE, we conducted the first-ever high-throughput metabolomics analysis (843 named metabolites) comparing PE patients across risk strata within a nested case-control study. Patients/methods We enrolled 92 patients diagnosed with acute PE and collected plasma within 24 h of PE diagnosis. We used linear regression and pathway analysis to identify metabolites and pathways associated with PE risk-strata. Results When we compared 46 low-risk with 46 intermediate/high-risk PEs, 50 metabolites were significantly different after multiple testing correction. These metabolites were enriched in the following pathways: tricarboxylic acid (TCA) cycle, fatty acid metabolism (acyl carnitine) and purine metabolism, (hypo)xanthine/inosine containing. Additionally, energy, nucleotide and amino acid pathways were downregulated in intermediate/high-risk PE patients. When we compared 28 intermediate-risk with 18 high-risk PE patients, 41 metabolites differed at a nominal P-value level. These metabolites were enriched in fatty acid metabolism (acyl cholines), and hemoglobin and porphyrin metabolism. Conclusion Our results suggest that high-throughput metabolomics can provide insight into the

  10. Baseline serum sitosterol level as predictor of adverse clinical events in acute coronary syndrome patients with dyslipidaemia: A sub-analysis of HIJ-PROPER.

    PubMed

    Yamaguchi, Junichi; Kawada-Watanabe, Erisa; Koyanagi, Ryo; Arashi, Hiroyuki; Sekiguchi, Haruki; Nakao, Koichi; Tobaru, Tetsuya; Tanaka, Hiroyuki; Oka, Toshiaki; Endo, Yasuhiro; Saito, Katsumi; Uchida, Tatsuro; Matsui, Kunihiko; Ogawa, Hiroshi; Hagiwara, Nobuhisa

    2018-05-05

    We aimed to examine the effect of serum sitosterol, a cholesterol absorption marker, on clinical outcomes in acute coronary syndrome patients with dyslipidaemia. This is a sub-analysis of the HIJ-PROPER trial that assesses the effect of aggressive low-density lipoprotein cholesterol (LDL-C) lowering treatment with pitavastatin + ezetimibe in 1734 acute coronary syndrome (ACS) patients with dyslipidaemia. Patients were divided into two groups based on sitosterol level at enrolment (cut-off value was 2.2 μg/mL; a median of baseline sitosterol level), and clinical outcomes were examined. The mean LDL-C level after 3 years in the low sitosterol group was 84.8 ± 20.1 mg/dL with pitavastatin-monotherapy and 64.6 ± 20.3 mg/dL with pitavastatin + ezetimibe, while corresponding values in the high sitosterol group were 91.0 ± 22.9 mg/dL and 71.1 ± 23.3 mg/dL, respectively. In the high sitosterol group, the Kaplan-Meier event rate for the primary endpoint at 3 years was 26.0% in the pitavastatin + ezetimibe group, as compared with 34.3% in the pitavastatin-monotherapy group (hazard ratio, 0.71; 95% confidence interval, 0.56-0.91; p = 0.006, p-value for interaction = 0.010). However, in the low sitosterol group, there was no significant reduction of the primary endpoint by pitavastatin + ezetimibe therapy. Aggressive lipid-lowering treatment with ezetimibe had a positive effect on clinical outcomes in the high sitosterol subset of ACS patients with dyslipidaemia, but not in the low sitosterol subset. This effect was independent of LDL-C reduction and suggests that sitosterol measurement on admission in ACS patients might contribute to a "personalised" lipid-lowering approach. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Asking the right questions to get the right answers: using cognitive interviews to review the acceptability, comprehension and clinical meaningfulness of patient self-report adverse event items in oncology patients.

    PubMed

    Holch, Patricia; Warrington, Lorraine; Potrata, Barbara; Ziegler, Lucy; Hector, Ceri; Keding, Ada; Harley, Clare; Absolom, Kate; Morris, Carolyn; Bamforth, Leon; Velikova, Galina

    Standardized reporting of treatment-related adverse events (AE) is essential in clinical trials, usually achieved by using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) reported by clinicians. Patient-reported adverse events (PRAE) may add value to clinician assessments, providing patient perspective on subjective toxicity. We developed an online patient symptom report and self-management system for real-time reporting and managing AE during cancer treatment integrated with electronic patient records (eRAPID). As part of this program we developed a patient version of the CTCAE (version 4.0), rephrasing terminology into a self-report format. We explored patient understanding of these items via cognitive interviews. Sixty patients (33 female, 27 male) undergoing treatment were purposively sampled by age, gender and tumor group (median age 61.5, range 35-84, 12 breast, 12 gynecological, 13 colorectal, 12 lung and 11 renal). Twenty-one PRAE items were completed on a touch-screen computer. Subsequent audio-recorded cognitive interviews and thematic analysis explored patients' comprehension of items via verbal probing techniques during three interview rounds (n = 20 patients/round). In total 33 item amendments were made; 29% related to question comprehension, 68% response option and 3% order effects. These amendments to phrasing and language improved patient understanding but maintained CTCAE grading and key medical information. Changes were endorsed by members of a patient advisory group (N = 11). Item adaptations resulted in a bank of consistently interpreted self-report AE items for use in future research program. In-depth analysis of items through cognitive interviews is an important step towards developing an internationally valid system for PRAE, thus improving patient safety and experiences during cancer treatment.

  12. Correlation of treatment-emergent adverse events and clinical response to endocrine therapy in early breast cancer: a retrospective analysis of the German cohort of TEAM.

    PubMed

    Hadji, P; Kieback, D G; Tams, J; Hasenburg, A; Ziller, M

    2012-10-01

    Previous studies have suggested a correlation between the occurrence of vasomotor or joint symptoms during tamoxifen or aromatase inhibitor treatment and improved clinical response. A retrospective analysis of the German cohort of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial was carried out to assess disease-free survival (DFS) and overall survival (OS) in patients with and without arthralgia/myalgia and/or menopausal symptoms during adjuvant endocrine treatment. A total of 1502 patients were included; 739 patients received tamoxifen followed by exemestane and 763 received exemestane. Patients reporting arthralgia/myalgia and patients reporting menopausal symptoms during endocrine treatment had significantly longer OS and DFS than those not reporting these events. The effect on OS was irrespective of treatment. DFS was significantly improved in exemestane-treated patients reporting arthralgia/myalgia or those reporting menopausal symptoms versus those not reporting these events. This effect on DFS was not observed in patients receiving sequential treatment. A combined analysis of patients reporting either menopausal symptoms or arthralgia/myalgia showed that OS and DFS were significantly improved in patients reporting one of these symptoms versus those not reporting either symptom. The occurrence of arthralgia/myalgia or menopausal symptoms during endocrine treatment is associated with significantly improved OS.

  13. Adverse Effects Associated With Newer Diabetes Therapies.

    PubMed

    Akiyode, Oluwaranti F; Adesoye, Adebola A

    2017-04-01

    The increasing number of newer type 2 diabetes therapies has allowed providers an increased armamentarium for the optimal management of patients with diabetes. In fact, these newer agents have unique benefits in the management of type 2 diabetes. However, they are also associated with certain adverse effects. This review article aims to describe the notable adverse effects of these newer antidiabetic therapies including the glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and the sodium-glucose cotransporter 2 inhibitors. The adverse effects reviewed herein include pancreatitis, medullary thyroid carcinoma, heart failure, gastrointestinal disturbances, renal impairment, and genitourinary infections. More clinical data are necessary to solidify the association of some of these adverse effects with the newer diabetes agents. However, it is important for health care practitioners to be well informed and prepared to properly monitor patients for these adverse effects.

  14. Relationship between Physician-Adjudicated Adverse Events and Patient-Reported Health-Related Quality of Life in a Phase II Clinical Trial (NCT01143402) of Patients with Metastatic Uveal Melanoma*

    PubMed Central

    Atkinson, Thomas M.; Hay, Jennifer L.; Shoushtari, Alexander; Li, Yuelin; Paucar, Daniel J.; Smith, Sloane C.; Kudchadkar, Ragini R.; Doyle, Austin; Sosman, Jeffrey A.; Quevedo, Jorge Fernando; Milhem, Mohammed M.; Joshua, Anthony M.; Linette, Gerald P.; Gajewski, Thomas F.; Lutzky, Jose; Lawson, David H.; Lao, Christopher D.; Flynn, Patrick J.; Albertini, Mark R.; Sato, Takami; Lewis, Karl; Marr, Brian; Abramson, David H.; Dickson, Mark Andrew; Schwartz, Gary K.; Carvajal, Richard D.

    2016-01-01

    Purpose Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the Common Terminology Criteria for Adverse Events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data is becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. Methods Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n=118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications. Results Ninety-four percent had a CTCAE grade ≥ 1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r=0.31, p<0.01) and end of treatment (r=0.42, p<0.05). There were no significant correlations between need for dose modification and HRQoL scores. Conclusions Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct. PMID:27921276

  15. Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma.

    PubMed

    Atkinson, Thomas M; Hay, Jennifer L; Shoushtari, Alexander; Li, Yuelin; Paucar, Daniel J; Smith, Sloane C; Kudchadkar, Ragini R; Doyle, Austin; Sosman, Jeffrey A; Quevedo, Jorge Fernando; Milhem, Mohammed